Clinical difference on the variants and co-mutation in a Chinese cohort with ALK-positive advanced non-small cell lung cancer.

PURPOSE: Despite the generally favourable prognoses observed in patients with ALK-positive non-small cell lung cancer (NSCLC), there remains significant variability in clinical outcomes. The objective of this study is to enhance patient stratification by examining both the specific sites of gene fusion and the presence of co-occurring mutations. METHODS: We collected retrospective clinical and pathological data on ALK-positive patients with locally advanced or metastatic disease. ALK fusion variants and concomitant mutations were identified through next-generation sequencing technology. We then assessed treatment efficacy via tumor response and survival metrics. RESULTS: This study included a total of 59 patients, with 49 harboring echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions and 10 presenting with rare fusions. The median follow-up period was 33 months. Clinical outcomes between non-EML4-ALK and EML4-ALK patients were comparable. Among the EML4-ALK cohort, patients with longer variants (v1, v2, v8) demonstrated superior progression-free survival (PFS) (median PFS: 34 months vs. 11 months; hazard ratio [HR]: 2.28; P = 0.05) compared to those with shorter variants (v3, v5). Furthermore, patients treated with second-generation ALK inhibitors (ALKi) displayed a progression-free survival advantage (median PFS: not reached [NR] vs. 9 months; HR: 5.37; P = 0.013). Baseline TP53 co-mutation were linked with a substantially shorter OS (median OS,37 months vs. NR; HR 2.74; P = 0.047). CONCLUSIONS: In ALK+ NSCLC, longer EML4-ALK variants correlate with improved prognosis and enhanced response to second-generation ALKi, while TP53 co-mutations indicate a negative prognosis.

Primary versus acquired epidermal growth factor receptor Thr790Met mutant non-small cell lung cancer: clinical features and prognoses.

PURPOSE: This study aimed to identify the impact of epidermal growth factor receptor (EGFR) T790M mutations on clinical characteristics and prognosis. METHODS: Retrospective analyses were conducted on the differences on clinicopathological features and prognosis between primary and acquired T790M mutations. Subgroup analyses were performed for primary T790M coexisting with other mutations. RESULTS: Patients with primary T790M mutations showed a 60.53% (23/38) incidence of concurrent L858R mutations, 18.42% (7/38) for 19del mutations and a 21.05% (8/38) occurrence of brain metastases. Conversely, those with acquired T790M mutations demonstrated respective frequencies of 36.53% (61/167), 58.68% (98/167) and 44.31% (74/167), with all comparisons yielding p < 0.05. The median overall survival differed significantly between the two groups, with a duration of 33 months for patients with primary T790M mutations as compared to 48 months for those with acquired mutations (p = 0.030). Notably, among patients with L858R co-mutations, when treated with third-generation EGFR-TKIs, those with acquired T790M mutations experienced a significantly prolonged median time to treatment failure compared to those with primary mutations (17 months vs. 9 months, p = 0.009). CONCLUSION: Patients with primary T790M have unique molecular features and had worse prognosis compared with acquired T790M. Resistance to third-generation EGFR-TKIs seems to be associated with the presence of EGFR co-mutations.

Comparison Between China and Brazil in the Two Waves of COVID-19 Prevention and Control.

OBJECTIVE: This study analyzes the effectiveness of COVID-19 prevention and control in China and Brazil from the perspectives of policy and meteorological conditions, and provides experience for epidemic prevention and control. METHODS: This study collects data on meteorological conditions, vaccination and mutant strains in the two countries to analyze the reasons for the differences in epidemic status between the two countries and extracts public data on COVID-19 through various official websites, summarizes the prevention and control policies implemented by the two countries, and evaluates their effectiveness. RESULTS: As of August 12, 2021, the total number of COVID-19 cases and the daily number of new COVID-19 cases in China have been growing steadily, showing remarkable results in epidemic control. The total number of confirmed cases and the daily number of new confirmed cases in Brazil have continued to increase rapidly. The total death case in Brazil has reached 560,000, far exceeding that in China, and the effect of epidemic prevention and control is not satisfactory. CONCLUSIONS: Multiple factors, such as meteorological conditions, policies and strategies, and economic conditions, can influence the spread of COVID-19, and therefore, the situation varies greatly from country to country. China and Brazil have chosen different interventions in the fight against COVID-19. The policy measures taken by China are typical containment measures and Brazil has a mitigation strategy. From the perspective of the current situation of the epidemic development in both countries, the cumulative death rate and daily new confirmed cases in Brazil are much higher than those in China, which indicates that the containment strategy is more effective than mitigation strategy in preventing and controlling COVID-19. Fighting the epidemic is a global long-lasting battle, and the two countries should learn from each other with the premise of respecting their national conditions. Countries should deepen cooperation and not let up prematurely.

Core policies disparity response to COVID-19 among BRICS countries.

OBJECTIVE: To provide experience for formulating prevention and control policies, this study analyzed the effectiveness of the Coronavirus disease 2019(COVID-19) prevention and control policies, and evaluated health equity and epidemic cooperation among BRICS countries. METHODS: This study summarized the pandemic prevention and control policies in BRICS countries and evaluated the effectiveness of those policies by extracting COVID-19 related data from official websites. RESULT: As of May 4, 2021, responding to COVID-19. China adopted containment strategies. China's total confirmed cases (102,560) were stable, without a second pandemic peak, and the total deaths per million (3.37) were much lower than others. India and South Africa who adopted intermediate strategies have similar pandemic curves, total confirmed cases in India (20,664,979) surpassed South Africa (1,586,148) as the highest in five countries, but total deaths per million (163.90) lower than South Africa (919.11). Brazil and Russia adopted mitigation strategies. Total confirmed cases in Brazil (14,856,888) and Russia (4,784,497) continued to increase, and Brazil's total deaths per million (1,936.34) is higher than Russia (751.50) and other countries. CONCLUSION: This study shows BRICS countries implemented different epidemic interventions. Containment strategy is more effective than intermediate strategy and mitigation strategy in limiting the spread of COVID-19. Especially when a strict containment strategy is implemented in an early stage, but premature relaxation of restrictions may lead to rebounding. It is a good choice to combat COVID-19 by improving the inclusiveness of intervention policies, deepening BRICS epidemic cooperation, and increasing health equities.

Alternariol 9-methyl ether from the endophytic fungus Alternaria sp. Samif01 and its bioactivities

Abstract One bioactive compound, identified as alternariol 9-methyl ether, was isolated from the crude extract of the endophytic fungus Alternaria sp. Samif01 residing in the roots of Salvia miltiorrhiza Bunge. Alternariol 9-methyl ether was active against bacteria with minimum inhibitory concentration values ranging from 25 to 75 µg/mL and median inhibitory concentration (IC50) values ranging from 16.00 to 38.27 µg/mL. The IC50 value of alternariol 9-methyl ether against spore germination of Magnaporthe oryzae was 87.18 µg/mL. Alternariol 9-methyl ether also showed antinematodal activity against Bursaphelenchus xylophilus and Caenorhabditis elegans with IC50 values of 98.17 µg/mL and 74.62 µg/mL, respectively. This work is the first report on alternariol 9-methyl ether and its biological activities from the endophytic fungus Alternaria sp. Samif01 derived from S. miltiorrhiza Bunge. The results indicate the potential of Alternaria sp. Samif01 as a source of alternariol 9-methyl ether and also support that alternariol 9-methyl ether is a natural compound with high potential bioactivity against microorganisms.

Alternariol 9-methyl ether from the endophytic fungus Alternaria sp. Samif01 and its bioactivities.

One bioactive compound, identified as alternariol 9-methyl ether, was isolated from the crude extract of the endophytic fungus Alternaria sp. Samif01 residing in the roots of Salvia miltiorrhiza Bunge. Alternariol 9-methyl ether was active against bacteria with minimum inhibitory concentration values ranging from 25 to 75µg/mL and median inhibitory concentration (IC50) values ranging from 16.00 to 38.27µg/mL. The IC50 value of alternariol 9-methyl ether against spore germination of Magnaporthe oryzae was 87.18µg/mL. Alternariol 9-methyl ether also showed antinematodal activity against Bursaphelenchus xylophilus and Caenorhabditis elegans with IC50 values of 98.17µg/mL and 74.62µg/mL, respectively. This work is the first report on alternariol 9-methyl ether and its biological activities from the endophytic fungus Alternaria sp. Samif01 derived from S. miltiorrhiza Bunge. The results indicate the potential of Alternaria sp. Samif01 as a source of alternariol 9-methyl ether and also support that alternariol 9-methyl ether is a natural compound with high potential bioactivity against microorganisms.

Alternariol 9-methyl ether from the endophytic fungus Alternaria sp. Samif01 and its bioactivities

One bioactive compound, identified as alternariol 9-methyl ether, was isolated from the crude extract of the endophytic fungus Alternaria sp. Samif01 residing in the roots of Salvia miltiorrhiza Bunge. Alternariol 9-methyl ether was active against bacteria with minimum inhibitory concentration values ranging from 25 to 75 µg/mL and median inhibitory concentration (IC50) values ranging from 16.00 to 38.27 µg/mL. The IC50 value of alternariol 9-methyl ether against spore germination of Magnaporthe oryzae was 87.18 µg/mL. Alternariol 9-methyl ether also showed antinematodal activity against Bursaphelenchus xylophilus and Caenorhabditis elegans with IC50 values of 98.17 µg/mL and 74.62 µg/mL, respectively. This work is the first report on alternariol 9-methyl ether and its biological activities from the endophytic fungus Alternaria sp. Samif01 derived from S. miltiorrhiza Bunge. The results indicate the potential of Alternaria sp. Samif01 as a source of alternariol 9-methyl ether and also support that alternariol 9-methyl ether is a natural compound with high potential bioactivity against microorganisms. (AU)

Effects of oligosaccharides from endophytic Fusarium oxysporum Dzf17 on activities of defense-related enzymes in Dioscorea zingiberensis suspension cell and seedling cultures

Background Three oligosaccharides (EOS, WOS and SOS) were respectively prepared from the corresponding polysaccharides, namely exopolysaccharide (EPS), water-extracted mycelial polysaccharide (WPS) and sodium hydroxide-extracted mycelial polysaccharides (SPS) from the endophytic fungus Fusarium oxysporum Dzf17. In this study, the effects of EOS, WOS and SOS on the activities of the defense-related enzymes, namely phenylalanine ammonia lyase (PAL), polyphenoloxidase (PPO) and peroxidase (POD) in its host plant Dioscorea zingiberensis cultures were investigated. Results For the suspension cell cultures of D. zingiberensis, the highest PAL activity was induced by 0.5 mg/mL of WOS at 48 h after treatment, which was 4.55-fold as that of control. Both PPO and POD activities were increased to the maximum values by 0.25 mg/mL of WOS at 48 h after treatment, which were respectively 3.74 and 3.45-fold as those of control. For the seedling cultures, the highest PAL activity was elicited by 2.5 mg/mL of EOS at 48 h after treatment, which was 3.62-fold as that of control. Both PPO and POD reached their maximum values treated with 2.5 mg/mL of WOS at 48 h after treatment, which were 4.61 and 4.19-fold as those of control, separately. Conclusions Both EOS and WOS significantly increased the activities of PAL, PPO and POD in the suspension cell and seedling cultures of D. zingiberensis. The results suggested that the oligosaccharides from the endophytic fungus F. oxysporum Dzf17 may be related to the activation and enhancement of the defensive mechanisms of D. zingiberensis suspension cell and seedling cultures.

Medium optimization for palmarumycin C13 production in liquid culture of endophytic fungus Berkleasmium sp. Dzf12 using response surface methodology

Background: Berkleasmium sp. Dzf12, an endophytic fungus from Dioscorea zingiberensis, was a high producer of palmarumycin C13 with various bioactivities. In the present study, the experimental designs based on statistics were employed to evaluate and optimize the medium for palmarumycin C13 production in mycelia liquid culture of Berkleasmium sp. Dzf12. Results: Among various carbon and nitrogen sources, glucose, peptone and yeast extract were found to be the most favourable for palmarumycin C13 production based on the one-factor-at-a-time experiments. After Plackett-Burman test on the medium, glucose, peptone and yeast extract were further verified to be the most significant factors to stimulate palmarumycin C13 accumulation. These three factors (i.e., glucose, peptone and yeast extract) were then optimized through the experiments of central composite design (CCD) and analysis of response surface methodology (RSM). The optimized medium compositions for palmarumycin C13 production were determined as 42.5 g/l of glucose, 6.5 g/l of peptone, 11.0 g/l of yeast extract, 1.0 g/l of KH2PO4, 0.5 g/l of MgSO4 x 7H2O, 0.05 g/l of FeSO4 x 7H2O, and pH 6.5. Under the optimal culture conditions, the maximum palmarumycin C13 yield of Berkleasmium sp. Dzf12 was increased to 318.63 mg/l, which was about 2.5-fold in comparison with that (130.44 mg/l) in the basal medium. Conclusions: The results indicate that the optimum production of palmarumycin C13 in Berkleasmium sp. Dzf12 liquid culture can be achieved by addition of glucose, peptone and yeast extract with their appropriate concentrations in the modified Sabouraud medium.