Health economics study of paliperidone palmitate in the treatment of schizophrenia: a 12-month cohort study.

BACKGROUND: To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. METHODS: We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. RESULTS: The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) (P > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P < 0.05). CONCLUSION: Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.

Multivariate modular metabolic engineering for enhanced L-methionine biosynthesis in Escherichia coli.

BACKGROUND: L-Methionine is the only bulk amino acid that has not been industrially produced by the fermentation method. Due to highly complex and strictly regulated biosynthesis, the development of microbial strains for high-level L-methionine production has remained challenging in recent years. RESULTS: By strengthening the L-methionine terminal synthetic module via site-directed mutation of L-homoserine O-succinyltransferase (MetA) and overexpression of metAfbr, metC, and yjeH, L-methionine production was increased to 1.93 g/L in shake flask fermentation. Deletion of the pykA and pykF genes further improved L-methionine production to 2.51 g/L in shake flask fermentation. Computer simulation and auxotrophic experiments verified that during the synthesis of L-methionine, equimolar amounts of L-isoleucine were accumulated via the elimination reaction of cystathionine γ-synthetase MetB due to the insufficient supply of L-cysteine. To increase the supply of L-cysteine, the L-cysteine synthetic module was strengthened by overexpression of cysEfbr, serAfbr, and cysDN, which further increased the production of L-methionine by 52.9% and significantly reduced the accumulation of the byproduct L-isoleucine by 29.1%. After optimizing the addition of ammonium thiosulfate, the final metabolically engineered strain MET17 produced 21.28 g/L L-methionine in 64 h with glucose as the carbon source in a 5 L fermenter, representing the highest L-methionine titer reported to date. CONCLUSIONS: In this study, a high-efficiency strain for L-methionine production was derived from wild-type Escherichia coli W3110 by rational metabolic engineering strategies, providing an efficient platform for the industrial production of L-methionine.

Karst grassland forage quality and its determinants in Guizhou Province of Southwest China.

Forage quality is a key property of grassland ecosystems. In this study, grassland forage qualities were measured at 373 sampling sites throughout Guizhou Province in the karst mountain region of Southwest China, and the factors affecting it were explored. The forage quality level of most plant species was categorized into four levels: (1) preferred forage species; (2) desirable forage species; (3) consumed but undesirable forage species; and (4) non-consumable or toxic forage species. High temperature and precipitation appeared to facilitate the growth of preferred forage species, but limited the growth of other plants. Increasing soil pH had a positive impact on the number and biomass of preferred forage plants, but a negative influence on other plants, especially non-consumable or toxic plants. Both GDP and population density had a positive correlation with the number and biomass of preferred forage species, while such correlations for other levels of forage species tended to be negative. Grazing could lead to a decrease in the preferred forage species. Therefore, it is suggested that by focusing on soil improvement in grassland and maintaining an appropriate grazing intensity, global warming and rapid economic growth in Guizhou Province will likely contribute to increase the forage quality of karst grasslands in Southwest China.

Genetic diversity and differentiation of populations of Chlorops oryzae (Diptera, Chloropidae).

BACKGROUND: Chlorops oryzae is an important pest of rice crops. There have been frequent outbreaks of this pest in recent years and it has become the main rice pest in some regions. To elucidate the molecular mechanism of frequent C. oryzae outbreaks, we estimated the genetic diversity and genetic differentiation of 20 geographical populations based on a dataset of ISSR markers and COI sequences. RESULTS: ISSR data revealed a high level of genetic diversity among the 20 populations as measured by Shannon's information index (I), Nei's gene diversity (H), and the percentage of polymorphic bands (PPB). The mean coefficient of gene differentiation (Gst) was 0.0997, which indicates that only 9.97% genetic variation is between populations. The estimated gene flow (Nm) value was 4.5165, indicating a high level of gene flow and low, or medium, genetic differentiation among some populations. The results of a Mantel test revealed no significant correlation between genetic and geographic distance among populations, which means there is no evidence of significant genetic isolation by distance. An UPGMA (unweighted pair-group method with arithmetic averages) dendrogram based on genetic identity, did not indicate any major geographic structure for the 20 populations examined. mtDNA COI data indicates low nucleotide (0.0007) and haplotype diversity (0.36) in all populations. Fst values suggest that the 20 populations have low, or medium, levels of genetic differentiation. And the topology of a Neighbor-Joining tree suggests that there are no independent groups among the populations examined. CONCLUSIONS: Our results suggest that C. oryzae populations have high genetic diversity at the species level. There is evidence of frequent gene flow and low, or medium, levels of genetic differentiation among some populations. There is no significant correlation between genetic and geographic distance among C. oryzae populations, and therefore no significant isolation by distance. All results are consistent with frequent gene exchange between populations, which could increase the genetic diversity, and hence, adaptability of C. oryzae, thereby promoting frequent outbreaks of this pest. Such knowledge may provide a scientific basis for predicting future outbreaks.

Knockdown of Methoprene-Tolerant Arrests Ovarian Development in the Sogatella furcifera (Hemiptera: Delphacidae).

Juvenile hormone (JH) is responsible for repressing larval metamorphosis and inducing vitellogenesis and egg production in insects. Methoprene-tolerant (Met) is known to be an intracellular receptor and transducer of JH. We examined the role of Met in ovarian development in the rice pest Sogatella furcifera (Horváth). We first cloned and sequenced S. furcifera Met (SfMet). The SfMet protein belongs to the basic helix-loop-helix/Per-Arnt-Sim (bHLH-PAS) family with a bHLH domain and two PAS domains (PAS-A and PAS-B). SfMet was expressed in all developmental stages and tissues but was most highly expressed in the ovaries of adult females. Furthermore, RNA interference (RNAi) mediated silencing of SfMet substantially reduced the expression of SfVg, decreased yolk protein deposition and blocked oocyte maturation and ovarian development. These results demonstrate that SfMet plays a key role in female reproduction in S. furcifera and suggest that targeting this gene could be an effective way of controlling this pest.

A seamless and iterative DNA assembly method named PS-Brick and its assisted metabolic engineering for threonine and 1-propanol production.

BACKGROUND: DNA assembly is an essential technique enabling metabolic engineering and synthetic biology. Combining novel DNA assembly technologies with rational metabolic engineering can facilitate the construction of microbial cell factories. Amino acids and derived biochemicals are important products in industrial biotechnology with wide application and huge markets. DNA assembly scenarios encountered in metabolic engineering for the construction of amino acid and related compound producers, such as design-build-test-learn cycles, construction of precise genetic circuits and repetitive DNA molecules, usually require for iterative, scarless and repetitive sequence assembly methods, respectively. RESULTS: Restriction endonuclease (RE)-assisted strategies constitute one of the major categories of DNA assembly. Here, we developed a Type IIP and IIS RE-assisted method named PS-Brick that comprehensively takes advantage of the properties of PCR fragments and REs for iterative, seamless and repetitive sequence assembly. One round of PS-Brick reaction using purified plasmids and PCR fragments was accomplished within several hours, and transformation of the resultant reaction product from this PS-Brick assembly reaction exhibited high efficiency (104-105 CFUs/µg DNA) and high accuracy (~ 90%). An application of metabolic engineering to threonine production, including the release of feedback regulation, elimination of metabolic bottlenecks, intensification of threonine export and inactivation of threonine catabolism, was stepwise resolved in E. coli by rounds of "design-build-test-learn" cycles through the iterative PS-Brick paradigm, and 45.71 g/L threonine was obtained through fed-batch fermentation. In addition to the value of the iterative character of PS-Brick for sequential strain engineering, seamless cloning enabled precise in-frame fusion for codon saturation mutagenesis and bicistronic design, and the repetitive sequence cloning ability of PS-Brick enabled construction of tandem CRISPR sgRNA arrays for genome editing. Moreover, the heterologous pathway deriving 1-propanol pathway from threonine, composed of Lactococcus lactis kivD and Saccharomyces cerevisiae ADH2, was assembled by one cycle of PS-Brick, resulting in 1.35 g/L 1-propanol in fed-batch fermentation. CONCLUSIONS: To the best of our knowledge, the PS-Brick framework is the first RE-assisted DNA assembly method using the strengths of both Type IIP and IIS REs. In this study, PS-Brick was demonstrated to be an efficient DNA assembly method for pathway construction and genome editing and was successfully applied in design-build-test-learn (DBTL) cycles of metabolic engineering for the production of threonine and threonine-derived 1-propanol. The PS-Brick presents a valuable addition to the current toolbox of synthetic biology and metabolic engineering.

Molecular Characterization of Vitellogenin and Its Receptor in Sogatella furcifera, and Their Function in Oocyte Maturation.

The yolk protein precursor, vitellogenin (Vg), provides nutrition for embryonic development whereas the vitellogenin receptor (VgR) is responsible for the uptake of yolk protein by maturing oocytes. These two proteins are key reproduction-related proteins in insects. We cloned and characterized Vg and VgR genes in Sogatella furcifera, and investigated their function in oocyte maturation. Cloned SfVg and SfVgR have open reading frames of 6,114 and 5,796 bp, encoding 2,037 and 1,931 amino acid residues, respectively. Structural analysis indicates that SfVg has the three conserved LPD_N, DUF1943, and VWFD domains, SfVgR contains all conservative motifs of the LDLR superfamily. Both genes were highly expressed in adult females; SfVg was most highly expressed in the fat body whereas SfVgR was mainly expressed in the ovary. Knockdown of either gene reduced yolk protein deposition in oocytes and arrested oocyte maturation. However, silencing one of these two genes did not affect the transcript level of the other. These results demonstrate the role of SfVgR in transporting SfVg into oocytes. Both SfVg and SfVgR are essential for oocyte maturation in S. furcifera and both genes could potentially be targeted as means of controlling this pest.