Berlin Green with tunable iron content as ultra-high rate host for efficient aqueous ammonium ion storage.

Prussian blue analogues (PBAs) are regarded as promising cathode materials for ammonium-ion batteries (AIBs) because of their low cost and superb theoretical capacity. However, its inherently poor conductivity and structural collapse can significantly limit the enhancement of rate property and cycling stability. In this work, Berlin Green (BG) electrode materials with similar wool-like clusters were constructed by direct precipitation method to accelerate the kinetic, which realizes outstanding cycling stability. Berlin Green with the appropriate amount of iron (BG-2) has a fast ion transport channel, enhanced structure stability, highly reversible insertion/extraction of NH4+, and fine electrochemical reaction activity. Benefiting from the unique architecture and component, the BG-2 electrode shows an excellent rate performance with a discharge/charge specific capacity of 60.1/59.3 mAh g-1 at 5 A g-1. Even at 5 A g-1, BG-2 exhibits remarkable cycling stability with an initial discharge capacity of 59.5 mAh g-1 and a capacity retention rate of approximately 76% after 30,000 cycles. The BG-2 reveals exceedingly good electrochemical reversibility during the process of NH4+ (de)insertion. BG materials indicate huge potential as a cathode material for the next generation of high-performance aqueous batteries.

Molecular classification reveals the sensitivity of lung adenocarcinoma to radiotherapy and immunotherapy: multi-omics clustering based on similarity network fusion.

BACKGROUND: Due to individual differences in tumors and immune systems, the response rate to immunotherapy is low in lung adenocarcinoma (LUAD) patients. Combinations with other therapeutic strategies improve the efficacy of immunotherapy in LUAD patients. Although radioimmunotherapy has been demonstrated to effectively suppress tumors, the underlying mechanisms still need to be investigated. METHODS: Total RNA from LUAD cells was sequenced before and after radiotherapy to identify differentially expressed radiation-associated genes. The similarity network fusion (SNF) algorithm was applied for molecular classification based on radiation-related genes, immune-related genes, methylation data, and somatic mutation data. The changes in gene expression, prognosis, immune cell infiltration, radiosensitivity, chemosensitivity, and sensitivity to immunotherapy were assessed for each subtype. RESULTS: We used the SNF algorithm and multi-omics data to divide TCGA-LUAD patients into three subtypes. Patients with the CS3 subtype had the best prognosis, while those with the CS1 and CS2 subtypes had poorer prognoses. Among the strains tested, CS2 exhibited the most elevated immune cell infiltration and expression of immune checkpoint genes, while CS1 exhibited the least. Patients in the CS2 subgroup were more likely to respond to PD-1 immunotherapy. The CS2 patients were most sensitive to docetaxel and cisplatin, while the CS1 patients were most sensitive to paclitaxel. Experimental validation of signature genes in the CS2 subtype showed that inhibiting the expression of RHCG and TRPA1 could enhance the sensitivity of lung cancer cells to radiation. CONCLUSIONS: In summary, this study identified a risk classifier based on multi-omics data that can guide treatment selection for LUAD patients.

AdipoRon reduces cisplatin-induced ototoxicity in hair cells:possible relation to the regulation of mitochondrial biogenesis.

AdipoRon (AR) can exert antidiabetic and anti-inflammatory effects by maintaining mitochondrial structure and function. The present study was designed to explore whether AR protects the auditory cells from cisplatin-induced damage and, if so, to probe the possible mechanisms underlying its action on this type of cells. Cell viability and apoptosis in House Ear Institute-Organization of Corti 1 (HEI-OC1 cells) and mouse cochlea hair cells (HCs) were detected by CCK8 and immunofluorescence. The expressions of apoptosis-related proteins (cleaved caspase-3 and Bcl-2), adiponectin receptor 1 (AdipoR 1) and the key factors relevant to mitochondrial biogenesis（SIRT1 and TFAM）were determined by Western blot and immunofluorescence. Changes in apoptotic rate and expression of SIRT1 and TFAM after silencing of AdipoR 1 (AdipoR 1-siRNA) in HEI-OC1 cells were measured by flow cytometry and Western blot. The levels of reactive oxygen species (ROS) were evaluated by MitoSox red staining. We found that 30 µM cisplatin exposure induced severe cellular damage, which resulted from activation of the mitochondrial apoptotic pathway. Cisplatin decreased the expression of AdipoR 1, SIRT1, and TFAM proteins, leading to impaired mitochondrial biogenesis and increased mitochondrial ROS production. 10 µM AR pre-treatment enhanced mitochondrial biogenesis, decreased mitochondrial ROS levels, alleviated imbalances in the mitochondrial apoptotic pathway, thus reducing cisplatin-induced apoptosis. Taken together, this work reveals that AR exerts anti-apoptotic effects, possibly via regulating mitochondrial biogenesis and function. Interestingly, AR might possess the promising potential to be a novel drug for the prevention and/ or treatment of cisplatin-induced ototoxicity.

GANT61, an inhibitor of Gli1, inhibits the proliferation and migration of hepatocellular carcinoma cells.

Constitutive activation of Hedgehog (Hh) signaling has been implicated in many cancers including hepatocellular carcinoma (HCC). Among them, the terminal glioma-associated oncogene homolog 1 (Gli1) regulates the expression of critical genes in the Hh pathway. The current study aims to evaluate the anti-HCC effect of the Gli1 inhibitor, GANT61. In vitro analysis including cell counting kit-8 (CCK-8) assay, flow cytometry, and migration and invasion assay were adopted to evaluate the effect of GANT61 on HCC cell lines. In vivo, xenograft studies were also performed to verify the effect of GANT61 on HCC. By CCK-8 assay, we found that GANT61 could significantly reduce the growth of HCC cell lines Huh7 and hemophagocytic lymphohistiocytosis (HLE), and their IC50 concentrations were 4.481 and 6.734 µM, respectively. Flow cytometry shows that GANT61 induced cell cycle arrest in the G2/M phase and accelerated apoptosis of both HLE and Huh7 cells. While migration and invasion assay shows that GANT61 weakens cells' migration and invasion ability. Besides that, GANT61 inhibits the expression of Gli1, FoxM1, CyclinD1, and Bcl-2, upregulates the level of Bax protein, and also reverses the epithelial-mesenchymal transition program by downregulating the expression of Vimentin and N-Cadherin and upregulating the expression of epithelial E-Cadherin expression. Furthermore, GANT61 inhibits the growth of subcutaneous xenografts of Huh7 cells in nude mice. Overall, this study suggests that Gli1 is a potential target for therapy and GANT61 shows promising therapeutic potential for future treatment in HCC.

Case Report: Autoimmune encephalitis and other neurological syndromes with rare neuronal surface antibody in children after hematopoietic stem cell transplantation.

Introduction: Neuronal surface antibody syndromes (NSAS) encompass a growing set of autoimmune neurological disorders, with their predominant clinical presentation being autoimmune encephalitis (AE). The most extensively documented form within NSAS is anti-N-methyl-D-aspartate receptor (NMDAR) autoimmunity. In contrast, other NSAS, such as anti-metabotropic glutamate receptor-5 (mGluR5) autoimmunity, are less common and less comprehensively characterized, particularly in pediatric cases. Case description: In this instance, we present the case of a 7-year-old girl who exhibited abnormal behaviors following hematopoietic stem cell transplantation (HSCT). She received a diagnosis of anti-mGluR5 AE, and her Electroencephalogram (EEG) displayed an increased number of generalized slow waves during wakefulness. Treatment involved intravenous administration of gamma globulin and methylprednisolone, followed by oral prednisone tablets. Levetiracetam was introduced as an antiepileptic therapy during the pulse steroid therapy. Notably, the abnormal behaviors exhibited significant improvement after treatment. Conclusions: To the best of our knowledge, this is the first report of rare pediatric NSAS involving anti-mGluR5 AE following HSCT. Enhancing our understanding and characterization of this condition may facilitate its recognition and treatment in children. Serum antibody testing could enable early identification and treatment of anti-mGluR5 AE.

Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level.

Introduction: Previous studies indicated that Wuda Granule (WDG) has been applied in the treatment of gastrointestinal motility disorder (GMD), but the effect and underlying mechanisms is yet to be elucidated. This study aimed to explore the mechanism and pharmacological effect of WDG for GMD via network analysis, verification of animal experiments and clinical experiments. Methods: The chemical components of WDG were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/index.php), and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/Index/) according to oral bioavailability (OB) ≥ 20% and drug-likeness (DL) ≥ 0.10. The targets of WDG compounds were retrieved from the Swiss Target Prediction database (http://www.swisstargetprediction.ch/) and targets related to GMD were retrieved from GeneCards database (https://www.genecards.org/). Network analysis were performed to screen the key active compounds of WDG and its hub targets. Then the pharmacological effect of WDG were verified via vivo experiments in rats and clinical experiments. Results: The results showed that 117 effective active compounds of WDG were screened and 494 targets of WDG compounds targeting GMD were selected. These targets were involved in the biological process of inflammatory regulation and the regulation of gastrointestinal motility. The mechanism was mainly involved in the regulation of PI3K-Akt signaling pathway and Rap1 signaling pathway. In addition, molecular docking analysis suggested that eight key active compounds of WDG may be mainly responsible for the effect of WDG on GMD by targeting HARS, AKT, and PIK3CA, respectively. Animal experiments and clinical trials both suggested that WDG could exert therapeutical effect on GMD via inhibiting inflammation and promoting gastrointestinal motility, it could also improve digestive function of patients with laparoscopic colorectal cancer after surgery. Conclusion: This study was the first to demonstrate that WDG improved GMD mainly via inhibiting inflammatory level and promoting gastrointestinal motility, providing new insights for the understanding of WDG for GMD, inspiration for future research and reference for clinical strategy in terms of the treatment of GMD.

Interfacial phenomenon and Marangoni convection of Fe-C melt on coke substrate under in situ observation.

The interfacial phenomenon between liqiuid iron and coke is important for determining the melting efficiency in the blast furnace iron-making process. In this study, the interaction observed in the case of the iron-carbon (Fe-C) melt on coke substrate was investigated using a high-temperature vacuum wettability test equipment. The Fe-C melt did not wet and spread on the coke substrate with different graphitization degrees (r0) at a high temperature of 1450 °C. The contact angles changed from 124.5° to 105.3°, and the r0 increased from 9.30 to 50.00%, thus indicating a nonwetting state. The deepening of graphitization decreased the contact angle. Thereby, increasing the contact area between liquid iron and the carbonaceous material, which facilitated carbon dissolution. The irregular movements of Fe-C melt were observed in situ during the wetting process. The horizontal force of the droplet caused by interfacial tension and the contact angle; the Marangoni convection owing to the gradient of carbon concentration; and the impulse force caused by the generation, aggregation, and release of SiO bubbles at the interface were attributed to the driving force.

Safety and efficacy of precision hepatectomy in the treatment of primary liver cancer.

BACKGROUND: The aim of this study was to investigate the safety and efficacy of precision hepatectomy in the treatment of primary liver cancer. METHODS: An randomized controlled trial of 98 patients with primary liver cancer admitted to our hospital from February 2020 to February 2021 were analyzed for the study, and they were divided into 49 cases each in the control group (conventional hepatectomy) and the study group (precision hepatectomy) according to the different surgical methods. The surgical condition, complications and follow-up results of the two groups were counted, and the liver function and immune function of the two groups were observed before and 1 week after surgery. RESULTS: The operation time, intraoperative bleeding, hospitalization time and anal venting time in the study group were less than those in the control group (P < 0.05). One week after surgery, AST, TBiL, ALT and ALB levels decreased, with in the study group significantly higher than those in the control group (P < 0.05); CD4+, CD3 + and CD4+/CD8 + levels were significantly higher in the study group (P < 0.05). The incidence of complications in the study group was significantly lower than that in the control group (P < 0.05). After 2 years of follow-up, the recurrence rate and mortality rate of the study group were lower than those of the control group (P < 0.05); the difference was not statistically significant when comparing the metastasis rate between the two groups (P > 0.05). CONCLUSION: Precision hepatectomy can effectively treat primary liver cancer with high safety and could be promoted in clinical practice.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) protects hair cells from cisplatin-induced ototoxicity in vitro: possible relation to the activities of p38 MAPK signaling pathway.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) gene encodes rate-limiting enzyme in cholesterol biosynthesis, which is related to cell proliferation and mitochondrial function. The present study was designed to explore the expression of HMGCR in murine cochlear hair cells and HEI-OC1 cells and the possible mechanisms underpinning the actions of HMGCR in cisplatin-induced ototoxicity, with special attention given to p38 mitogen-activated protein kinase (MAPK) activities in vitro. The expressions of HMGCR, p-p38, cleaved caspase-3 and LC3B was measured by immunofluorescence and western blot. JC-1 staining and MitoSOX Red were used to detect mitochondria membrane potential (MMP) and reactive oxygen species (ROS) levels respectively. The apoptosis of auditory cells was assessed by TUNEL staining and flow cytometry. Protein levels of bcl2/bax and beclin1 were examined by western blot. We found that HMGCR was widely expressed in the auditory cells, of both neonatal mice and 2-month-old mice, in cytoplasm, nucleus and stereocilia. Moreover, 30 µM cisplatin elicited the formation of ROS, which, in turn, led to HMGCR reduction, activating p38 kinase-related apoptosis and autophagy in auditory cells. Meanwhile, co-treatment with ROS scavenger at a concentration of 2 mM, N-acetyl-L-cysteine (NAC), could alleviate the aforementioned changes. In addition, HMGCR silencing resulted in higher p38 MAPK-mediated apoptosis and autophagy under cisplatin injury. Taken together, we demonstrate that, for the first time, that HMGCR is expressed in the cochlear. Furthermore, HMGCR exerts protective benefit on auditory cells against cisplatin-mediated injury stimulated by ROS, culminating in regulation of p38 MAPK-dependent apoptosis and autophagy.

YTHDF2 negatively correlates with tumor immune infiltration in small cell lung cancer.

In recent times, RNA modifications have garnered increased attention due to their involvement in the onset and progression of tumors, with N6-methyladenosine (m6A) modification being the most prevalent form. YTHDF2 is an m6A reading protein that can modulate RNA stability, transcription, and translation. This study aimed to explore the role of YTHDF2 in small cell lung cancer (SCLC) by collecting 20 SCLC patients from our hospital (cohort 1) and 48 Chinese SCLC patients from the GEO database (cohort 2). We evaluated the prognostic value of YTHDF2 using Kaplan-Meier survival analysis, Log-rank test, and Cox regression analysis. Additionally, we employed Gene Set Enrichment Analysis (GSEA) to screen different signaling pathways. We also investigated the correlation between the expression of m6A-related genes and SCLC molecular subtype and tumor immune microenvironment (TIME). Furthermore, we utilized multiplex immunofluorescence (mIF) staining to validate the immune infiltration of SCLC patient tissue sections. Our study revealed that YTHDF2 is an independent prognostic factor, which high expression is associated with low overall survival rate in SCLC. Low expression of YTHDF2 in SCLC tumors may enhance the molecular subtype transition from neuroendocrine (NE) to non-neuroendocrine (non-NE) subtype. Low YTHDF2 expression was closely associated with high immune infiltration, immune checkpoints, and other immune-related molecular features. Additionally, mIF detection showed a correlation between the low expression of YTHDF2 and CD4 + T cells and CD8 + T cells. Taken together, YTHDF2 could serve as a potential prognostic biomarker negatively correlated with tumor immune infiltration in SCLC.

Silencing Notch4 promotes tumorigenesis and inhibits metastasis of triple-negative breast cancer via Nanog and Cdc42.

Elucidation of individual Notch protein biology in specific cancer is crucial to develop safe, effective, and tumor-selective Notch-targeting therapeutic reagents for clinical use [1]. Here, we explored the Notch4 function in triple-negative breast cancer (TNBC). We found that silencing Notch4 enhanced tumorigenic ability in TNBC cells via upregulating Nanog expression, a pluripotency factor of embryonic stem cells. Intriguingly, silencing Notch4 in TNBC cells suppressed metastasis via downregulating Cdc42 expression, a key molecular for cell polarity formation. Notably, downregulation of Cdc42 expression affected Vimentin distribution, but not Vimentin expression to inhibit EMT shift. Collectively, our results show that silencing Notch4 enhances tumorigenesis and inhibits metastasis in TNBC, indicating that targeting Notch4 may not be a potential strategy for drug discovery in TNBC.

Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study.

BACKGROUND: Befotertinib (D-0316) is a novel, selective oral third-generation epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor. This phase 3 trial compared the efficacy and safety of befotertinib with icotinib as a first-line treatment for patients with EGFR mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: This study was a multicentre, open-label, randomised, controlled phase 3 study at 39 hospitals in China. Eligible patients were 18 years of age or older, had histologically confirmed locally advanced or metastatic stage IIIB, IIIC, or IV unresectable NSCLC, and had confirmed exon 19 deletions or exon 21 Leu858Arg mutation. Patients were randomly assigned (1:1) via an interactive web response system to receive either oral befotertinib (75-100 mg once daily) or oral icotinib (125 mg three times per day) in 21-day cycles until disease progression or withdrawal criteria were met. Randomisation was stratified by type of EGFR mutation, CNS metastasis status, and gender, and participants, investigators, and data analysts were not masked to treatment allocation. The primary endpoint was independent review committee (IRC)-assessed progression-free survival in the full analysis set, which comprised all randomly assigned patients. All patients who received at least one dose of the study drug were included in safety analyses. This study was registered with ClinicalTrials.gov, NCT04206072, and the overall survival follow-up is still in progress. FINDINGS: Between Dec 24, 2019, and Dec 18, 2020, 568 patients were screened, of whom 362 were randomly assigned to the befotertinib (n=182) or icotinib (n=180) group; all 362 patients were included in the full analysis set. Median follow-up was 20·7 months (IQR 10·2-23·5) in the befotertinib group and 19·4 months (10·3-23·5) in the icotinib group. Median IRC-assessed progression-free survival was 22·1 months (95% CI 17·9-not estimable) in the befotertinib group and 13·8 months (12·4-15·2) in the icotinib group (hazard ratio 0·49 [95% CI 0·36-0·68], p<0·0001). Grade 3 or higher treatment-related adverse events occurred in 55 (30%) of 182 patients in the befotertinib group and in 14 (8%) of 180 patients in the icotinib group. Treatment-related serious adverse events were reported in 37 (20%) patients in the befotertinib group and in five (3%) patients in the icotinib group. Two (1%) patients in the befotertinib group and one (1%) patient in the icotinib group died due to treatment-related adverse events. INTERPRETATION: Befotertinib demonstrated superior efficacy compared with icotinib in first-line treatment for patients with EGFR mutation-positive NSCLC. Although serious adverse events were more common in the befotertinib than the icotinib arm, the safety profile of befotertinib was manageable overall. FUNDING: Betta Pharmaceuticals (China). TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Experimental Investigation on Shear Capacity of Steel-Fiber-Reinforced High-Strength Concrete Corbels.

As short cantilever members, corbels are mainly used to transfer eccentric loads to columns. Because of the discontinuity of load and geometric structure, corbels cannot be analyzed and designed using the method based on beam theory. Nine steel-fiber-reinforced high-strength concrete (SFRHSC) corbels were tested. The width of the corbels was 200 mm, the cross-section height of the corbel column was 450 mm, and the cantilever end height was 200 mm. The shear span/depth ratios considered were 0.2, 0.3, and 0.4; the longitudinal reinforcement ratios were 0.55%, 0.75%, and 0.98%; the stirrup reinforcement ratios were 0.39%, 0.52%, and 0.785%; and the steel fiber volume ratios were 0, 0.75%, and 1.5%. According to the test results, this paper discusses the failure process and failure mode of corbel specimens with a small shear span/depth ratio and analyzes the effects of variables such as shear span/depth ratio, longitudinal reinforcement ratio, stirrup reinforcement ratio, and steel fiber volume content on the shear capacity of corbels. The shear capacity of corbels is significantly affected by the shear span/depth ratio, followed by the longitudinal reinforcement ratio and the stirrup reinforcement ratio. Moreover, it is shown that steel fibers have little impact on the failure mode and ultimate load of corbels, but can enhance the crack resistance of corbels. In addition, the bearing capacities of these corbels were calculated by Chinese code GB 50010-2010 and further compared with ACI 318-19 code, EN 1992-1-1:2004 code, and CSA A23.3-19 code, which adopt the strut-and-tie model. The results indicate that the calculation results by the empirical formula in the Chinese code are close to the corresponding test results, while the calculation method based on the strut-and-tie model of a clear mechanical concept yields conservative results, and hence the related parameter values must be further modified.

Maximal Margin Support Vector Machine for Feature Representation and Classification.

High-dimensional small sample size data, which may lead to singularity in computation, are becoming increasingly common in the field of pattern recognition. Moreover, it is still an open problem how to extract the most suitable low-dimensional features for the support vector machine (SVM) and simultaneously avoid singularity so as to enhance the SVM's performance. To address these problems, this article designs a novel framework that integrates the discriminative feature extraction and sparse feature selection into the support vector framework to make full use of the classifiers' characteristics to find the optimal/maximal classification margin. As such, the extracted low-dimensional features from high-dimensional data are more suitable for SVM to obtain good performance. Thus, a novel algorithm, called the maximal margin SVM (MSVM), is proposed to achieve this goal. An alternatively iterative learning strategy is adopted in MSVM to learn the optimal discriminative sparse subspace and the corresponding support vectors. The mechanism and the essence of the designed MSVM are revealed. The computational complexity and convergence are also analyzed and validated. Experimental results on some well-known databases (including breastmnist, pneumoniamnist, colon-cancer, etc.) show the great potential of MSVM against classical discriminant analysis methods and SVM-related methods, and the codes can be available on https://www.scholat.com/laizhihui.

Melatonin-mediated development and abiotic stress tolerance in plants.

Melatonin is a multifunctional molecule that has been widely discovered in most plants. An increasing number of studies have shown that melatonin plays essential roles in plant growth and stress tolerance. It has been extensively applied to alleviate the harmful effects of abiotic stresses. In view of its role in regulating aspects of plant growth and development, we ponder and summarize the scientific discoveries about seed germination, root development, flowering, fruit maturation, and senescence. Under abiotic and biotic stresses, melatonin brings together many pathways to increase access to treatments for the symptoms of plants and to counteract the negative effects. It has the capacity to tackle regulation of the redox, plant hormone networks, and endogenous melatonin. Furthermore, the expression levels of several genes and the contents of diverse secondary metabolites, such as polyphenols, terpenoids, and alkaloids, were significantly altered. In this review, we intend to examine the actions of melatonin in plants from a broader perspective, explore the range of its physiological functions, and analyze the relationship between melatonin and other metabolites and metabolic pathways.

Cyanidin-3-O-glucoside Contributes to Leaf Color Change by Regulating Two bHLH Transcription Factors in Phoebe bournei.

Anthocyanins produce different-colored pigments in plant organs, which provide ornamental value. Thus, this study was conducted to understand the mechanism of anthocyanin synthesis in ornamental plants. Phoebe bournei, a Chinese specialty tree, has high ornamental and economic value due to its rich leaf color and diverse metabolic products. Here, the metabolic data and gene expression of red P. bournei leaves at the three developmental stages were evaluated to elucidate the color-production mechanism in the red-leaved P. bournei species. First, metabolomic analysis identified 34 anthocyanin metabolites showing high levels of cyanidin-3-O-glucoside (cya-3-O-glu) in the S1 stage, which may suggest that it is a characteristic metabolite associated with the red coloration of the leaves. Second, transcriptome analysis showed that 94 structural genes were involved in anthocyanin biosynthesis, especially flavanone 3'-hydroxy-lase (PbF3'H), and were significantly correlated with the cya-3-O-glu level. Third, K-means clustering analysis and phylogenetic analyses identified PbbHLH1 and PbbHLH2, which shared the same expression pattern as most structural genes, indicating that these two PbbHLH genes may be regulators of anthocyanin biosynthesis in P. bournei. Finally, overexpression of PbbHLH1 and PbbHLH2 in Nicotiana tabacum leaves triggered anthocyanin accumulation. These findings provide a basis for cultivating P. bournei varieties that have high ornamental value.

A case of late and lethal Trousseau's syndrome induced by pembrolizumab in lung adenocarcinoma.

Trousseau's syndrome is a relatively rare reported event in immunotherapy-related clinical trials, mostly occurring in the early period of immune checkpoint inhibitor (ICI) therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. The patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.

In clinical practice, symptoms associated with abnormal coagulation or fibrinolytic function in malignant tumors are known as Trousseau's syndrome. Its main clinical features include cerebral infarction, myocardial infarction, peripheral arterial embolism, etc. Trousseau's syndrome is a relatively rare reported event in immune checkpoint inhibitors (ICIs)-related clinical studies, mostly occurring in the early period of ICI therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab, one of the ICI agents, maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. This patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.

Efficacy evaluation and prognostic risk factors analysis of precise hepatectomy in the treatment of intermediate and advanced hepatocellular carcinoma.

BACKGROUND: To investigate the efficacy of precise hepatectomy in the treatment of patients with intermediate and advanced hepatocellular carcinoma and analyze the risk factors affecting prognosis. METHODS: Totally 104 patients with intermediate and advanced hepatocellular carcinoma from January 2018 to January 2019 were enrolled in this retrospective analysis. Of these, four patients lost to follow-up. Logistic regression was conducted to explore the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Compared with the control group, the precise hepatectomy decreased intraoperative blood loss (331.2928.91 to 203.29 ± 29.34 ml), operation time (198.29 ± 19.38 to 150.28 ± 18.27 min), perioperative blood transfusion volume (376.22 ± 25.93 to 228.29 ± 22.19 ml) (all P < 0.001). Logistic regression analysis of study group showed that hepatitis B infection (OR = 1.746; 95% CI, 1.068-2.976), P = 0.021, Child-Pugh classification (OR = 2.319; 95% CI, 1.428-3.213), P < 0.001, Eastern Cooperative Oncology Group (ECOG) score (OR = 2.287; 95% CI, 1.098-3.876; P = 0.013) and Barcelona-Clinic Liver Cancer (BCLC) staging (OR = 2.029; 95% CI, 1.086-3.671; P = 0.022) were independent risk factors for prognosis of the precise hepatectomy. CONCLUSION: Hepatitis B virus infection, Child-Pugh grade, ECOG score and BCLC staging grade were the independent risk factors affecting the prognosis of precise hepatectomy.

Genomic profiling of relapsed small cell lung cancer reveals potential pathways of therapeutic targets.

Background: Almost all patients with small cell lung cancer (SCLC) relapse. The therapeutic options of relapsed SCLC are limited, and the clinical outcomes are poor. Thus, genomic profiling of relapsed SCLC patients may help to develop more effective therapeutic options. Methods: We collected blood specimens and follow-up information from a consecutive cohort of 31 patients diagnosed with relapsed SCLC in Zhongnan Hospital, Wuhan University, between 2018 and 2019, to analyze the comprehensive genomic profiling, and to investigate the impact of genomic alterations on therapeutic options and survival. Results: In our cohort of relapsed SCLC, the median number of genomic alterations was 5 (range, 1-11) per sample. The majority of patients were defined as low tumor mutation burden (TMB; 83.9%) and microsatellite stability (MSS; 87.1%). Immune checkpoint inhibitors (ICIs)-based treatment still brought considerable progression-free survival (PFS; 4.93-20.27 months) for patients with low TMB and MSS. Additionally, the most frequent genetic alterations observed in relapsed SCLC were TP53 (77%) and RB1 (52%). Other genomic alterations of high frequency were breast cancer 2 (BRCA2) (32%), ataxia telangiectasia mutated (ATM) (13%), epidermal growth factor receptor (EGFR) (10%), Notch receptor 1 (NOTCH1) (10%), and Fanconi anemia complementation group A (FANCA) (10%), in turn. Finally, based on the survival of therapeutic strategies targeting potential mutation genes, the role of genotyping in relapsed SCLC was confirmed. Conclusions: Our studies first exhibited comprehensive genomic profiling of relapsed SCLC, identifying several candidate genes, and briefly analyzed the association of survival and genomic alterations. Our data from a small cohort of relapsed SCLC will benefit further exploration the potential targets or biomarkers.