Search

Abstract Background Sepsis-induced pulmonary injury (SPI) is a common complication of sepsis with a high rate of mortality. N4-acetylcytidine (ac4C) is mediated by the ac4C “writer”, N-acetyltransferase (NAT)10, to regulate the stabilization of mRNA. This study aimed to investigate the role of NAT10 in SPI and the underlying mechanism. Methods Twenty-three acute respiratory distress syndrome (ARDS) patients and 27 non-ARDS volunteers were recruited. A sepsis rat model was established. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of NAT10 and transferrin receptor (TFRC). Cell viability was detected by cell counting kit-8. The levels of Fe2+, glutathione, and malondialdehyde were assessed by commercial kits. Lipid reactive oxygen species production was measured by flow cytometric analysis. Western blot was used to detect ferroptosis-related protein levels. Haematoxylin & eosin staining was performed to observe the pulmonary pathological symptoms. Results The results showed that NAT10 was increased in ARDS patients and lipopolysaccharide-treated human lung microvascular endothelial cell line-5a (HULEC-5a) cells. NAT10 inhibition increased cell viability and decreased ferroptosis in HULEC-5a cells. TFRC was a downstream regulatory target of NAT10-mediated ac4C acetylation. Overexpression of TFRC decreased cell viability and promoted ferroptosis. In in vivo study, NAT10 inhibition alleviated SPI. Conclusion NAT10-mediated ac4C acetylation of TFRC aggravated SPI through promoting ferroptosis. Graphical Abstract

Abstract Objective Tongue squamous cell carcinoma (TSCC) accounts for 43.4% of oral cancers in China and has a poor prognosis. This study aimed to explore whether radiomics features extracted from preoperative magnetic resonance imaging (MRI) could predict overall survival (OS) in patients with TSCC. Methods The clinical imaging data of 232 patients with pathologically confirmed TSCC at Xiangyang No. 1 People’s Hospital were retrospectively analyzed from February 2010 to October 2022. Based on 2–10 years of follow-up, patients were categorized into two groups: control (healthy survival, n = 148) and research (adverse events: recurrence or metastasis-related death, n = 84). A training and a test set were established using a 7:3 ratio and a time node. Radiomics features were extracted from axial T2-weighted imaging, contrast-enhanced T1-weighted imaging, and diffusion-weighted imaging (DWI) sequences. The corresponding radiomics scores were generated using the least absolute shrinkage and selection operator algorithm. Kaplan–Meier and multivariate Cox regression analyses were used to screen for independent factors affecting adverse events in patients with TSCC using clinical and pathological results. A novel nomogram was established to predict the probability of adverse events and OS in patients with TSCC. Results The incidence of adverse events within 2–10 years after surgery was 36.21%. Kaplan–Meier analysis revealed that hot pot consumption, betel nut chewing, platelet–lymphocyte ratio, drug use, neutrophil–lymphocyte ratio, Radscore, and other factors impacted TSCC survival. Multivariate Cox regression analysis revealed that the clinical stage (P 0.05) in the training and test sets, accurately predicting the risk of adverse events and survival. Conclusion The nomogram constructed using clinical data and MRI radiomics parameters may accurately predict TSCC-OS noninvasively, thereby assisting clinicians in promptly modifying treatment strategies to improve patient prognosis.

Abstract Purpose Preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) belong to lung function injury. PRISm is a precursor to COPD. We compared and evaluated the different basic information, imaging findings and survival curves of 108 lung cancer patients with different pulmonary function based on high resolution computed tomography (HRCT). Methods This retrospective study was performed on 108 lung cancer patients who did pulmonary function test (PFT) and thoracic HRCT. The basic information was evaluated: gender, age, body mass index (BMI), smoke, smoking index (SI). The following pulmonary function findings were evaluated: forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio. The following computed tomography (CT) findings were evaluated: appearance (bronchiectasis, pneumonectasis, atelectasis, ground-glass opacities [GGO], interstitial inflammation, thickened bronchial wall), diameter (aortic diameter, pulmonary artery diameter, MPAD/AD ratio, inferior vena cava diameter [IVCD]), tumor (volume, classification, distribution, staging [I, II, III, IV]). Mortality rates were calculated and survival curves were estimated using the Kaplan-Meier method. Results Compared with normal pulmonary function group, PRISm group and COPD group were predominantly male, older, smoked more, poorer lung function and had shorter survival time after diagnosis. There were more abnormal images in PRISm group and COPD group than in normal lung function group (N-C group). In PRISm group and COPD group, lung cancer was found late, and the tumor volume was larger, mainly central squamous carcinoma. But the opposite was true for the N-C group. The PRISm group and COPD group had significant poor survival probability compared with the normal lung function group. Conclusions Considerable differences regarding basic information, pulmonary function, imaging findings and survival curves are found between normal lung function group and lung function injury group. Lung function injury (PRISm and COPD) should be taken into account in future lung cancer screening studies.

Abstract To maximize training programs and improve individual performance, the sports fitness profession is always looking for new and innovative solutions. Fuzzy decision support systems provide a strong basis for improving training regimen efficacy through flexible and adaptive decision-making. In sports fitness, doing things differently might affect the way one can train and even lead to injury. Particularly if exercises call for expert training regimens, determining if fitness requirements are sufficiently satisfied is a difficult task. Athletes participate in training programs focusing on strengthening their bodies and minds to perform better. Each sport has unique needs, and athletes should prepare to meet those demands while still meeting their sport’s general fitness activity requirements. A novel strategy for assisting athletes with fitness-related decision-making is presented in this study as the Fitness Mamdani Decision System. At the outset, the system provides an adaptive decision framework to improve the effectiveness of training programs by applying the principles of intuitionistic fuzzy numbers and fuzzy logic. The study wants to know how to train effectively, and it takes important factors like your mood, degree of preparation, sleep quality, and stress levels into account. Using language-specific terminology and triangle membership functions, the Mamdani fuzzy inference system generates rules based on analyzing these crucial elements. Regarding measures like adaptability index, training load capacity, long-term program efficiency, and participation ratio among sports fitness individuals, the system is guided by fuzzy rules that infer decisions.

ObjectiveTo predict postoperative anastomotic leakage (AL) following radical resection of esophageal squamous cell carcinoma (ESCC) based on clinical data and preoperative enhanced Computed tomography(CT) radiomics of the esophagus.MethodWe retrospectively analyzed the clinicopathological and radiological data of 213 patients with ESCC who received radical resection at Xiangyang No.1 People’s Hospital from July 2011 to February 2024. 3D slicer software was used in combination with Lasso extraction and 10-fold cross-validation to extract texture parameters from contrast-enhanced CT images and generate Delta-Radscores. Several models were built using logistic regression to predict postoperative AL in ESCC.ResultsIn the training set, the univariate analysis confirmed that duration of surgery, surgical method, delta radscore 1, delta radscore 2, contrast enhancement patterns, peripheral lymph node metastasis, post thoracotomy pulmonary infection(PTPI), and hot pot were risk factors for ESCC-AL (P

Inductive link prediction (ILP) in knowledge graphs (KGs) aims to predict missing links between entities that were not seen during the training phase. Recent some subgraph-based methods have shown some advancements, but they all overlook the relational semantics between entities during subgraph extraction. To overcome this limitation, we introduce a novel inductive link prediction model named SASILP (Structure and Semantic Inductive Link Prediction), which comprehensively incorporates relational semantics in both subgraph extraction and node initialization processes. The model employs a random walk strategy to calculate the structural scores of neighboring nodes and utilizes an enhanced graph attention network to determine their semantic scores. By integrating both structural and semantic scores, SASILP strategically selects key nodes to form a subgraph. Furthermore, the subgraph is initialized with a node initialization technique that integrates information about neighboring relations. The experiments conducted on benchmark datasets demonstrate that SASILP outperforms state-of-the-art methods on inductive link prediction tasks, and verify the effectiveness of our approach.

Objective To evaluate the impact of peripheral nerve aggression (PNI) on prognosis in patients with stage Ⅰ-Ⅲ early-onset colorectal cancer (EO-CRC) and to create a PNI-based nomogram prediction model. Methods This study analyzed data on 5 920 EO-CRC patients aged 50 years and younger enrolled in the U.S. Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. The patients were divided into the training group (n=4 164) and the validation group (n=1 756) by a ratio of 7∶3. Kaplan-Meier survival curve was drawn and Cox proportional risk model was used for univariate and multivariate prognosis analysis. Based on the significant variables of the multivariate model, a nomogram was constructed, and the predictive ability was evaluated by receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA). Results Compared with PNI negative patients, PNI positive patients tended to be young, lesions located in the left colon, with poorer differentiation, higher TNM stage, chemotherapy intervention, and higher CEA level (P＜0.05). Kaplan-Meier curve suggested that PNI positive group had a worse prognosis than PNI negative group. Cox univariate analysis suggested that age, sex, degree of tumor differentiation, TNM stage, T stage, N stage, whether to receive radiation therapy, whether to receive chemotherapy, CEA level, maximum tumor diameter and PNI status were variables affecting the survival and prognosis of patients. Multivariate analysis showed that PNI was an independent prognostic indicator for patients with stage Ⅰ to Ⅲ EO-CRC (HR=1.73, 95%CI: 1.44-2.08, P＜0.01). The area under ROC curve of nomogram model based on PNI was more than 0.7 in both 3-year and 5-year lifetime. Conclusion PNI can be used as an independent prognostic marker in patients with stage Ⅰ-Ⅲ EO-CRC, and PNI-based nomogram model can be used as an effective prognostic tool.

Ting Wang,1,2,* Lin Wang,1,* Yunliang Yao,2,* Nan Liu,1 Aiqin Peng,1 Min Ling,2 Fei Ye,1 JiaoJiao Sun1 1Affliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou Mental Health Center, Yangzhou, Jiangsu, People’s Republic of China; 2School of Medicine & Nursing, Huzhou University, Huzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Ye; Jiaojiao Sun, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou mental health center, Yangzhou, Jiangsu, 225000, People’s Republic of China, Tel +8613645251172 ; +8615150805127, Email 850906053@qq.com; sun15150805127@163.comBackground: The global incidence of acute events in psychiatric patients is intensifying, and models to successfully predict acute events have attracted much attention.Objective: To explore the influence factors of acute incident severe mental disorders (SMDs) and the application of Rstudio statistical software, and build and verify a nomogram prediction model.Methods: SMDs were taken as research objects. The questionnaire survey method was adopted to collect data. Patients with acute event independent factors were screened. R software multivariable Logistic regression model was constructed and a nomogram was drawn.Results: A total of 342 patients with SMDs were hospitalized, and the number of patients who encountered acute events was 64, which accounted for 18.70% of all patients. Statistical significances were found in many aspects (all P ˂ 0.05). Such aspects included Medication adherence, disease diagnosis, marital status, caregivers, social support and the hospitalization environment (odds ratio (OR) = 4.08, 11.62, 12.06, 10.52, 0.04 and 0.61, respectively) were independent risk factors for the acute events of patients with SMDs. The prediction model was modeled, and the AUC was 0.77 and 0.80. The calibration curve shows that the model has good calibration. The clinical decision curve shows that the model has a good clinical effect.Conclusion: The constructed risk prediction model shows good prediction effectiveness in the acute events of patients with SMDs, which is helpful for the early detection of clinical mental health staff at high risk of acute events.Keywords: SMDs, acute event, influencing factors, predictive model and nomogram

Background and objective As a new technique developed in recent years, bronchoscopic intervention therapy has the advantages of minimal invasion, high safety and repeatability. The aim of this study is to investigate the clinical characteristics of bronchopleural fistula (BPF) induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF, so as to provide support for prevention and treatment of BPF. Methods Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Center of Dongzhimen Hospital, Beijing University of Chinese Medicine from June 2020 to September 2023 were collected. Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol, combined with blocking therapy with N-butyl cyanoacrylate, medical bioprotein glue or silicone prosthesis. Patients with fistula diameter >5 mm were implanted with different stents and cardiac occluders. Locations and characteristics of fistulas were summarized, meanwhile, data including Karnofsky performance status (KPS), shortbreath scale (SS), body temperature, pleural drainage volume and white blood cell count before and after operation were observed. Results For all 64 patients, 96 anatomic lung resections including pneumonectomy, lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations. The proportion of fistula in the right lung (63.5%) was significantly higher than that in the left (36.5%). Besides, the right inferior lobar bronchial fistula was the most common (40.5%). After operation, KPS was significantly increased, while SS, body temperature, pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values (P

Aineng Peng,1 Jianbo Chai,2 Haiyuan Wu,1 Bing Bai,3 Huihui Yang,1 Weizhi He,1 Yonghou Zhao2 1Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China; 2Heilongjiang Mental Hospital, Harbin, 150036, People’s Republic of China; 3Tongde Hospital of Zhejiang Province, Hangzhou, 311100, People’s Republic of ChinaCorrespondence: Yonghou Zhao, Heilongjiang Mental Hospital, 153 Hengdao Street, Harbin, Heilongjiang, 150036, People’s Republic of China, Tel +86 13904638645, Email zyszbx2020@126.comAbstract: Schizophrenia is a disease with a complex pathological mechanism that is influenced by multiple genes. The study of its pathogenesis is dominated by the dopamine hypothesis, as well as other hypotheses such as the 5-hydroxytryptamine hypothesis, glutamate hypothesis, immune-inflammatory hypothesis, gene expression abnormality hypothesis, and neurodevelopmental abnormality hypothesis. The first generation of antipsychotics was developed based on dopaminergic receptor antagonism, which blocks dopamine D2 receptors in the brain to exert antipsychotic effects. The second generation of antipsychotics acts by dual blockade of 5-hydroxytryptamine and dopamine receptors. From the third generation of antipsychotics onwards, the therapeutic targets for antipsychotic schizophrenia expanded beyond D2 receptor blockade to explore D2 receptor partial agonism and the antipsychotic effects of new targets such as D3, 5-HT1A, 5-HT7, and mGlu2/3 receptors. The main advantages of the second and third generation antipsychotics over first-generation antipsychotics are the reduction of side effects and the improvement of negative symptoms, and even though third-generation antipsychotics do not directly block D2 receptors, the modulation of the dopamine transmitter system is still an important part of their antipsychotic process. According to recent research, several receptors, including 5-hydroxytryptamine, glutamate, γ-aminobutyric acid, acetylcholine receptors and norepinephrine, play a role in the development of schizophrenia. Therefore, the focus of developing new antipsychotic drugs has shifted towards agonism or inhibition of these receptors. Specifically, the development of NMDARs stimulants, GABA receptor agonists, mGlu receptor modulators, cholinergic receptor modulators, 5-HT2C receptor agonists and alpha-2 receptor modulators has become the main direction. Animal experiments have confirmed the antipsychotic effects of these drugs, but their pharmacokinetics and clinical applicability still require further exploration. Research on alternative targets for antipsychotic drugs, beyond the dopamine D2 receptor, has expanded the potential treatment options for schizophrenia and gives an important way to address the challenge of refractory schizophrenia. This article aims to provide a comprehensive overview of the research on therapeutic targets and medications for schizophrenia, offering valuable insights for both treatment and further research in this field.Keywords: schizophrenia, target, neurotransmitter, antipsychotic drugs

Abstract Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.

Background: Medium- to high-risk classification-gastrointestinal stromal tumors (MH-GIST) have a high recurrence rate and are difficult to treat. This study aims to predict the recurrence of MH-GIST within 3 years after surgery based on clinical data and preoperative Delta-CT Radiomics modeling. Methods: A retrospective analysis was conducted on clinical imaging data of 242 cases confirmed to have MH-GIST after surgery, including 92 cases of recurrence and 150 cases of normal. The training set and test set were established using a 7:3 ratio and time cutoff point. In the training set, multiple prediction models were established based on clinical data of MH-GIST and the changes in radiomics texture of enhanced computed tomography (CT) at different time periods (Delta-CT radiomics). The area under curve (AUC) values of each model were compared using the Delong test, and the clinical net benefit of the model was tested using decision curve analysis (DCA). Then, the model was externally validated in the test set, and a novel nomogram predicting the recurrence of MH-GIST was finally created. Results: Univariate analysis confirmed that tumor volume, tumor location, neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), diabetes, spicy hot pot, CT enhancement mode, and Radscore 1/2 were predictive factors for MH-GIST recurrence ( P

Nasopharyngeal Carcinoma (NC) refers to the malignant tumor that occurs at the top and side walls of the nasopharyngeal cavity. The NC incidence rate always dominates the first among the malignant tumors of the ear, nose and throat, and mainly occurs in Asia. NC cases are mainly concentrated in southern provinces in China, with about 4 million existing NC. With the pollution of environment and pickled diet, and the increase of life pressure, the domestic NC incidence rate has reached 4.5-6.5/100000 and is increasing year by year. It was reported that the known main causes of NC include hereditary factor, genetic mutations, and EB virus infection, common clinical symptoms of NC include nasal congestion, bloody mucus, etc. About 90% of NC is highly sensitive to radiotherapy which is regard as the preferred treatment method; However, for NC with lower differentiation, larger volume, and recurrence after treatment, surgical resection and local protons and heavy ions therapy are also indispensable means. According to reports, the subtle heterogeneity and diversity exists in some NC, with about 80% of NC undergone radiotherapy and about 25% experienced recurrence and death within five years after radiotherapy in China. Therefore, screening the NC population with suspected recurrence after concurrent chemoradiotherapy may improve survival rates in current clinical decision-making.

The efficacy of functional lipids with antioxidant properties in reducing cardiovascular risk has not been consistent. Randomized controlled trials (RCTs) reporting estimates for the effects of antioxidant functional lipid supplementations on cardiometabolic risk factors were searched up to 1 May 2024. Overall, antioxidant lipid supplementations, compared with placebo, had favorable effects on systolic blood pressure (lycopene: −1.95 [−3.54, −0.36] mmHg), low-density lipoprotein cholesterol (n6 fatty acid: −0.39 [−0.71, −0.06] mmol/L; astaxanthin: −0.11 [−0.21, −0.01] mmol/L), high-density lipoprotein cholesterol (n3 fatty acid: 0.20 [0.13, 0.27] mmol/L; n6 fatty acid: 0.08 [0.01, 0.14] mmol/L; astaxanthin: 0.13 [0.05, 0.21] mmol/L), total cholesterol (n6 fatty acid: −0.24 [−0.37, −0.11] mmol/L; astaxanthin: −0.22 [−0.32, −0.12] mmol/L; beta-carotene: −0.13 [−0.23, −0.04] mmol/L), triglyceride (n3 fatty acid: −0.37 [−0.47, −0.28] mmol/L; astaxanthin: −0.46 [−0.83, −0.10] mmol/L), and fasting blood insulin (astaxanthin: −2.66 [−3.98, −1.34] pmol/L). The benefits of antioxidant lipid supplementations appeared to be most evident in blood pressure and blood lipids in participants with different cardiometabolic health statuses. Notably, n9 fatty acid increased triglyceride and hemoglobin A1C in the total population, which increases CVD risk. Antioxidant lipid supplementations ameliorate cardiometabolic risk factors, while their effect may depend on type and cardiometabolic health status. Long-term RCTs are needed to corroborate risk–benefit ratios across different antioxidant functional lipid supplementation settings.

Background: Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, strength, and function. The occurrence of sarcopenia has a huge impact on physical, psychological, and social health. Therefore, the prevention and treatment of sarcopenia is becoming an important public health issue. Method: 35 six-week-old male C57BL/6 mice were randomly divided into five groups, one of which served as a control group, while the rest of the groups were constructed as a model of sarcopenia by intraperitoneal injection of D-galactose. The intervention with lactoferrin, creatine, and their mixtures, respectively, was carried out through gavage for 8 weeks. Muscle function was assessed based on their endurance, hanging time, and grip strength. The muscle tissues were weighed to assess the changes in mass, and the muscle RNA was extracted for myogenic factor expression and transcriptome sequencing to speculate on the potential mechanism of action by GO and KEGG enrichment analysis. Result: The muscle mass (lean mass, GAS index), and muscle function (endurance, hanging time, and grip strength) decreased, and the size and structure of myofiber was smaller in the model group compared to the control group. The intervention with lactoferrin and creatine, either alone or combination, improved muscle mass and function, restored muscle tissue, and increased the expression of myogenic regulators. The combined group demonstrated the most significant improvement in these indexes. The RNA-seq results revealed enrichment in the longevity-regulated pathway, MAPK pathway, focal adhesion, and ECM–receptor interaction pathway in the intervention group. The intervention group may influence muscle function by affecting the proliferation, differentiation, senescence of skeletal muscle cell, and contraction of muscle fiber. The combined group also enriched the mTOR-S6K/4E-BPs signaling pathway, PI3K-Akt signaling pathway, and energy metabolism-related pathways, including Apelin signaling, insulin resistance pathway, and adipocytokine signaling pathway, which affect energy metabolism in muscle. Conclusions: Lactoferrin and creatine, either alone or in combination, were found to inhibit the progression of sarcopenia by influencing the number and cross-sectional area of muscle fibers and muscle protein synthesis. The combined intervention appears to exert a more significant effect on energy metabolism.

ObjectiveTo understand the situation about time interval between the onset and medical visit among tuberculosis patients in Huaibei City， Anhui Province from 2017 to 2021， and to determine the delayed medical visit and its risk factors， as to provide evidence for tuberculosis prevention and control.MethodsCase information of confirmed tuberculosis patients in Huaibei City in 2017‒2021 was collected from the tuberculosis management information system. Factors associated with time interval between the onset and medical visit were analyzed using rank sum test and multivariate linear regression. Furthermore， factors associated with the delayed medical visit were determined by Chi-square test， Chi-square Cocharan⁃Mantel⁃Haensze test and logistic regression.ResultsThe median time interval between the onset of tuberculosis and medical visit were 22 days among the tuberculosis patients in Huaibei City from 2017‒2021， and the proportion of delayed medical visit was 68.57%. There was an overall decreasing trend in the proportion of delayed medical visit over years （χtrend2=17.342， P=0.002）. Using the multivariate linear regression， positive for Mycobacterium Tuberculosis in the pathogenic diagnosis， and presence of comorbidities were determined to be the risk factors associated with increased time interval between the onset and medical visit. Furthermore， logistic regression analysis showed that patients aged ≤24 years （OR=0.596， 95%CI：0.503‒0.706， P

Abstract Cervical cancer is one of the leading causes of cancer death in women. Mitochondrial-mediated ferroptosis (MMF) is a recently discovered form of cancer cell death. However, the role and the underlying mechanism of MMF in cervical cancer remain elusive. Here, using an unbiased screening for mitochondrial transmembrane candidates, we identified mitochondrial carrier 1 (MTCH1) as a central mediator of MMF in cervical cancers. MTCH1-deficiency disrupted mitochondrial oxidative phosphorylation while elevated mitochondrial reactive oxygen species (ROS) by decreasing NAD+ levels. This mitochondrial autonomous event initiated a mitochondria-to-nucleus retrograde signaling involving reduced FoxO1 nuclear translocation and subsequently downregulation of the transcription and activity of a key anti-ferroptosis enzyme glutathione peroxidase 4 (GPX4), thereby elevating ROS and ultimately triggering ferroptosis. Strikingly, targeting MTCH1 in combination with Sorafenib effectively and synergistically inhibited the growth of cervical cancer in a nude mouse xenograft model by actively inducing ferroptosis. In conclusion, these findings enriched our understanding of the mechanisms of MMF in which MTCH1 governed ferroptosis though retrograde signaling to FoxO1-GPX4 axis, and provided a potential therapeutic target for treating cervical cancer.

Atherosclerosis, a chronic inflammatory disease, is the major cause of arteriosclerotic cardiovascular diseases. Nicotinamide mononucleotide (NMN), an effective NAD+ booster, has been shown to reduce inflammation and protect vascular cell function, which are strongly associated with the progression of atherosclerosis. In this study, we explored the anti-atherosclerotic effects of NMN and its potential mechanism in ApoE−/− mice. We found that NMN significantly reduced the size of atherosclerotic plaque (36 %) and necrotic core (48 %) in aortic sinus. Additionally, NMN decreased lipid area (43 %) and increased collagen content (51 %) in atherosclerotic lesions. In addition, NMN reduced the level of malondialdehyde (MDA) in serum while elevating the enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Moreover, NMN reduced the expression of pro-inflammatory cytokines (Tnfα, Il-1β, Il-6 and Mcp-1) while increased the expression of anti-inflammatory factors (Arg-1, Mrc-1, Retlna and Irf-4) in aortic tissues. These results indicate that NMN exerts anti-atherosclerotic effects and inhibits oxidative stress and inflammatory response in HFD-fed ApoE−/− mice.

The past decade witnessed remarkable success in synthetic molecular nanographenes. Encouraged by the widespread application of chiral nanomaterials, the design, and construction of chiral nanographenes is a hot topic recently. As a classic nanographene unit, hexa-peri-hexabenzocoronene generally serves as the building block for nanographene synthesis. This review summarizes the representative examples of hexa-peri-hexabenzocoronene-based chiral nanographenes.

Two-dimensional Sc2CO2 MXene materials have been considered highly potential for gas capture and gas sensor applications. In this study, the adsorption behaviors of small molecules such as NH3, SO3, O2, H2CO and C2H4 on Sc2CO2 monolayer were investigated using first-principles methods. Our results demonstrate the preferential adsorption of NH3 over other species with adsorption energies as high as −0.55 eV. And Sc2CO2 is transformed from an indirect bandgap semiconductor to a direct bandgap semiconductor after NH3 adsorption, and the appropriate band gap makes it potential for light absorption and photodetection. In addition, the carrier mobility of Sc2CO2 monolayer is significantly enhanced by adsorption, making it easy to detect changes in resistance. The room-temperature electron mobilities of NH3-adsorbed Sc2CO2 along armchair and zigzag directions are predicted to be as high as 16.75 × 103 and 13.19 × 103 cm2V−1S−1, while the room-temperature hole mobilities along armchair and zigzag directions are determined to be 10.77 × 103 and 11.09 × 103 cm2V−1S−1, respectively. According to the present results, Sc2CO2 monolayer is expected to be promising for the design and application of efficient NH3 gas sensor devices with high selectivity, high sensitivity and low recovery time through analytical methods based on optical and/or electronic responses.

Hanqing Yu,* Wen Xue,* Hanjie Yu, Hongchen Gu, Ling Qin, Ai Peng Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ai Peng; Ling Qin, Center for Nephrology and Clinical Metabolomics, Division of Nephrology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Email pengai@tongji.edu.cn; qinling@tongji.edu.cnPurpose: This study aimed to explore the accuracy for joint application of inflammatory cytokines in diagnosis of gout flare by comparison with peripheral blood cells.Methods: We collected the clinical data of 96 acute gout patients and 144 remission gout patients, and compared the levels of peripheral blood cells, inflammatory cytokines and blood biochemistry indexes between acute and remission gout. We respectively assessed the area under curves (AUCs) for single and multiple inflammatory cytokines including C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and single and multiple peripheral blood cells including platelet (PLT), white blood cell (WBC), percentages of neutrophils (N%), lymphocytes (L%), eosinophils (E%), basophils (B%) in diagnosis of acute gout by receiver operating characteristic (ROC) curve analysis.Results: By contrast with remission gout, the levels of PLT, WBC, N%, CRP, IL-1β, IL-6 and TNF-α increased, and the levels of L%, E% and B% decreased in acute gout. The AUCs of PLT, WBC, N%, L%, E% and B% in diagnosis of acute gout were respectively 0.591, 0.601, 0.581, 0.567, 0.608 and 0.635, while the AUC for joint application of these peripheral blood cells was 0.674. Moreover, the AUCs of CRP, IL-1β, IL-6 and TNF-α in diagnosis of acute gout were respectively 0.814, 0.683, 0.622 and 0.746, while the AUC for joint application of these inflammatory cytokines was 0.883, reflecting significantly higher levels than peripheral blood cells.Conclusion: The joint application of multiple inflammatory cytokines can better distinguish acute gout from remission gout compared with peripheral blood cells.Keywords: acute gout, diagnosis, multiple inflammatory cytokines

Objective: To predict COVID-19 severity by building a prediction model based on the clinical manifestations and radiomic features of the thymus in COVID-19 patients. Method: We retrospectively analyzed the clinical and radiological data from 217 confirmed cases of COVID-19 admitted to Xiangyang NO.1 People's Hospital and Jiangsu Hospital of Chinese Medicine from December 2019 to April 2022 (including 118 mild cases and 99 severe cases). The data were split into the training and test sets at a 7:3 ratio. The cases in the training set were compared in terms of clinical data and radiomic parameters of the lasso regression model. Several models for severity prediction were established based on the clinical and radiomic features of the COVID-19 patients. The DeLong test and decision curve analysis (DCA) were used to compare the performances of several models. Finally, the prediction results were verified on the test set. Result: For the training set, the univariate analysis showed that BMI, diarrhea, thymic steatosis, anorexia, headache, findings on the chest CT scan, platelets, LDH, AST and radiomic features of the thymus were significantly different between the two groups of patients (P < 0.05). The combination model based on the clinical and radiomic features of COVID-19 patients had the highest predictive value for COVID-19 severity [AUC: 0.967 (OR 0.0115, 95%CI: 0.925-0.989)] vs. the clinical feature-based model [AUC: 0.772 (OR 0.0387, 95%CI: 0.697-0.836), P < 0.05], laboratory-based model [AUC: 0.687 (OR 0.0423, 95%CI: 0.608-0.760), P < 0.05] and model based on CT radiomics [AUC: 0.895 (OR 0.0261, 95%CI: 0.835-0.938), P < 0.05]. DCA also confirmed the high clinical net benefits of the combination model. The nomogram drawn based on the combination model could help differentiate between the mild and severe cases of COVID-19 at an early stage. The predictions from different models were verified on the test set. Conclusion: Severe cases of COVID-19 had a higher level of thymic involution. The thymic differentiation in radiomic features was related to disease progression. The combination model based on the radiomic features of the thymus could better promote early clinical intervention of COVID-19 and increase the cure rate.

Objective: Tongue squamous cell carcinoma (TSCC) is one of the most common and poor prognosis head and neck tumors. The purpose of this study is to establish a model for predicting TSCC prognosis based on clinical and MR radiomics data and to develop a nomogram. Methods: A retrospective analysis was performed on the clinical and imaging data of 211 patients with pathologically confirmed TSCC who underwent radical surgery at xx hospital from February 2011 to January 2020. Patients were divided into a study group (recurrence, metastasis, and death, n = 76) and a control group (normal survival, n = 135) according to 1 to 6 years of follow-up. A training set and a test set were established based on a ratio of 7:3 and a time point. In the training set, 3 prediction models (clinical data model, imaging model, and combined model) were established based on the MR radiomics score (Radscore) combined with clinical features. The predictive performance of these models was compared using the Delong curve, and the clinical net benefit of the model was tested using the decision curve. Then, the external validation of the model was performed in the test set, and a nomogram for predicting TSCC prognosis was developed. Results: Univariate analysis confirmed that betel nut consumption, spicy hot pot or pickled food, unclean oral sex, drug use, platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), depth of invasion (DOI), low differentiation, clinical stage, and Radscore were factors that affected TSCC prognosis ( P

Within natural language processing, multi-label classification is an important but challenging task. It is more complex than single-label classification since the document representations need to cover fine-grained label information, while the labels predicted by the model are often related. Recently, large pre-trained language models have achieved great performance on multi-label classification tasks, typically using embedding of [CLS] vector as the semantic representation of entire document and matching it with candidate labels. However, existing methods tend to ignore label semantics, and the relationships between labels and documents are not effectively mined. In addition, the linear layers used for fine-tuning do not take the correlations between labels into account. In this work, we propose a Multi-Label Guided Network (MLGN) capable to guide document representation with multi-label semantic information. Furthermore, we utilize correlation knowledge to enhance the original label prediction in downstream tasks. The extensive experimental trials show that MLGN transcends previous works on several publicly available datasets. Our source code is available at https://github.com/L199Q/MLGN.

Abstract Autophagy is a multi-step catabolic process that delivers cellular components to lysosomes for degradation and recycling. The dysregulation of this precisely controlled process disrupts cellular homeostasis and leads to many pathophysiological conditions. The mechanistic target of rapamycin (mTOR) is a central nutrient sensor that integrates growth signals with anabolism to fulfil biosynthetic and bioenergetic requirements. mTOR nucleates two distinct evolutionarily conserved complexes (mTORC1 and mTORC2). However, only mTORC1 is acutely inhibited by rapamycin. Consequently, mTORC1 is a well characterized regulator of autophagy. While less is known about mTORC2, the availability of acute small molecule inhibitors and multiple genetic models has led to increased understanding about the role of mTORC2 in autophagy. Emerging evidence suggests that the regulation of mTORC2 in autophagy is mainly through its downstream effector proteins, and is variable under different conditions and cellular contexts. Here, we review recent advances that describe a role for mTORC2 in this catabolic process, and propose that mTORC2 could be a potential clinical target for the treatment of autophagy-related diseases. Video abstract Graphical abstract

Yong Chen,1,&ast; An-Zhou Peng,2,&ast; Kun Li,3 Lei Liu,1 Fazhen Zhang,2 Jin Chen,2 Huifen Zhang,2 Linyang Li,2 Hailin Yang,4 Xihai Xu,3 Qiu Zhang1 1Department of Endocrinology, First Affiliated Hospital of Anhui Medical, University, Hefei, 230022, People’s Republic of China; 2Department of the Fifth Tuberculosis, Chongqing Public Health Medical Center, Chongqing, 400030, People’s Republic of China; 3Department of Health Management Center, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 4Department of Infection, the People’s Hospital of Shizhu, Chongqing, 400000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiu Zhang, Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email zhangqiu@ahmu.edu.cn Xihai Xu, Department of Health Management Center, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email 2xhai@163.comBackground: Deficiency vitamin D and hyperglycemia could be related to weakened innate immune response and aggravate the progression of tuberculosis (TB). This study hypothesized that DNA promoter methylation of the pivotal genes in the vitamin D metabolic pathway might be related to diabetes and tuberculosis co-morbidity (TB-DM) susceptibility.Methods: A total of 50 TB-DM and 50 healthy subjects (HS) were included in the present study. Targeted bisulfite sequencing was applied to detect the methylation of the promoter regions of candidate genes in the vitamin D metabolic pathway (CYP24A1, CYP27B1, CYP2R1, DHCR7, and VDR) in whole blood.Results: The overall methylation level of candidate genes in this study was lower in patients with TB-DM than HS, except for CYP2R1. The results of the ROC demonstrated the potential of CYP24A1, CYP27B1, DHCR7, and VDR promoter methylation as a biomarker for diagnosing TB-DM, with all the AUC above 0.7. In subgroup analysis, we found that lower circulating vitamin D is related to a low level of CYP24A1, CYP27B1, and DHCR7 promoter methylation in patients with TB-DM. With decreasing methylation level, risk of TB-DM was significantly decreased (odds ratio, 95% CI 0.343, 0.144– 0.821 for CYP24A1; 0.461, 0.275– 0.773 for CYP27B1; 0.09, 0.015– 0.530 for DHCR7; 0.006, 0.0003– 0.115 for VDR). Besides, our results revealed that there was a significant correlation between DNA promoter methylation of selected genes in the vitamin D metabolic pathway and platelet indices in TB-DM. However, there was no correlation between DNA methylation of the four genes and fasting glucose and HbA1c.Conclusion: Our results could suggest that the selected genes in the vitamin D metabolic pathway may be involved in the pathological process of TB-DM, but independent of the process of hyperglycemia to impaired immune responses to Mtb.Keywords: tuberculosis, diabetes, epigenetics, DNA methylation, vitamin D

Background Thalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden. Considering its high prevalence in low and middle-income countries, a cheap, accurate and high-throughput screening test of thalassaemia prior to a more expensive confirmatory diagnostic test is urgently needed. Methods In this study, we constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains in blood, and for the first time, evaluated its diagnostic efficacy in 674 thalassaemia (including both asymptomatic carriers and symptomatic patients) and control samples collected in three hospitals. Parameters related to haemoglobin imbalance (α-globin, β-globin, γ-globin, α/β and α-β) were used for feature selection before classification model construction with 8 machine learning methods in cohort 1 and further model efficiency validation in cohort 2. Results The logistic regression model with 5 haemoglobin peak features achieved good classification performance in validation cohort 2 (AUC 0.99, 95% CI 0.98–1, sensitivity 98.7%, specificity 95.5%). Furthermore, the logistic regression model with 6 haemoglobin peak features was also constructed to specifically identify β-thalassaemia (AUC 0.94, 95% CI 0.91–0.97, sensitivity 96.5%, specificity 87.8% in validation cohort 2). Conclusions For the first time, we constructed an inexpensive, accurate and high-throughput classification model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains and demonstrated its great potential in rapid screening of thalassaemia in large populations.Key messages Thalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden. We constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains to screen for thalassaemia.

Although research has always related e-portfolios to self-regulated learning, recently agency, which includes individual, relational, and contextual domains, has also been highlighted. Likewise, agency has been explored in technological environments that support collaborative and co-design learning processes. This study, investigating the enactment of student agency within e-portfolio learning co-design with 68 secondary students in Hong Kong, focuses on how students perceive their agency within a co-design e-portfolio learning framework, which was coined as the Co-PIRS model in previous stages of research. With descriptive aims, a mixed research methodology was designed using quantitative and qualitative data collection instruments. Among the findings, it is argued that students report a greater awareness of agency, characterized by competence beliefs (individual domain) in the showcase phase of e-portfolios, peer learning (relational domain), and the opportunities to make choices (contextual domain) in the implementation phase. The study also reveals students' positive attitudes towards reflection, which suggests the suitability of structuring collaboration in the co-design approach. These insights serve as a foundation for implementing e-portfolio co-design frameworks to empower students' agency and provide educators with guidance in Secondary Education and beyond. [Note: The page range (190-203) shown on the PDF is incorrect. The correct page range is 190-202.]

Objective: This study aimed to improve the tenderness and flavor content of Yanbian cattle beef. Methods: Rump beef of Yanbian cattle were dry-aged by using three different methods, i.e., Method A: RH（65±5）% aging for 10 days, RH（75±5）% aging for 10 days, and then RH （85±5）% aging for 20 days; Method B: RH（75±5）% aging for 20 days and then RH（85±5）% aging for 20 days; Method C: RH（85±5）% aging for 40 days. The quality changes caused by the different aging processes were then analyzed and compared. Results: The cooking loss of the beef processed by all the three methods increased significantly with the extension of aging time, but the beef loss (39.14%) in Group A was the highest. The TBARS and TVB-N values of group C were 1.387 and 14.833, respectively, significantly higher than those of the other two groups. The fat and protein contents of each group showed an increasing trend, while the shear force value decreased by 50%. No significant difference in the changes of cooking loss rate, color and pH value were found among the groups. The results showed that with dry-aging, the richness of taste attributes was elevated with higher freshness and aftertaste. The bitterness in group B was lower, and the relative content of aldehydes and ketones among volatile flavor compounds was higher. Conclusion: Method B was the best dry-aging process for Yanbian cattle rump beef.

Objective: To collect the clinical, pathological, and computed tomography (CT) data of 143 accepted surgical cases of pancreatic body tail cancer (PBTC) and to model and predict its prognosis. Methods: The clinical, pathological, and CT data of 143 PBTC patients who underwent surgical resection or endoscopic ultrasound biopsy and were pathologically diagnosed in Xiangyang No.1 People's Hospital Hospital from December 2012 to December 2022 were retrospectively analyzed. The Kaplan-Meier method was adopted to make survival curves based on the 1 to 5 years’ follow-up data, and then the log-rank was employed to analyze the survival. According to the median survival of 6 months, the PBTC patients were divided into a group with a good prognosis (survival time ≥ 6 months) and a group with a poor prognosis (survival time

Objective: To establish a predictive model distinguishing focal mass-forming pancreatitis (FMFP) from pancreatic ductal adenocarcinoma (PDAC) based on computed tomography (CT) radiomics and clinical data. Methods: A total of 78 FMFP patients (FMFP group) and 120 PDAC patients (PDAC group) who were admitted to Xiangyang No.1 People's Hospital and Xiangyang Central Hospital from February 2012 to May 2021 and were pathologically diagnosed were included in this study, and were input to set up the training set and test set at a ratio of 7:3. The 3Dslicer software was used to extract the radiomic features and radiomic scores (Radscores) of the 2 groups, and the clinical data (age, gender, etc), CT imaging features (lesion location, size, enhancement degree, vascular wrapping, etc) and CT radiomic features of the 2 groups were compared. Logistic regression was used to screen the independent risk factors of the 2 groups, and multiple prediction models (clinical imaging model, radiomics model, and combined model) were established. Then the receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were conducted to compare the prediction performance and net benefit of the models. Results: The multivariate logistic regression results indicated that dilation of the main pancreatic duct, vascular wrapping, Radscore1 and Radscore2 were independent influencing factors for distinguishing FMFP from PDAC. In the training set, the combined model showed the best predictive performance (area under the ROC curve [AUC] 0.857, 95% CI [0.787-0.910]), significantly higher than the clinical imaging model (AUC 0.650, 95% CI [0.565–0.729]) and the radiomics model (AUC 0.812, 95% CI [0.759–0.890]). DCA confirmed that the combined model had the highest net benefit. These results were further validated by the test set. Conclusion: The combined model based on clinical–CT radiomics data can effectively identify FMFP and PDAC, providing a reference for clinical decision-making.

Mutations of the FBN1 gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is currently no effective treatment for MFS. Here, we studied the role of mitochondrial dysfunction in the phenotypic transformation of human smooth muscle cells (SMCs) and whether a mitochondrial boosting strategy can be a potential treatment. We knocked down FBN1 in SMCs to create an MFS cell model and used rotenone to induce mitochondrial dysfunction. Furthermore, we incubated the shFBN1 SMCs with Coenzyme Q10 (CoQ10) to assess whether restoring mitochondrial function can reverse the phenotypic transformation. The results showed that shFBN1 SMCs had decreased TFAM (mitochondrial transcription factor A), mtDNA levels and mitochondrial mass, lost their contractile capacity and had increased synthetic phenotype markers. Inhibiting the mitochondrial function of SMCs can decrease the expression of contractile markers and increase the expression of synthetic genes. Imposing mitochondrial stress causes a double-hit effect on the TFAM level, oxidative phosphorylation and phenotypic transformation of FBN1-knockdown SMCs while restoring mitochondrial metabolism with CoQ10 can rapidly reverse the synthetic phenotype. Our results suggest that mitochondria function is a potential therapeutic target for the phenotypic transformation of SMCs in MFS.

Cellulolytic microorganisms play a crucial role in agricultural waste disposal. Strain QXD-8T was isolated from soil in northern China. Similarity analyses of the 16S rRNA gene, as well as the 120 conserved genes in the whole-genome sequence, indicate that it represents a novel species within the genus Microbacterium. The Microbacterium sp. QXD-8T was able to grow on the CAM plate with sodium carboxymethyl cellulose as a carbon source at 15 °C, forming a transparent hydrolysis circle after Congo red staining, even though the optimal temperature for the growth and cellulose degradation of strain QXD-8T was 28 °C. In the liquid medium, it effectively degraded cellulose and produced reducing sugars. Functional annotation revealed the presence of encoding genes for the GH5, GH6, and GH10 enzyme families with endoglucanase activity, as well as the GH1, GH3, GH39, and GH116 enzyme families with β-glucosidase activity. Additionally, two proteins in the GH6 family, one in the GH10, and two of nine proteins in the GH3 were predicted to contain a signal peptide and transmembrane region, suggesting their potential for extracellularly degrade cellulose. Based on the physiological features of the type strain QXD-8T, we propose the name Microbacterium psychrotolerans for this novel species. This study expands the diversity of psychrotolerant cellulolytic bacteria and provides a potential microbial resource for straw returning in high-latitude areas at low temperatures.

Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case–control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D (p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status (p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.

Experimental research on flow characteristics of open natural circulation system was performed, to figure out the mechanism of the open natural circulation behaviors. The influence factors, such as the heating power, the inlet subcooled and the level of cooling tank on the flow characteristics of the system were examined. It was shown that within the scope of the experimental conditions, there are five flow types: single-phase stable flow, flash and geyser coexisting unstable flow, flash stable flow, flash unstable flow, and flash and boiling coexisting unstable flow. The geyser flow in flash and geyser coexisting unstable flow is different from classic geysers flow. The flow oscillation period and amplitude of the former are more regular, is a newly discovered flow pattern. By drawing the flow instability boundary diagram and sorting out the flow types, it is found that the two-phase unstable flow is mainly characterized by boiling and flash, which determine the behavior of open natural circulation respectively or jointly. Moreover, compared with full liquid level system, non-full liquid level system is more prone to boiling phenomenon, and the range of heat flux density and undercooling degree corresponding to unstable flow is larger.

Aihong Peng,1 Funa Lu,1 Jianxiao Xing,1 Yu Dou,1 Yuanjun Yao,1 Juan Li,1 Junqin Li,1 Ruixia Hou,1 Kaiming Zhang,2 Guohua Yin1 1Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, People’s Republic of ChinaCorrespondence: Guohua Yin, Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5, Dong San Dao Xiang, Jiefang Road, Taiyuan, People’s Republic of China, Tel +86-0351-5656080, Email yinguohua1999@sina.comPurpose: Our recent studies found a splice region mutation in C3 accompanied by a significantly increased C3 in psoriatic peripheral blood. Mesenchymal stem cells (MSCs) are a key immunological suppression cell. We further investigate the regulation of MSCs on C3 in psoriasis.Patients and Methods: We analyzed the C3 and its upstream S100A9, S100A8 and downstream MCP1 in psoriatic and control skin, and in normal human epidermal keratinocytes (NHEKs) co-cultured with psoriatic versus control dermal-derived mesenchymal stem cells (DMSCs) by mRNA, iTRAQ (isobaric tags for relative and absolute quantitative) and simple Western analysis.Results: The mRNA and Simple Western analysis showed that the expression of C3, S100A8 and S100A9 are upregulated in psoriatic lesion (C3: mRNA, 9.23-fold, p = 0.0092; protein, 3.56-fold, p = 0.0244. S100A8: mRNA, 28.35-fold, p = 0.0015; protein, 4.68-fold, p = 0.0215. S100A9: mRNA, 79.45-fold, p = 0.0066; protein, 12.42-fold, p > 0.05). Moreover, the iTRAQ showed that C3 and S100A9 were significantly increased in NHEKs after co-cultured with psoriatic DMSCs compared to that of control DMSCs (C3: 3.40-fold, p = 0, FDR = 0; S100A9: 2.30-fold, p = 9.86E-241, FDR = 6.50E-239), verified by Simple Western. However, the expression of S100A8 and MCP1 was slightly different between the two groups.Conclusion: Our results suggest that psoriatic DMSCs contribute to the increased C3 expression in psoriatic lesion via upregulating S100A9, providing the theoretical basis for the role of C3 and DMSCs in the pathogenesis of psoriasis.Keywords: psoriasis, dermal mesenchymal stem cells, keratinocytes, C3, S100A9