The safety of trastuzumab deruxtecan (DS-8201) with a focus on interstitial lung disease and/or pneumonitis: A systematic review and single-arm meta-analysis.

BACKGROUND: Previous studies involving risk-benefit analysis of trastuzumab deruxtecan (DS-8201) have indicated the benefit of this treatment, although it may increase the risk of interstitial lung disease (ILD) and/or pneumonitis in certain patients. This study aimed to assess the safety of DS-8201. METHODS: A search was done for relevant articles in four electronic databases: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. All reports published up until November 2, 2022, were included, and study types were restricted to clinical trials; the last search was then updated to January 10, 2023. We also assessed the quality of the literature with the Cochrane Handbook for Systematic Reviews of Interventions and the Methodological Index for Non-Randomized Studies tool, and then performed a meta-analysis with R version 4.2.1. RESULTS: A total of 1428 patients reported in 13 articles were included in this study. The analysis revealed that the most common all-grade treatment-emergent adverse events (TEAEs) were nausea and fatigue. The most common TEAE of grade 3 or above (grade ≥3) was neutropenia. The incidences of ILD and/or pneumonitis for all-grade and grade ≥3 TEAEs were 12.5% and 2.2%, respectively. CONCLUSIONS: This comprehensive summary of the incidence of TEAEs associated with DS-8201 in clinical trials provides an important guide for clinicians. The most common TEAEs were gastrointestinal reactions and fatigue; meanwhile, the most common grade ≥3 TEAE was hematological toxicity. ILD and/or pneumonitis were specific adverse drug reactions associated with DS-8201, of which physicians should be particularly aware for their higher morbidity and rates of grade ≥3 TEAEs.

Efficacy and safety of dabigatran and rivaroxaban in atrial fibrillation patients with impaired liver function: a multicenter retrospective cohort study.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with impaired liver function (ILF) have not been sufficiently studied. The aim of this study was to evaluate the efficacy and safety of DOACs for stroke prevention in patients with AF and ILF. METHOD: This study was based on data from 15 centers in China, including 4,982 AF patients. The patients were divided into 2 subgroups based on their liver function status: patients with normal liver function (NLF)(n = 4213) and patients with ILF (n = 769). Logistic regression analysis was used to investigate the risk of total bleeding, major bleeding, thromboembolism, and all-cause deaths in AF patients with NLF and ILF after taking dabigatran or rivaroxaban, respectively. RESULTS: Among AF patients treated with dabigatran or rivaroxaban, patients with ILF were associated with significantly higher major bleeding, compared with NLF patients (aOR: 4.797; 95% CI: 2.224-10.256; P < 0.001). In patients with NLF, dabigatran (n = 2011) had considerably lower risk of total bleeding than rivaroxaban (n = 2202) (aOR: 1.23; 95% CI: 1.002-1.513; P = 0.049). In patients with ILF, dabigatran (n = 321) significantly favored lower risks of major bleeding compared with rivaroxaban(n = 448) (aOR: 5.484; 95% CI: 1.508-35.269; P = 0.026). CONCLUSION: After using dabigatran or rivaroxaban, patients with ILF had remarkably increased risk of major bleeding compared with patients with NLF. In AF patients with NLF, dabigatran had the distinct strength of significantly reduced risk of total bleeding compared with rivaroxaban. In patients with AF and ILF, dabigatran use was associated with lower risk for major bleeding compared with rivaroxaban.

Zn-Doped MnCO3/CS Composite Photocatalyst for Visible-Light-Driven Decomposition of Organic Pollutants.

Zn-doped MnCO3/carbon sphere (Zn-doped MnCO3/CS) composites were synthesized using a simple hydrothermal procedure. Among various samples (ZM-50, ZM-05, and ZMC-0), the ternary Zn-doped MnCO3/CS (ZMC-2) catalyst demonstrated excellent visible light-induced photocatalytic activity. This improvement comes from the Zn addition and the conductive CS, which facilitate electron movement and charge transport. The catalyst exhibited efficient degradation of methylene blue (MB) over a wide pH range, achieving a removal efficiency of 99.6% under visible light. Radical trapping experiments suggested that •OH and •O2- played essential roles in the mechanism of organic pollutant degradation. Moreover, the catalyst maintained good degradation performance after five cycles. This study offers valuable perspectives into the fabrication of carbon-based composites with promising photocatalytic activity.

High-yield production of FK228 and new derivatives in a Burkholderia chassis.

FK228 (romidepsin) is the only natural histone deacetylases (HDACs) inhibitor approved by FDA to treat cutaneous and peripheral T-cell lymphoma. However, the limited supply and severe cardiotoxicity of FK228 underscore the importance to develop an effective synthetic biology platform for the manufacturing and fine-tuning of this drug lead. In this work, we constructed a Burkholderia chassis for the high-yield production of FK228-family (unnatural) natural products. By virtue of the optimized Burkholderia-specific recombineering system, the biosynthetic gene cluster (BGC) encoding the FK228-like skeleton thailandepsins (tdp) in Burkholderia thailandensis E264 was replaced with an attB integration site to afford the basal chassis KOGC1. The tdp BGC directly captured from E264 was hybridized with the FK228-encoding BGC (dep) using the versatile Red/ET technology. The hybrid BGC (tdp-dep) was integrated into the attB site of KOGC1, resulting in the heterologous expression of FK228. Remarkably, the titer reached 581 mg/L, which is 30-fold higher than that of native producer Chromobacterium violaceum No. 968. This success encouraged us to further engineer the NRPS modules 4 or 6 of hybrid tdp-dep BGC by domain units swapping strategy, and eight new FK228 derivatives (1-8) varying in the composition of amino acids were generated. Especially, the titers of 2 and 3 in KOGC1 were up to 985 mg/L and 453 mg/L, respectively. 2 and 3 displayed stronger cytotoxic activity than FK228. All in all, this work established a robust platform to produce FK228 and its new derivatives in sufficient quantities for anticancer drug development.

An ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry method based on a four-step analysis strategy to investigate metabolites of Qi-Yu-San-Long decoction in rat plasma.

Metabolism is undoubtedly significantly correlated with the efficacy and safety of traditional Chinese medicine. In clinic, Qi-Yu-San-Long decoction (QYSLD) has achieved good results in the treatment of non-small-cell lung cancer (NSCLC). Nevertheless, a detailed understanding of the compounds (prototypes and metabolites) of QYSLD and its dynamic metabolic profile in plasma has not been revealed. METHODS: In this study, a rapid and sensitive method based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF/MSE ), combined with a four-step analysis strategy, was established to investigate QYSLD metabolic profile in rat plasma. RESULTS: In all, 101 xenobiotics (41 prototypes and 60 QYSLD-related metabolites) were identified in rat plasma. The research uncovered metabolic profiles of alkaloids, saponins, flavonoids, iridoids, anthraquinones, and phenylpropanoids of QYSLD in rat plasma. The dynamic changes in these xenobiotics were also observed at different time intervals. At 0.5 h after oral administration, only 15 prototypes and 11 metabolites were detected. Within 24 h, 4 prototypes and 20 metabolites can still be detected. Four prototypes and 10 metabolites had the phenomenon of emergence-disappearance-reappearance in vivo. CONCLUSION: In rat plasma, 101 xenobiotics of QYSLD were identified and their dynamic metabolic profiles were systematically delineated, which laid a material basis for further research of the pharmacodynamic substances of QYSLD inhibiting NSCLC.

Safety and efficacy of direct oral anticoagulation in patients with and without radiofrequency ablation of non-valvular atrial fibrillation: a multicenter retrospective cohort study.

BACKGROUND: Based on the few available studies on the prognostic benefit of using direct oral anticoagulants (DOACs) after atrial fibrillation (AF) ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs. METHODS: This is a multicenter retrospective cohort study enrolling 6137 patients with non-valvular AF (NVAF) at 15 hospitals in China. Patient information was collected through a mean follow-up of 10 months and medical record queries. Clinical outcomes included major bleeding, total bleeding, thrombosis, all-cause death, and a composite endpoint of bleeding, thrombosis, and all-cause death. RESULTS: After adjusting for confounders and propensity score matching (PSM), patients with RFA of NVAF had a significantly lower risk of major bleeding [OR 0.278 (95% CI, 0.150-0.515), P<0.001], thrombosis [OR 0.535 (95% CI, 0.316-0.908), P=0.020] and the composite endpoint [ OR 0.835 (95% CI, 0.710-0.982), P=0.029]. In the RFA PSM cohort, dabigatran was associated with reduced all-cause death in patients with RFA of NVAF [OR 0.420 (95% CI, 0.212-0.831), P=0.010]. In the no RFA PSM cohort, rivaroxaban was associated with a reduction in major bleeding [OR 0.521 (95% CI, 0.403-0.673), P<0.001], total bleeding [OR 0.114 (95% CI, 0.049-0.266), P<0.001], and the composite endpoint [OR 0.659 ( 95% CI, 0.535-0.811), P<0.001]. CONCLUSION: Among patients with NVAF treated with DOACs, RFA was a negative correlate of major bleeding, thrombosis, and composite endpoints but was not associated with total bleeding or all-cause mortality.

Safety and efficacy of direct oral anticoagulants in stroke prevention in patients with atrial fibrillation complicated with anemia and/or thrombocytopenia: a retrospective cohort study.

BACKGROUND: There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia. METHODS: This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 109/L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 109/L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis. RESULTS: Higher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12-2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19-2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14-4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66-5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46-6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23-13.54, P = 0.577). CONCLUSIONS: Higher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia.

Association between Body Mass Index and Clinical Outcomes in Patients with Non-valvular Atrial Fibrillation Receiving Direct Oral Anticoagulants: A New Piece of Evidence on the Obesity Paradox from China.

PURPOSE: We conducted a multicenter real-world study in China to assess the association between body mass index (BMI) and clinical outcomes in patients with atrial fibrillation (AF) taking direct oral anticoagulants (DOACs). METHOD: This is a retrospective multicenter cohort study conducted in 15 centers in China. We collected demographic information through the hospital information system and obtained clinical events through follow-up visits to patients or relatives. Clinical outcomes include major, minor, total bleeding, thromboembolism, and all-cause death. RESULT: A total of 6164 patients with non-valvular AF (NVAF) were included in this study. The incidence of major bleeding in patients with NVAF differed significantly by BMI category (P < 0.001), with 5.2% in the underweight group, 2.6% in the normal group, 1.4% in the overweight group, 1.1% in the obese I group, and 1.3% in the obese II group. There was no significant difference in minor, total bleeding, and thrombosis in the five groups (P = 0.493; P = 0.172; P = 0.663). All-cause death was significantly different among the five groups (P < 0.001), with 8.9% in the underweight group, 6.3% in the normal group, 4.8% in the overweight group, 2.2% in the obese I group, and 0.4% in the obese II group. High BMI was negatively associated with major bleeding (OR = 0.353, 95% CI 0.205-0.608), total bleeding (OR = 0.664, 95% CI 0.445-0.991), and all-cause death (OR = 0.370, 95% CI 0.260-0.527). CONCLUSION: In patients with NVAF treated with DOACs, higher BMI was associated with lower major bleeding and better survival. BMI was a negative correlate of total bleeding, but not minor bleeding and thrombosis.

An integrated analytical strategy to decipher the metabolic profile of alkaloids in Compound Kushen injection based on UHPLC-ESI-QTOF/MSE.

Compound Kushen injection (CKI) is a kind of sterilised water-soluble traditional Chinese medicine preparation that has been used for the clinical treatment of a variety of cancers (hepatocellular carcinoma, lung cancer, etc.) for 19 years. However, to date, the metabolism-related study on CKI in vivo has not been conducted.An integrated analytical strategy was established to investigate the metabolic profile of alkaloids of CKI in rat plasma, urine, and faeces based on ultra-high performance liquid chromatography-electrospray quadrupole time-of-flight mass spectrometry in MSE mode (UHPLC-ESI-QTOF/MSE).Nineteen prototype alkaloids (including 12 matrine-type alkaloids, 2 cytisine-type alkaloids, 3 lupinine-type alkaloids, and 2 aloperine-type alkaloids) of CKI were identified in vivo. Furthermore, 71 metabolites of alkaloids (including 11 of lupanine-related metabolites, 14 of sophoridine-related metabolites, 14 of lamprolobine-related metabolites, and 32 of baptifoline-related metabolites) were tentatively characterised. Metabolic pathways involved in the metabolism of phase I (include oxidation, reduction, hydrolysis, and desaturation), phase II (mainly include glucuronidation, acetylcysteine or cysteine conjugation, methylation, acetylation, and sulphation), and associated combination reactions.The integrated analytical strategy was successfully used to characterise the prototype alkaloids and their metabolites of CKI in vivo, and the results laying a foundation for further study its pharmacodynamic substances.

Diterpenoids from Streptomyces: Structures, Biosyntheses and Bioactivities.

Bacteria, especially Streptomyces spp., have emerged as a rich source for natural diterpenoids with diverse structures and broad bioactivities. Here, we review diterpenoids biosynthesized by Streptomyces, with an emphasis on their structures, biosyntheses, and bioactivities. Although diterpenoids from Streptomyces are relatively rare compared to those from plants and fungi, their novel skeletons, biosyntheses and bioactivities present opportunities for discovering new drugs, enzyme mechanisms, and applications in biocatalysis and metabolic pathway engineering.

Development of a New Recombineering System for Agrobacterium Species.

The discovery of new and efficient genetic engineering technologies for Agrobacterium will broaden the capacity for fundamental research on this genus and its utilization as a transgenic vehicle. In this study, we aim to develop an efficient recombineering system for Agrobacterium species. We examined isolates of Agrobacterium and the closely related genus Rhizobium to identify pairs of ET-like recombinases that would aid in the recombineering of Agrobacterium species. Four pairs of ET-like recombinases, named RecETh1h2h3h4AGROB6, RecETh1h2P3RHI597, RecETRHI145, and RecEThRHI483, were identified in Agrobacterium tumefaciens strain B6, Rhizobium leguminosarum bv. trifolii WSM597, Rhizobium sp. strain LC145, and Rhizobium sp. strain Root483D2, respectively. Eight more candidate recombineering systems were generated by combining the new ET-like recombinases with Redγ or Pluγ. The PluγETRHI145 system, the RecETh1h2h3h4AGROB6 system, and the PluγEThRHI483 system were determined to be the most efficient recombineering systems for the type strains A. tumefaciens C58, A. tumefaciens EHA105, and Rhizobium rhizogenes NBRC 13257, respectively. The utility of these systems was demonstrated by knocking out the istB-istA fusion gene in C58, the celI gene in EHA105, and the 3'-to-5' exonuclease gene and endoglucanase gene in NBRC 13257. Our work provides an effective genetic manipulation strategy for Agrobacterium species. IMPORTANCEAgrobacterium is a powerful transgenic vehicle for the genetic manipulation of numerous plant and fungal species and even animal cells. In addition to improving the utility of Agrobacterium as a transgenic vehicle, genetic engineering tools are important for revealing crucial components that are functionally involved in transfer DNA (T-DNA) translocation events. This work developed an efficient and versatile recombineering system for Agrobacterium. The successful genome modification of Agrobacterium strains revealed that this new recombineering system could be used for the genetic engineering of Agrobacterium.

Isolation, complete genome sequencing and in silico genome mining of Burkholderia for secondary metabolites.

Recent years, Burkholderia species have emerged as a new source of natural products (NPs) with increasing attractions. Genome mining suggests the Burkholderia genomes include many natural product biosynthetic gene clusters (BGCs) which are new targets for drug discovery. In order to collect more Burkholderia, here, a strain S-53 was isolated from the soil samples on a mountain area in Changde, P.R. China and verified by comparative genetic analysis to belong to Burkholderia. The complete genome of Burkholderia strain S-53 is 8.2 Mbps in size with an average G + C content of 66.35%. Its taxonomy was both characterized by 16S rRNA- and whole genome-based phylogenetic trees. Bioinformatic prediction in silico revealed it has a total of 15 NP BGCs, some of which may encode unknown products. It is expectable that availability of these BGCs will speed up the identification of new secondary metabolites from Burkholderia and help us understand how sophisticated BGC regulation works.

RedEx: a method for seamless DNA insertion and deletion in large multimodular polyketide synthase gene clusters.

Biosynthesis reprograming is an important way to diversify chemical structures. The large repetitive DNA sequences existing in polyketide synthase genes make seamless DNA manipulation of the polyketide biosynthetic gene clusters extremely challenging. In this study, to replace the ethyl group attached to the C-21 of the macrolide insecticide spinosad with a butenyl group by refactoring the 79-kb gene cluster, we developed a RedEx method by combining Redαß mediated linear-circular homologous recombination, ccdB counterselection and exonuclease mediated in vitro annealing to insert an exogenous extension module in the polyketide synthase gene without any extra sequence. RedEx was also applied for seamless deletion of the rhamnose 3'-O-methyltransferase gene in the spinosad gene cluster to produce rhamnosyl-3'-desmethyl derivatives. The advantages of RedEx in seamless mutagenesis will facilitate rational design of complex DNA sequences for diverse purposes.

Discovery of recombinases enables genome mining of cryptic biosynthetic gene clusters in Burkholderiales species.

Bacterial genomes encode numerous cryptic biosynthetic gene clusters (BGCs) that represent a largely untapped source of drugs or pesticides. Mining of the cryptic products is limited by the unavailability of streamlined genetic tools in native producers. Precise genome engineering using bacteriophage recombinases is particularly useful for genome mining. However, recombinases are usually host-specific. The genome-guided discovery of novel recombinases and their transient expression could boost cryptic BGC mining. Herein, we reported a genetic system employing Red recombinases from Burkholderiales strain DSM 7029 for efficient genome engineering in several Burkholderiales species that currently lack effective genetic tools. Using specialized recombinases-assisted in situ insertion of functional promoters, we successfully mined five cryptic nonribosomal peptide synthetase/polyketide synthase BGCs, two of which were silent. Two classes of lipopeptides, glidopeptins and rhizomides, were identified through extensive spectroscopic characterization. This recombinase expression strategy offers utility within other bacteria species, allowing bioprospecting for potentially scalable discovery of novel metabolites with attractive bioactivities.

Sustainable management of cadmium-contaminated soils as affected by exogenous application of nutrients: A review.

Cadmium (Cd) pollution in arable land is of great concern as it impairs plant growth and further threats human health via food-chain. Exogenous supplementation of nutrients is an environmentally-friendly, cost-effective, convenient and feasible strategy for regulating Cd uptake, transport and accumulation in plants. To sustain Cd-contaminated soils management, on the one hand, a low level of the Cd-contaminated soil is expected to cultivate crops with decreased Cd accumulation as affected by exogenous nutrients application, on another hand, a high level of the Cd-contaminated soil is suggested to cultivate phytoextraction plants with increased Cd accumulation as affected by exogenous nutrients application. Nevertheless, effects of nutrients on Cd accumulation in plants are still ambiguous. Thus, data of Cd accumulation in shoots of plants as affected by exogenous application of nutrients were collected from previously published articles between 2005 and 2021 in the present study. According to the data, exogenous supply of calcium (Ca), magnesium (Mg), iron (Fe), manganese (Mn) and silicon (Si) to a larger extent decrease Cd amounts in shoots of plants. By contrast, exogenous nitrogen (N), and deficient Ca, Mg and Fe supply have a great possibility to increase Cd amounts in shoots of plants. Although exogenous application of phosphorus (P), sulfur (S), potassium (K), zinc (Zn) and selenium (Se) have a great opportunity to increase biomass, they show different effects on Cd concentrations. As a result, the odds are even for increasing and decreasing Cd amounts in shoots of plants. Taken together, exogenous application of Ca, Mg, Fe, Mn and Si might decrease Cd accumulation in plants that are recommended for crops production. Exogenous N and deficient Ca, Mg and Fe supply might increase Cd accumulation in plants that are recommended for phytoextraction plants. Exogenous application of P, S, K, Zn and Se have half a chance to increase or decrease Cd accumulation in plants. Therefore, dosages, forms and species should be taken into account when exogenous P, S, K, Zn and Se are added.

Genome Mining of Pseudomonas Species: Diversity and Evolution of Metabolic and Biosynthetic Potential.

Microbial genome sequencing has uncovered a myriad of natural products (NPs) that have yet to be explored. Bacteria in the genus Pseudomonas serve as pathogens, plant growth promoters, and therapeutically, industrially, and environmentally important microorganisms. Though most species of Pseudomonas have a large number of NP biosynthetic gene clusters (BGCs) in their genomes, it is difficult to link many of these BGCs with products under current laboratory conditions. In order to gain new insights into the diversity, distribution, and evolution of these BGCs in Pseudomonas for the discovery of unexplored NPs, we applied several bioinformatic programming approaches to characterize BGCs from Pseudomonas reference genome sequences available in public databases along with phylogenetic and genomic comparison. Our research revealed that most BGCs in the genomes of Pseudomonas species have a high diversity for NPs at the species and subspecies levels and built the correlation of species with BGC taxonomic ranges. These data will pave the way for the algorithmic detection of species- and subspecies-specific pathways for NP development.

PB-10, a thiazolo[4,5-d] pyrimidine derivative, targets p21-activated kinase 4 in human colorectal cancer cells.

Targeting p21-activated kinase 4 (PAK4) is a potential therapeutic strategy against human colorectal cancer (CRC). In this study, we synthesized a series of novel thiazolo[4,5-d]pyrimidine derivatives (PB-1-12) and identified PB-10 (PAK4 IC50 = 15.12 µM) as a potential and potent PAK4 inhibitor. Our results showed that PB-10 significantly suppressed the proliferation and colony formation of human CRC cells. PB-10 also arrested HCT-116 CRC cells at sub G0/G1 phase while promoting the expression of proapoptotic proteins. In addition, PB-10 inhibited migration, invasion, and adhesion as well as the PAK4 downstream signaling pathway in HCT-116 cells. Molecular docking analysis showed possible binding modes between PB-10 and PAK4. Our study provides a novel compound that may block the PAK4 signaling in CRC cells.

Aggregation behavior of aqu/nC60 produced via extended mixing: Influence of sunlight and agitation intensity.

Aggregation of C60, as an important process governing its mobility and toxicity, has been quantitatively investigated. However, effects of sunlight and agitation intensity on the aggregation behavior of aqu/nC60 produced via extended mixing, have not been clarified. Therefore, in the present study, the aggregation behavior of aqu/nC60 produced at 500 and 800 rpm in the absence and presence of sunlight was investigated. Aggregation with increasing concentrations could be accelerated, while changes of Zave and zeta potential were not obvious. Critical coagulation concentrations (CCCs) of aqu/nC60 obtained at 800 rpm in the absence/presence of sunlight and that at 500 rpm under sunlight were 330, 205 and 170 mM NaCl, and 10.0, 2.6 and 3.1 mM CaCl2, respectively. These CCCs indicated that the aqu/nC60 prepared by the extended mixing were more stable than those produced by other methods. Salt-induced aggregation occurred more easily for aqu/nC60 formed under sunlight than that formed in the dark. Extra surface oxidation induced by high agitation intensity remarkably increased the stability of aqu/nC60 in NaCl solutions. In contrast, in CaCl2 solutions, aqu/nC60 formed at high agitation intensity had similar stability or even inadequate stability to that obtained at low agitation intensity due to the charge neutralization and cross-link bridging.

Biosynthesis of polyketides by trans-AT polyketide synthases in Burkholderiales.

Widely used as drugs and agrochemicals, polyketides are a family of bioactive natural products, with diverse structures and functions. Polyketides are produced by megaenzymes termed as polyketide synthases (PKSs). PKS biosynthetic pathways are divided into the cis-AT PKSs and trans-AT PKSs; a division based mainly on the absence of an acyltransferase (AT) domain in the trans-AT PKS modules. In trans-AT biosynthesis, the AT activity is contributed via one or several independent proteins, and there are few other characteristics that distinguish trans-AT PKSs from cis-AT PKSs, especially in the formation of the ß-branch. The trans-AT PKSs constitute a major PKS pathway, and many are found in Burkholderia species, which are prevalent in the environment and prolific sources of polyketides. This review summarizes studies from 1973 to 2017 on the biosynthesis of natural products by trans-AT PKSs from Burkholderia species.

Longitudinal relations between future planning and adolescents' academic achievement in China.

INTRODUCTION: Planning for the future is important for adolescents' development and academic adaptation. Most prior research has focused primarily on the effects of future planning on adolescents' academic achievement, and there is a dearth of literature examining the effects of adolescents' academic achievement on their future planning. The current study examined the longitudinal reciprocal relations between adolescents' future planning and academic achievement in China. METHODS: The study sample consisted of 775 Chinese junior high school students (391 boys, 384 girls; Mage = 13.38 years, SD = 0.89). Future planning and academic achievement were measured at three time points that were equally spaced by a 6-month lag. Path analyses with cross-lagged effects were used to examine the longitudinal reciprocal relations between adolescents' future planning and academic achievement. RESULTS: The associations between future educational planning and academic achievement were reciprocal. Future occupational commitment predicted adolescents' academic achievement, and academic achievement predicted adolescents' affects concerning future occupation. However, there was no significant association between future occupational exploration and academic achievement. Moreover, these patterns of longitudinal relations applied equally to boys and girls, and younger and older adolescents. CONCLUSIONS: The reciprocal relations between future planning processes and academic achievement differed across domains (e.g., educational and occupational domains). These findings suggest that future planning may be a protective factor for improving adolescents' academic achievement, and high academic achievement may also be beneficial for Chinese adolescents' future planning.