Platycodon grandiflorum saponins: Ionic liquid-ultrasound-assisted extraction, antioxidant, whitening, and antiaging activity.

This study explored the use of ionic liquid-ultrasound (ILU)-assisted extraction to enhance the extraction rate of Platycodon grandiflorum saponins (PGSs), and the content, extraction mechanism, antioxidant activity, whitening, and antiaging activity of PGSs prepared using ILU, ultrasound-water, thermal reflux-ethanol, and cellulase hydrolysis were compared. The ILU method particularly disrupted the cell wall, improved PGS extraction efficiency, and yielded a high total saponin content of 1.45 ± 0.02 mg/g. Five monomeric saponins were identified, with platycodin D being the most abundant at 1.357 mg/g. PGSs displayed excellent in vitro antioxidant activity and exhibited inhibitory effects on tyrosinase, elastase, and hyaluronidase. The results suggest that PGSs may have broad antioxidant, skin-whitening, and antiaging potential to a large extent. Overall, this study provided valuable insights into the extraction, identification, and bioactivities of PGSs, which could serve as a reference for future development and application of these compounds in the functional foods industry.

Hope experiences in parents of children with cancer: A qualitative meta-synthesis.

PURPOSE: To synthesise qualitative research on the parental hope experiences for children with cancer and identify the levels of parental hope experiences and psychosocial adjustment during cancer events. METHODS: Five electronic databases (Cochrane Library, PubMed, Embase, Web of Science, and CINAHL) and three Chinese databases (CNKI, Wanfang, and VIP) were used to retrieve qualitative studies on the hope experiences of parents of children with cancer from inception to February 2023. The Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) was used to assess the methodological quality of the included studies. Data were synthesised using a thematic analysis. RESULTS: Four analytical themes were identified: the process and way hope exists, sources of hope, positive effects of hope, and obstacles to hope maintenance. CONCLUSIONS: Maintaining hope is crucial for parents who are caring for their children with cancer. There are different sources of hope, and targeted interventions can enhance the experience of hope for parents of children with cancer. Families, healthcare providers, and society should pay more attention to the parents of children with cancer and provide them with psychological, social, and financial support to improve their level of hope and quality of care.

Inclusion of reeling wastewater-derived sericin peptides in high-protein nutrition bars for antihardening and storage stability.

The utilization of agroindustrial wastes to enrich food protein resources and the exploration of their broader applications are crucial for addressing the food crisis and achieving sustainable development goals. In this study, reeling wastewater-derived sericin was hydrolyzed using papain and trypsin to prepare sericin peptide (SRP) and was used as an antihardening ingredient of high-protein nutrition bars (HPNBs). The mechanism of the antihardening effect of SRP was elucidated by investigating the content of advanced glycation end products and protein oxidation products (carbonyl and free sulfhydryl), and the molecular weight change of HPNBs during storage before and after the addition of SRP. Our results confirmed the fortification of HPNBs with SRP, which is beneficial for the promotion and expansion of sericin applications in the food industry, with positive implications for the rational utilization of protein resources and the enrichment of food protein sources.

Effects of Clip Anchoring on Preventing Migration of Fully Covered Self-Expandable Metal Stent in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Fully covered self-expandable metal stents (FCSEMSs) are commonly placed in patients with biliary stricture during endoscopic retrograde cholangiopancreatography (ERCP). However, up to 40% of migration has been reported, resulting in treatment failure or the requirement for further intervention. Here, we aimed to investigate the effects of metal clip anchoring on preventing the migration of FCSEMS. METHODS: Consecutive patients requiring placement of FCSEMS were included in this multicenter randomized trial. The enrolled patients were randomly assigned in a 1:1 ratio to receive clip anchoring (clip group) or not (control group). The primary outcome was the migration rate at 6 months after stent insertion. The secondary outcomes were the rates of proximal and distal migration and stent-related adverse events. The analysis followed the intention-to-treat principle. RESULTS: From February 2020 to November 2022, 180 patients with biliary stricture were enrolled, with 90 in each group. The baseline characteristics were comparable between the 2 groups. The overall rate of stent migration at 6 months was significantly lower in the clip group compared with the control group (16.7% vs 30.0%, P = 0.030). The proximal and distal migration rates were similar in the 2 groups (2.2% vs 5.6%, P = 0.205; 14.4% vs 22.2%, P = 0.070). Notably, none of the patients (0/8) who received 2 or more clips experienced stent migration. There were no significant differences in stent-related adverse events between the 2 groups. DISCUSSION: Our data suggest that clip-assisted anchoring is an effective and safe method for preventing migration of FCSEMS without increasing the adverse events.

Carbon Dot-Mediated Photodynamic Treatment Improves the Quality Attributes of Post-Harvest Goji Berries (Lycium barbarum L.) via Regulating the Antioxidant System.

Carbon dots (CDs) have been proposed as photosensitizers in photodynamic treatment (PDT), owing to their excellent biological attributes and budding fruit preservation applications. In the present study, CDs (4.66 nm) were synthesized for photodynamic treatment to improve the quality attributes in post-harvest goji berries. The prepared CDs extended the storage time of the post-harvest goji berries by 9 d. The CD-mediated PDT postponed the hardness and decay index loss, reduced the formation of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2•-) significantly, and delayed the loss of vital nutrients like the total protein, phenols, and flavonoids. The CD-mediated PDT improved the catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), phenylalanine ammonia-lyase (PAL), glutathione reductase (GR), and superoxide dismutase (SOD) activities, but did not improve polyphenol oxidase (PPO) activity. In addition, The CD-mediated PDT induced the accumulation of ascorbic acid (ASA) and glutathione (GSH). Overall, a CD-mediated PDT could extend the storage time and augment the quality attributes in post-harvest fresh goji berries by regulating the antioxidant system.

Effects of different chemical modifications on physicochemical and antioxidation properties of Lycium barbarum seed dreg polysaccharides.

Recent studies have witnessed that chemical modification can improve the physicochemical and functional properties of plants' polysaccharides. Herein, we modified the natural Lycium barbarum seed dreg polysaccharides (LBSDPs) by sulfation (S-LBSDPs), phosphorylation (P-LBSDPs), and carboxymethylation (C-LBSDPs), and evaluated the chemical composition and antioxidant activity of their derivatives. Natural polysaccharides and their derivatives exhibited typical polysaccharide absorption peaks and characteristic group absorption peaks in FT-IR spectra along with maximum UV absorption. After modification, the total sugar and protein contents of the derivatives were decreased, whereas the uronic acid content was increased. Among the three derivatives, sulfated polysaccharides displayed excellent thermal stability. S-LBSDP and P-LBSDP showed the highest ABTS radical scavenging and reducing power while S-LBSDPs and C-LBSDPs showed better DPPH radical scavenging effect, and P-LBSDPs showed considerable Fe2+ chelating ability. Our data indicate that chemical modifications can impart a positive effect on the antioxidant potential of plant-derived polysaccharides.

Physicochemical and functional properties of carboxymethylated insoluble dietary fiber of Lycium barbarum seed dreg.

Lycium barbarum seed dregs (LBSDs) were used for carboxymethyl modification, resulting in three degree of substitution samples (DS). Based on the substitution degree, samples were designated as low degree of substitution insoluble dietary fiber (L-IDF), medium degree of substitution insoluble dietary fiber (M-IDF) and high degree of substitution insoluble dietary fiber (H-IDF). Physicochemical and functional properties of IDFs were examined in relation to carboxymethylation degree. Infrared Fourier transform spectroscopy (FT-IR) confirmed the carboxymethyl group. According to the results, IDF, L-IDF, M-IDF, and H-IDF acquired higher enthalpy changes, and their thermal stability improved significantly. A higher DS resulted in an increase in hydration properties such as water retention capacity and water swelling capacity, as well as functional properties such as glucose adsorption capacity, nitrite ion adsorption capacity, and cholesterol adsorption capacity. As a result, carboxymethylation could effectively enhance the biological properties of L. barbarum seed dreg insoluble dietary fiber (LBSDIDF).

Lactate modulates RNA splicing to promote CTLA-4 expression in tumor-infiltrating regulatory T cells.

RNA splicing is involved in cancer initiation and progression, but how it influences host antitumor immunity in the metabolically abnormal tumor microenvironment (TME) remains unclear. Here, we demonstrate that lactate modulates Foxp3-dependent RNA splicing to maintain the phenotypic and functional status of tumor-infiltrating regulatory T (Treg) cells via CTLA-4. RNA splicing in Treg cells was correlated with the Treg cell signatures in the TME. Ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, maintained RNA-splicing-mediated CTLA-4 expression to control Treg cell function. Mechanistically, lactate promoted USP39-mediated RNA splicing to facilitate CTLA-4 expression in a Foxp3-dependent manner. Moreover, the efficiency of CTLA-4 RNA splicing was increased in tumor-infiltrating Treg cells from patients with colorectal cancer. These findings highlight the immunological relevance of RNA splicing in Treg cells and provide important insights into the environmental mechanism governing CTLA-4 expression in Treg cells.

Nursing students'experience of flipped classroom combined with problem-based learning in a paediatric nursing course: a qualitative study.

BACKGROUND: Problem-based learning (PBL) is a student-centred approach that triggers learning by presenting problems cenarios early in the learning process.Flipped classrooms have been used in various disciplines using various models.Pre-class e- learning in aflipped classrooms can enrich knowledge acquisition in PBL teaching. This study was conducted to explore nursing students'experience of flipped classroom combined with problem-based learning in a paediatric nursing course. METHOD: This descriptive qualitative study was conducted between January and June 2022.Semi-structured interviews were conducted with nursing students who were participated in flipped classrooms combined with PBL teaching in a paediatric nursing course at Soochow university in China. Nursing students were selected using a purposive sampling method until no new data were generated (n = 16). RESULTS: We identified ten sub-themes and four higher-order themes based on these sub-themes: (1)stimulating interest in learning and enhancing autonomous learning,(2)improving independent thinking and problem-solving skills,(3)cultivating team work spirit, and (4) gaining knowledge and improving skills.The findings of our research contribute to show the effectiveness of the flipped classroom combined with PBL in a paediatric nursing course. CONCLUSION: The flipped classroom combined with PBL in a paediatric nursing course can enhances communication and cooperation abilities among nursing students, promoting common progress and the comprehensive development of nursing students.

USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis.

The functional integrity of Tregs is interwoven with cellular metabolism; however, the mechanisms governing Treg metabolic programs remain elusive. Here, we identified that the deubiquitinase USP47 inhibited c-Myc translation mediated by the RNA N6-methyladenosine (m6A) reader YTHDF1 to maintain Treg metabolic and functional homeostasis. USP47 positively correlated with the tumor-infiltrating Treg signature in samples from patients with colorectal cancer and gastric cancer. USP47 ablation compromised Treg homeostasis and function in vivo, resulting in the development of inflammatory disorders, and boosted antitumor immune responses. USP47 deficiency in Tregs triggered the accumulation of the c-Myc protein and in turn exacerbated hyperglycolysis. Mechanistically, USP47 prevented YTHDF1 ubiquitination to attenuate the association of YTHDF1 with translation initiation machinery, thereby decreasing m6A-based c-Myc translation efficiency. Our findings reveal that USP47 directs m6A-dependent metabolic programs to orchestrate Treg homeostasis and suggest novel approaches for selective immune modulation in cancer and autoimmune diseases by targeting of USP47.

Enantioselective Total Syntheses of the Cephalotaxus Alkaloids (-)-Fortuneicyclidins A and B and (-)-Cephalotine B.

Fortuneicyclidins A and B are a pair of recently isolated Cephalotaxus alkaloids with an unprecedented rearranged polycyclic skeleton possessing multiple complex stereocenters and functionalization. In this work, highly stereocontrolled asymmetric total syntheses for title alkaloids were outlined. Key features include an underexplored Ir-catalyzed α-allylation of aldehyde to strategically install a vicinal N-substituted quaternary center and a tertiary stereocenter, Heck and RCM reactions to construct the critical polycyclic framework rapidly, two different tandem oxidation-transannular aldol cyclization processes, one through ozonolysis and another via Swern oxidation, to forge the last ring for fortuneicyclidins A and B, respectively. In this approach, the challenging C-2 hydroxyl group can be installed stereospecifically.

New classification system for radical rectal cancer surgery based on membrane anatomy.

BACKGROUND: Total mesorectal excision along the "holy plane" is the only radical surgery for rectal cancer, regardless of tumor size, localization or even tumor stage. However, according to the concept of membrane anatomy, multiple fascial spaces around the rectum could be used as the surgical plane to achieve radical resection. AIM: To propose a new membrane anatomical and staging-oriented classification system for tailoring the radicality during rectal cancer surgery. METHODS: A three-dimensional template of the member anatomy of the pelvis was established, and the existing anatomical nomenclatures were clarified by cadaveric dissection study and laparoscopic surgical observation. Then, we suggested a new and simple classification system for rectal cancer surgery. For simplification, the classification was based only on the lateral extent of resection. RESULTS: The fascia propria of the rectum, urogenital fascia, vesicohypogastric fascia and parietal fascia lie side by side around the rectum and form three spaces (medial, middle and lateral), and blood vessels and nerves are precisely positioned in the fascia or space. Three types of radical surgery for rectal cancer are described, as are a few subtypes that consider nerve preservation. The surgical planes of the proposed radical surgeries (types A, B and C) correspond exactly to the medial, middle, and lateral spaces, respectively. CONCLUSION: Three types of radical surgery can be precisely defined based on membrane anatomy, including nerve-sparing procedures. Our classification system may offer an optimal tool for tailoring rectal cancer surgery.

Enantioselective Total Synthesis of the Cephalotaxus Alkaloid (-)-Cephalotine A.

Cephalotine A, a recently isolated Cephalotaxus alkaloid, was first synthesized enantioselectively through three critical reactions. SmI2 -mediated radical cyclization of lactone and aldehyde to forge the final ring system, Chang's iridium-catalyzed C-H amidation to construct pyrrolidone stereoselectively, and Carreria's dual Ir/amine catalyzed allylation to install the vicinal tertiary stereocenters.

Individualized Positive End-expiratory Pressure on Postoperative Atelectasis in Patients with Obesity: A Randomized Controlled Clinical Trial.

BACKGROUND: Individualized positive end-expiratory pressure (PEEP) guided by dynamic compliance improves oxygenation and reduces postoperative atelectasis in nonobese patients. The authors hypothesized that dynamic compliance-guided PEEP could also reduce postoperative atelectasis in patients undergoing bariatric surgery. METHODS: Patients scheduled to undergo laparoscopic bariatric surgery were eligible. Dynamic compliance-guided PEEP titration was conducted in all patients using a downward approach. A recruitment maneuver (PEEP from 10 to 25 cm H2O at 5-cm H2O step every 30 s, with 15-cm H2O driving pressure) was conducted both before and after the titration. Patients were then randomized (1:1) to undergo surgery under dynamic compliance-guided PEEP (PEEP with highest dynamic compliance plus 2 cm H2O) or PEEP of 8 cm H2O. The primary outcome was postoperative atelectasis, as assessed with computed tomography at 60 to 90 min after extubation, and expressed as percentage to total lung tissue volume. Secondary outcomes included Pao2/inspiratory oxygen fraction (Fio2) and postoperative pulmonary complications. RESULTS: Forty patients (mean ± SD; 28 ± 7 yr of age; 25 females; average body mass index, 41.0 ± 4.7 kg/m2) were enrolled. Median PEEP with highest dynamic compliance during titration was 15 cm H2O (interquartile range, 13 to 17; range, 8 to 19) in the entire sample of 40 patients. The primary outcome of postoperative atelectasis (available in 19 patients in each group) was 13.1 ± 5.3% and 9.5 ± 4.3% in the PEEP of 8 cm H2O and dynamic compliance-guided PEEP groups, respectively (intergroup difference, 3.7%; 95% CI, 0.5 to 6.8%; P = 0.025). Pao2/Fio2 at 1 h after pneumoperitoneum was higher in the dynamic compliance-guided PEEP group (397 vs. 337 mmHg; group difference, 60; 95% CI, 9 to 111; P = 0.017) but did not differ between the two groups 30 min after extubation (359 vs. 375 mmHg; group difference, -17; 95% CI, -53 to 21; P = 0.183). The incidence of postoperative pulmonary complications was 4 of 20 in both groups. CONCLUSIONS: Postoperative atelectasis was lower in patients undergoing laparoscopic bariatric surgery under dynamic compliance-guided PEEP versus PEEP of 8 cm H2O. Postoperative Pao2/Fio2 did not differ between the two groups.

E2F family play important roles in tumorigenesis.

Tumors are serious threats to human health. The transcription factors are regarded as the potential targets for tumor treatment. As an important family of transcription factors, E2F family transcription factors (E2Fs) play vital roles in cell proliferation and regulation. However, the expression feature, gene functions, and molecular interactions of E2Fs in tumorigenesis are not clear. In this study, the transcriptome data, mutation data, and protein-protein interaction data of 10 high-incidence tumors in China from the TCGA database were integrated and analyzed to explore the expression, structure, function, mutation, and phylogenetic characteristics of E2Fs. The results showed that E2F1 and E2F7 were regularly upregulated in the tumor samples. Moreover, E2Fs participated in the regulation of the cell cycle, cell aging, and other signaling pathways. As an important regulator, E2F1 interacted with more proteins than other E2Fs. At the same time, the genetic mutation types of E2Fs varied in tumor type and patient sex, of which gene amplification accounts for the largest proportion. Phylogenetic analysis showed that E2Fs were conserved in 41 species, including fruit flies, nematodes, and humans. Meanwhile, E2Fs had a tendency for gene expansion during evolution. In conclusion, this study clarified the expression pattern, mutation characteristics, and evolutionary trend of E2Fs in high-incidence tumors in China, and suggested that E2F family transcription factors could be novel diagnostic markers for tumor diseases. Furthermore, this work can provide a theoretical basis for the development of anti-tumor-targeted drugs.

TRAF3/STAT6 axis regulates macrophage polarization and tumor progression.

Converting tumor-associated macrophages (TAMs) from the M2 to the M1 phenotype is considered an effective strategy for cancer therapy. TRAF3 is known to regulate NF-κB signaling. However, the role of TRAF3 in TAM polarization has not yet been completely elucidated. Here, we found that ablation of TRAF3 increased M1 markers, iNOS, FGR and SLC4A7, while down-regulated M2 markers, CD206, CD36 and ABCC3, expression levels in macrophages. Moreover, TRAF3 deficiency enhanced LPS-induced M1 and abolished IL-4-induced macrophage polarization. Next, quantitative ubiquitomics assays demonstrated that among the quantitative 7618 ubiquitination modification sites on 2598 proteins, ubiquitination modification of IL-4 responding proteins was the most prominently reduced according to enrichment analysis. STAT6, a key factor of IL-4 responding protein, K450 and K129 residue ubiquitination levels were dramatically decreased in TRAF3-deficient macrophages. Ubiquitination assay and luciferase assay demonstrated that TRAF3 promotes STAT6 ubiquitination and transcriptional activity. Site mutation analysis revealed STAT6 K450 site ubiquitination played a vital role in TRAF3-mediated STAT6 activation. Finally, B16 melanoma mouse model demonstrated that myeloid TRAF3 deficiency suppressed tumor growth and lung metastasis in vivo. Taken together, TRAF3 plays a vital role in M2 polarization via regulating STAT6 K450 ubiquitination in macrophages.

Saikosaponin D exerts cytotoxicity on human endometrial cancer ishikawa cells by inducing apoptosis and inhibiting metastasis through MAPK pathways.

Saikosaponin D (SSD) is one of plant secondary metabolic active substance with effective anti-tumor ability; however, the toxicity of Saikosaponin D on human endometrial cancer Ishikawa cells is still unclear. Our results revealed that SSD displayed cytotoxicity on the Ishikawa cell with an IC50 = 15.69 µM, but was non-toxic to the human normal cell line HEK293. SSD could upregulate p21 and Cyclin B to keep cells in the G2/M stage. In addition, it activated the death receptor and mitochondrion routes to induce apoptosis in Ishikawa cells. The transwell chamber and wound healing results showed that SSD inhibited the cell migration and invasion. In addition, we found that it was closely related to the MAPK cascade pathway, and it could mediate the three classical MAPK pathways to block cell metastasis. In conclusion, SSD could be potentially beneficial as a natural secondary metabolite in preventing and treating endometrial carcinoma.

Post-traumatic growth among childhood cancer survivors: A qualitative meta-synthesis.

PURPOSE: To conduct a meta-synthesis of qualitative studies on the post-traumatic growth experiences of childhood cancer survivors. METHOD: Various databases, including PubMed, Cochrane Library, Web of Science, EMBASE, PsycInfo, ProQuest, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang Data, China Science and Technology Journal Database (CSTJ), and China Biology Medicine (CBM) were used to retrieve qualitative studies on childhood cancer survivors who experienced post-traumatic growth. RESULTS: Eight papers were included in this study, and similar fragments were combined to form eight categories, which were further combined into four synthesized findings: adjustment of cognitive system, enhancement of personal strength, improving relationships with others, resetting of life goals. CONCLUSIONS: Post-traumatic growth was observed in some childhood cancer survivors. The potential resources and positive forces contributing to this growth are of great significance in the fight against cancer, in tapping into individual and social resources to help survivors grow, and in improving their survival rates and quality of life. It also provides a new perspective for healthcare providers regarding the relevant psychological interventions.

Structural characterization and stability of glycated bovine serum albumin-kaempferol nanocomplexes.

Kaempferol (Kae), a flavonoid is endowed with various functions. However, due to its poor water solubility and stability, its application in the food and pharmaceutical fields remains elusive. Emerging reports have emphasized the importance of bovine serum albumin (BSA), and glycosylated BSA (GBSA) prepared in the nature deep eutectic solvent system as drug delivery system carriers. In our study, ultraviolet and fluorescence spectra revealed the higher interactions of BSA and GBSA with Kae. Through analysis of Z-average diameter, zeta-potential, polydispersity index (PDI), encapsulation efficiency (EE), loading capacity (LC) of BSA-Kae nanocomplexes (NPs) and GBSA-Kae NPs, GBSA-Kae NPs showed a higher absolute value of zeta-potential and lower PDI, while its EE and LC were also higher. Structural characterization and stability analysis revealed that GBSA-Kae NPs had more stable properties. This study laid the theoretical foundation for improving the solubility and stability of Kae during its delivery and transport.