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To investigate the clinical application value of pharmacogenetic testing in individualized drug therapy for adult male patients with schizophrenia. A total of 186 adult patients with schizophrenia were enrolled and randomised into the pharmacogenetic (PGx) intervention group and the standard care group. In the PGx intervention group, PGx testing was performed, and the medication regimen was adjusted according to the results of the pharmacogenomic analysis. In contrast, in the standard care group, patients were treated according to the physician's medication experience. Differences in the primary indicator of schizophrenia, the Positive and Negative Symptom Scale (PANSS), and the secondary efficacy measures, the Clinical Global Impressions–Severity of Illness scale (CGI-SI) and Clinical Global Impressions–Global Improvement (CGI-GI) scale, were compared between the intervention and standard care groups. At baseline, the PGx intervention group consisted of 109 individuals, while the standard care group had 77 participants. After 12 weeks of treatment, 49 individuals withdrew from the PGx group (a dropout rate of 45.0%), and 34 withdrew from the standard care group (a dropout rate of 44.2%), with no significant difference in dropout rates between the two groups. The PANSS score reduction rate in the PGx intervention group significantly exceeded that of the standard care group during weeks 3, 6, and 12 of follow-up (P < 0.05). At the 12th week, the PGx intervention group achieved a treatment response rate of 81.7%, significantly surpassing the 48.8% of the standard care group (odds ratio of 4.67, 95% confidence interval of 1.96–11.41; P = 0.001). Furthermore, the PGx intervention was significantly more effective than standard care regardless of whether the patient had a first episode or a relapse (P < 0.05). Furthermore, the Global Assessment of Functioning (GAF) scores and the Personal and Social Performance Scale (PSP) score changes in the PGx intervention group were both significantly different from those in the standard care group (P < 0.05). It is noteworthy that the PGx intervention similarly improves the prognostic outcomes for patients with and without a family history of mental disorders. In conclusion, the application of a PGx intervention treatment model based on PGx testing can significantly improve medication efficacy and shorten the time to achieve the effects of medication in schizophrenia. [ABSTRACT FROM AUTHOR]

• Plasmodium yoelii can repair CRISPR/Cas9-generated DNA breaks by microhomology-mediated end joining. • Size mutants of the central repeat in circumsporozoite surface protein (CSP) were successfully generated. • A minimum size of the CSP central repeat region is required for mosquito stage development. CRISPR/Cas9 is a powerful genome editing method that has greatly facilitated functional studies in many eukaryotic organisms including malaria parasites. Due to the lack of genes encoding enzymes necessary for the non-homologous end joining DNA repair pathway, genetic manipulation of malaria parasite genomes is generally accomplished through homologous recombination requiring the presence of DNA templates. Recently, an alternative double-strand break repair pathway, microhomology-mediated end joining, was found in the Plasmodium falciparum parasite. Taking advantage of the MMEJ pathway, we developed a MMEJ-based CRISPR/Cas9 (mCRISPR) strategy to efficiently generate multiple mutant parasites simultaneously in genes with repetitive sequences. As a proof of principle, we successfully produced various size mutants in the central repeat region of the Plasmodium yoelii circumsporozoite surface protein without the use of template DNA. Monitoring mixed parasite populations and individual parasites with different sizes of CSP-CRR showed that the CSP-CRR plays a role in the development of mosquito stages, with severe developmental defects in parasites with large deletions in the repeat region. However, the majority of the csp mutant parasite clones grew similarly to the wild type P. yoelii 17XL parasite in mice. This study develops a useful technique to efficiently generate mutant parasites with deletions or insertions, and shows that the CSP-CRR plays a role in parasite development in mosquito. [ABSTRACT FROM AUTHOR]

In order to fabricate antibacterial nanofiber membranes for tissue engineering field, the oxidative damage of magnesium hydroxide nanoparticles (Mg(OH) 2 NPs) against the model system of Escherichia coli (E. coli) was researched by measuring the oxidative stress response, oxidative stress products and glucose metabolism. The toxicity of Mg(OH) 2 NPs to a normal biological system was evaluated in vivo through the acute oral toxicity, blood physiological and serum biochemical markers and acute skin irritation, indicating that the Mg(OH) 2 NPs exhibited great biosafety. The Mg(OH) 2 NPs with antibacterial property and biosafety were loaded on PCL/PVP nanofiber substrates through electrospinning technology to fabricate the Mg(OH) 2 /PCL/PVP nanofiber membranes. The results of characterization and antibacterial test showed that the Mg(OH) 2 /PCL/PVP nanofiber membranes with 8.0 wt% Mg(OH) 2 NPs present excellent antibacterial rate of 100% against E. coli that the Mg(OH) 2 NPs can be physically and evenly loaded on nanofiber substrates. • Oxidative damage of Mg(OH) 2 NPs against E. coli was evaluated. • Biosafety of Mg(OH) 2 NPs was evaluated in vivo. • Mg(OH) 2 /PCL/PVP nanofiber membranes were fabricated for the first time. • Mg(OH) 2 NPs were loaded on nanofiber substrates by electrospinning method. [ABSTRACT FROM AUTHOR]

Silicon (Si) has crucial effects on plant development and stress resistance. Silicon transporters regulate Si absorption, transport, and distribution in plants. In this study, we identified and characterized the Si transporter gene family of moso bamboo (Phyllostachys edulis) and cloned seven putative Si transporter genes. Moso bamboo Si transporters contain conserved functional domains that mediate the accumulation of considerable amounts of Si. The analysis of gene duplication patterns and divergence times suggested that the expansion of the moso bamboo Si transporter family was mainly due to segmental duplications. The expression of moso bamboo Si transporter genes, which varied among organs, was significantly modulated by Si treatments. The subcellular localization analysis showed that Si transporters are plasma membrane proteins. The Si content increased in transgenic Arabidopsis overexpressing PeLsi1-1 or PeLsi1-2 , which affected vegetative and reproductive growth. Our single-particle tracking analysis revealed the four diffusion modes of PeLsi1-1 on the plasma membrane. Moreover, the particle velocity, dwell time, and motion range of PeLsi1-1 decreased in response to Si treatments. The results of this study will further clarify the molecular mechanisms underlying Si absorption and accumulation in bamboo plants. • Moso bamboo has the molecular basis of high silicon accumulation. • The excessive accumulation of silicon affected the growth of transgenic Arabidopsis. • The distribution and dynamic changes of PeLsi1-1 were affected by silicon. • A hypothetical model for silicon transport in moso bamboo seedlings was established. [ABSTRACT FROM AUTHOR]

Mirabilis himalaica is an important Tibetan medicinal plant in China. However, it has become a rare and class I endangered Tibetan medicine plant. Therefore, the use of callus to propagate germplasm resources is of great significance. We found that the flavonoid content of M. himalaica callus increased continuously with the extension of UV-B treatment. Multi-omics profiles were used to reveal the co-expression patterns of gene networks of flavonoid metabolism in M. himalaica callus during UV-B radiation. Results showed that five medicinal metabolics, including geranin, eriodictyol, astragalin, isoquercetin, pyrotechnic acid, and one anthocyanin malvide-3-O-glucoside were identified. The transcriptome data were divided into 46 modules according to the expression pattern by WGCNA (weighted gene co-expression network analysis), of which the module Turquoise had the strongest correlation with six target metabolites. We found that seven structural genes and twenty-five transcription factors were related to the metabolism of flavonoid synthesis, among which the structural genes CHI , C4H and UGT79B6 had strong co-expression relationships with the 6 target metabolites. WRKY42, WRKY7, bHLH128 and other transcription factors had strong co-expression relationships with multiple structural genes. Consequently, these findings suggest callus grown under UV-B treatment could be an effective alternative medical resource of M. himalaica , which is valuable for conservation and usage of this wild and endangered plant. • Six key medicinal metabolic were identified in M. himalaica callus by UV-B radiation. • WGCNA was used to analyze the relationship between gene modules and metabolites. • CHI , C4H and UGT79B6 had strong co-expression relationship with 6 target metabolites. • WRKY42, WRKY7, bHLH128 had strong co-expression relationships with structural genes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Controllable synthesis of structures and effective modulation of catalytic properties. • Three-dimensional multi-channel structure enhances the catalytic activity. • The 3D NiCo alloy show excellent performance both in HER and OER. The development of high activity and low cost electrocatalysts for enhancing hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is the focus of overall water splitting. It has been found that transition metals have the potential to be highly efficient catalysts. In this paper, NiCo alloy electrode and three-dimensional multi-channel NiCo alloy (3D NiCo alloy) electrode were prepared by chemical coprecipitation-thermal reduction method and impregnation method respectively, which were used for efficient overall water splitting. By adjusting the pH value, alloy electrodes with different morphologies were obtained. The 3D multi-channel structure improved the catalytic activity of the NiCo alloy electrode for HER and OER. In 0.5 M H 2 SO 4 , the 3D NiCo 3 alloy electrode shows excellent catalytic activity for HER and OER. The HER overpotential of the 3D NiCo 3 alloy electrode is 109.6 mV at the current density of −10 mA cm−2, while the corresponding Tafel is 81.23 mV dec−1. The overpotential is as low as 296 mV when the OER current density is 40 mA cm−2, and the corresponding Tafel is 32.58 mV dec−1. This is due to the large specific surface area of the 3D NiCo 3 alloy electrode, and the synergistic effect between Ni-Co alloys and more active sites exposed by the three-dimensional multi-channel structure. It is shown that the morphology and structure have a great influence on the catalytic performance, and the transition metal electrocatalyst has a bright industrial application prospect. [ABSTRACT FROM AUTHOR]