Unlocking the potentials of cyanobacterial photosynthesis for directly converting carbon dioxide into glucose.

Glucose is the most abundant monosaccharide, serving as an essential energy source for cells in all domains of life and as an important feedstock for the biorefinery industry. The plant-biomass-sugar route dominates the current glucose supply, while the direct conversion of carbon dioxide into glucose through photosynthesis is not well studied. Here, we show that the potential of Synechococcus elongatus PCC 7942 for photosynthetic glucose production can be unlocked by preventing native glucokinase activity. Knocking out two glucokinase genes causes intracellular accumulation of glucose and promotes the formation of a spontaneous mutation in the genome, which eventually leads to glucose secretion. Without heterologous catalysis or transportation genes, glucokinase deficiency and spontaneous genomic mutation lead to a glucose secretion of 1.5 g/L, which is further increased to 5 g/L through metabolic and cultivation engineering. These findings underline the cyanobacterial metabolism plasticities and demonstrate their applications for supporting the direct photosynthetic production of glucose.

Detection of multiple types of cancer driver mutations using targeted RNA sequencing in non-small cell lung cancer.

BACKGROUND: DNA-based next-generation sequencing has been widely used in the selection of target therapies for patients with nonsmall cell lung cancer (NSCLC). RNA-based next-generation sequencing has been proven to be valuable in detecting fusion and exon-skipping mutations and is recommended by National Comprehensive Cancer Network guidelines for these mutation types. METHODS: The authors developed an RNA-based hybridization panel targeting actionable driver oncogenes in solid tumors. Experimental and bioinformatics pipelines were optimized for the detection of fusions, single-nucleotide variants (SNVs), and insertion/deletion (indels). In total, 1253 formalin-fixed, paraffin-embedded samples from patients with NSCLC were analyzed by DNA and RNA panel sequencing in parallel to assess the performance of the RNA panel in detecting multiple types of mutations. RESULTS: In analytical validation, the RNA panel achieved a limit of detection of 1.45-3.15 copies per nanogram for SNVs and 0.21-6.48 copies per nanogram for fusions. In 1253 formalin-fixed, paraffin-embedded NSCLC samples, the RNA panel identified a total of 124 fusion events and 26 MET exon 14-skipping events, in which 14 fusions and six MET exon 14-skipping mutations were missed by DNA panel sequencing. By using the DNA panel as the reference, the positive percent agreement and the positive predictive value of the RNA panel were 98.08% and 98.62%, respectively, for detecting targetable SNVs and 98.15% and 99.38%, respectively, for detecting targetable indels. CONCLUSIONS: Parallel DNA and RNA sequencing analyses demonstrated the accuracy and robustness of the RNA sequencing panel in detecting multiple types of clinically actionable mutations. The simplified experimental workflow and low sample consumption will make RNA panel sequencing a potentially effective method in clinical testing.

Surveillance and Control of Malaria Vectors in Hainan Province, China from 1950 to 2021: A Retrospective Review.

Malaria is a serious mosquito-borne tropical disease impacting populations in tropical regions across the world. Malaria was previously hyperendemic in Hainan Province. Due to large-scale anti-malarial intervention, malaria elimination in the province was achieved in 2019. This paper reviews the literature on the ecology, bionomics, and control of malaria vectors in Hainan from 1951 to 2021. We searched PubMed, and the China national knowledge infrastructure (CNKI) database for relevant articles published and included three other important books published in Chinese or English in order to summarize research on species, distribution, vectorial capacity, ecology, the resistance of malaria vectors to insecticides, and malaria vector control in Hainan Province. A total of 239 references were identified, 79 of which met the criteria for inclusion in our review. A total of six references dealt with the salivary gland infection of Anophelines, six with vectorial capacity, 41 with mosquito species and distribution, seven with seasonality, three with blood preference, four with nocturnal activity, two with flight distance, 13 with resistance to insecticides, and 14 with vector control. Only 16 published papers met the criteria of addressing malaria vectors in Hainan over the last 10 years (2012-2021). Anopheles dirus and Anopheles minimus are primary malaria vectors, mainly distributed in the southern and central areas of Hainan. Indoor residual spraying with DDT and the use of ITNs with pyrethroid insecticides were the main interventions taken for malaria control. Previous studies on ecology, bionomics, and resistance of vectors provided scientific evidence for optimizing malaria vector control and contributed to malaria elimination in Hainan Province. We hope our study will contribute to preventing malaria reestablishment caused by imported malaria in Hainan. Research on malaria vectors should be updated to provide scientific evidence for malaria vector control strategies post-elimination as the ecology, bionomics, and resistance of vectors to insecticides may change with changes in the environment.

Rapidly Improving High Light and High Temperature Tolerances of Cyanobacterial Cell Factories Through the Convenient Introduction of an AtpA-C252F Mutation.

Photosynthetic biomanufacturing is a promising route for green production of biofuels and biochemicals utilizing carbon dioxide and solar energy. Cyanobacteria are important microbial platforms for constructing photosynthetic cell factories. Toward scaled outdoor cultivations in the future, high light and high temperature tolerances of cyanobacterial chassis strains and cell factories would be determinant properties to be optimized. We proposed a convenient strategy for rapidly improving high light and high temperature tolerances of an important cyanobacterial chassis Synechococcus elongatus PCC 7942 and the derived cell factories. Through introduction and isolation of an AtpA-C252F mutation, PCC 7942 mutants with improved high light and high temperature tolerances could be obtained in only 4 days with an antibiotics-free mode. Adopting this strategy, cellular robustness and sucrose synthesizing capacities of a PCC 7942 cell factory were successfully improved.

[Epidemiological characteristics and related influencing factors on Japanese encephalitis in Hainan Province].

OBJECTIVE: To understand the epidemiological characteristics and the influencing factors of Japanese encephalitis (Abbreviated JE) at different periods in Hainan province, and to provide evidence for JE control strategies. METHODS: Data on JE had been collected since 1952 and related incidence, mortality, fatality rates of JE and the rate of JE vaccination were calculated for four periods: the natural epidemic period (1952-1978), period for inactivated JE vaccine promotion (1979-1986), national immunization program period (1987-1990) and the promotion of live-attenuated JE vaccine period (1991-2007). History on the immunity of JE and data from the monitoring programs on cases and insect vectors were also analyzed. RESULTS: The average annual incidence in natural epidemic period was 7.12/100,000, which was also the highest among the 4 periods with the mortality rate as 0.89/100,000. The average annual incidence was 0.11/100,000 which was the lowest while the mortality rate was 0.01/100,000 in the period when live-attenuated JE vaccination was under promotion. Since the establishment of JE surveillance system was set up in Hainan province in 2002, the specimen collection rate of JE reported suspected cases had reached 92.8%, while the incidence of confirmed JE cases fluctuated between 0.05/100,000 and 0.2/100,000. Of the confirmed cases, 86% did not have clear history of JE vaccination. The annual average protective rate reached 95.69% in 2004-2007. The density of insect vectors was high in Hainan province. The infection rate of JE in host animal swine, kept rising from April to October, and in some surveillance points, the rate reached 99.3%. The density of insect vector plotted in trans-curve with the infection of host animals. CONCLUSION: The application of live-attenuated JE vaccine was found to have had significant protective effect on JE in susceptible children. It helped reducing the incidence and controlling the epidemics of JE. It appears feasible to include live-attenuated JE vaccine into the expanded immunization program.

[Evaluation on the effect of implementation regarding the measles surveillance system in Hainan province].

OBJECTIVE: To evaluate the development and operation on measles surveillance system. METHODS: To formulate surveillance program, and then establish surveillance system on measles in Hainan province before the case surveillance was conducted. Descriptive epidemiological method was used to analyze the measles cases reported through the notifiable diseases epidemic situation report system and measles surveillance system during 2004 - 2008 in Hainan province. RESULTS: From 2004 to 2008, through surveillance system, 3040 suspected measles cases were reported which was 96.00% higher than that from the notifiable diseases epidemic situation report system. When the measles surveillance system was first established in 2004, the number of cases reported by the surveillance system was less than that from the epidemic report system, however, the sensitivity of the surveillance system had been increasing since 2005. In 2008, the number of suspected cases reported by surveillance system was 19.12 times more than from the epidemic report system. The proportion of confirmed cases in the total suspected cases was decreasing annually, from 90.34% to 4.48%, along with the increase of the sample collection rate, from 22.73% to 99.12%. The proportion of laboratory confirmed cases in the total confirmed cases increased from 7.55% to 86.97%. With suspected cases, the IgM antibody positive rate on measles and rubella were 31.57% and 34.52%, respectively. In Hainan, the epidemic pattern of measles had been sporadic, except for 2006 as there occurred several outbreaks in that year. The of disease incidence had an obvious seasonal peaks, from March to June. Measles mainly attacked children under 15 years of age, accounted for 86.68% of the age group. Children with no immunity or unknown immune history accounted for 85.67%. CONCLUSION: The sensitivity of surveillance system had been increasing annually since it was developed and the incidence had been dropping to its lowest level. These achievements had built a solid foundation for the eventual elimination of measles.