Depletion of NUAK2 blocks the stemness and angiogenesis and facilitates senescence of lung adenocarcinoma cells via enhancing ferroptosis.

BACKGROUND: NUAK family kinase 2 (NUAK2) has been identified as an important mediator for tumor progression in multiple malignancies. Nevertheless, its role in lung adenocarcinoma (LUAD) remains unclear. METHODS: Bioinformatic analysis was performed to assess the expression and prognosis of NUAK2 in patients with LUAD. The NUAK2 expression was measured in multiple LUAD cell lines, and the loss-of-function experiment was conducted. Cell proliferation ability was assessed using CCK-8 and colony formation assays. Spheroid formation, alkaline phosphatase (AP) staining, tube formation and SA-ß-gal staining assays were performed to examine stemness, angiogenesis and senescence. Lipid peroxidase was assessed by TBARS production and lipid ROS. Western blot was used to detect critical proteins. In addition, A549 cells were treated with ferroptosis inhibitor ferrostatin-1 (Fer-1) for a rescue assay. Finally, A549 cells were subcutaneously injected into the right flank of mice to establish LUAD-bearing mouse model, and the tumor weight and size were detected. RESULTS: NUAK2 was upregulated in patients with LUAD and LUAD cell lines. NUAK2 depletion inhibited cell viability, colonies, tumor spheres and decreased Oct4 and Nanog expression, confirming NUAK2 depletion inhibited proliferation and stemness of A549 cells. Meanwhile, NUAK2 depletion blocked angiogenesis via reducing formed tubes and VEGFR1/2 expression, and promoted senescence of A549 cells by elevating SA-ß-gal-positive cells and p16, p21 and p53 expression. Moreover, NUAK2 depletion elevated lipid ROS, TBARS production and Fe2+ level, demonstrating that NUAK2 depletion could trigger ferroptosis in A549 cells. Furthermore, the rescue experiments revealed that the impacts of NUAK2 depletion on malignant behaviors in A549 cells were partly weakened by additional Fer-1 treatment. Finally, in vivo experiments demonstrated that NUAK2 knockdown greatly inhibited tumor growth in LUAD-bearing mice. CONCLUSION: In summary, NUAK2 depletion impeded oncogenic phenotypes of A549 cells partly via triggering ferroptosis, suggesting NUAK2 as a novel target for treating LUAD.

Chloride intracellular channel 4 participates in the regulation of lipopolysaccharide-induced inflammatory responses in human bronchial epithelial cells.

The airway epithelium is located at the interactional boundary between the external and internal environments of the organism and is often exposed to harmful environmental stimuli. Inflammatory response that occurs after airway epithelial stress is the basis of many lung and systemic diseases. Chloride intracellular channel 4 (CLIC4) is abundantly expressed in epithelial cells. The purpose of this study was to investigate whether CLIC4 is involved in the regulation of lipopolysaccharide (LPS)-induced inflammatory response in airway epithelial cells and to clarify its potential mechanism. Our results showed that LPS induced inflammatory response and decreased CLIC4 levels in vivo and in vitro. CLIC4 silencing aggravated the inflammatory response in epithelial cells, while overexpression of CLIC4 combined with LPS exposure significantly decreased the inflammatory response compared with cells exposed to LPS without CLIC4 overexpression. By labeling intracellular chloride ions with chloride fluorescent probe MQAE, we showed that CLIC4 mediated intracellular chloride ion-regulated LPS-induced cellular inflammatory response.

Low-dose radiation promotes high-fat diet-induced atherosclerosis by activating cGAS signal pathway.

BACKGROUND: Atherosclerosis (AS) is the most prevalent cardiovascular disease, with an exceptionally high burden. High-fat diet (HFD) is a popular diet behavior, whereas low-dose radiation (LDR) is an environmental physical factor. There is evidence to suggest that an HFD may exacerbate the onset of atherosclerosis. Whether the combination effect of HFD and LDR would have potential on atherosclerosis development remains incompletely unclear. METHODS: In this study, ApoE-/- mice were used as atherosclerosis model animals to investigate the combination effects of HFD and LDR (10 × 0.01Gy, or 20 × 0.01Gy) on vascular lesions. Doppler ultrasound imaging, H&E staining, oil red O staining, western blotting, and immunohistochemistry (IHC) were used to assess the pro-atherosclerotic effects. LC-MS was used to detect the non-targeted lipidomic. RESULTS: Long-term exposure of low-dose radiation at an accumulated dose of 0.2Gy significantly increased the occurrence of vascular stiffness and the aortic lesion in ApoE-/- mice. The synergistic effect of HFD and LDR was observed in the development of atherosclerosis, which might be linked to both the dysbiosis of lipid metabolism and the stimulation of the inflammatory signaling system. Moreover, LDR but not HFD can activate the cGAS-STING signaling through increasing the yield of cytosolic mitochondrial DNAs as well as the expression of cGAS protein. The activation of cGAS-STING signal triggers the release of IFN-α/-ß, which functions as an inflammatory amplifier in the formation of atherosclerotic plaque. CONCLUSION: The current study offers fresh insights into the risks and mechanism that underlie the development of atherosclerosis by LDR, and there is a combination effect of LDR and HFD with the involvement of cGAS-STING signal pathway.

The weight-adjusted waist index and frailty: A cohort study from the China Health and Retirement Longitudinal Study.

OBJECTIVES: This cohort study's aim was to assess the association between the weight-adjusted waist index (WWI) and frailty among middle-aged and elderly individuals in China. METHODS: Seven-year complete follow-up data from 10,349 adults aged ≥45 years, initially surveyed in 2 011 in the China Health and Retirement Longitudinal Study, were analyzed, including clinical demographic characteristics, anthropometric indices, frailty scores, and relevant covariates. The WWI was calculated as waist circumference divided by the square root of the body weight. Frailty was evaluated using the Frailty Index. Relationships between the WWI and frailty were evaluated via Cox proportional hazards modeling. Receiver operating characteristic curve analyses assessed the effectiveness of obesity-related indicators in predicting frailty. RESULTS: Over a median 84-month follow-up period, frailty occurred in 23.7% (2453/10,349) of participants. After potential confounder adjustment, the WWI positively correlated with frailty (adjusted hazard ratio: 1.14; 95% confidence interval: 1.08-1.20; p < 0.001). After WWI-stratification into quartiles based on frailty and covariate adjustment, regression analyses were conducted; the adjusted hazard ratios exhibited a significant upward trend (p < 0.001). The subgroup analyses revealed higher positive correlations between the WWI and frailty in males and those aged ≥65 years and lower correlations in those with a high school or higher educational level and in married or cohabiting individuals. The strong positive correlation was unaltered in the other subgroup analyses. The WWI outperformed all other obesity-related indicators as a frailty predictor. CONCLUSIONS: The WWI is a dependable and innovative obesity-related predictor of frailty and could help in mitigating its development.

Prediction analysis of TBI 24-h survival outcome based on machine learning.

Background: Traumatic brain injury (TBI) is the major reason for the death of young people and is well known for its high mortality and morbidity. This paper aim to predict the 24h survival of patients with TBI. Methods: A total of 1224 samples were involved in this analysis, and the clinical indicators involved included age, gender, blood pressure, MGAP and other fields, among which the target variable was "outcome", which was a binary variable. The methods mainly involved in this paper include data visualization analysis, single factor analysis, feature engineering analysis, random forest model (RF), K-Nearst Neighbors (KNN) model, and so on. Logistic regression model (LR) and deep neural network model (DNN). We will oversample the training set using the SMOTE method because of the very unbalanced labeling of the sample itself. Results: Although the accuracy of all models is very high, the recall rate is relatively low. The DNN model with the best performance only reaches 0.17, and the corresponding AUC is 0.80. After resampling, we find that the recall rate of positive samples of all models has increased a lot, but the AUC of some models has decreased. Finally, the optimal model is LR, whose positive sample recall rate is 0.67 and AUC is 0.82. Conclusion: Through resampling, we obtained that the best model is the RF model, whose recall rate and AUC are the best, and the AUC level is about 0.87, indicating that the accuracy performance of the model is still good.

Correlation between the triglyceride-glucose index and arterial stiffness in Japanese individuals with normoglycaemia: a cross-sectional study.

BACKGROUND: The association between the triglyceride-glucose (TyG) index and arterial stiffness in individuals with normoglycaemia remains unclear. We aimed to evaluate the relationship between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia, providing additional evidence for predicting early arterial stiffness. METHODS: This study included 15,453 adults who participated in the NAGALA Physical Examination Project of the Murakami Memorial Hospital in Gifu, Japan, from 2004 to 2015. Data on clinical demographic characteristics and serum biomarker levels were collected. The TyG index was calculated from the logarithmic transformation of fasting triglycerides multiplied by fasting glucose, and arterial stiffness was measured using the estimated pulse wave velocity calculated based on age and mean blood pressure. The association between the TyG index and arterial stiffness was analysed using a logistic regression model. RESULTS: The prevalence of arterial stiffness was 3.2% (500/15,453). After adjusting for all covariates, the TyG index was positively associated with arterial stiffness as a continuous variable (adjusted odds ratio (OR) = 1.86; 95% Confidence Interval = 1.45-2.39; P<0.001). Using the quartile as the cutoff point, a regression analysis was performed for arterial stiffness when the TyG index was converted into a categorical variable. After adjusting for all covariates, the OR showed an upward trend; the trend test was P<0.001. Subgroup analysis revealed a positive association between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia and different characteristics. CONCLUSION: The TyG index in Japanese individuals with normoglycaemia is significantly correlated with arterial stiffness, and the TyG index may be a predictor of early arterial stiffness.

TAB182 regulates glycolytic metabolism by controlling LDHA transcription to impact tumor radiosensitivity.

Metabolic reprogramming, a hallmark of cancer, is closely associated with tumor development and progression. Changes in glycolysis play a crucial role in conferring radiation resistance to tumor cells. How radiation changes the glycolysis status of cancer cells is still unclear. Here we revealed the role of TAB182 in regulating glycolysis and lactate production in cellular response to ionizing radiation. Irradiation can significantly stimulate the production of TAB182 protein, and inhibiting TAB182 increases cellular radiosensitivity. Proteomic analysis indicated that TAB182 influences several vital biological processes, including multiple metabolic pathways. Knockdown of TAB182 results in decreased lactate production and increased pyruvate and ATP levels in cancer cells. Moreover, knocking down TAB182 reverses radiation-induced metabolic changes, such as radioresistant-related lactate production. TAB182 is necessary for activating LDHA transcription by affecting transcription factors SP1 and c-MYC; its knockdown attenuates the upregulation of LDHA by radiation, subsequently suppressing lactate production. Targeted suppression of TAB182 significantly enhances the sensitivity of murine xenograft tumors to radiotherapy. These findings advance our understanding of glycolytic metabolism regulation in response to ionizing radiation, which may offer significant implications for developing new strategies to overcome tumor radioresistance.

Stress stimulation promotes the injury repair process of airway epithelial cells through the [Cl-]i-FAK signaling axis.

The airway epithelium serves as a critical interface with the external environment, making it vulnerable to various external stimuli. Airway epithelial stress acts as a catalyst for the onset of numerous pulmonary and systemic diseases. Our previous studies have highlighted the impact of acute stress stimuli, especially bacterial lipopolysaccharide (LPS) and hydrogen peroxide (H2O2), on the continuous elevation of intracellular chloride concentration ([Cl-]i). However, the precise mechanism behind this [Cl-]i elevation and the consequential effects of such stress on the injury repair function of airway epithelial cells remain unclear. Our findings indicate that H2O2 induces an elevation in [Cl-]i by modulating the expression of CF transmembrane conductance regulator (CFTR) and Ca-activated transmembrane protein 16 A (TMEM16A) in airway epithelial cells (BEAS-2B), whereas LPS achieves this solely through CFTR. Subsequently, the elevated [Cl-]i level facilitated the injury repair process of airway epithelial cells by activating focal adhesion kinase (FAK). In summary, the [Cl-]i-FAK axis appears to play a promoting effect on the injury repair process triggered by stress stimulation. Furthermore, our findings suggest that abnormalities in the [Cl-]i-FAK signaling axis may play a crucial role in the pathogenesis of chronic airway diseases. Therefore, controlling the structure and function of airway epithelial barriers through the modulation of [Cl-]i holds promising prospects for future applications in managing and treating such conditions.

SERS microfluidic chip integrated with double amplified signal off-on strategy for detection of microRNA in NSCLC.

In this work, based on Fe3O4@AuNPs and double amplified signal Off-On strategy, a simple and sensitive SERS microfluidic chip was constructed to detect microRNA associated with non-small cell lung cancer (NSCLC). Fe3O4@AuNPs have two advantages of SERS enhanced and magnetic adsorption, the introduction of microfluidic chip can realize double amplification of SERS signal. First, the binding of complementary ssDNA and hpDNA moved the Raman signaling molecule away from Fe3O4@AuNPs, at which point the signal was turned off. Second, in the presence of the target microRNA, they were captured by complementary ssDNA and bound to them. HpDNA restored the hairpin conformation, the Raman signaling molecule moved closer to Fe3O4@AuNPs. At this time, the signal was turned on and strong Raman signal was generated. And last, through the magnetic component of SERS microfluidic chip, Fe3O4@AuNPs could be enriched to realize the secondary enhancement of SERS signal. In this way, the proposed SERS microfluidic chip can detect microRNA with high sensitivity and specificity. The corresponding detection of limit (LOD) for miR-21 versus miR-125b was 6.38 aM and 7.94 aM, respectively. This SERS microfluidic chip was promising in the field of early detection of NSCLC.

Radiation-targeted immunotherapy: A new perspective in cancer radiotherapy.

In contemporary oncology, radiation therapy and immunotherapy stand as critical treatments, each with distinct mechanisms and outcomes. Radiation therapy, a key player in cancer management, targets cancer cells by damaging their DNA with ionizing radiation. Its effectiveness is heightened when used alongside other treatments like surgery and chemotherapy. Employing varied radiation types like X-rays, gamma rays, and proton beams, this approach aims to minimize damage to healthy tissue. However, it is not without risks, including potential damage to surrounding normal cells and side effects ranging from skin inflammation to serious long-term complications. Conversely, immunotherapy marks a revolutionary step in cancer treatment, leveraging the body's immune system to target and destroy cancer cells. It manipulates the immune system's specificity and memory, offering a versatile approach either alone or in combination with other treatments. Immunotherapy is known for its targeted action, long-lasting responses, and fewer side effects compared to traditional therapies. The interaction between radiation therapy and immunotherapy is intricate, with potential for both synergistic and antagonistic effects. Their combined use can be more effective than either treatment alone, but careful consideration of timing and sequence is essential. This review explores the impact of various radiation therapy regimens on immunotherapy, focusing on changes in the immune microenvironment, immune protein expression, and epigenetic factors, emphasizing the need for personalized treatment strategies and ongoing research to enhance the efficacy of these combined therapies in cancer care.

Predictive metabolomic signatures for safety assessment of three plastic nanoparticles using intestinal organoids.

Nanoplastic particles are pervasive environmental contaminants with potential health risks, while mouse intestinal organoids provide accurate in vitro models for studying these interactions. Metabolomics, especially through LC-MS, enables detailed cellular response studies, and there's a novel interest in comparing metabolic changes across nanoparticle species using gut organoids. This study used a mouse intestinal organoid combined with cell model to explore the differences in metabolites and toxicity mechanisms induced by exposure to three nanoplastics (PS, PTFE, and PMMA). The results showed that PS, PTFE, and PMMA exposure reduced mitochondrial membrane potential, intracellular ROS accumulation and oxidative stress, and inhibited the AKT/mTOR signaling pathway. Non-targeted metabolomics results confirmed that three types of nanoplastic particles regulate cellular status by regulating fatty acid metabolism, nucleotide metabolism, necroptosis and autophagy pathways. More importantly, these representative metabolites were further validated in model groups after mouse intestinal organoids and HCT116 cells were exposed to the respective NPs, indicating that organoid metabolomics results can be used to effectively predict toxicity. Untargeted metabolomics is sensitive enough to detect subtle metabolomic changes when functional cellular analysis shows no significant differences. Overall, our study reveals the underlying metabolic mechanism of NPs-induced intestinal organoid toxicity and provides new insights into the possible adverse consequences of NPs.

Lactate exacerbates lung damage induced by nanomicroplastic through the gut microbiota-HIF1a/PTBP1 pathway.

Exposure to nanomicroplastics (nano-MPs) can induce lung damage. The gut microbiota is a critical modulator of the gut-lung axis. However, the mechanisms underlying these interactions have not been elucidated. This study explored the role of lactate, a key metabolite of the microbiota, in the development of lung damage induced by nano-MPs (LDMP). After 28 days of exposure to nano-MPs (50-100 nm), mice mainly exhibited damage to the lungs and intestinal mucosa and dysbiosis of the gut microbiota. Lactate accumulation was observed in the lungs, intestines and serum and was strongly associated with the imbalance in lactic acid bacteria in the gut. Furthermore, no lactate accumulation was observed in germ-free mice, while the depletion of the gut microbiota using a cocktail of antibiotics produced similar results, suggesting that lactate accumulation in the lungs may have been due to changes in the gut microbiota components. Mechanistically, elevated lactate triggers activation of the HIF1a/PTBP1 pathway, exacerbating nano-MP-induced lung damage through modulation of the epithelial-mesenchymal transition (EMT). Conversely, mice with conditional knockout of Ptbp1 in the lungs (Ptbp1flfl) and PTBP1-knockout (PTBP1-KO) human bronchial epithelial (HBE) cells showed reversal of the effects of lactate through modulation of the HIF1a/PTBP1 signaling pathway. These findings indicate that lactate is a potential target for preventing and treating LDMP.

Association between relative muscle strength and hypertension in middle-aged and older Chinese adults.

BACKGROUND: The association between muscle defects and hypertension is well-established. However, the absence of pertinent and uncomplicated clinical indicators presents a challenge. Relative muscle strength (RMS) may offer a viable indicator. This study aimed to explore the association between RMS and hypertension. METHODS: A total of 12,720 individuals aged ≥ 45 years from the 2011 wave of the China Health and Retirement Longitudinal Study (CHARLS) were included. Grip strength was recorded and appendicular skeletal muscle mass (ASM) was estimated using a validated mathematical formula. The RMS was calculated as the ratio of grip strength to ASM. Hypertension was determined based on previous diagnosis, history of hypertension medication use, and current blood pressure. Logistic regression models were employed to investigate the relationship between RMS and hypertension. RESULTS: The prevalence of hypertension was 41.7% (5,307/12,720 patients). RMS was negatively correlated with hypertension with an OR (95% CI) of 0.68 (0.59-0.79) for males, 0.81 (0.73-0.90) for females, and 0.78 (0.72-0.85) for the entire population after adjusting for related covariates including age, education, marital history, smoking history, drinking history, diabetes, hyperlipidemia, and obesity. The trend test showed a linear association among males, females, or the entire population. Stratified analysis showed a consistent negative correlation between RMS and hypertension. CONCLUSIONS: Higher RMS is an independent protective factor against hypertension and efforts to promote RMS may be beneficial for the prevention and management of hypertension.

P53-response circRNA_0006420 aggravates lung cancer radiotherapy resistance by promoting formation of HUR/PTBP1 complex.

BACKGROUND: p53 wild-type lung cancer cells can develop radiation resistance. Circular RNA (circRNA) consists of a family of transcripts with exclusive structures. circRNA is critical in tumorigenesis and is a potential biomarker or therapeutic target. It is uncertain how circRNA expression and functions are regulated post-radiation in p53 wild-type cancer cells. METHODS: A549 or H1299 cells were divided into p53-wt and p53-KO groups by CRISPR/Cas9; both groups were subjected to 4 Gy ionizing radiation (IR: p53-wt-IR and p53-KO-IR). RNA-seq, CCK8, cell cycle, and other functional and mechanism experiments were performed in vivo. p53 gene knockout mice were generated to test the cell results in vitro. RESULTS: circRNAs were found in differential groups. circRNA_0006420 (IRSense) was upregulated in p53-wt cells but had the same expression level as p53-KO cells after radiation, indicating that p53 silencing prevents its upregulation after IR. In the presence of p53, upregulated IRSense post-radiation induces G2/M arrest by regulating DNA damage repair (DDR) pathway-related proteins. Meanwhile, upregulated IRSense post-radiation aggravates the radiation-induced epithelial-mesenchymal transition (EMT). Interestingly, in the presence of p53, it promotes IRSense/HUR/PTBP1 complex formation resulting in the promotion of the radiation-induced EMT. Moreover, c-Jun regulates the upregulation of p53 transcription after radiation treatment. For these lung cancer cells with p53, upregulated IRSense aggravates lung cancer cell proliferation and increases radiation resistance by interacting with HUR (ElAV-like protein 1) and PTBP1 (polypyrimidine tract-binding protein 1) in the nucleus. CONCLUSIONS: Lung cancer cells retaining p53 may upregulate circRNA_0006420 (IRSense) expression post radiation to form an IRSense/HUR/PTBP1 complex leading to radiotherapy resistance. This study furthers our understanding of the roles of circRNA in regulating the effect of radiotherapy and provides novel therapeutic avenues for effective clinical lung cancer therapies.

PARP1 modulates METTL3 promoter chromatin accessibility and associated LPAR5 RNA m6A methylation to control cancer cell radiosensitivity.

Chromatin remodeling and N6-methyladenosine (m6A) modification are two critical layers in controlling gene expression and DNA damage signaling in most eukaryotic bioprocesses. Here, we report that poly(ADP-ribose) polymerase 1 (PARP1) controls the chromatin accessibility of METTL3 to regulate its transcription and subsequent m6A methylation of poly(A)+ RNA in response to DNA damage induced by radiation. The transcription factors nuclear factor I-C (NFIC) and TATA binding protein (TBP) are dependent on PARP1 to access the METTL3 promoter to activate METTL3 transcription. Upon irradiation or PARP1 inhibitor treatment, PARP1 disassociated from METTL3 promoter chromatin, which resulted in attenuated accessibility of NFIC and TBP and, consequently, suppressed METTL3 expression and RNA m6A methylation. Lysophosphatidic Acid Receptor 5 (LPAR5) mRNA was identified as a target of METTL3, and m6A methylation was located at A1881. The level of m6A methylation of LPAR5 significantly decreased, along with METTL3 depression, in cells after irradiation or PARP1 inhibition. Mutation of the LPAR5 A1881 locus in its 3' UTR results in loss of m6A methylation and, consequently, decreased stability of LPAR5 mRNA. METTL3-targeted small-molecule inhibitors depress murine xenograft tumor growth and exhibit a synergistic effect with radiotherapy in vivo. These findings advance our comprehensive understanding of PARP-related biological roles, which may have implications for developing valuable therapeutic strategies for PARP1 inhibitors in oncology.

Machine learning for prediction of delirium in patients with extensive burns after surgery.

AIMS: Machine learning-based identification of key variables and prediction of postoperative delirium in patients with extensive burns. METHODS: Five hundred and eighteen patients with extensive burns who underwent surgery were included and randomly divided into a training set, a validation set, and a testing set. Multifactorial logistic regression analysis was used to screen for significant variables. Nine prediction models were constructed in the training and validation sets (80% of dataset). The testing set (20% of dataset) was used to further evaluate the model. The area under the receiver operating curve (AUROC) was used to compare model performance. SHapley Additive exPlanations (SHAP) was used to interpret the best one and to externally validate it in another large tertiary hospital. RESULTS: Seven variables were used in the development of nine prediction models: physical restraint, diabetes, sex, preoperative hemoglobin, acute physiological and chronic health assessment, time in the Burn Intensive Care Unit and total body surface area. Random Forest (RF) outperformed the other eight models in terms of predictive performance (ROC:84.00%) When external validation was performed, RF performed well (accuracy: 77.12%, sensitivity: 67.74% and specificity: 80.46%). CONCLUSION: The first machine learning-based delirium prediction model for patients with extensive burns was successfully developed and validated. High-risk patients for delirium can be effectively identified and targeted interventions can be made to reduce the incidence of delirium.

An overview of current research on nutritional support for burn patients: A bibliometric analysis from 1983 to 2022.

OBJECTIVES: Burn patients are reportedly prone to complications, such as skeletal muscle wasting, anemia, and slow wound healing, during treatment, due to disease and metabolic depletion, which affect prognosis. Nutritional support is essential in treating burns and can significantly improve patient survival and reduce complications such as infection. This study aimed to perform a bibliometric analysis of the existing literature on nutritional support for burns and to explore possible future research trends. METHODS: The literature related to nutritional support for burns from 1983 to 2022 was searched on Web of Science. The included literature was used for bibliometric analysis using VOSviewer and CiteSpace software. RESULTS: There were 260 publications on nutritional support for burns. The United States contributes significantly to research in this area. The United States has the highest number of publications (n = 119) and citations (n = 4424). Nutrition support was the keyword with strongest burst intensity. A diet of ≥ 60% carbohydrates and 12% to 15% fat is suitable for burn patients, but the optimal ratios have not been fully determined. CONCLUSIONS: An optimal nutritional support program is essential for treating burn patients. Individualized nutritional support programs are the trend in this field. At present, more rigorous multicenter prospective studies with large samples are needed to explore the optimal ratios for specific dietary programs, especially macronutrients, to achieve satisfactory nutritional support and improve patient prognosis.

Neoadjuvant sintilimab and chemotherapy in patients with potentially resectable esophageal squamous cell carcinoma (KEEP-G 03): an open-label, single-arm, phase 2 trial.

BACKGROUND: The standard neoadjuvant treatments in patients with esophageal squamous cell carcinoma (ESCC) still have either poor safety or efficacy. Better therapies are needed in China. METHODS: This was an open-label, single-arm, phase 2 trial. Patients with potentially resectable ESCC (cT1b-3, Nany, M0 or T4a, N0-1, or M0) received preoperative intravenous sintilimab plus triplet chemotherapy (liposomal paclitaxel, cisplatin, and S-1) every 3 weeks for two cycles. The primary endpoints were safety and surgical feasibility; the secondary endpoint was major pathological response (MPR) rate. Genomic biomarkers (genetic mutations, tumor mutational burden (TMB), circulating tumor DNA status and immune microenvironment) in baseline tumor samples were investigated. RESULTS: All 30 patients completed two cycles of neoadjuvant treatment and underwent surgical resection. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 36.7% (11/30) of patients. The most frequent TRAEs were decreased white cell count (76.7%), anemia (76.7%), and decreased neutrophil count (73.3%). All TRAEs were hematological toxicities; none caused ≥30 days surgical delay. The MPR and pathological complete response (pCR) rates were 50.0% (15/30; 95% CI 33.2 to 66.9) and 20.0% (6/30; 95% CI 9.5 to 37.3), respectively. Patients with higher TMB and more clonal mutations were more likely to respond. ERBB2 alterations and ctDNA high-releaser status have a negative correlation with neoadjuvant ICI response. No significant difference was observed between therapeutic response and tumor immune microenvironment. CONCLUSIONS: Neoadjuvant sintilimab plus platinum-based triplet chemotherapy appeared safe and feasible, did not delay surgery and induced a pCR rate of 20.0% in patients with potentially resectable ESCC. TRIAL REGISTRATION NUMBER: NCT03946969.

Lactobacillus rhamnosus GG ameliorates radiation-induced lung fibrosis via lncRNASNHG17/PTBP1/NICD axis modulation.

Radiation-induced pulmonary fibrosis (RIPF) is a major side effect experienced for patients with thoracic cancers after radiotherapy. RIPF is poor prognosis and limited therapeutic options available in clinic. Lactobacillus rhamnosus GG (LGG) is advantaged and widely used for health promotion. However. Whether LGG is applicable for prevention of RIPF and relative underlying mechanism is poorly understood. Here, we reported a unique comprehensive analysis of the impact of LGG and its' derived lncRNA SNHG17 on radiation-induced epithelial-mesenchymal transition (EMT) in vitro and RIPF in vivo. As revealed by high-throughput sequencing, SNHG17 expression was decreased by LGG treatment in A549 cells post radiation and markedly attenuated the radiation-induced EMT progression (p < 0.01). SNHG17 overexpression correlated with poor overall survival in patients with lung cancer. Mechanistically, SNHG17 can stabilize PTBP1 expression through binding to its 3'UTR, whereas the activated PTBP1 can bind with the NICD part of Notch1 to upregulate Notch1 expression and aggravated EMT and lung fibrosis post radiation. However, SNHG17 knockdown inhibited PTBP1 and Notch1 expression and produced the opposite results. Notably, A549 cells treated with LGG also promoted cell apoptosis and increased cell G2/M arrest post radiation. Mice of RIPF treated with LGG decreased SNHG17 expression and attenuated lung fibrosis. Altogether, these data reveal that modulation of radiation-induced EMT and lung fibrosis by treatment with LGG associates with a decrease in SNHG17 expression and the inhibition of SNHG17/PTBP1/Nothch1 axis. Collectively, our results indicate that LGG exerts protective effects in RIPF and SNHG17 holds a potential marker of RIPF recovery in patients with thoracic cancers.

Novel ZnFe2O4/BC/ZnO photocatalyst for high-efficiency degradation of tetracycline under visible light irradiation.

Developing broad-spectrum light reactions, effective charge separation, and easily recoverable photocatalysts were considered cost-effective pollution remediation methods. The ZnFe2O4/BC/ZnO composite was prepared to achieve these objectives, where biochar (BC) was used as a conductive channel and ZnFe2O4 as a magnetic substance. Among them, the 0.6-ZBO composite performed the best, with photocatalytic removal of tetracycline (TC) reaching 85.6%. The photocatalytic degradation rated constant of 0.6-ZBO composite was 23.36 × 10-3 min-1, which was 7.6, 4.1, and 2.5 times higher than that of ZnFe2O4/BC, ZnO, and ZnFe2O4/ZnO samples, respectively. According to several characterization data, it was demonstrated that successful Z-scheme heterojunctions were constructed between ZnFe2O4 and ZnO. The 0.6-ZBO complex increased the range of light absorption and strengthened the separation of electron-hole pairs, thus improving the redox ability of the complex. In the different water matrices, the stability of 0.6-ZBO was excellent and its ability to remove TC decreased slightly to about 11% after 5 cycles. This work provided a valuable approach to design a novel and efficient system for degrading organic pollutants in wastewater using magnetic biochar.