Amino Acid Metabolism-Regulated Nanomedicine for Enhanced Tumor Immunotherapy through Synergistic Regulation of Immune Microenvironment.

The reprogramming of tumor metabolism presents a substantial challenge for effective immunotherapy, playing a crucial role in developing an immunosuppressive microenvironment. In particular, the degradation of the amino acid L-tryptophan (Trp) to kynurenine (Kyn) by indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) is one of the most clinically validated pathways for immune suppression. Thus, regulating the Trp/Kyn metabolism by IDO1 inhibition represents a promising strategy for enhancing immunotherapy. Herein, metabolism-regulated nanoparticles are prepared through metal coordination-driven assembly of an IDO1 inhibitor (NLG919) and a stimulator of interferon genes (STING) agonist (MSA-2) for enhanced immunotherapy. After intravenous administration, the assembled nanoparticles could efficiently accumulate in tumors, enhancing the bioavailability of NLG919 and down-regulating the metabolism of Trp to Kyn to remodel the immunosuppressive tumor microenvironment. Meanwhile, the released MSA-2 evoked potent STING pathway activation in tumors, triggering an effective immune response. The antitumor immunity induced by nanoparticles significantly inhibited the development of primary and metastatic tumors, as well as B16 melanoma. Overall, this study provided a novel paradigm for enhancing tumor immunotherapy through synergistic amino acid metabolism and STING pathway activation.

Hydrogen therapy promotes macrophage polarization to the M2 subtype in radiation lung injury by inhibiting the NF-κB signalling pathway.

Background: Radiotherapy has become a standard treatment for chest tumors, but a common complication of radiotherapy is radiation lung injury. Currently, there is still a lack of effective treatment for radiation lung injury. Methods: A mouse model of radioactive lung injury (RILI) was constructed and then treated with different cycles of hydrogen inhalation. Lung function tests were performed to detect changes in lung function.HE staining was used to detect pathological changes in lung tissue. Immunofluorescence staining was used to detect the polarization of macrophages in lung tissue. Immunohistochemistry was used to detect changes in cytokine expression in lung tissues. Western Blot was used to detect the expression of proteins related to the NF-κB signalling pathway. Results: Lung function test results showed that lung function decreased in the model group and improved in the treatment group.HE staining showed that inflammatory response was evident in the model group and decreased in the treatment group. Immunohistochemistry results showed that the expression of pro-inflammatory factors was significantly higher in the model group, and the expression of pro-inflammatory factors was significantly higher in the treatment group. The expression of pro-inflammatory factors in the treatment group was significantly lower than that in the model group, and the expression of anti-inflammatory factors in the treatment group was higher than that in the model group. Immunofluorescence showed that the expression of M1 subtype macrophages was up-regulated in the model group and down-regulated in the treatment group. The expression of M2 subtype macrophages was up-regulated in the treatment group relative to the model group. Western Blot showed that P-NF-κB p65/NF-κB p65 was significantly increased in the model group, and P-NF-κB p65/NF-κB p65 was decreased in the treatment group. Conclusion: Hydrogen therapy promotes macrophage polarization from M1 to M2 subtypes by inhibiting the NF-κB signalling pathway, thereby attenuating the inflammatory response to radiation lung injury.

A preliminary investigation of precise visualization, localization, and resection of pelvic lymph nodes in bladder cancer by using indocyanine green fluorescence-guided approach through intracutaneous dye injection into the lower limbs and perineum.

Objective: This study aimed to investigate the feasibility and effectiveness of using indocyanine green (ICG) injected intracutaneously through the lower limbs and perineum for visualized tracking, localization, and qualitative assessment of pelvic lymph nodes (LNs) in bladder cancer to achieve their accurate resection. Methods: First, ICG was injected into the LN metastasis model mice lower limbs, and real-time and dynamic in vivo and ex vivo imaging was conducted by using a near-infrared fluorescence imaging system. Additionally, 26 patients with bladder cancer were enrolled and divided into intracutaneous group and transurethral group. A near-infrared fluorescence imaging device with internal and external imaging probes was used to perform real-time tracking, localization, and resection of the pelvic LNs. Results: The mice normal LNs and the metastatic LNs exhibited fluorescence. The metastatic LNs showed a significantly higher signal-to-background ratio than the normal LNs (3.9 ± 0.2 vs. 2.0 ± 0.1, p < 0.05). In the intracutaneous group, the accuracy rate of fluorescent-labeled LNs was 97.6%, with an average of 11.3 ± 2.4 LNs resected per patient. Six positive LNs were detected in three patients (18.8%). In the transurethral group, the accuracy rate of fluorescent-labeled LNs was 84.4%, with an average of 8.6 ± 2.3 LNs resected per patient. Two positive LNs were detected in one patient (12.5%). Conclusion: Following the intracutaneous injection of ICG into the lower limbs and perineum, the dye accumulates in pelvic LNs through lymphatic reflux. By using near-infrared fluorescence laparoscopic fusion imaging, physicians can perform real-time tracking, localization, and precise resection of pelvic LNs.

Jinkui Shenqi pills ameliorate diabetes by regulating hypothalamic insulin resistance and POMC/AgRP expression and activity.

BACKGROUND: Research on the imbalance of proopiomelanocortin (POMC)/agouti-related protein (AgRP) neurons in the hypothalamus holds potential insights into the pathophysiology of diabetes. Jinkui Shenqi pills (JSP), a prevalent traditional Chinese medicine, regulate hypothalamic function and treat diabetes. PURPOSE: To investigate the hypoglycemic effect of JSP and explore the probable mechanism in treating diabetes. METHODS: A type 2 diabetes mouse model was used to investigate the pharmacodynamics of JSP. The glucose-lowering efficacy of JSP was assessed through various metrics including body weight, food consumption, fasting blood glucose (FBG), serum insulin levels, and an oral glucose tolerance test (OGTT). To elucidate the modulatory effects of JSP on hypothalamic mechanisms, we quantified the expression and activity of POMC and AgRP and assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (AKT)/forkhead box O1 (FOXO1) pathway in diabetic mice via western blotting and immunohistochemistry. Additionally, primary hypothalamic neurons were exposed to high glucose and palmitic acid levels to induce insulin resistance, and the influence of JSP on POMC/AgRP protein expression and activation was evaluated by PI3K protein inhibition using western blotting and immunofluorescence. RESULTS: Medium- and high-dose JSP treatment effectively inhibited appetite, resulting in a steady declining trend in body weight, FBG, and OGTT results in diabetic mice (p < 0.05). These JSP groups also had significantly increased insulin levels (p < 0.05). Importantly, the medium-dose group exhibited notable protection of hypothalamic neuronal and synaptic structures, leading to augmentation of dendritic length and branching (p < 0.05). Furthermore, low-, medium-, and high-dose JSP groups exhibited increased phosphorylated (p) INSR, PI3K, pPI3K, AKT, and pAKT expression, as well as decreased FOXO1 and increased pFOXO1 expression, indicating improved hypothalamic insulin resistance in diabetic mice (p < 0.05). Treatment with 10% JSP-enriched serum produced a marked elevation of both expression and activation of POMC (p < 0.05), with a concurrent reduction in AgRP expression and activation within primary hypothalamic neurons (p < 0.05). Intriguingly, these effects could be attributed to the regulatory dynamics of PI3K activity. CONCLUSION: Our findings suggest that JSP can ameliorate diabetes by regulating POMC/AgRP expression and activity. The insulin-mediated PI3K/AKT/FOXO1 pathway plays an important regulatory role in this intricate process.

[Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study]. / é‡ç»„äººç”Ÿé•¿æ¿€ç´ æ²»ç–—ä¸åŒåž‚ä½“å‘è‚²çŠ¶å†µç”Ÿé•¿æ¿€ç´ ç¼ºä¹ç—‡æ‚£å„¿ç–—æ•ˆçš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS: In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.

The SOD7/DPA4-GIF1 module coordinates organ growth and iron uptake in Arabidopsis.

Organ growth is controlled by both intrinsic genetic factors and external environmental signals. However, the molecular mechanisms that coordinate plant organ growth and nutrient supply remain largely unknown. We have previously reported that the B3 domain transcriptional repressor SOD7 (NGAL2) and its closest homologue DPA4 (NGAL3) act redundantly to limit organ and seed growth in Arabidopsis. Here we report that SOD7 represses the interaction between the transcriptional coactivator GRF-INTERACTING FACTOR 1 (GIF1) and growth-regulating factors (GRFs) by competitively interacting with GIF1, thereby limiting organ and seed growth. We further reveal that GIF1 physically interacts with FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT), which acts as a central regulator of iron uptake and homeostasis. SOD7 can competitively repress the interaction of GIF1 with FIT to influence iron uptake and responses. The sod7-2 dpa4-3 mutant enhances the expression of genes involved in iron uptake and displays high iron accumulation. Genetic analyses support that GIF1 functions downstream of SOD7 to regulate organ and seed growth as well as iron uptake and responses. Thus, our findings define a previously unrecognized mechanism that the SOD7/DPA4-GIF1 module coordinates organ growth and iron uptake by targeting key regulators of growth and iron uptake.

Investigation of awareness rate of prostate-specific antigen (PSA) among the general public in China and analysis of influencing factors.

Objective: This study aimed to evaluate the awareness rate of prostate-specific antigen (PSA) among the general public in China and provide data about prostate cancer (PCa) for related scientific research. Methods: A cross-sectional survey of PSA awareness was conducted in multiple regional populations using an online questionnaire. The questionnaire included basic information, knowledge about PCa, the awareness rate and application of PSA, and future expectations toward applying PSA screening in clinical practice. The study applied the methods of Pearson chi-square analysis and Logistic regression analysis. Results: A total of 493 valid questionnaires were included. Two hundred and nineteen respondents (44.4%) were males, and 274 (55.6%) were females. Of all respondents, 212 (43.0%) were under 20 years old, 147 (29.8%) were 20-30 years old, 74 (15.0%) were 30-40 years old, and 60 (12.2%) were over 40 years old. There are 310 people (62.9%) with medical educational background and 183 (37.1%) without. One hundred eighty-seven (37.9%) of the respondents were aware of PSA, and 306 (62.1%) were unaware of PSA. Statistically significant differences were obtained between the two groups regarding different ages, educational backgrounds, occupations, departments, and habits of knowing medical knowledge (all p < 0.05). In addition, the differences between the group of aware of PSA (AP) and the group unaware of PSA (UAP) in terms of whether they had been exposed to PSA screening and whether they had exposure to PCa patients or related knowledge were also observed (all p < 0.05). Age ≥30 years, medical educational background, understanding of medical knowledge, exposure to PCa patients or related knowledge, exposure to PSA screening, and status as a graduate student and above were independent factors for the occurrence of PSA awareness events (all p < 0.05). In addition, age ≥ 30 years, medical educational background, and awareness of PSA were independent factors for future expectations toward PSA (all p < 0.05). Conclusions: We first analyzed the public awareness of PSA. Cognition degrees of PSA and PCa awareness vary among different populations in China. Therefore, we should designate corresponding widespread scientific educational programs for different populations to increase the awareness rate of PSA.

Renin-angiotensin system inhibitors mitigate radiation pneumonitis by activating ACE2-angiotensin-(1-7) axis via NF-κB/MAPK pathway.

Radiation pneumonitis (RP) affects both patients and physicians during radiation therapy for lung cancer. To date, there are no effective drugs for improving the clinical outcomes of RP. The activation of angiotensin-converting enzyme 2 (ACE2) improves experimental acute lung injury caused by severe acute respiratory syndrome coronavirus, acid inhalation, and sepsis. However, the effects and underlying mechanisms of ACE2 in RP remain unclear. Therefore, this study aimed to investigate the effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on RP and ACE2/angiotensin-(1-7)/Mas receptor pathway activation. We found that radiotherapy decreased the expression of ACE2 and that overexpression of ACE2 alleviated lung injury in an RP mouse model. Moreover, captopril and valsartan restored ACE2 activation; attenuated P38, ERK, and p65 phosphorylation; and effectively mitigated RP in the mouse model. Further systematic retrospective analysis illustrated that the incidence of RP in patients using renin-angiotensin system inhibitors (RASis) was lower than that in patients not using RASis (18.2% vs. 35.8% at 3 months, p = 0.0497). In conclusion, the current findings demonstrate that ACE2 plays a critical role in RP and suggest that RASis may be useful potential therapeutic drugs for RP.

Prognostic significance of increased preoperative red cell distribution width (RDW) and changes in RDW for colorectal cancer.

BACKGROUND: Increased preoperative red cell distribution width (RDW) is associated with poor prognosis in several cancers, but the relationships between preoperative RDW and changes in RDW (ΔRDW) and colorectal cancer (CRC) prognosis remain unclear. Our study aimed to demonstrate the prognostic significance of increased preoperative RDW and ΔRDW for CRC. METHODS: In this retrospective analysis, we enrolled 833 patients who underwent CRC surgery between 2015 and 2019 at the Affiliated Hospital of Xuzhou Medical University, China. ΔRDW in our study was defined as RDW at 1 month after discharge minus preoperative RDW. According to receiver operating characteristic (ROC) curve analysis, we used cut-off values of 13.5% for RDW, 0.9% for ΔRDW. The cumulative survival rate was determined using the Kaplan-Meier method, and significant differences were evaluated by the log-rank test. Multivariable Cox regression model was applied to clarify the independent risk factors for overall survival (OS), which were used to construct a nomogram prediction model. The competing risk method was also applied, and we analyzed only patients with early-stage disease (stage 0-II) for sensitivity analysis. RESULTS: Multivariable Cox regression analysis demonstrated that age, RDW, ΔRDW, postoperative adjuvant chemotherapy, CEA, CA19-9, ASA, TNM stage, and pathological type were independent factors for OS in CRC patients (all p < 0.05). These prognostic factors were used to establish and verify the OS nomogram. Poorer OS was linked to higher RDW (HR = 1.52; 95% CI, 1.11-2.08; p < 0.01) and ΔRDW (HR = 1.65; 95% CI, 1.19-2.28; p < 0.01) in all-stage patients, and was only linked to higher RDW in early-stage patients. In competing risk model, H-RDW and H-ΔRDW were confirmed to be independent risk factors for CSS in CRC patients. CONCLUSIONS: High preoperative RDW and ΔRDW are both risk factors for OS and CSS in CRC.

CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS.

The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and endocrine therapy resistance remain incompletely understood. Here, we report that circPVT1, a circular RNA generated from the lncRNA PVT1, is highly expressed in ERα-positive breast cancer cell lines and tumor samples and is functionally important in promoting ERα-positive breast tumorigenesis and endocrine therapy resistance. CircPVT1 acts as a competing endogenous RNA (ceRNA) to sponge miR-181a-2-3p, promoting the expression of ESR1 and downstream ERα-target genes and breast cancer cell growth. Furthermore, circPVT1 directly interacts with MAVS protein to disrupt the RIGI-MAVS complex formation, inhibiting type I interferon (IFN) signaling pathway and anti-tumor immunity. Anti-sense oligonucleotide (ASO)-targeting circPVT1 inhibits ERα-positive breast cancer cell and tumor growth, re-sensitizing tamoxifen-resistant ERα-positive breast cancer cells to tamoxifen treatment. Taken together, our data demonstrated that circPVT1 can work through both ceRNA and protein scaffolding mechanisms to promote cancer. Thus, circPVT1 may serve as a diagnostic biomarker and therapeutic target for ERα-positive breast cancer in the clinic.

Segmentation Algorithm of Magnetic Resonance Imaging Glioma under Fully Convolutional Densely Connected Convolutional Networks.

This work focused on the application value of magnetic resonance imaging (MRI) image segmentation algorithm based on fully convolutional DenseNet neural network (FCDNN) in glioma diagnosis. In this work, based on the fully convolutional DenseNet algorithm, a new MRI image automatic semantic segmentation method cerebral gliomas semantic segmentation network (CGSSNet) was established and was applied to glioma MRI image segmentation by using the BraTS public dataset as research data. Under the same conditions, compare the differences of dice similarity coefficient (DSC), sensitivity, and Hausdroff distance (HD) between this algorithm and other algorithms in MRI image processing. The results showed that the CGSSNet network segmentation algorithm significantly improved the segmentation accuracy of glioma MRI images. In addition, its DSC, sensitivity, and HD values for glioma MRI images were 0.937, 0.811, and 1.201, respectively. Under different iteration times, the DSC, sensitivity, and HD values of the CGSSNet network segmentation algorithm are significantly better than other algorithms. It showed that the CGSSNet model based on the DenseNet can improve the segmentation accuracy of glioma MRI images, and has potential application value in clinical practice.

Effect of Intranasal Dexmedetomidine or Midazolam for Premedication on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.

Importance: Perioperative respiratory adverse events (PRAEs) are the most common complication during pediatric anesthesia, and they may be affected by the administration of preoperative sedatives. Objective: To investigate the effect of intranasal dexmedetomidine or midazolam used for premedication on the occurrence of PRAEs. Design, Setting, and Participants: This single-center, double-blind, randomized clinical trial was conducted among children aged 0 to 12 years undergoing elective tonsillectomy and adenoidectomy from October 2020 to June 2021 at Children's Hospital of Xuzhou Medical University, Xuzhou, China. Data analysis was performed from June to October 2021. Interventions: Children were randomly assigned to 3 groups: the midazolam group received intranasal midazolam (0.1 mg/kg), and the dexmedetomidine group received intranasal dexmedetomidine (2.0 µg/kg) for premedication. The normal saline group received intranasal 0.9% saline for control. Main Outcomes and Measures: The primary outcome was the difference in the incidence of PRAEs among the 3 groups. The secondary outcomes were the frequency of the individual PRAEs, including the incidence of such events during the induction and recovery periods, postoperative emergence delirium, postoperative pain score, sedation success rate, and heart rate values. Results: A total of 384 children (median [IQR] age, 7 [5-10] years; 227 boys [59.1%]) were enrolled and randomized; 373 data sets were available for intention-to-treat analysis (124 children in the midazolam group, 124 children in the dexmedetomidine group, and 125 children in the normal saline group). After the data were adjusted for age, sex, American Society of Anesthesiologists physical status, body mass index, obstructive sleep apnea, upper respiratory tract infection, and passive smoking, children in the midazolam group were more likely to experience PRAEs than those in the normal saline group (70 of 124 children [56.5%] vs 51 of 125 children [40.8%]; adjusted odds ratio [aOR], 1.99; 95% CI, 1.18-3.35), whereas the dexmedetomidine group had a significantly lower PRAEs incidence than the normal saline group (30 of 124 children [24.2%] vs 51 of 125 children [40.8%]; aOR, 0.45; 95% CI, 0.26-0.78). Compared with the dexmedetomidine group, the midazolam group had a higher risk of PRAEs (aOR, 4.44; 95% CI, 2.54-7.76), but no other serious clinical adverse events were observed. Conclusions and Relevance: In this randomized clinical trial, intranasal midazolam used for premedication was associated with increased incidence of PRAEs, whereas premedication with intranasal dexmedetomidine was associated with reduced incidence of PRAEs. Where clinically appropriate, anesthesiologists should consider using intranasal dexmedetomidine for sedation in children undergoing tonsillectomy and adenoidectomy. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2000038359.

Self-Assembly 3D Porous Crumpled MXene Spheres as Efficient Gas and Pressure Sensing Material for Transient All-MXene Sensors.

Environmentally friendly degradable sensors with both hazardous gases and pressure efficient sensing capabilities are highly desired for various promising applications, including environmental pollution monitoring/prevention, wisdom medical, wearable smart devices, and artificial intelligence. However, the transient gas and pressure sensors based on only identical sensing material that concurrently meets the above detection needs have not been reported. Here, we present transient all-MXene NO2 and pressure sensors employing three-dimensional porous crumpled MXene spheres prepared by ultrasonic spray pyrolysis technology as the sensing layer, accompanied with water-soluble polyvinyl alcohol substrates embedded with patterned MXene electrodes. The gas sensor achieves a ppb-level of highly selective NO2 sensing, with a response of up to 12.11% at 5 ppm NO2 and a detection range of 50 ppb-5 ppm, while the pressure sensor has an extremely wide linear pressure detection range of 0.14-22.22 kPa and fast response time of 34 ms. In parallel, all-MXene NO2 and pressure sensors can be rapidly degraded in medical H2O2 within 6 h. This work provides a new avenue toward environmental monitoring, human physiological signal monitoring, and recyclable transient electronics.

Comparative Study of Radiation-induced Lung Injury Model in Two Strains of Mice.

ABSTRACT: Radiation-induced lung injury (RILI) is a common complication of radiotherapy for thoracic tumor. Its incidence rate is as high as 20%. At present, there is no effective treatment in clinical practice. However, to study the mechanism of radiation-induced lung injury, we should first establish an appropriate animal model. In a series of scientific studies on RILI, mice are the animals most often chosen by researchers. However, there are few reports on which strain of mice is more suitable as a model of RILI. In this study, Kunming (KM) and C57BL/6 strains of mice were used as research objects to find the most suitable mice to replicate the RILI model. C57BL/6 mice and KM mice were exposed to irradiation at a dose of 20 Gy. The lung tissue of C57BL/6 mice exposed to radiation showed dilation and hyperemia of capillaries, infiltration of inflammatory cells, and thickening of alveolar septum, while the lung tissue of KM mice exposed to radiation was not as obvious as that of C57BL/6 mice. After irradiation, the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the lung tissue of C57BL/6 mice was significantly increased, while the expression of IL-6 and TNF-α in KM mice was almost unchanged. These studies showed that C57BL/6 mice are more suitable for the model of radiation-induced lung injury because of sensitive inflammatory reaction and the pathological changes of lung tissue.

Development and Validation of a Risk Nomogram Model for Perioperative Respiratory Adverse Events in Children Undergoing Airway Surgery: An Observational Prospective Cohort Study.

PURPOSE: The aim of this study was to explore the associated risk factors of perioperative respiratory adverse events (PRAEs) in children undergoing airway surgery and establish and validate a nomogram prediction model for PRAEs. PATIENTS AND METHODS: This study involved 709 children undergoing airway surgery between November 2020 and July 2021, aged ≤18 years in the affiliated hospital of Xuzhou Medical University. They were divided into training (70%; n = 496) and validation (30%; n = 213) cohorts. The least absolute shrinkage and selection operator (LASSO) was used to develop a risk nomogram model. Concordance index values, calibration plot, decision curve analysis, and the area under the curve (AUC) were examined. RESULTS: PRAEs were found in 226 of 496 patients (45.6%) and 88 of 213 patients (41.3%) in the training and validation cohorts, respectively. The perioperative risk factors associated with PRAEs were age, obesity, degree of upper respiratory tract infection, premedication, and passive smoking. The risk nomogram model showed good discrimination power, and the AUC generated to predict survival in the training cohort was 0.760 (95% confidence interval, 0.695-0.875). In the validation cohort, the AUC of survival predictions was 0.802 (95% confidence interval, 0.797-0.895). Calibration plots and decision curve analysis showed good model performance in both datasets. The sensitivity and specificity of the risk nomogram model were calculated, and the result showed the sensitivity of 69.5% and 64.8% and specificity of 73.3% and 81.6% for the training and validation cohorts, respectively. CONCLUSION: The present study showed the proposed nomogram achieved an optimal prediction of PRAEs in patients undergoing airway surgery, which can provide a certain reference value for predicting the high-risk population of perioperative respiratory adverse events and can lead to reasonable preventive and treatment measures.

Machine Learning-Assisted Development of Sensitive Electrode Materials for Mixed Potential-Type NO2 Gas Sensors.

Yttrium-stabilized zirconia (YSZ)-based mixed potential-type NOx sensors have broad application prospects in automotive exhaust gas detection. Great efforts continue to be made in developing high-performance sensitive electrode materials for mixed potential-type NO2 gas sensors. However, only five kinds of new sensing electrode materials have been developed for this type of gas sensor in the last 3 years. In this work, four different tree-based machine learning models were trained to find potentially sensitive electrode materials for NO2 detection. More than 400 materials were selected from 8000 materials by the above machine learning models. To further verify the reliability of the model, 13 of these materials containing unexploited elements were selected as sensitive electrode materials for making sensors and testing their gas-sensing performances. The experimental results showed that all 13 materials exhibited good gas-sensing performance for NO2. More interestingly, an electrode material BPO4, which does not contain any metal elements, was also screened out and showed good sensing properties to NO2. In a short period of time, 13 new sensitive electrode materials for NO2 detection were targeted and screened, which was difficult to achieve by a trial-and-error procedure.

Development and Validation of Nomogram Prediction Model for Postoperative Sleep Disturbance in Patients Undergoing Non-Cardiac Surgery: A Prospective Cohort Study.

PURPOSE: To develop a risk prediction nomogram of postoperative sleep disturbance (PSD) in patients undergoing non-cardiac surgery. PATIENTS AND METHODS: Data on 881 consecutive patients who underwent non-cardiac surgery at the Affiliated Hospital of Xuzhou Medical University between June 2020 and April 2021 were prospectively collected. Of these, we randomly divided 881 non-cardiac patients into two groups, training cohort (n = 617) and validation cohort (n = 264) at the ratio of 7:3. Characteristic variables were selected based on the data of training cohort through least absolute shrinkage and selection operator (LASSO) regression. Multivariate logistic regression was used to identify the independent risk factors associated with PSD that then were incorporated into the nomogram. The predictive performance of the nomogram was measured by concordance index (C index), receiver operating characteristic (ROC) curve, and calibration with 1000 bootstrap samples to decrease the over-fit bias. RESULTS: PSD was found in 443 of 617 patients (71.8%) and 190 of 264 patients (72.0%) in the training and validation cohorts, respectively. The perioperative risk factors associated with PSD were female sex, anxiety, dissatisfaction of ward environment, absence of combined regional nerve block, postoperative nausea and vomiting (PONV), the longer duration stayed in post anesthesia care unit (PACU), the higher dose of midazolam and sufentanil, the higher postoperative numeric rating score for pain (NRS) score. Incorporating these 9 factors, the nomogram achieved good concordance indexes of 0.82 (95% confidence interval [CI], 0.78-0.85) and 0.80 (95% CI, 0.74-0.85) in predicting PSD in the training and validation cohorts, respectively, and obtained well-fitted calibration curves. The sensitivity and specificity (95% CIs) of the nomogram were calculated, resulting in sensitivity of 74.0% (70.0-78.2%) and 75.3% (68.4-81.7%) and specificity of 79.3% (72.5-85.2%) and 70.3% (58.4-80.7%) for the training and validation cohorts, respectively. Patients who had a nomogram score of less than 262 or 262 or greater were considered to have low or high risks of PSD presence, respectively. CONCLUSION: The proposed nomogram achieved an optimal prediction of PSD in patients undergoing non-cardiac surgery. The risks for an individual patient to harbor PSD can be determined by this model, which can lead to a reasonable preventive and treatment measures.

Synaptosomal Actin Dynamics in the Developmental Visual Cortex Regulate Behavioral Visual Acuity in Rats.

Purpose: Synaptosomal actin dynamics are essential for synaptic structural stability. Whether actin dynamics are involved in structural and functional synaptic plasticity within the primary visual cortex (V1) or behavioral visual acuity in rats has still not been thoroughly investigated. Methods: Synaptosome preparation and western blot analysis were used to analyze synaptosomal actin dynamics. Transmission electron microscopy was used to detect synaptic density and mitochondrial area alterations. A visual water maze task was applied to assess behavioral visual acuity. Microinjection of the actin polymerization inhibitor or stabilizer detected the effect of actin dynamics on visual function. Results: Actin dynamics, the mitochondrial area, and synaptic density within the area of V1 are increased during the critical period for the development of binocularity. Microinjection of the actin polymerization inhibitor cytochalasin D into the V1 decreased the mitochondrial area, synaptic density, and behavioral visual acuity. Long-term monocular deprivation reduced actin dynamics, the mitochondrial area, and synaptic density within the V1 contralateral to the deprived eye compared with those ipsilateral to the deprived eye and impaired visual acuity in the amblyopic eye. In addition, the mitochondrial area, synaptic density, and behavioral visual acuity were improved by stabilization of actin polymerization by jasplakinolide microinjection. Conclusions: During the critical period of visual development of binocularity, synaptosomal actin dynamics regulate synaptic structure and function and play roles in behavioral visual acuity in rats.

Applications and therapeutic mechanisms of action of mesenchymal stem cells in radiation-induced lung injury.

Radiation-induced lung injury (RILI) is one of the most common complications associated with radiotherapy, characterized by early-stage radiation pneumonia and subsequent radiation pulmonary fibrosis. However, effective therapeutic strategies for RILI are currently lacking. Recently, an increasing number of studies reported that mesenchymal stem cells (MSCs) can enhance the regeneration of damaged tissue, modulate the inflammatory response, reduce the levels of fibrotic cytokines and reactive oxygen species, and inhibit epithelial-mesenchymal transformation. Interestingly, MSCs can also exert immunosuppressive effects, which highlights a new potential therapeutic activity of MSCs for managing RILI. Here, we reviewed the potential applications and therapeutic mechanisms of action of MSCs in RILI, which will represent a good compendium of information for researchers in this field.

Nuclear translocation of ATG5 induces DNA mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) via interacting with Mis18α in colorectal cancer.

BACKGROUND AND PURPOSE: It is well known that microsatellite instability-high (MSI-H) is associated with 5-fluorouracil (5-FU) resistance in colorectal cancer. MSI-H is the phenotype of DNA mismatch repair deficiency (MMR-D), mainly occurring due to hypermethylation of MLH1 promoter CpG island. However, the mechanisms of MMR-D/MSI-H are unclear. We aim to investigate the pathway of MMR-D/MSI-H involved in 5-FU resistance. EXPERIMENTAL APPROACH: Human colorectal cancer specimens were diagnosed for MSI-H by immunohistochemistry and western blotting. Proteome microarray interactome assay was performed to screen nuclear proteins interacting with ATG5. Nuclear ATG5 and ATG5-Mis18α overexpression were analysed in ATG5high colorectal cancer bearing mice. The methylation assay determined the hypermethylation of hMLH1 promoter CpG island in freshly isolated human colorectal cancer tissue samples and HT29atg5 and SW480atg5 cancer cells. KEY RESULTS: In ATG5high colorectal cancer patients, 5-FU-based therapy resulted in nuclear translocation of ATG5, leading to MSI-H. Colorectal cancer in Atg5 Tg mice demonstrated 5-FU resistance, compared to Atg5+/- and WT mice. Proteome microarray assay identified Mis18α, a protein localized on the centromere and a source for methylation of the underlying chromatin, which responded to the translocated nuclear ATG5 leading to ATG5-Mis18α conjugate overexpression. This resulted in MLH1 deficiency due to hypermethylation of hMLH1 promoter CpG island, while the deletion of nuclear Mis18α failed to induce ATG5-Mis18α complex and MMR-D/MSI-H. CONCLUSIONS AND IMPLICATIONS: Nuclear ATG5 resulted in MMR-D/MSI-H through its interaction with Mis18α in ATG5high colorectal cancer cells. We suggest that ATG5-Mis18α or Mis18α may be a therapeutic target for treating colorectal cancer.