Horizontally Transferred Salivary Protein Promotes Insect Feeding by Suppressing Ferredoxin-Mediated Plant Defenses.

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.

Dissection of the Pearl of Csaba pedigree identifies key genomic segments related to early ripening in grape.

Pearl of Csaba (PC) is a valuable backbone parent for early-ripening grapevine (Vitis vinifera) breeding, from which many excellent early ripening varieties have been bred. However, the genetic basis of the stable inheritance of its early ripening trait remains largely unknown. Here, the pedigree, consisting of 40 varieties derived from PC, was re-sequenced for an average depth of ∼30×. Combined with the resequencing data of 24 other late-ripening varieties, 5,795,881 high-quality single nucleotide polymorphisms (SNPs) were identified following a strict filtering pipeline. The population genetic analysis showed that these varieties could be distinguished clearly, and the pedigree was characterized by lower nucleotide diversity and stronger linkage disequilibrium than the non-pedigree varieties. The conserved haplotypes (CHs) transmitted in the pedigree were obtained via identity-by-descent analysis. Subsequently, the key genomic segments were identified based on the combination analysis of haplotypes, selective signatures, known ripening-related quantitative trait loci (QTLs), and transcriptomic data. The results demonstrated that varieties with a superior haplotype, H1, significantly (one-way ANOVA, P < 0.001) exhibited early grapevine berry development. Further analyses indicated that H1 encompassed VIT_16s0039g00720 encoding a folate/biopterin transporter protein (VvFBT) with a missense mutation. VvFBT was specifically and highly expressed during grapevine berry development, particularly at veraison. Exogenous folate treatment advanced the veraison of "Kyoho". This work uncovered core haplotypes and genomic segments related to the early ripening trait of PC and provided an important reference for the molecular breeding of early-ripening grapevine varieties.

Effect of apolipoprotein E ε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD.

BACKGROUND: We investigated the effects of apolipoprotein E (APOE) ε4 and its interactions with sociodemographic characteristics on cognitive measures in South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD). METHODS: Linear regression was used to assess the association between APOE ε4 and global- and domain-specific cognitive function in 2563 participants (mean age 69.6 ± 7.3 years; 53% female). Effect modification by age, sex, and education were explored using interaction terms and subgroup analyses. RESULTS: APOE ε4 was inversely associated with most cognitive measures (p < 0.05). This association was stronger with advancing age for the Hindi Mental State Examination (HMSE) score (ßε4×age = -0.44, p = 0.03), orientation (ßε4×age = -0.07, p = 0.01), and language/fluency (ßε4×age = -0.07, p = 0.01), as well as in females for memory (ßε4×male = 0.17, p = 0.02) and language/fluency (ßε4×male = 0.12, p = 0.03). DISCUSSION: APOE Îµ4 is associated with lower cognitive function in South Asians from India, with a more pronounced impact observed in females and older individuals. HIGHLIGHTS: APOE Îµ4 carriers had lower global and domain-specific cognitive performance. Females and older individuals may be more susceptible to ε4 effects. For most cognitive measures, there was no interaction between ε4 and education.

A comparative cadaveric study for percutaneous scaphoid fixation: robotic vs freehand.

PURPOSES: To compare the robotic-assisted and the traditional freehand percutaneous scaphoid fixation in number of guidewire attempts, duration of fluoroscopy time, amount of radiation dose, and screw centrality. METHODS: Twenty cadaveric specimens were randomized into either the robotic or freehand group. The scaphoids in both groups were fixed by either the same attending or resident from our hand surgery department. The operation duration, amount of radiation from intraoperative fluoroscopy, total fluoroscopy time, and the number of guidewire attempts were documented and compared. Postoperatively, all the specimens had a computed tomography (CT) scan performed, and the difference in the final position of the screw and the central axis of the scaphoid was examined. RESULTS: In the robotic group, all the guide wires were satisfactorily positioned within a single attempt, while the median number of attempts in the traditional freehand group was 18 (quaternion 14-65). This also meant that the surgeon in the robotic group experienced significantly lower radiation exposure dose and time as compared to the freehand group. There were no significant differences in the final screw position as compared to the central axis of the scaphoid in both groups. Although there was no difference in surgeon performance in the robotic group, the operative time for the attending was significantly lower as compared to the resident in the freehand group. CONCLUSION: Robotic-assisted surgery for scaphoid fracture fixation is superior to the traditional freehand method as it facilitates accurate screw placement with lower radiation exposure and fewer guide wire attempts.

Comparative Analysis of Six Complete Plastomes of Tripterospermum spp.

The Tripterospermum, comprising 34 species, is a genus of Gentianaceae. Members of Tripterospermum are mostly perennial, entwined herbs with high medicinal value and rich in iridoids, xanthones, flavonoids, and triterpenes. However, our inadequate understanding of the differences in the plastid genome sequences of Tripterospermum species has severely hindered the study of their evolution and phylogeny. Therefore, we first analyzed the 86 Gentianae plastid genomes to explore the phylogenetic relationships within the Gentianae subfamily where Tripterospermum is located. Then, we analyzed six plastid genomes of Tripterospermum, including two newly sequenced plastid genomes and four previously published plastid genomes, to explore the plastid genomes' evolution and phylogenetic relationships in the genus Tripterospermum. The Tripterospermum plastomes have a quadripartite structure and are between 150,929 and 151,350 bp in size. The plastomes of Tripterospermum encoding 134 genes were detected, including 86 protein-coding genes (CDS), 37 transfer RNA (tRNA) genes, eight ribosomal RNA (rRNA) genes, and three pseudogenes (infA, rps19, and ycf1). The result of the comparison shows that the Tripterospermum plastomes are very conserved, with the total plastome GC content ranging from 37.70% to 37.79%. In repeat sequence analysis, the number of single nucleotide repeats (A/T) varies among the six Tripterospermum species, and the identified main long repeat types are forward and palindromic repeats. The degree of conservation is higher at the SC/IR boundary. The regions with the highest divergence in the CDS and the intergenic region (IGS) are psaI and rrn4.5-rrn5, respectively. The average pi of the CDS and the IGS are only 0.071% and 0.232%, respectively, indicating that the Tripterospermum plastomes are highly conserved. Phylogenetic analysis indicated that Gentianinae is divided into two clades, with Tripterospermum as a sister to Sinogeniana. Phylogenetic trees based on CDS and CDS + IGS combined matrices have strong support in Tripterospermum. These findings contribute to the elucidation of the plastid genome evolution of Tripterospermum and provide a foundation for further exploration and resource utilization within this genus.

Modular Access to meta-Substituted Benzenes via Mo-Catalyzed Intermolecular Deoxygenative Benzene Formation.

The substituted benzene derivatives are essential to organic synthesis, medicinal chemistry, and material science. However, the 1,3-di- and 1,3,5-trisubstituted benzenes are far less prevalent in small-molecule drugs than other substitution patterns, likely due to the lack of robust, efficient, and convenient synthetic methods. Here, we report a Mo-catalyzed intermolecular deoxygenative benzene-forming reaction of readily available ynones and allylic amines. A wide range of unsymmetric and unfunctionalized 1,3-di- and 1,3,5-trisubstituted benzenes were obtained in up to 88% yield by using a commercially available molybdenum catalyst. The synthetic potential of the method was further illustrated by synthetic transformations, a scale-up synthesis, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this benzene-forming process might proceed through a Mo-catalyzed aza-Michael addition/[1,5]-hydride shift/cyclization/aromatization cascade. This strategy not only provided a facile, robust, and modular approach to various meta-substituted benzene derivatives but also demonstrated the potential of molybdenum catalysis in the challenging intermolecular deoxygenative cross-coupling reactions.

Fusarium BP1 is a reader of H3K27 methylation.

Histone H3 lysine 27 methylation catalyzed by polycomb repressive complex 2 (PRC2) is conserved from fungi to humans and represses gene transcription. However, the mechanism for recognition of methylated H3K27 remains unclear, especially in fungi. Here, we found that the bromo-adjacent homology (BAH)-plant homeodomain (PHD) domain containing protein BAH-PHD protein 1 (BP1) is a reader of H3K27 methylation in the cereal fungal pathogen Fusarium graminearum. BP1 interacts with the core PRC2 component Suz12 and directly binds methylated H3K27. BP1 is distributed in a subset of genomic regions marked by H3K27me3 and co-represses gene transcription. The BP1 deletion mutant shows identical phenotypes on mycelial growth and virulence, as well as similar expression profiles of secondary metabolite genes to the strain lacking the H3K27 methyltransferase Kmt6. More importantly, BP1 can directly bind DNA through its PHD finger, which might increase nucleosome residence and subsequently reinforce transcriptional repression in H3K27me3-marked target regions. A phylogenetic analysis showed that BP1 orthologs are mainly conserved in fungi. Overall, our findings provide novel insights into the mechanism by which PRC2 mediates gene repression in fungi, which is distinct from the PRC1-PRC2 system in plants and mammals.

Portfolio use in postgraduate medical education: a systematic scoping review.

BACKGROUND: Portfolios are increasingly commonplace in postgraduate medical education. However, poor understanding of and variations in their content, quality, and structure have hindered their use across different settings, thus dampening their efficacy. METHODS: This systematic scoping review on portfolios in postgraduate medical education utilized Krishna's Systematic Evidence Based Approach (SEBA). Braun and Clarke's thematic analysis and Hsieh and Shannon's directed content analysis were independently used to evaluate the data. RESULTS: In total, 12 313 abstracts were obtained, and 76 full-text articles included. Six key themes/categories were identified: (i) portfolio definitions and functions, (ii) platforms, (iii) design, (iv) implementation, (v) use in assessments, and (vi) evaluations of their usage. CONCLUSIONS: Portfolios allow for better appreciation and assessments of knowledge, skills, and attitudes in time-, learner-, and context-specific competencies through the establishment of smaller micro-competencies and micro-credentialling. Organized into three broad stages-development, implementation, and improvement-a six-step framework for optimizing and instituting portfolios in postgraduate medical education is offered.

[Therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation on respiratory failure in preterm infants with a gestational age of 28-34 weeks: a prospective randomized controlled study]. / 容量保证的高频振荡通气模式对胎龄28~34å‘¨æ—©äº§å„¿å‘¼å¸è¡°ç«­ç–—æ•ˆçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation (HFOV-VG) versus conventional mechanical ventilation (CMV) in the treatment of preterm infants with respiratory failure. METHODS: A prospective study was conducted on 112 preterm infants with respiratory failure (a gestational age of 28-34 weeks) who were admitted to the Department of Neonatology, Jiangyin Hospital Affiliated to Medical School of Southeast University, from October 2018 to December 2022. The infants were randomly divided into an HFOV-VG group (44 infants) and a CMV group (68 infants) using the coin tossing method based on the mode of mechanical ventilation. The therapeutic efficacy was compared between the two groups. RESULTS: After 24 hours of treatment, both the HFOV-VG and CMV groups showed significant improvements in arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, and partial pressure of oxygen/fractional concentration of inspired oxygen ratio (P<0.05), and the HFOV-VG group had better improvements than the CMV group (P<0.05). There were no significant differences between the two groups in the incidence rate of complications, 28-day mortality rate, and length of hospital stay (P>0.05), but the HFOV-VG group had a significantly shorter duration of invasive mechanical ventilation than the CMV group (P<0.05). The follow-up at the corrected age of 6 months showed that there were no significant differences between the two groups in the scores of developmental quotient, gross motor function, fine motor function, adaptive ability, language, and social behavior in the Pediatric Neuropsychological Development Scale (P>0.05). CONCLUSIONS: Compared with CMV mode, HFOV-VG mode improves partial pressure of oxygen and promotes carbon dioxide elimination, thereby enhancing oxygenation and shortening the duration of mechanical ventilation in preterm infants with respiratory failure, while it has no significant impact on short-term neurobehavioral development in these infants.

Genome-wide identification and expression analysis of JmjC domain-containing genes in grape under MTA treatment.

Histone demethylases containing the JmjC domain play an extremely important role in maintaining the homeostasis of histone methylation and are closely related to plant growth and development. Currently, the JmjC domain-containing proteins have been reported in many species; however, they have not been systematically studied in grapes. In this paper, 21 VviJMJ gene family members were identified from the whole grape genome, and the VviJMJ genes were classified into five subfamilies: KDM3, KDM4, KDM5, JMJD6, and JMJ-only based on the phylogenetic relationship and structural features of Arabidopsis and grape. After that, the conserved sites of VviJMJ genes were revealed by protein sequence analysis. In addition, chromosomal localization and gene structure analysis revealed the heterogeneous distribution of VviJMJ genes on grape chromosomes and the structural features of VviJMJ genes, respectively. Analysis of promoter cis-acting elements demonstrated numerous hormone, light, and stress response elements in the promoter region of the VviJMJ genes. Subsequently, the grape fruit was treated with MTA (an H3K4 methylation inhibitor), which significantly resulted in the early ripening of grape fruits. The qRT-PCR analysis showed that VviJMJ genes (except VviJMJ13c) had different expression patterns during grape fruit development. The expression of VviJMJ genes in the treatment group was significantly higher than that in the control group. The results indicate that VviJMJ genes are closely related to grape fruit ripening.

Complete genome analysis of a novel iflavirus from the spotted lanternfly Lycorma delicatula.

The spotted lanternfly (Lycorma delicatula) is an invasive pest that causes serious economic losses in fruit and wood production. Here, we identified a novel iflavirus named "Lycorma delicatula iflavirus 1" (LDIV1), in a spotted lanternfly. The full genome sequence of LDIV1 is 10,222 nt in length and encodes a polyprotein containing a picornavirus capsid-protein-domain-like domain, a cricket paralysis virus capsid superfamily domain, an RNA helicase domain, a peptidase C3 superfamily domain, and an RNA-dependent RNA polymerase (RdRp) domain. LDIV1 replicates in the host insect and activates small interfering RNA (siRNA)-based host antiviral immunity. Phylogenetic analysis demonstrated that LDIV1 is most closely related to an unspecified member of the order Picornavirales, with 61.7% sequence identity in the RdRp region and 57.6% sequence identity in the coat protein region, and thus meets the demarcation criteria for new species in the genus Iflavirus. To the best of our knowledge, LDIV1 is the first virus discovered in L. delicatula.

A comprehensive review of BET-targeting PROTACs for cancer therapy.

Targeted protein degradation using proteolysis-targeting chimeras (PROTACs) has emerged as an effective strategy for drug discovery, given their unique advantages over target protein inhibition. The bromodomain and extra-terminal (BET) family proteins play a key role in regulating oncogene expression and are considered attractive therapeutic targets for cancer therapy. Considering the therapeutic potential of BET proteins in cancer and the marked attractiveness of PROTACs, BET-targeting PROTACs have been extensively pursued. Recently, BET-targeting PROTACs based on new E3 ligases and novel strategies, such as light-activated, macrocyclic, folate-caged, aptamer-PROTAC conjugation, antibody-coupling, and autophagy-targeting strategies, have emerged. In the present review, we provide a comprehensive summary of advances in BET-targeting PROTACs.

The current scenario on anticancer activity of artemisinin metal complexes, hybrids, and dimers.

Cancer, the most significant cause of morbidity and mortality, has already posed a heavy burden on health care systems globally. In recent years, cancer treatment has made a significant breakthrough, but cancer cells inevitably acquire resistance, and the efficacy of the treatment is greatly reduced as the tumor progresses. To overcome the above issues, novel chemotherapeutics are needed urgently. Artemisinin and its derivatives-sesquiterpene lactone compounds possessing a unique peroxy bridge moiety-exhibit excellent safety and tolerability profiles. Mechanistically, artemisinin derivatives can promote cancer cell apoptosis, induce cell cycle arrest and autophagy, and inhibit cancer cell invasion and migration. Accordingly, artemisinin derivatives demonstrate promising anticancer efficacy both in vitro and in vivo, and even in clinical Phase I/II trials. The purpose of the present review article is to provide an emphasis on the current scenario (January 2017-January 2022) of artemisinin derivatives with potential anticancer activity, inclusive of artemisinin metal complexes, hybrids, and dimers. The structure-activity relationships and mechanisms of action are also discussed to facilitate the further rational design of more effective candidates.

Effects of 5.8 GHz microwave on hippocampal synaptic plasticity of rats.

OBJECTIVE: 5.8 GHz spectrum is gaining more attention in wireless technology. To explore the potential hazards, we investigated the effect of exposure to 5.8 GHz microwave on learning and memory ability of rats. Methods: Morris Water maze (MWM), Novel object recognition (NOR) and Fear conditioning test (FCT) were used to evaluate the ability of spatial and non-spatial memory of rats. The hippocampal morphology, the level of brain injury factors in serum and the mitochondrial membrane potential of hippocampal neurons was examined to evaluate the damage of hippocampal neurons. The density of dendritic spines, the ultrastructure of synapses and the level of PSD95, Synaptophysin, p-CREB and CREB were detected to evaluate the hippocampal synaptic plasticity. RESULTS: Compared with Sham group, there was no significant difference in the performance of ethology (in MWM, NOR, FCT) in Microwave 2 h group or Microwave 4 h group. The hippocampal morphology, the serum level of brain injury factors and the content of mitochondrial JC-1 monomer in Microwave 2 h group or Microwave 4 h group did not change obviously, compared with Sham group. The density of dendritic spines, the ultrastructure of synapse and the level of PSD95, Synaptophysin, p-CREB and CREB in hippocampus in Microwave 2 h group or Microwave 4 h group did not significantly change, compared with Sham group. CONCLUSION: Under this experimental condition, exposure to 5.8 GHz microwave could not affect the hippocampal synaptic plasticity of rats.

Effects of radiofrequency field from 5G communications on the spatial memory and emotionality in mice.

The rapid development of 5G network technology has gained much popularity as well as concerns about its adverse effects. In this study, we investigated the effects of 4.9 GHz (one of working frequencies of 5G communication) radiofrequency (RF) field on emotional behaviours and spatial memory in adult male mice. Open field test (OFT), tail suspension test (TST) and Y maze were used to evaluate anxiety, depression-like behaviour and spatial memory ability, respectively. It was found that the anxiety-like behaviour and spatial memory ability of mice did not change, but the depression-like behaviour was induced in mice after 4.9 GHz RF exposure. In addition, the number of neurons significantly reduced and the level of pyroptosis obviously increased in amygdala rather than hippocampus. These results suggested that 4.9 GHz RF exposure could induce depression-like behaviour, which might be associated with the neuronal pyroptosis in amygdala.

Genome-wide distribution and functions of the AAE complex in epigenetic regulation in Arabidopsis.

Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context. Previous studies have shown that a protein complex, the ASI1-AIPP1-EDM2 (AAE) complex, participates in polyadenylation regulation of several intronic heterochromatin-containing genes. However, the genome-wide functions of AAE are still unknown. Here, we show that the ASI1 and EDM2 mostly target the common genomic regions on a genome-wide level and preferentially interacts with genetic heterochromatin. Polyadenylation (poly(A) sequencing reveals that AAE complex has a substantial influence on poly(A) site usage of heterochromatin-containing genes, including not only intronic heterochromatin-containing genes but also the genes showing overlap with heterochromatin. Intriguingly, AAE is also involved in the alternative splicing regulation of a number of heterochromatin-overlapping genes, such as the disease resistance gene RPP4. We provided evidence that genic heterochromatin is indispensable for the recruitment of AAE in polyadenylation and splicing regulation. In addition to conferring RNA processing regulation at genic heterochromatin-containing genes, AAE also targets some transposable elements (TEs) outside of genes (including TEs sandwiched by genes and island TEs) for epigenetic silencing. Our results reveal new functions of AAE in RNA processing and epigenetic silencing, and thus represent important advances in epigenetic regulation.

[Application Test of the AI-Automatic Diagnostic System for Ki-67 in Breast Cancer].

OBJECTIVE: To study the different methods of artificial intelligence (AI)-assisted Ki-67 scoring of clinical invasive ductal carcinoma (IDC) of the breast and to compare the results. METHODS: A total of 100 diagnosed IDC cases were collected, including slides of HE staining and immunohistochemical Ki-67 staining and diagnosis results. The slides were scanned and turned into whole slide image (WSI), which were then scored with AI. There were two AI scoring methods. One was fully automatic counting by AI, which used the scoring system of Ki-67 automatic diagnosis to do counting with the whole image of WSI. The second method was semi-automatic AI counting, which required manual selection of areas for counting, and then relied on an intelligent microscope to conduct automatic counting. The diagnostic results of pathologists were taken as the results of pure manual counting. Then the Ki-67 scores obtained by manual counting, semi-automatic AI counting and automatic AI counting were pairwise compared. The Ki-67 scores obtained from the manual counting (pathological diagnosis results), semi-automatic AI and automatic AI counts were pair-wise compared and classified according to three levels of difference: difference ≤10%, difference of >10%-<30% and difference ≥30%. Intra-class correlation coefficient ( ICC) was used to evaluate the correlation. RESULTS: The automatic AI counting of Ki-67 takes 5-8 minutes per case, the semi-automatic AI counting takes 2-3 minutes per case, and the manual counting takes 1-3 minutes per case. When results of the two AI counting methods were compared, the difference in Ki-67 scores was all within 10% (100% of the total), and the ICC index being 0.992. The difference between manual counting and semi-automatic AI was less than 10% in 60 cases (60% of the total), between 10% and 30% in 37 cases (37% of the total), and more than 30% in only 3 cases (3% of the total), ICC index being 0.724. When comparing automatic AI with manual counting, 78 cases (78% of the total) had a difference of ≤10%, 17 cases (17% of the total) had a difference of between 10% and 30%, and 5 cases (5%) had a difference of ≥30%, the ICC index being 0.720. The ICC values showed that there was little difference between the results of the two AI counting methods, indicating good repeatability, but the repeatability between AI counting and manual counting was not particularly ideal. CONCLUSION: AI automatic counting has the advantage of requiring less manpower, for the pathologist is involved only for the verification of the diagnosis results at the end. However, the semi-automatic method is better suited to the diagnostic habits of pathologists and has a shorter turn-over time compared with that of the fully automatic AI counting method. Furthermore, in spite of its higher repeatability, AI counting, cannot serve as a full substitute for pathologists, but should instead be viewed as a powerful auxiliary tool.

[Determination of five saponins in Xuesaitong Dropping Pills by micellar electrokinetic chromatography and evaluation method of between-batch consistency].

The present study determined five saponins in Xuesaitong Dropping Pills(XDP) by micellar electrokinetic chromatography(MEKC), and evaluated between-batch consistency by MEKC fingerprints and similarity analysis. A background buffer was composed of 20 mmol·L~(-1) sodium tetraborate-20 mmol·L~(-1) boric acid solution(pH 8.5), 55 mmol·L~(-1) sodium dodecyl sulfate(SDS), 23 mmol·L~(-1) ß-cyclodextrin, and 13% isopropyl alcohol. All separations were performed at 25 ℃,20 kV and the detection wavelength was set at 203 nm. The separation channel was a fused silica capillary with a dimension of 75 µm I.D. and a total length of 50.2 cm(effective length of 40.0 cm). The contents of notoginsenoside R_1, and ginsenosides Rg_1, Re, Rb_1, Rd were determined with their quality control ranges set. The fingerprints of XDP were established and the between-batch consistency was evaluated by similarity analysis. The contents of five saponins from the 19 batches of XDP were stable in the fixed ranges. Statistical analysis was carried out on the results of multiple batches of samples, and the specific quality control ranges were recommended as follows: notoginsenoside R_1 21.92-34.16 mg·g~(-1), ginsenosides Rg_1 83.54-131.78 mg·g~(-1), ginsenosides Re 13.58-19.82 mg·g~(-1), ginsenosides Rb_1 89.40-129.90 mg·g~(-1), and ginsenosides Rd 22.34-35.67 mg·g~(-1). Eleven characteristic peaks were identified in the fingerprints. Five peaks, notoginsenoside R_1 and ginsenosides Rg_1, Re, Rb_1, Rd, were identified with reference standards. The similarities of the 19 batches of samples were all above 0.988, indicating good between-batch consistency. This method is green and simple, and can be used for the quantitative determination and quality evaluation of XDP. It can also provide references for the quality control of other Chinese medicinal dripping pills.

[Identification of critical influencing factors in dropping process of Xuesaitong Dropping Pills].

With the dropping process of Xuesaitong Dropping Pills(XDP) as the study object, critical factors affecting the quality indicators of pill pass rate, average weight of drop pills and roundness were screened out, so as to deepen the understanding of the dropping process. The critical process units, critical quality attributes and potential critical process influencing factors of XDP were determined by risk analysis and prior knowledge, and then the critical influencing factors were screened out by Plackett-Burman design. First, according to the risk assessment, the critical technique of XDP preparation process was dropping, and then the critical quality attributes of dropping process were pill pass rate, average weight of drop pills and roundness. Then, according to fishbone diagram and failure mode and effects analysis(FMEA), potential critical influencing factors were determined as flow rate, matrix ratio, solid-liquid ratio, feed-liquid temperature, top temperature of condensate, bottom temperature of condensate and dropping distance. Finally, among these seven potential factors, the critical influencing factors were determined as material liquid ratio, dropping distance, top temperature of condensate, bottom temperature of condensate. This study revealed the potential of Plackett-Burman design in screening and understanding the influence of selected factors on XDP dropping process, which could provide a reference for studying the dropping process.

Computational Design of Enhanced Enantioselectivity in Chiral Phosphoric Acid-Catalyzed Oxidative Desymmetrization of 1,3-Diol Acetals.

A general method for the highly enantioselective desymmetrization of 2-alkyl-substituted 1,3-diols is presented. A combination of computational and experimental studies has been utilized to understand the origin of the stereocontrol of oxidative desymmetrization of 1,3-diol benzylideneacetals. DFT calculations demonstrate that the acetal protecting group is highly influential for high enantioselectivity, and a simple but effective new protecting group has been designed. The desymmetrization reactions proceed with high enantioselectivity for a variety of substrates. Moreover, the reaction conditions are also shown to be effective for desymmetrization of 2,2-dialkyl-substituted 1,3-diols, which provides chiral products bearing acyclic all-carbon quaternary stereocenters. The method has been applied to the formal synthesis of indoline alkaloids.