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Abstract Background Renal epithelioid angiomyolipoma is a rare and unique subtype of classic angiomyolipoma, characterized by the presence of epithelioid cells. It often presents with nonspecific symptoms and can be easily misdiagnosed due to its similarity to renal cell carcinoma and classic angiomyolipoma in clinical and radiological features. This case report is significant for its demonstration of the challenges in diagnosing epithelioid angiomyolipoma and its emphasis on the importance of accurate differentiation from renal cell carcinoma and classic angiomyolipoma. Case presentation A 58-year-old Asian female presented with sudden left flank pain and was initially diagnosed with a malignant renal tumor based on imaging studies. She underwent laparoscopic radical nephrectomy, and postoperative histopathology confirmed the diagnosis of epithelioid angiomyolipoma. The patient recovered well and is currently in good health with regular follow-ups. This case highlights the diagnostic challenges, with a focus on the clinical, radiological, and histopathological features that eventually led to the identification of epithelioid angiomyolipoma. Conclusions Epithelioid angiomyolipoma is easily misdiagnosed in clinical work. When dealing with these patients, it is necessary to make a comprehensive diagnosis based on clinical symptoms, imaging manifestations, and pathological characteristics.

Long non-coding RNAs (LncRNAs) are a class of RNA molecules with nucleic acid lengths ranging from 200 bp to 100 kb that cannot code for proteins, which are diverse and widely expressed in both animals and plants. Scholars have found that lncRNAs can regulate human physiological processes at the gene and protein levels, mainly through the regulation of epigenetic, transcriptional and post-transcriptional levels of genes and proteins, as well as in the immune response by regulating the expression of immune cells and inflammatory factors, and thus participate in the occurrence and development of a variety of diseases. From the downstream targets of lncRNAs, we summarize the new research progress of lncRNA mechanisms other than miRNA sponges in recent years, aiming to provide new ideas and directions for the study of lncRNA mechanisms.

Abstract To improve locomotion and operation integration, this paper presents an integrated leg-arm quadruped robot (ILQR) that has a reconfigurable joint. First, the reconfigurable joint is designed and assembled at the end of the leg-arm chain. When the robot performs a task, reconfigurable configuration and mode switching can be achieved using this joint. In contrast from traditional quadruped robots, this robot can stack in a designated area to optimize the occupied volume in a nonworking state. Kinematics modeling and dynamics modeling are established to evaluate the mechanical properties for multiple modes. All working modes of the robot are classified, which can be defined as deployable mode, locomotion mode and operation mode. Based on the stability margin and mechanical modeling, switching analysis and evaluation between each mode is carried out. Finally, the prototype experimental results verify the function realization and switching stability of multimode and provide a design method to integrate and perform multimode for quadruped robots with deployable characteristics.

Abstract Background There is an urgent need for therapeutic strategies for inpatients with severe or critical COVID-19. The evaluation of the clinical benefits of nirmatrelvir and ritonavir (Nmr/r) for these patients beyond five days of symptom onset is insufficient. Methods A new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated. Results In the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited. Conclusions Our study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings.

Background In China, both nirmatrelvir-ritonavir (Paxlovid) and azvudine have been granted approval to treat adult SARS-CoV-2-infected patients with moderate symptoms. Information about the clinical effect of the two available agents among inpatients with severe or critical COVID-19 is scarce.Purpose To compare the clinical outcomes of Paxlovid and azvudine among adult inpatients with severe or critical COVID-19.Method We conducted a retrospective cohort study in two large medical centres after the epidemic control measures were lifted in China. A new propensity score matched-inverse probability of treatment weighting cohort was constructed to evaluate the in-hospital all-cause mortality, hospital length of stay, Sequential Organ Failure Assessment (SOFA) score and safety.Results A total of 955 individuals were in the cohort. The antiviral therapy strategies were decided by the senior physician and the supplies of the pharmacy. A total of 451 patients were in the Paxlovid group, and 504 patients were in the azvudine group. Compared with Paxlovid, the effects of azvudine on in-hospital all-cause mortality were not significantly different, and the OR (95% CI) was 1.084 (0.822 to 1.430), and the average hospital length of stay of patients discharged alive was also similar in the azvudine group, and the difference (day) and (95% CI) was 0.530 (−0.334 to 1.393). After 7 days of therapy, the degree of decline in the SOFA score was greater in the Paxlovid group than in the azvudine group (p

Background: With the spread of COVID-19, concerns regarding its adverse effects have arisen. Based on affect regulation theory and construal level theory, this study explored how COVID-19 affects intertemporal choice in the health and economy domains, self-other differences for intertemporal choice were also inspected. The study examined whether psychological safety can moderate the relationship between COVID-19 and intertemporal choice. Methods: A 2 (COVID-19 status: pre-COVID-19, during-COVID-19) × 2 (decision maker role: decision for self, decision for others) × 2 (domain: health, economy) three-factor hybrid experiment was employed. Results: (1) Individuals in during-COVID-19 condition preferred more immediate options. (2) Delayed options were preferred more in the health domain. Preference for immediate money options enhanced during than before COVID-19. However, COVID-19 status did not affect choices related to health. (3) Delayed options were preferred more when making intertemporal choices for others than for oneself under the pre-COVID-19 condition. Self-other differences for intertemporal choice disappeared during COVID-19. (4) Psychological safety moderated the effect of COVID-19 on intertemporal choice. Conclusions: During COVID-19, individuals’ impulsive preference of intertemporal choice increased. COVID-19 affected intertemporal choice regarding economy and the self-other differences for intertemporal choice. Psychological safety could buffer the effect of COVID-19 on intertemporal choice. Value: This study can provide empirical evidence to affect regulation theory and level of explanation theory as well as guide individuals in making scientific decisions in health and economic domains under public health emergencies.

As one of the earliest discovered lncRNA molecules, lncRNA H19 is usually expressed in large quantities during embryonic development and is involved in cell differentiation and tissue formation. In recent years, the role of lncRNA H19 in tumors has been gradually recognized. Increasing evidence suggests that its aberrant expression is closely related to cancer development. LncRNA H19 as an oncogene not only promotes the growth, proliferation, invasion and metastasis of many tumors, but also develops resistance to treatment, affecting patients' prognosis and survival. Therefore, in this review, we summarise the extensive research on the involvement of lncRNA H19 in tumor progression and discuss how lncRNA H19, as a key target gene, affects tumor sensitivity to radiotherapy, chemotherapy and immunotherapy by participating in multiple cellular processes and regulating multiple signaling pathways, which provides a promising prospect for further research into the treatment of cancer.

Abstract Pyroptotic cell death, an inflammatory form of programmed cell death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT is commonly used for cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized by cell swelling, membrane rupture, and release of pro-inflammatory cytokines, has been shown to enhance the immune response against cancer cells. By inducing pyroptotic cell death in tumor cells, RT has the potential to enhance treatment outcomes by stimulating anti-tumor immune responses and improving the overall efficacy of RT. Furthermore, the release of danger signals from pyroptotic cells can promote the recruitment and activation of immune cells, leading to a systemic immune response that may target distant metastases. Although further research is needed to fully understand the mechanisms and optimize the use of pyroptotic cell death in RT, it holds promise as a novel therapeutic strategy for improving cancer treatment outcomes. This review aims to synthesize recent research on the regulatory mechanisms underlying radiation-induced pyroptosis and to elucidate the potential significance of this process in RT. The insights gained from this analysis may inform strategies to enhance the efficacy of RT for tumors.

Abstract Radiopharmaceuticals play a vital role in cancer therapy. The carrier of radiopharmaceuticals can precisely locate and guide radionuclides to the target, where radionuclides kill surrounding tumor cells. Effective application of radiopharmaceuticals depends on the selection of an appropriate carrier. Herein, different types of carriers of radiopharmaceuticals and the characteristics are briefly described. Subsequently, we review radiolabeled monoclonal antibodies (mAbs) and their derivatives, and novel strategies of radiolabeled mAbs and their derivatives in the treatment of lymphoma and colorectal cancer. Furthermore, this review outlines radiolabeled peptides, and novel strategies of radiolabeled peptides in the treatment of neuroendocrine neoplasms, prostate cancer, and gliomas. The emphasis is given to heterodimers, bicyclic peptides, and peptide-modified nanoparticles. Last, the latest developments and applications of radiolabeled nucleic acids and small molecules in cancer therapy are discussed. Thus, this review will contribute to a better understanding of the carrier of radiopharmaceuticals and the application in cancer therapy.

AbstractThe R-spondin protein family comprises four members (RSPO1-4), which are agonists of the canonical Wnt/β-catenin pathway. Emerging evidence revealed that RSPOs should not only be viewed as agonists of the Wnt/β-catenin pathway but also as regulators for tumor development and progression. Aberrant expression of RSPOs is related to tumorigenesis and tumor development in multiple cancers and their expression of RSPOs has also been correlated with anticancer immune cell signatures. More importantly, the role of RSPOs as potential target therapies and their implication in cancer progressions has been studied in the preclinical and clinical settings. These findings highlight the possible therapeutic value of RSPOs in cancer medicine. However, the expression pattern, effects, and mechanisms of RSPO proteins in cancer remain elusive. Investigating the many roles of RSPOs is likely to expand and improve our understanding of the oncogenic mechanisms mediated by RSPOs. Here, we reviewed the recent advances in the functions and underlying molecular mechanisms of RSPOs in tumor development, cancer microenvironment regulation, and immunity, and discussed the therapeutic potential of targeting RSPOs for cancer treatment. In addition, we also explored the biological feature and clinical relevance of RSPOs in cancer mutagenesis, transcriptional regulation, and immune correlation by bioinformatics analysis.KEY MESSAGESAberrant expressions of RSPOs are detected in various human malignancies and are always correlated with oncogenesis.Although extensive studies of RSPOs have been conducted, their precise molecular mechanism remains poorly understood.Bioinformatic analysis revealed that RSPOs may play a part in the development of the immune composition of the tumor microenvironment.

The worldwide urbanization has resulted in a massive loss of natural habitats, which is threatening biodiversity and socio-ecological sustainability. Urban rewilding is a strategy aiming to restore the complexity, autonomy and self-sustainability of urban ecosystems by interlinking ecological processes while minimizing or gradually reducing human disturbances. The benefits of urban rewilding are widely acknowledged; however, there remains a knowledge gap concerning the identification of suitable locations for urban rewilding and the methodologies for assessing the rewilding potential of urban areas. In this study, we proposed an approach that can be used to accurately identify urban rewilding opportunity spaces (UROS, the existing wildness areas and spaces offering ecological conditions conducive to the establishment of new urban wildness), by integrating data on spatial heterogeneity, biodiversity and human disturbance. UROS in Chongqing, China was evaluated and mapped at the city-wide scale, with a subsequent validation of the UROS results through an assessment of species richness of spontaneous herbaceous communities, which serve as the pioneer species in rewilding processes. The results revealed a positive correlation between high-scoring UROS and increased species richness of spontaneous herbs, thus confirming the feasibility of the UROS assessment method. Eleven primary types of UROS were identified, with the majority displaying scattered or linear distributions. Most very high-scoring UROS are characterized by expansive woodland expanses situated on the outskirts of high-density built-up areas and substantial water bodies within the built-up urban areas. Notably, nearly half of the UROS encompass areas of 900 m2 or less, underscoring the importance of urban rewilding initiatives targeting not only the preservation of extensive UROS with robust connectivity but also the revitalization of fragmented UROS with limited areas situated within central urban regions. The methodology is applicable to offer insights and spatial guidance in the execution of urban rewilding initiatives and biodiversity conservation efforts, contributing to sustainable regional development in the context of rapid urbanization.

Abstract Objectives To identify and describe international practice in incontinence management after radical cystectomy and orthotopic neobladder. Materials and Methods A systematic scoping review following the methodology of the Joanne Briggs Institute was conducted in which the application searched 15 data sources to identify papers published in English, from 1979 to 2022. Results Of the 16 papers that met the eligibility criteria, articles in Eastern countries mainly focus on the effect of conservative treatment, while in Western countries, more attention is paid to the effect of surgical treatment. Clinical characteristics of patients included conservative treatment failure, duration of post‐operative intervention and unique differential treatment of male and female patients. Reported factors influencing the achievement of urinary incontinence (UI) include lack of evidence to guide management practice, limited value of conservative treatment, high risk of surgical treatment and uncertainty of efficacy; currently, early behavioural research and multimodal rehabilitation training have good results. Conclusions UI in neobladder patients is a distressing condition that is difficult to treat and often requires high‐quality rehabilitation guidance and surgical intervention. Further research to address current knowledge gaps is important to inform practice.

Abstract Background Ferroptosis is a regulated cell death mode triggered by iron-dependent toxic membrane lipid peroxidation. As a novel cell death modality that is morphologically and mechanistically different from other forms of cell death, such as apoptosis and necrosis, ferroptosis has attracted extensive attention due to its association with various diseases. Evidence on ferroptosis as a potential therapeutic strategy has accumulated with the rapid growth of research on targeting ferroptosis for tumor suppression in recent years. Methods We summarize the currently known characteristics and major regulatory mechanisms of ferroptosis and present the role of ferroptosis in cellular stress responses, including ER stress and autophagy. Furthermore, we elucidate the potential applications of ferroptosis in radiotherapy and immunotherapy, which will be beneficial in exploring new strategies for clinical tumor treatment. Result and conclusion Based on specific biomarkers and precise patient-specific assessment, targeting ferroptosis has great potential to be translated into practical new approaches for clinical cancer therapy, significantly contributing to the prevention, diagnosis, prognosis, and treatment of cancer.

BackgroundProkinetic agents are currently considered the first-line therapy to improve gastric emptying when feeding intolerance occurred in critically ill adults. In this study, we developed a technique to assess the feasibility of predicting prokinetic agent efficacy in critically ill patients.MethodsThe first images of each patient were obtained after EFI had occurred but before the first dose of prokinetic agents was administered and additional images were obtained every morning until the seventh day. The gastric antrum echodensity was recorded based on grayscale values (50th percentile, ED50; 85th percentile, ED85; mean, EDmean) and daily energy and protein intake was collected as the judgment for effective and ineffective group. A receiver operating characteristic curve was analyzed to distinguish the thresholds between the two groups and thus determine the ability of the gastric antrum echodensity to predict the efficacy of prokinetic agents.ResultsIn total, 83 patients were analyzed. Patients in the ineffective group had a higher ED50 (58.13 ± 14.48 vs. 49.88 ± 13.78, p

Abstract TP53, a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53 (mutp53) often acquires inherent, novel oncogenic functions, which is termed “gain-of-function”. Emerging evidence suggests that mutp53 is highly associated with advanced malignancies and poor prognosis, which makes it a target for development of novel cancer therapies. Herein, we provide a summary of our knowledge of the mutp53 types and mutp53 spectrum in cancers. The mechanisms of mutp53 accumulation and gain-of-function are also summarized. Furthermore, we discuss the gain-of-function of mutp53 in cancers: genetic instability, ferroptosis, microenvironment, and stemness. Importantly, the role of mutp53 in the clinic is also discussed, particularly with regard to chemotherapy and radiotherapy. Last, emphasis is given to emerging strategies on how to target mutp53 for tumor therapy. Thus, this review will contribute to better understanding of the significance of mutp53 as a target for therapeutic strategies.

Abstract Background Associated with increased morbidity and mortality, postoperative pulmonary complications (PPCs) often occur after major abdominal surgery. Diaphragmatic dysfunction is suggested to play an important role in the development of PPCs and diaphragm echodensity can be used as an indicator of diaphragm function. This study aimed to determine whether diaphragm echodensity could predict the occurrence of PPCs in patients after major abdominal surgery. Methods Diaphragm ultrasound images of patients after major abdominal surgery were collected during spontaneous breathing trials. Echodensity was quantified based on the right-skewed distribution of grayscale values (50th percentile, ED50; 85th percentile, ED85; mean, EDmean). Intra- and inter-analyzer measurement reproducibility was determined. Outcomes including occurrence of PPCs, reintubation rate, duration of ventilation, and length of ICU stay were recorded. Results Diaphragm echodensity was measured serially in 117 patients. Patients who developed PPCs exhibited a higher ED50 (35.00 vs. 26.00, p 36, n = 35) and low-risk group (ED50 ≤ 36, n = 82). Compared with the low-risk group, the high-risk group had a higher incidence of PPCs (unadjusted p = 0.003; multivariate-adjusted p

Abstract Background Fibroproliferative repair starts early in the inflammatory phase of acute respiratory distress syndrome (ARDS) and indicates a poor prognosis. Lumican, a small leucine-rich proteoglycan, is implicated in homeostasis and fibrogenesis, but its role in ARDS is unclear. Methods Bronchoalveolar lavage fluid (BALF) samples were obtained from ARDS patients (n = 55) enrolled within 24 h of diagnosis and mechanically ventilated (n = 20) and spontaneously breathing (n = 29) control subjects. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse models were intratracheally administered an adeno-associated virus (AAV) vector expressing lumican shRNA. Primary human lung fibroblasts (HLF) and small airway epithelial cells (SAECs) were cultured with tumour necrosis factor (TNF)-α or lumican. Luminex/ELISA, histochemistry/immunohistochemistry, immunofluorescence microscopy, quantitative real-time PCR, and western blotting were performed. Results Lumican levels were significantly higher in the BALF of ARDS patients than in that of ventilated or spontaneously breathing controls (both p

Objective During major resection of liver carcinoma, liver regeneration (LR) is induced by various clinical and biological factors. Heme oxygenase (HO)-1 has been found as a key inducer of LR in preclinical trial. The clinical evidence for the role of HO-1 in liver dysfunction (LD) including LR is still unknown and has been included in this study. Methods Therefore, plasma HO-1 were monitored during perioperative period in 65 patients with hepatectomy, with 35 training and 30 validation cohorts. LD were evaluated by liver function serum markers and calculation of regeneration indices, respectively. Results In the training setting, HO-1 levels were remarkably reduced after liver resection (P

Abstract Background Current sedatives have different side effects in long-term sedation. The sequential use of midazolam and dexmedetomidine for prolonged sedation may have distinct advantages. We aimed to evaluate the efficacy and safety of the sequential use of midazolam and either dexmedetomidine or propofol, and the use of midazolam alone in selected critically ill, mechanically ventilated patients. Methods This single-center, randomized controlled study was conducted in medical and surgical ICUs in a tertiary, academic medical center. Patients enrolled in this study were critically ill, mechanically ventilated adult patients receiving midazolam, with anticipated mechanical ventilation for ≥ 72 h. They passed the spontaneous breathing trial (SBT) safety screen, underwent a 30-min-SBT without indication for extubation and continued to require sedation. Patients were randomized into group M-D (midazolam was switched to dexmedetomidine), group M-P (midazolam was switched to propofol), and group M (sedation with midazolam alone), and sedatives were titrated to achieve the targeted sedation range (RASS − 2 to 0). Results Total 252 patients were enrolled. Patients in group M-D had an earlier recovery, faster extubation, and more percentage of time at the target sedation level than those in group M-P and group M (all P 0.05). Conclusions The sequential use of midazolam and dexmedetomidine was an effective and safe sedation strategy for long-term sedation and could provide clinically relevant benefits for selected critically ill, mechanically ventilated patients. Trial registration NCT02528513 . Registered August 19, 2015.

Abstract Background and aims The existing evidence has indicated that hyperthermia ablation (HA) and HA combined with transarterial chemoembolization (HATACE) are the optimal alternative to surgical resection for patients with hepatocellular carcinoma (HCC) in the COVID‐19 crisis. However, the evidence for decision‐making is lacking in terms of comparison between HA and HATACE. Herein, a comprehensive evaluation was performed to compare the efficacy and safety of HATACE with monotherapy. Materials and Methods Worldwide studies were collected to evaluate the HATACE regimen for HCC due to the practical need for global extrapolation of applicative population. Meta‐analyses were performed using the RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Results Thirty‐six studies involving a large sample of 5036 patients were included finally. Compared with HA alone, HATACE produced the advantage of 5‐year overall survival (OS) rate (OR:1.90; 95%CI:1.46,2.46; p 3 cm) HCC with comparable safety. However, the survival benefit of adjuvant TACE in HATACE regimen was not found for the patients with small (≤3 cm) HCC.

Abstract Background The lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. However, the role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown. Methods The expression profiles of lncRNAs in NSCLC were explored via transcriptome sequencing. CCK-8, EdU incorporation and clonogenic survival assays were conducted to evaluate the proliferation and radiosensitivity of NSCLC cells. Flow cytometry and Western blotting were conducted to measure the level of apoptosis. The binding relationship between the lncRNA H19 and miR-130a-3p was determined by a dual-luciferase reporter assay. A binding relationship was also identified between miR-130a-3p and With-No-Lysine Kinase 3 (WNK3). Results Expression patterns of lncRNAs revealed that the lncRNA H19 was upregulated in radioresistant NSCLC (A549-R11) cells compared with A549 cells. Knockdown of the lncRNA H19 enhanced the sensitivity of NSCLC cell lines to X-ray and carbon ion irradiation. Mechanistically, the lncRNA H19 serves as a sponge of miR-130a-3p, which downregulates WNK3 expression. The lncRNA H19–miR-130a-3p–WNK3 axis modulates radiosensitivity by regulating apoptosis in NSCLC cell lines. Conclusion Knockdown of the lncRNA H19 promotes the sensitivity of NSCLC cells to X-ray and carbon ion irradiation. Hence, the lncRNA H19 might function as a potential therapeutic target that enhances the antitumor effects of radiotherapy in NSCLC.

Abstract Background Increasing evidence has indicated that pyroptosis could regulate the tumor immune microenvironment (TIME) to affect the tumor development. As a highly immunogenic tumor, clear cell renal cell carcinoma (ccRCC) can benefit from immunotherapy, but related research on pyroptosis in the TIME of ccRCC is still deficient. Methods Available data derived from TCGA and GEO databases were analyzed to identify the different expression profiles of pyroptosis in ccRCC and normal tissues, and the correlation of pyroptosis regulators with TIME was evaluated in ccRCC. Results According to consensus clustering analysis, two differential expression levels of subtypes were identified to affect patient prognosis, and were related to histological tumor stage and grade. Immune cells were calculated by the CIBERSORT algorithm. Higher infiltrated levels of B cells naive, T cells CD4 memory resting, NK cells resting, monocytes, macrophages were observed in Cluster 1, while higher infiltrated levels of CD8+ T cells, T follicular helper cells, and Tregs were observed in Cluster 2. Gene set enrichment analysis indicated that Cluster 2 was enriched in multiple immune-related pathways, including the JAK-STAT signaling pathway. Moreover, overexpression of eight immune checkpoints was related to ccRCC development, especially in Cluster 2. As four potentially key pyroptosis regulators, AIM2, CASP5, NOD2, and GZMB were confirmed to be upregulated in ccRCC by RT-qPCR analysis and further verified by the HPA database. Further pan-cancer analysis suggested that these four pyroptosis regulators were differentially expressed and related to the TIME in multiple cancers. Conclusion The present study provided a comprehensive view of pyroptosis regulators in the TIME of ccRCC, which may provide potential value for immunotherapy.

Abstract Bladder cancer (BCa) is one of the 10 most common cancers with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNAs), a large class of noncoding RNA transcripts, consist of more than 200 nucleotides and play a significant role in the regulation of molecular interactions and cellular pathways during the occurrence and development of various cancers. In recent years, with the rapid advancement of high-throughput gene sequencing technology, several differentially expressed lncRNAs have been discovered in BCa, and their functions have been proven to have an impact on BCa development, such as cell growth and proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and drug-resistance. Furthermore, evidence suggests that lncRNAs are significantly associated with BCa patients’ clinicopathological characteristics, especially tumor grade, TNM stage, and clinical progression stage. In addition, lncRNAs have the potential to more accurately predict BCa patient prognosis, suggesting their potential as diagnostic and prognostic biomarkers for BCa patients in the future. In this review, we briefly summarize and discuss recent research progress on BCa-associated lncRNAs, while focusing on their biological functions and mechanisms, clinical significance, and targeted therapy in BCa oncogenesis and malignant progression.

Circular RNAs (circRNAs) are a sort of long, non-coding RNA molecules with a covalently closed continuous ring structure without 5'-3' polarity and poly-A tail. The modulative role of circRNAs in malignant diseases has been elucidated by many studies in recent years via bioinformatics and high-throughput sequencing technologies. Generally, circRNA affects the proliferative, invasive, and migrative capacity of malignant cells via various mechanisms, exhibiting great potential as novel biomarkers in the diagnoses or treatments of malignancies. Meanwhile, autophagy preserves cellular homeostasis, serving as a vital molecular process in tumor progression. Mounting studies have demonstrated that autophagy can not only contribute to cancer cell survival but can also induce autophagic cell death in specific conditions. A growing number of research studies have indicated that there existed abundant associations between circRNAs and autophagy. Herein, we systemically reviewed and discussed recent studies on this topic in different malignancies and concluded that the circRNA–autophagy axis played crucial roles in the proliferation, metastasis, invasion, and drug or radiation resistance of different tumor cells.

Abstract Studies of radiation interaction with tumor cells often take apoptosis as the desired results. However, mitotic catastrophe and senescence are also promoted by clinically relevant doses of radiation. Furthermore, p53 is a well-known transcription factor that is closely associated with radiosensitivity and radiation-induced cell death. Therefore, we aimed to investigate the involvement of radiosensitivity, cell death modalities and p53 status in response to carbon-ion radiation (CIR) here. Isogenic human colorectal cancer cell lines HCT116 (p53+/+ and p53−/−) were irradiated with high-LET carbon ions. Cell survival was determined by the standard colony-forming assay. 53BP1 foci were visualized to identify the repair kinetics of DNA double-strand breaks (DSBs). Cellular senescence was measured by SA-β-Gal and Ki67 staining. Mitotic catastrophe was determined with DAPI staining. Comparable radiosensitivities of p53+/+ and p53− /− HCT116 colorectal cells induced by CIR were demonstrated, as well as persistent 53BP1 foci indicated DNA repair deficiency in both cell lines. Different degree of premature senescence in isogenic HCT116 colorectal cancer cells suggested that CIR-induced premature senescence was more dependent on p21 but not p53. Sustained upregulation of p21 played multifunctional roles in senescence enhancement and apoptosis inhibition in p53+/+ cells. p21 inhibition further increased radiosensitivity of p53+/+ cells. Complex cell death modalities rather than single cell death were induced in both p53+/+ and p53− /− cells after 5 Gy CIR. Mitotic catastrophe was predominant in p53− /− cells due to inefficient activation of Chk1 and Chk2 phosphorylation in combination with p53 null. Senescence was the major cell death mechanism in p53+/+ cells via p21-dependent pathway. Taken together, p21-mediated premature senescence might be used by tumor cells to escape from CIR-induced cytotoxicity, at least for a time.

Abstract Bcl-x pre-mRNA splicing serves as a typical example to study the impact of alternative splicing in the modulation of cell death. Dysregulation of Bcl-x apoptotic isoforms caused by precarious equilibrium splicing is implicated in genesis and development of multiple human diseases, especially cancers. Exploring the mechanism of Bcl-x splicing and regulation has provided insight into the development of drugs that could contribute to sensitivity of cancer cells to death. On this basis, we review the multiple splicing patterns and structural characteristics of Bcl-x. Additionally, we outline the cis-regulatory elements, trans-acting factors as well as epigenetic modifications involved in the splicing regulation of Bcl-x. Furthermore, this review highlights aberrant splicing of Bcl-x involved in apoptosis evade, autophagy, metastasis, and therapy resistance of various cancer cells. Last, emphasis is given to the clinical role of targeting Bcl-x splicing correction in human cancer based on the splice-switching oligonucleotides, small molecular modulators and BH3 mimetics. Thus, it is highlighting significance of aberrant splicing isoforms of Bcl-x as targets for cancer therapy.

Myasthenia gravis (MG) is an acquired autoimmune disease. Its clinical manifestations comprise ptosis, diplopia, dysarthria, dysphagia, limb weakness, and in severe cases, respiratory muscle involvement. Dysarthria as an exclusive initial and primary complaint in MG is rare and seldom reported. In this paper, we report a case of type IIIb MG with isolated dysarthria as the only clinical manifestation and we review the relevant literature. The patient was a 62-year-old man who presented with episodes of slurred speech for 20 days that had worsened in the previous 9 days. His medical history comprised hypertension, diabetes mellitus, and coronary heart disease. The initial diagnosis on admission was transient ischemic attack. Careful re-examination of the patient’s history revealed that his symptoms mainly involved increasingly worse slurred speech episodes without drinking or swallowing difficulties, and no significant improvement with rest was observed. Electromyography and autoantibody profiling led to a diagnosis of type IIIb MG. His symptoms improved after the oral administration of pyridostigmine bromide 60 mg. Laryngeal MG is important to differentiate from stroke. It is necessary to perform a computerized voice analysis when encountering patients with atypical symptoms of MG.

Abstract Background Transcriptional coactivator with PDZ-binding motif (TAZ) has been reported to be involved in tumor progression, angiogenesis, epithelial-mesenchymal transition (EMT), glycometabolic modulation and reactive oxygen species (ROS) buildup. Herein, the underlying molecular mechanisms of the TAZ-induced biological effects in bladder cancer were discovered. Methods qRT-PCR, western blotting and immunohistochemistry were performed to determine the levels of TAZ in bladder cancer cells and tissues. CCK-8, colony formation, tube formation, wound healing and Transwell assays and flow cytometry were used to evaluate the biological functions of TAZ, miR-942-3p and growth arrest-specific 1 (GAS1). QRT-PCR and western blotting were used to determine the expression levels of related genes. Chromatin immunoprecipitation and a dual-luciferase reporter assay were performed to confirm the interaction between TAZ and miR-942. In vivo tumorigenesis and colorimetric glycolytic assays were also conducted. Results We confirmed the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p expression amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the impacts on cell proliferation, angiogenesis, EMT, glycolysis and ROS levels induced by TAZ knockdown. Furthermore, miR-942-3p restrained the expression of GAS1 to modulate biological behaviors. Conclusion Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression and illustrated that TAZ, miR-942-3p and GAS1 might be potential therapeutic targets for bladder cancer treatment.

Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal uroepithelial cells, circRIMS1 was selected as a research object. We further verified by qRT-PCR that circRIMS1 is upregulated in both bladder cancer tissue and cell lines. Proliferation, colony-formation, Transwell migration, invasion, apoptosis, western blotting, and in vivo experiments were utilized to clarify the roles of circRIMS1, microRNA (miR)-433-3p, and cell cycle and apoptosis regulator 1 (CCAR1). For mechanistic investigation, RNA pulldown, fluorescence in situ hybridization (FISH), and luciferase reporter assay confirmed the binding of circRIMS1 with miR-433-3p. Inhibition of circRIMS1 suppressed the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Moreover, the circRIMS1/miR-433-3p/CCAR1 regulatory axis was confirmed to be responsible for the biological functions of circRIMS1. Taken together, our research demonstrated that circRIMS1 promotes tumor growth, migration, and invasion through the miR-433-3p/CCAR1 regulatory axis, representing a potential therapeutic target and biomarker in bladder cancer.

Objective:Precise segmentation of human organs and anatomic structures (especially organs at risk, OARs) is the basis and prerequisite for the treatment planning of radiation therapy. In order to ensure rapid and accurate design of radiotherapy treatment planning, an automatic organ segmentation technique was investigated based on deep learning convolutional neural network.MethodA deep learning convolutional neural network (CNN) algorithm called BCDU-Net has been modified and developed further by us. Twenty two thousand CT images and the corresponding organ contours of 17 types delineated manually by experienced physicians from 329 patients were used to train and validate the algorithm. The CT images randomly selected were employed to test the modified BCDU-Net algorithm. The weight parameters of the algorithm model were acquired from the training of the convolutional neural network.ResultThe average Dice similarity coefficient (DSC) of the automatic segmentation and manual segmentation of the human organs of 17 types reached 0.8376, and the best coefficient reached up to 0.9676. It took 1.5–2 s and about 1 h to automatically segment the contours of an organ in an image of the CT dataset for a patient and the 17 organs for the CT dataset with the method developed by us, respectively.ConclusionThe modified deep neural network algorithm could be used to automatically segment human organs of 17 types quickly and accurately. The accuracy and speed of the method meet the requirements of its application in radiotherapy.

Abstract Background Patients with acute pancreatitis usually exhibit dyslipidemia and oxidative stress. However, the significance of high-density lipoprotein cholesterol (HDL-C) level, low-density lipoprotein cholesterol (LDL-C) level and the HDL-C/LDL-C ratio (H/L ratio) as markers for disease progression remain unknown. Aim The aim of this study was to evaluate the role of HDL-C levels, LDL-C levels and the H/L ratio as markers of disease progression in patients admitted to the intensive cate unit with acute pancreatitis. Methods This retrospective study was conducted at a tertiary critical care center in China. Plasma HDL-C and LDL-C levels were measured in 166 patients with acute pancreatitis. The associations between HDL-C, LDL-C, H/L ratio, as well as other inflammatory index and mortality, were analyzed. Multivariate cox analysis based on two models was used to determine the independent prognostic factor. Predictive ability of in-hospital mortality for variables was determined using the receiver operating characteristics curves. Results Significantly higher H/L ratios at admission were observed in patients with acute pancreatitis who died compared with survivors (0.93 vs. 0.64, p

The coronavirus disease 2019 (COVID-19) pandemic has greatly disrupted the normal treatment of patients with liver cancer and increased their risk of death. The weight of therapeutic safety was significantly amplified for decision-making to minimize the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, the safety and effectiveness of carbon ion radiotherapy (CIRT) for unresectable liver cancer (ULC) were evaluated, and Chinese experiences were shared to solve the predicament of ULC treatment caused by SARS-CoV-2. Worldwide studies were collected to evaluate CIRT for ULC as the world has become a community due to the COVID-19 pandemic. We not only searched five international databases including the Cochrane Library, Web of Science, PubMed, Embase, and Scopus but also performed supplementary retrieval with other sources. Chinese experiences of fighting against COVID-19 were introduced based on the advancements of CIRT in China and a prospective clinical trial of CIRT for treating ULC. A total of 19 studies involving 813 patients with ULC were included in the systematic review. The qualitative synthetic evaluation showed that compared with transarterial chemoembolization (TACE), CIRT could achieve superior overall survival, local control, and relative hepatic protection. The systematic results indicated that non-invasive CIRT could significantly minimize harms to patients with ULC and concurrently obtain superior anti-cancer effectiveness. According to the Chinese experience, CIRT allows telemedicine within the hospital (TMIH) to keep a sufficient person-to-person physical distance in the whole process of treatment for ULC, which is significant for cutting off the transmission route of SARS-CoV-2. Additionally, CIRT could maximize the utilization rate of hospitalization and outpatient care (UHO). Collectively, CIRT for ULC patients not only allows TMIH and the maximized UHO but also has the compatible advantages of safety and effectiveness. Therefore, CIRT should be identified as the optimal strategy for treating appropriate ULC when we need to minimize the risk of SARS-CoV-2 infection and to improve the capacity of medical service in the context of the unprecedented COVID-19 crisis.

(1) Background: Studies on the long-term patterns of using vasopressors in patients with shock and their correlations with the risk of feeding intolerance (FI) are limited. This study aimed to characterize the norepinephrine equivalent dose (NEQ) trajectories and explore its correlations with FI in patients with shock. (2) Methods: This study prospectively enrolled patients with shock, who received vasopressors from August 2020 to June 2022. The Growth Mixed Model (GMM) was used to traverse longitudinal NEQ data at six-hour intervals and identify the latent trajectories of NEQ use in these patients. Cox proportional hazards regression models were used to examine the correlations of NEQ trajectories with FI. (3) Results: This study included a total of 210 patients with shock recruited from August 2020 to June 2022. Four trajectories of NEQ dose were identified and characterized by low-dose stable NEQ (L-NEQ, n = 98), moderate-dose stable NEQ (M-NEQ, n = 74), high-dose stable NEQ (H-NEQ, n = 21), and rapidly rising NEQ (R-NEQ, n = 17), with NEQ doses of 0.2, 0.4, 0.4, and 0.5 µg/kg/min at enteral nutrition (EN) initiation, respectively. The incidences of FI were 37.76%, 67.57%, 80.95%, and 76.47% in the L-NEQ, M-NEQ, H-NEQ, and R-NEQ groups, respectively (p < 0.001). As compared to the L-NEQ group, the risk of FI occurrence increased in the M-NEQ, H-NEQ, and R-NEQ groups (all p < 0.05). (4) Conclusions: The risk of FI was significantly associated with NEQ trajectories. It might be appropriate to initiate EN when the NEQ dose is stabilized below 0.2 µg/kg/min in patients with shock.

Hypoxia is a common feature in various tumors that regulates aggressiveness. Previous studies have demonstrated that some dysregulated long non-coding RNAs (lncRNAs) are correlated with tumor progression, including bladder cancer (BCa). However, the prognostic effect of hypoxia-related lncRNAs (HRLs) and their clinical relevance, as well as their regulatory effect on the tumor immune microenvironment, are largely unknown in BCa. A co-expression analysis between hypoxia genes and lncRNA expression, which was downloaded from the TCGA database, was performed to identify HRLs. Univariate Cox regression analysis was performed to select the most desirable lncRNAs for molecular subtype, and further LASSO analysis was performed to develop a prognostic model. This molecular subtype based on four HRLs (AC104653, AL136084, AL139393, and LINC00892) showed good performance in the tumor microenvironment and tumor mutation burden. The prognostic risk model suggested better performance in predicting BCa patients’ prognosis and obtained a close correlation with clinicopathologic features. Furthermore, four of five first-line clinical chemotherapies showed different sensitivities to this model, and nine immune checkpoints showed different expression in the molecular subtypes or the risk model. In conclusion, this study indicates that this molecular subtype and risk model based on HRLs may be useful in improving the prognostic prediction of BCa patients with different clinical situations and may help to find a useful target for tumor therapy.

During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. To explore the underlying mechanism, we collected blood samples from these patients and analyzed the gene expression profiles of peripheral immune cells. We found that all enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. In addition, no significant change was found in the expression of classic immunosuppression molecules including PD-1, PD-L1, and CTLA-4, suggesting that the adaptive immune suppression may not be due to the change of these genes. According to the published literatures and our data, this adaptive immunosuppression is likely to be caused by the “dysregulated host response” to severe infection, similar to the immunosuppression that exists in other severely infected patients with sepsis.

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA (ncRNA), which is characterized with a closed circular structure. A growing body of evidence has verified the vital roles of circRNAs in human cancer. In this research, we selected circPPP1CB as a study object by circRNA sequencing and quantitative real-time PCR (qRT-PCR) validation in human bladder cancer (BC). CircPPP1CB is downregulated in BC and is negatively correlated with clinical stages and histological grades. Functionally, circPPP1CB modulated cell growth, metastasis, and epithelial-to-mesenchymal transition (EMT) process in vitro and in vivo. Mechanically, we performed various experiments to verify the circPPP1CB/miR-1307-3p/SMG1 regulatory axis. Taken together, our results demonstrated that circPPP1CB participates in tumor growth, metastasis, and EMT process by interacting with the miR-1307-3p/SMG1 axis, and that circPPP1CB might be a novel therapeutic target and diagnostic biomarker in human BC.

Abstract Gadolinium-based nanomaterials can not only serve as contrast agents but also contribute to sensitization in the radiotherapy of cancers. Among radiotherapies, carbon ion irradiation is considered one of the superior approaches with unique physical and biological advantages. However, only a few metallic nanoparticles have been used to improve carbon ion irradiation. In this study, gadolinium oxide nanocrystals (GONs) were synthesized using a polyol method to decipher the radiosensitizing mechanisms in non-small cell lung cancer (NSCLC) cell lines irradiated by carbon ions. The sensitizer enhancement ratio at the 10% survival level was correlated with the concentration of Gd in NSCLC cells. GONs elicited an increase in hydroxyl radical production in a concentration-dependent manner, and the yield of reactive oxygen species increased obviously in irradiated cells, which led to DNA damage and cell cycle arrest. Apoptosis and cytostatic autophagy were also significantly induced by GONs under carbon ion irradiation. The GONs may serve as an effective theranostic material in carbon ion radiotherapy for NSCLC. Graphical Abstract

Abstract Background Radiotherapy (RT) is considered an important therapeutic strategy in the fight against colorectal cancer (CRC). However, the existence of some radioresistance factors becomes the main challenge for the RT. Recently, non-coding RNAs (ncRNAs) have shown an important role in modulating cancer cell responses to ionizing radiation (IR). It is therefore of great significance to elucidate the exact mechanisms of ncRNAs in IR-mediated responses to CRC. Methods Microarrays were used to identify specific miRNAs that may be altered in response to IR. Bioinformatics, luciferase reporter analyses were used to explore the targets of miR-6778-5p. CircRNA CBL.11 was identified to bind with miR-6778-5p by bioinformatic analysis, AGO2 immunoprecipitation and biotinylated RNA pull-down assay. Functional experiments, including CCK-8 assay, cell colony formation assay and EdU incorporation were conducted to investigate the biological roles of miR-6778-5p and circular RNA CBL.11. Results MiR-6778-5p was suppressed in CRC cells after irradiation. Results of functional experiments indicated that miR-6778-5p promoted the proliferation of CRC cells. Luciferase reporter analyses showed that YWHAE was a target of miR-6778-5p, which mediated the function of miR-6778-5p in the proliferation of CRC cells via the p53 pathway. Furthermore, we have noticed that after carbon ion irradiation, circRNA CBL.11 was increased in CRC cells and could function as a competing endogenous RNA (ceRNA) to regulate YWHAE expression by sponging miR-6778-5p, resulting in regulation the proliferation of CRC cells. Conclusion CircRNA CBL.11 may play an important role in improving the efficacy of carbon ion RT against CRC.

Background: Acute kidney injury (AKI) is a common complication after surgery. Because of unpredictable and variable age-dependent physical decline, the incidence, risk factor of postsurgical AKI and the predictive power of estimated glomerular filtration rate prior to surgery (eGFRpreSurg) has not been fully elucidated in very elderly patients. Methods: All discharged patients aged ≥80 years without chronic kidney disease who underwent surgery prior to intensive care unit (ICU) admission from 2017 through 2018 were included. Clinical, biological and surgical data were recorded. Mean of outpatient creatinine values from the year prior to ICU admission was used as the baseline value to determine the occurrence of AKI. Postoperative AKI was diagnosed according to Kidney Disease Improving Global Outcomes criteria. Results: Among 243 very elderly postoperative patients admitted during the study period, 48 had AKI during their ICU stay. The occurrence of postsurgical AKI was associated with longer ventilation times (p

(1) Background: Acute muscle inflammation leads to increased sonographic echodensity. We developed a technique to characterize the echodensity of the gastric antrum wall and assess its feasibility in evaluating the severity of acute gastrointestinal injury (AGI); (2) Methods: The B-mode images of the gastric antrum of each enrolled patient were obtained daily by point-of-care ultrasound (POCUS). The 50th percentile, 85th percentile, and mean value of the grayscale distribution according to histogram analysis (ED50, ED85, and EDmean, respectively) were used to characterize the gastric antrum echodensity. Consistency and correlation analyses were performed to evaluate the feasibility and reproducibility of gastric antrum echodensity measurement. The association of gastric antrum echodensity with the severity of AGI and its ability to predict feeding intolerance (FI) were analyzed; (3) Results: In total, 206 POCUS images of 43 patients were analyzed. The gastric antrum echodensity measurements had sufficient intra- and inter-investigator reliabilities (intraclass correlation coefficient >0.9 for all parameters). The ED50 showed a significant upward trend as AGI severity increased, as well as ED85 and EDmean (p for trend 50 (67.8 vs. 56.1, p = 0.02), ED85 (85.6 vs. 71.2, p = 0.01), and EDmean (70.3 vs. 57.6, p = 0.01) upon enteral feeding initiation; (4) Conclusions: Measurement of gastric antrum echodensity was technically feasible and reproducible in ventilated patients. Increased gastric antrum echodensity was associated with greater severity of AGI. Patients with higher gastric antrum echodensity upon enteral nutrition initiation via a nasogastric tube were more likely to develop FI.

In this work, a novel intumescent flame retardant (IFR) system was fabricated by the introduction of chitin as a green charring agent, ammonium polyphosphate (APP) as the acid source, and melamine (MEL) as the gas source. The obtained chitin-based IFR was then incorporated into a polylactic acid (PLA) matrix using melt compounding. The fire resistance of PLA/chitin composites was investigated via the limiting oxygen index (LOI), UL-94 vertical burning, and cone calorimeter (CONE) tests. The results demonstrated that the combination of 10%APP, 5%chitin and 5%MEL could result in a 26.0% LOI, a V-0 rating after UL and a 51.2% reduction in the peak heat release rate during the CONE test. Based on the mechanism analysis from both the morphology and the chemical structure of the char, it was suggested that chitin was a promising candidate as a charring agent for chitin reacted with APP and MEL with the formation of an intumescent layer on the surface.

Hospital acquired thrombocytopenia (HAT) is a common hematological complication after surgery. This research aimed to develop and compare the performance of seven machine learning (ML) algorithms for predicting patients that are at risk of HAT after surgery. We conducted a retrospective cohort study which enrolled adult patients transferred to the intensive care unit (ICU) after surgery in West China Hospital of Sichuan University from January 2016 to December 2018. All subjects were randomly divided into a derivation set (70%) and test set (30%). ten-fold cross-validation was used to estimate the hyperparameters of ML algorithms during the training process in the derivation set. After ML models were developed, the sensitivity, specificity, area under the curve (AUC), and net benefit (decision analysis curve, DCA) were calculated to evaluate the performances of ML models in the test set. A total of 10,369 patients were included and in 1354 (13.1%) HAT occurred. The AUC of all seven ML models exceeded 0.7, the two highest were Gradient Boosting (GB) (0.834, 0.814–0.853, p < 0.001) and Random Forest (RF) (0.828, 0.807–0.848, p < 0.001). There was no difference between GB and RF (0.834 vs. 0.828, p = 0.293); however, these two were better than the remaining five models (p < 0.001). The DCA revealed that all ML models had high net benefits with a threshold probability approximately less than 0.6. In conclusion, we found that ML models constructed by multiple preoperative variables can predict HAT in patients transferred to ICU after surgery, which can improve risk stratification and guide management in clinical practice.

Biomass char is accepted as an environmentally friendly energy resource, and is promising for NO removal in industrial furnaces. NO reduction with biomass char (rice husk) was investigated in a fixed-bed quartz reactor. The influence of CO concentration, reaction temperature, initial NO concentration, and char loading on the NO reduction were evaluated. The results showed that the overall NO reduction reaction was dominated by the direct reaction of NO with char without CO. Increasing CO concentration resulted in an enhanced catalytic reaction between NO and CO over the char surface and a decreased carbon consumption of char. With decreasing temperature, the influence of CO concentration on NO reduction was strengthened. Over the test temperature range, char provided a surface to catalyze the NO–CO reaction at excess CO/NO ratio. Increasing the initial NO concentration led to an increasingly significant influence on NO reduction with the enhanced CO/NO ratio. With increased char loading, the enhancement of NO reduction became unobservable for excess CO/NO ratio. Reaction orders of NO and activation energy for NO reduction by char were 0.71 and 60.21 kJ·mol−1, respectively, against 0.82 and 34.60 kJ·mol−1, respectively, for NO reduction by CO, catalyzed by char.

Hypertriglyceridaemia is one of the most common causes of severe acute pancreatitis (SAP). However, the association between elevated triglycerides (TG) level in hospital stay and outcome in SAP patients with normal TG level at admission has not been clearly demonstrated. This retrospective study assessed the serum TG levels of patients with SAP admitted to the intensive care unit (ICU) in 2017. Variables with a statistically significant association with the incidence of in-hospital TG elevation, as determined by univariate analysis, were analysed using a logistic regression model to predictors. Of the 99 patients included in the study, TG levels were within the normal range in 59 (59.59%) patients at admission. Among patients with normal TG level when admitted to ICU, 28 (47.46%) experienced at least one episode of TG level elevation during their ICU stay. Elevated TG level in hospitalization is associated with an increased length of ICU stay, as well as increased mortality. In addition to other factors, propofol usage was independently associated with the occurrence of in-hospital-TG elevation. To conclude, we retrospectively investigated the incidence, outcome, and risk factors for in-hospital TG elevation events in SAP patients admitted to the ICU. We found a high incidence of both preexisting and in-hospital-acquired TG elevation in SAP patients admitted to the ICU. The TG elevation that occurred during the ICU stay was associated with worse outcomes and long-term hospitalization of the ICU. Propofol usage was independently associated with the TG elevation occurrence in the ICU.

Satellite orbit error and clock bias are the keys to precise point positioning (PPP). The traditional PPP algorithm requires precise satellite products based on worldwide permanent reference stations. Such an algorithm requires considerable work and hardly achieves real-time performance. However, real-time positioning service will be the dominant mode in the future. IGS is providing such an operational service (RTS) and there are also commercial systems like Trimble RTX in operation. On the basis of the regional Continuous Operational Reference System (CORS), a real-time PPP algorithm is proposed to apply the coupling estimation of clock bias and orbit error. The projection of orbit error onto the satellite-receiver range has the same effects on positioning accuracy with clock bias. Therefore, in satellite clock estimation, part of the orbit error can be absorbed by the clock bias and the effects of residual orbit error on positioning accuracy can be weakened by the evenly distributed satellite geometry. In consideration of the simple structure of pseudorange equations and the high precision of carrier-phase equations, the clock bias estimation method coupled with orbit error is also improved. Rovers obtain PPP results by receiving broadcast ephemeris and real-time satellite clock bias coupled with orbit error. By applying the proposed algorithm, the precise orbit products provided by GNSS analysis centers are rendered no longer necessary. On the basis of previous theoretical analysis, a real-time PPP system was developed. Some experiments were then designed to verify this algorithm. Experimental results show that the newly proposed approach performs better than the traditional PPP based on International GNSS Service (IGS) real-time products. The positioning accuracies of the rovers inside and outside the network are improved by 38.8% and 36.1%, respectively. The PPP convergence speeds are improved by up to 61.4% and 65.9%. The new approach can change the traditional PPP mode because of its advantages of independence, high positioning precision, and real-time performance. It could be an alternative solution for regional positioning service before global PPP service comes into operation.

In this work, a multi-functional nanoparticle (TiO2-KH570-DOPO) has been successfully synthesized through the attachment of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO)-methacryloxy propyl trimethoxyl silane on the surface of titanium dioxide (TiO2). Supercritical carbon dioxide was used as the solvent in order to increase the grafting level. The chemical structure of TiO2-KH570-DOPO was fully characterized using Fourier transform infrared spectra, thermogravimetric analysis and transmission electron microscopy. The modified TiO2 was incorporated into flexible polyurethane foam (FPUF). The fire performance of FPUF blends was evaluated using microscale combustion calorimetry. Peak heat release rate and total heat release values were reduced from 657.0 W/g and 28.9 kJ/g for neat FPUF sample to 519.2 W/g and 26.8 kJ/g of FPUF specimen containing 10 wt % of TiO2-KH570-DOPO. Analysis of thermal stability and the observation of char formation suggests that TiO2-KH570-DOPO is active in the condensed phase.

The aim of the present study was to investigate the radiosensitizing effect of genistein, and the corresponding mechanisms of action on breast cancer cells with different estrogen receptor (ER) status. Human breast cancer cell lines such as MCF-7 (ER-positive, harboring wild-type p53) and MDA-MB-231 (ER-negative, harboring mutant p53) were irradiated with X-rays in the presence or absence of genistein. Cell survival, DNA damage and repair, cell cycle distribution, cell apoptosis, expression of proteins related to G2/M cell cycle checkpoint and apoptosis were measured with colony formation assays, immunohistochemistry, flow cytometry and western blot analysis, respectively. Genistein showed relatively weak toxicity to both cell lines at concentrations in the range of 5–20 μM. Using the dosage of 10 μM genistein, the sensitizer enhancement ratios after exposure to X-rays at a 10% cell survival (IC10) were 1.43 for MCF-7 and 1.36 for MDA-MB-231 cells, respectively. Significantly increased DNA damages, arrested cells at G2/M phase, decreased homologous recombination repair protein Rad51 foci formation and enhanced apoptotic rates were observed in both cell lines treated by genistein combined with X-rays compared with the irradiation alone. The combined treatment obviously up-regulated the phosphorylation of ATM, Chk2, Cdc25c and Cdc2, leading to permanent G2/M phase arrest, and up-regulated Bax and p73, down-regulated Bcl-2, finally induced mitochondria-mediated apoptosis in both cell lines. These results suggest that genistein induces G2/M arrest by the activation of the ATM/Chk2/Cdc25C/Cdc2 checkpoint pathway and ultimately enhances the radiosensitivity of both ER+ and ER- breast cancer cells through a mitochondria-mediated apoptosis pathway.