Extraction of Heracleum dissectum soluble dietary fiber by different methods: Structure and antioxidant properties.

Heracleum dissectum is rich in nutrients, but there is little research on its soluble dietary fiber (SDF). In this study, SDF from H. dissectum was extracted by enzyme extraction (E-SDF), enzyme chemical extraction (EC-SDF), and fermentation extraction (F-SDF). The composition, molecular weight (Mw), structural characterization, and antioxidant activity of SDF extracted by the three methods were compared. This study showed that different extraction methods lead to differences in their structure. The Mw results showed that F-SDF had the largest Mw, the structure of SDF could be destroyed by enzymatic hydrolysis, and large molecules could be converted into small molecules. The monosaccharide composition analysis showed that the main sugars of E-SDF, EC-SDF, and F-SDF were galacturonic acid and galactose, and the main components of the three SDF samples were hemicellulose hydrolyzed pectin and soluble polysaccharide. Notably, E-SDF had the greatest antioxidant effect at the same concentration. In summary, different extraction methods can affect the structure and antioxidant capacity of H. dissectum SDF, among which E-SDF has potential as a functional food ingredient.

Sex-related cortical asymmetry in antipsychotic-naïve first-episode schizophrenia.

Schizophrenia has been considered to exhibit sex-related clinical differences that might be associated with distinctly abnormal brain asymmetries between sexes. One hundred and thirty-two antipsychotic-naïve first-episode patients with schizophrenia and 150 healthy participants were recruited in this study to investigate whether cortical asymmetry would exhibit sex-related abnormalities in schizophrenia. After a 1-yr follow-up, patients were rescanned to obtain the effect of antipsychotic treatment on cortical asymmetry. Male patients were found to show increased lateralization index while female patients were found to exhibit decreased lateralization index in widespread regions when compared with healthy participants of the corresponding sex. Specifically, the cortical asymmetry of male and female patients showed contrary trends in the cingulate, orbitofrontal, parietal, temporal, occipital, and insular cortices. This result suggested male patients showed a leftward shift of asymmetry while female patients showed a rightward shift of asymmetry in these above regions that related to language, vision, emotion, and cognition. Notably, abnormal lateralization indices remained stable after antipsychotic treatment. The contrary trends in asymmetry between female and male patients with schizophrenia together with the persistent abnormalities after antipsychotic treatment suggested the altered brain asymmetries in schizophrenia might be sex-related disturbances, intrinsic, and resistant to the effect of antipsychotic therapy.

Novel artesunate-metformin conjugate inhibits bladder cancer cell growth associated with Clusterin/SREBP1/FASN signaling pathway.

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

Effects of sodium arsenite exposure on behavior, ultrastructure and gene expression of brain in adult zebrafish (Danio rerio).

Arsenic, a common metal-like substance, has been demonstrated to pose potential health hazards and induce behavioral changes in humans and rodents. However, the chronic neurotoxic effects of arsenic on aquatic animals are still not fully understood. This study aimed to investigate the effects of arsenic exposure on adult zebrafish by subjecting 3-month-old zebrafish to three different sodium arsenite water concentrations: 0 µg/L (control group), 50 µg/L, and 500 µg/L, over a period of 30 days. To assess the risk associated with arsenic exposure in the aquatic environment, behavior analysis, transmission electron microscopy techniques, and quantitative real-time PCR were employed. The behavior of adult zebrafish was evaluated using six distinct tests: the mirror biting test, shoaling test, novel tank test, social preference test, social recognition test, and T maze. Following the behavioral tests, the brains of zebrafish were dissected and collected for ultrastructural examination and gene expression analysis. The results revealed that sodium arsenite exposure led to a significant reduction in aggression, cohesion, social ability, social cognition ability, learning, and memory capacity of zebrafish. Furthermore, ultrastructure and genes regulating behavior in the zebrafish brain were adversely affected by sodium arsenite exposure.

A novel Nlrp3 knock-in mouse model with hyperactive inflammasome in development of lethal inflammation.

NOD-like receptor family, pyrin domain-containing 3 (NLRP3) is a central protein contributing to human inflammatory disorders, including cryopyrin-associated periodic syndrome and sepsis. However, the molecular mechanisms and functions of NLRP3 activation in various diseases remain unknown. Here, we generated gain-of-function knock-in mice associated with Muckle-Wells syndromes using the Cre-LoxP system allowing for the constitutive T346M mutation of NLRP3 to be globally expressed in all cells under the control of tamoxifen. The mice were treated with tamoxifen for 4 days before determining their genotype by PCR and sequence analysis. In vitro, we found that bone marrow-derived macrophage from homozygous T346M mutation mice displayed a robust ability to produce IL-1ß in response to lipopolysaccharide exposure. Moreover, ASC specks and oligomerization were observed in the homozygous mutant bone marrow-derived macrophages in the presence of lipopolysaccharides alone. Mechanistically, K+ and Ca2+ depletion and mitochondrial depolarization contribute to the hyperactivation of mutant NLRP3. In vivo, homozygous mice carrying the T346M mutation exhibit weight loss and mild inflammation in the resting state. In the lipopolysaccharide-mediated sepsis model, homozygous mutant mice exhibited higher mortality and increased serum circulating cytokine levels, accompanied by serious liver injury. Furthermore, an increase in myeloid cells in the spleen has been suggested to be a risk factor for inducing sepsis sensitivity. Altogether, we describe a cryopyrin-associated syndrome animal model with the T346M mutation of NLRP3 and suggest that the hyperactivated inflammasome aggregated by the mutant NLRP3 lowers the inflammatory response threshold both in vitro and in vivo.

Unveiling the LncRNA-miRNA-mRNA Regulatory Network in Arsenic-Induced Nerve Injury in Rats through High-Throughput Sequencing.

Arsenic is a natural toxin which is widely distributed in the environment, incurring diverse toxicities and health problems. Previous studies have shown that long non-coding RNAs (LncRNAs) are also reported to contribute to As-induced adverse effects. LncRNAs are involved in the development of nerve injury, generally acting as sponges for microRNAs (miRNAs). This study aimed to investigate the competitive endogenous RNA (ceRNA) regulatory networks associated with arsenic-induced nerve damage. A total of 40 male Wistar rats were exposed to different doses of arsenic for 12 weeks, and samples were collected for pathological observation and high-throughput sequencing. The ceRNA network was constructed using Cytoscape, and key genes were identified through the PPI network and CytoHubba methods. A real-time quantitative PCR assay was performed to validate gene expression levels. The results showed that subchronic exposure to arsenic in drinking water resulted in pathological and ultrastructural damage to the hippocampal tissue, including changes in neuron morphology, mitochondria, and synapses. Exposure to arsenic results in the dysregulation of LncRNA and mRNA expression in the hippocampal tissues of rats. These molecules participated in multiple ceRNA axes and formed a network of ceRNAs associated with nerve injury. This study also verified key molecules within the ceRNA network and provided preliminary evidence implicating the ENRNOT-00000022622-miR-206-3p-Bdnf axis in the mechanism of neural damage induced by arsenic in rats. These findings provide novel insights into the underlying mechanism of nervous system damage induced by arsenic exposure.

Carboxyamidotriazole alleviates pannus formation and cartilage erosion in rats with adjuvant arthritis.

Carboxyamidotriazole (CAI) was initially considered a non-cytotoxic anticancer agent. However, recently, pronounced anti-inflammatory properties of CAI have been reported. Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by aberrant activation of signaling pathways. Therefore, this study explored the therapeutic effects and potential mechanism of action of CAI on RA in the adjuvant arthritis (AA) model. The results showed that CAI reduced the severity of arthritis in AA rats as demonstrated by inhibited hind paw swelling, reduced body weight, and decreased infiltration of joint pathological inflammatory cells. Importantly, pathological scoring of new blood vessels and immunohistochemical assays revealed that CAI inhibited pannus formation. CAI decreased the expression of pro-angiogenic growth factors, such as vascular epidermal growth factor, basic fibroblast growth factor, and metalloproteinases (MMPs), namely, MMP-1 and MMP-3 in the synovium of AA rats. Furthermore, CAI significantly reduced the increased levels of phosphorylated p38, c-Jun N-terminal kinase (JNK)1/2, and extracellular signal-regulated kinase (ERK)1/2 proteins in AA rats. In addition, the proliferation of fibroblast-like synoviocytes (FLS) was downregulated by CAI both in vivo and in vitro. In conclusion, this investigation illustrates the therapeutic effect of CAI on synovitis and erosion of articular cartilage in RA. Furthermore, the mechanism might involve inhibition of aberrantly activated mitogen-activated protein kinase signaling, as well as a decrease in pro-angiogenic factors, MMP expression, and FLS proliferation.

Natural Resources Depletion, Financial Risk, and Human Well-Being: What is the Role of Green Innovation and Economic Globalization?

Human well-being is the top priority of all nations in the twenty-first century. However, depletion of natural resources and financial risk can negatively impact human well-being, which in turn can make it difficult to realize human well-being. Also, green innovation and economic globalization may play a significant role in human well-being. In this context, this study assesses the impacts of natural resources, financial risk, green innovation, and economic globalization on human well-being in emerging countries from 1990 to 2018. The empirical results from the Common Correlated Effects Mean Group estimator unveiled that natural resources and financial risk negatively affect the human well-being of emerging nations. Furthermore, the results show that green innovation and economic globalization positively contribute to human well-being. These findings are also verified using alternative methods. In addition, natural resources, financial risk, and economic globalization Granger cause human well-being but not the other way round. Furthermore, bidirectional causality exists between green innovation and human well-being. Considering these novel findings, sustainable utilization of natural resources and controlling financial risk are necessary strategies for realizing human well-being. More resources should be allocated for green innovation, and government should encourage economic globalization to attain sustainable development in emerging countries.

Predicting the efficacy of radiotherapy for esophageal squamous cell carcinoma based on enhanced computed tomography radiomics and combined models.

Purpose: This study aimed to investigate the ability of enhanced computed tomography (CT)-based radiomics and dosimetric parameters in predicting response to radiotherapy for esophageal cancer. Methods: A retrospective analysis of 147 patients diagnosed with esophageal cancer was performed, and the patients were divided into a training group (104 patients) and a validation group (43 patients). In total, 851 radiomics features were extracted from the primary lesions for analysis. Maximum correlation minimum redundancy and minimum least absolute shrinkage and selection operator were utilized for feature screening of radiomics features, and logistic regression was applied to construct a radiotherapy radiomics model for esophageal cancer. Finally, univariate and multivariate parameters were used to identify significant clinical and dosimetric characteristics for constructing combination models. The area evaluated the predictive performance under the receiver operating characteristics (AUC) curve and the accuracy, sensitivity, and specificity of the training and validation cohorts. Results: Univariate logistic regression analysis revealed statistically significant differences in clinical parameters of sex (p=0.031) and esophageal cancer thickness (p=0.028) on treatment response, whereas dosimetric parameters did not differ significantly in response to treatment. The combined model demonstrated improved discrimination between the training and validation groups, with AUCs of 0.78 (95% confidence interval [CI], 0.69-0.87) and 0.79 (95% CI, 0.65-0.93) in the training and validation groups, respectively. Conclusion: The combined model has potential application value in predicting the treatment response of patients with esophageal cancer after radiotherapy.

Functionalized nickel(II)-iron(II) dithiolates as biomimetic models of [NiFe]-H2ases.

To develop the structural and functional modeling chemistry of [NiFe]-H2ases, a series of new biomimetics for the active site of [NiFe]-H2ases have been prepared by various synthetic methods. Treatment of the mononuclear Ni complex (pnp)NiCl2 (pnp = (Ph2PCH2)2NPh) with (dppv)Fe(CO)2(pdt) (dppv = 1,2-(Ph2P)2C2H2, pdt = 1,3-propanedithiolate) and KPF6 gave the dicarbonyl complex [(pnp)Ni(pdt)Fe(CO)2(dppv)](PF6)2 ([1](PF6)2). Further treatment of [1](PF6)2 and [(dppe)Ni(pdt)Fe(CO)2(dppv)](BF4)2 (dppe = 1,2-(Ph2P)2C2H4) with the decarbonylation agent Me3NO and pyridine afforded the novel sp3 C-Fe bond-containing complexes [(pnp)Ni(SCH2CH2CHS)Fe(CO)(dppv)]PF6 ([2]PF6) and [(dppe)Ni(SCH2CH2CHS)Fe(CO)(dppv)]BF4 ([3]BF4). More interestingly, the first t-carboxylato complexes [(pnp)Ni(pdt)Fe(CO)(t-O2CR)(dppv)]PF6 ([4]PF6, R = H; [5]PF6, R = Me; [6]PF6, R = Ph) could be prepared by reactions of [1]PF6 with the corresponding carboxylic acids RCO2H in the presence of Me3NO, whereas further reactions of [4]PF6-[6]PF6 with aqueous HPF6 and 1.5 MPa H2 gave rise to the µ-hydride complex [(pnp)Ni(pdt)Fe(CO)(µ-H)(dppv)]PF6 ([7]PF6). Except for H2 activation by t-carboxylato complexes [4]PF6-[6]PF6 to give a µ-hydride complex ([7]PF6), the sp3 C-Fe bond-containing complex [2]PF6 was found to be a catalyst for proton reduction to H2 under CV conditions. Furthermore, the chemical reactivity of the µ-hydride complex [7]PF6 displayed in the e- transfer reaction with FcPF6 in the presence of CO, the H2 evolution reaction with the protonic acid HCl, and the H- transfer reaction with N-methylacridinium hexafluorophosphate ([NMA]PF6) was systematically studied. As a result, a series of the expected products such as H2, ferrocene, the dicarbonyl complex [1](PF6)2, the µ-chloro complex [(pnp)Ni(pdt)Fe(CO)(µ-Cl)(dppv)]PF6 ([8]PF6), the t-MeCN-coordinated complex [(pnp)Ni(pdt)Fe(CO)(t-MeCN)(dppv)](PF6)2 ([9](PF6)2) and the H- transfer product AcrH2 were produced. While all the newly prepared model complexes were structurally characterized by spectroscopic methods, the molecular structures of some of their representatives were confirmed by X-ray crystallography.

Combined Morphological and Spectroscopic Diagnostic of HER2 Expression in Breast Cancer Tissues Based on Label-Free Surface-Enhanced Raman Scattering.

Breast cancer is the most commonly diagnosed cancer type worldwide. Overexpression of human epidermal growth factor receptor 2 (HER2) is an important subtype of breast cancer and results in an increased risk of recurrence and metastasis in patients. At present, immunohistochemistry (IHC) is used to detect the expression of HER2 in breast cancer tissues as the golden standard. However, IHC has some shortcomings, such as large subjective impact, long time consumption, expensive reagents, etc. In this paper, a combined morphological and spectroscopic diagnostic method based on label-free surface-enhanced Raman scattering (SERS) for HER2 expression in breast cancer is proposed. It can not only quantitively detect HER2 expression in breast cancer tissues by spectroscopic measurements but also give morphological images reflecting the distribution of HER2 in tissues. The results show that the consistency between this method and IHC is 95% and achieves the annotation of tumor regions on tissue sections. This method is time-consuming, quantifiable, intuitive, scalable, and easy to understand. Combined with deep learning approaches, it is expected to promote the development of clinical detection and diagnosis technology for breast cancer and other cancers.

Synthesis and Antitumor Activities of Novel Mitochondria-Targeted Dihydroartemisinin Ether Derivatives.

Ten novel mitochondria-targeted dihydroartemisinin ether derivatives were designed, synthesized, and evaluated for antitumor activity against five cancer cell lines in vitro. Profoundly, compound D8-T (IC50 = 56.9 nM) showed the most potent antiproliferative activity against the T24 cells with low cytotoxicity in normal human umbilical vein endothelial cells. High-performance liquid chromatography analysis confirmed that D8-T targeted mitochondria 6.3-fold higher than DHA. ATP content assay demonstrated that D8-T decreased the ATP level of bladder cancer cells. The effect of D8-T on cell apoptosis was determined by flow cytometry and western blot of Bax and Bcl-2. Surprisingly, the results indicated that D8-T did not induce bladder cancer cell apoptosis. In contrast, the cell cycle analysis and western blot of CDK4, CDK6, cyclin D1, and p21 demonstrated that the cancer cell cycle was arrested at the G1 phase after D8-T treatment. Furthermore, the consistent results were received by RNA-seq assay. These promising findings implied that D8-T could serve as a great candidate against bladder cancer for further investigation.

Erratum: circRNA Mediates Silica-Induced Macrophage Activation Via HECTD1/ZC3H12A-Dependent Ubiquitination: Erratum.

[This corrects the article DOI: 10.7150/thno.21648.].

High-Altitude Exposure and Time Interval Perception of Chinese Migrants in Tibet.

High-altitude exposure can negatively impact one's ability to accurately perceive time. This study focuses on Chinese migrants who have traveled to the Tibetan plateau and explores the effects of high-altitude exposure on their time interval judgment abilities based on three separate studies. In Study 1, it was found that exposure to high altitudes negatively impacted the time interval judgment functions of the migrants compared with a low-altitude control group; they exhibited a prolonged response time (540 ms: p = 0.006, 95% CI (−1.70 −0.32)) and reduced accuracy (1080 ms: p = 0.032, 95% CI (0.06 1.26)) in certain behavioral tasks. In Study 2, the results showed that high-altitude exposure and sleepiness had an interactive effect on time interval judgment (1080 ms) (p < 0.05, 95% CI (−0.83 −0.40)). To further verify our interaction hypothesis, in Study 3, we investigated the time interval judgment of interactions between acute high-altitude exposure and sleepiness level. The results revealed that the adaptation effect disappeared and sleepiness significantly exacerbated the negative effects of high-altitude exposure on time interval judgment (p < 0.001, 95% CI (−0.85 −0.34)). This study is the first to examine the effects of high-altitude exposure on time interval judgment processing functions and the effects of sleep-related factors on individual time interval judgment.

Natural resources, population aging, and environmental quality: analyzing the role of green technologies.

Depletion of natural resources and population aging are the two most critical challenges for environmental sustainability. However, the research that integrates natural resources and population aging in the same environmental policy framework is still scant. Therefore, this study investigates the linkage between natural resources, population aging, green technologies, and ecological footprint (EF) of G7 countries. In addition, this study also explores the moderating effects of green technologies on the relationship between natural resources and EF. Drawing on the panel times series data from 1970 to 2017, we employ a cross-sectional autoregressive distributed lags (CS-ARDL) model for short- and long-run empirical estimation. Our empirical analysis indicates that natural resource use exacerbates ecological degradation by increasing EF. By contrast, population aging and green technologies present positive ameliorative effects on EF. Interestingly, the interaction effect of green technologies and natural resources indicates that the damage to ecological quality from natural resources can be effectively improved by means of green technologies, thus maintaining environmental sustainability. Furthermore, the results of panel quantile regression show that the effects of population aging and green technologies on the overall ecological footprint distribution in G7 countries are heterogeneous, while the effects of natural resources on the distribution of all conditions of the ecological footprint are positive. In addition, this paper verifies the causal relationship between the variables using the Dumitrescu and Hurlin test. The findings reveal that the relevant changes in all explanatory variables are bilaterally causally associated with EF. Based on these results, this paper provides some feasible policy recommendations.

Study on the impact of comprehensive urbanization on urban civil building CO2 emissions in China.

With the rapid development of China, urbanization has become an important research topic of China's CO2 emissions. To fill the gap in considering the spatial correlation of the comprehensive urbanization that includes multi-dimensional factors on CO2 emissions from urban civil buildings (UBEC), this study constructs a comprehensive evaluation indicator of urbanization from four aspects including population, economy, society, and land urbanization by using the entropy method. The spatial spillover effect of UBEC and the impact of comprehensive urbanization on UBEC are also studied by using the spatial panel model in this paper. This study finds out that UBEC has obvious spatial spillover effects. During the early years of the study period, the eastern coastal areas had greater carbon emissions, while in recent years, they have gradually transitioned to the northwestern regions. Comprehensive urbanization has a significant promotion effect on it. And foreign direct investment and per capita energy consumption also have positive impact on UBEC. This study provides a reference for measuring the effects of urbanization on sector-specific CO2 emissions and may be useful for energy efficiency and emission abatement efforts in China.

Impact of Coronavirus Disease 2019 on Clinical Characteristics in Patients With Lung Cancer: A Large Single-Centre Retrospective Study.

Lung cancer is the most common cancer malignancy worldwide. With the continuous spread of the coronavirus disease 2019 (COVID-19) globally, it is of great significance to explore the impact of this disease on the clinical characteristics of lung cancer. Thus, we aimed to investigate whether the COVID-19 pandemic had any influence on the clinical characteristics and diagnosis of patients with lung cancer. We collected clinical and demographic data of patients who were newly diagnosed with lung cancer at our hospital between February 2019 and July 2020. Overall, 387 patients with lung cancer were divided into two groups for analysis: epidemic group (from February to July 2020) and pre-epidemic group (from February to July 2019). The source of diagnosis and clinical characteristics of the two groups were analysed. T-test and Mann-Whitney U were used for continuous variables, and Chi-squared or Fisher's exact test for categorical variable. We found that during the epidemic period, 110 cases of lung cancer were incidentally diagnosed during COVID-19 screening, accounting for 47.6% of all newly diagnosed lung cancer cases at our hospital. The proportions of patients who were diagnosed based on symptoms and physical examination in the epidemic group were 34.2 and 18.2%, respectively, while that in the pre-epidemic group were 41.7 and 58.3%, respectively. There was significant difference in the source of diagnosis between the two groups. In a subgroup analysis of the epidemic group, the average tumour volume of the patients diagnosed with COVID-19 screening was significantly smaller than that of the patients diagnosed with symptoms and physical examination. In conclusion, the continuation of the COVID-19 pandemic may impact the screening and clinical characteristics of lung cancer and require large-scale and longer-term observation.

Chilling injury mechanism of hardy kiwifruit (Actinidia arguta) was revealed by proteome of label-free techniques.

Refrigeration is an important method to extend shelf life of hardy kiwifruit. However, the inappropriate storage temperature can lead to chilling injury in the fruit. We found that firmness, total soluble solids, and total polyphenolic content of the fruit exposed to 0℃ environment were apparently lower, and titratable acidity content, browning rate, weight loss rate, electrolyte leakage, proline content, and malondialdehyde content were higher obviously than 4℃. A total of 244 differentially expressed proteins were found result from differential temperatures, among which 113 were up-regulated and 131 were down-regulated. Subcellular localization results presented that the differentially expressed proteins which were affected by low temperature were located in cytoplasmic, chloroplast, nuclear, mitochondrial, plasma membrane, and extracellular. Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed proteins were mainly participated in synthesis of citrate cycle, oxidative phosphorylation, fatty acid biosynthesis, and starch and sucrose metabolism. Protein-protein interaction results revealed that central proteins interaction points respectively are 30S ribosomal proteins, 30S ribosomal protein S7, chloroplastic, cell division cycle 5-like protein, 50S ribosomal protein, ribosomal protein, ribosomal protein L6 protein, and SRP54 subunit protein. The quality deviations of all identified peptides were mainly distributed within 10 ppm, and MS2 has an ideal andromeda score, with more than 87.82% peptide scores above 60 points, and the median peptide score of 99.28 points. Therefore, the results of this study provide important information for new gene revelation and gene interaction relationship in hardy kiwifruit of chilling injury. PRACTICAL APPLICATIONS: Inhibition of cold damage in hardy kiwifruit under low temperature is very important work for the development of its storage industry. However, many qualities of fruit will deteriorate after long-term cold storage and those biological activities of the fruits are regulated by proteins. It is, therefore, of great significance to reveal the key proteins caused cold damage in hardy kiwifruit. Moreover, the study results could provide a scientific information for the quality improvement and genetic modification of hardy kiwifruit.

Anlotinib Combined with S-1 in Third- or Later-Line Stage IV Non-Small Cell Lung Cancer Treatment: A Phase II Clinical Trial.

LESSONS LEARNED: The combination of anlotinib and S-1 exhibited good antitumor activity in third- or later-line treatment for stage IV non-small cell lung cancer (NSCLC). Combination therapy of anlotinib with S-1 has manageable toxicities in patients with NSCLC. BACKGROUND: This study aimed to evaluate the efficacy and safety of anlotinib combined with S-1 as a third- or later-line treatment for patients with stage IV non-small cell lung cancer (NSCLC). Anlotinib was approved in 2018 by the Chinese Food and Drug Administration (FDA) as a third-line treatment for patients with refractory advanced NSCLC and is under study in the U.S. and Europe. METHODS: Simon's phase II clinical trial design with an α error of 5% and a power ß of 80% was used, anticipating a 10% objective response rate (ORR) of anlotinib and a 30% ORR of anlotinib combined with S-1; the required sample size was 29. A total of 29 patients were enrolled in the clinical trial. Patients were treated with anlotinib plus S-1 over a 21-day treatment course until disease progression or unacceptable toxic effects. If the efficacy was assessed as stable disease, partial response, or complete response after six cycles, anlotinib was maintained until disease progression or death. The primary endpoint was the objective response rate. Somatic mutations were not required for study enrollment. RESULTS: The median follow-up time was 11.1 months. Objective responses were observed in 11 of 29 (37.9%) patients making up the intention-to-treat population, which reached the target primary endpoint of 30% ORR. The median overall and progression-free survival were 16.7 and 5.8 months, respectively. The most common grade 3 adverse events (AEs) were gastrointestinal, including nausea, vomiting and diarrhea, fatigue, and hypertension. No grade 4 treatment-related AEs or treatment-related deaths occurred. CONCLUSION: The combination of anlotinib with S-1 in the third- or later-line treatment of stage IV NSCLC shows promising antitumor activity and manageable toxicity in patients with NSCLC; phase III trials will be planned in the future.