Moon-forming impactor as a source of Earth's basal mantle anomalies.

Seismic images of Earth's interior have revealed two continent-sized anomalies with low seismic velocities, known as the large low-velocity provinces (LLVPs), in the lowermost mantle1. The LLVPs are often interpreted as intrinsically dense heterogeneities that are compositionally distinct from the surrounding mantle2. Here we show that LLVPs may represent buried relics of Theia mantle material (TMM) that was preserved in proto-Earth's mantle after the Moon-forming giant impact3. Our canonical giant-impact simulations show that a fraction of Theia's mantle could have been delivered to proto-Earth's solid lower mantle. We find that TMM is intrinsically 2.0-3.5% denser than proto-Earth's mantle based on models of Theia's mantle and the observed higher FeO content of the Moon. Our mantle convection models show that dense TMM blobs with a size of tens of kilometres after the impact can later sink and accumulate into LLVP-like thermochemical piles atop Earth's core and survive to the present day. The LLVPs may, thus, be a natural consequence of the Moon-forming giant impact. Because giant impacts are common at the end stages of planet accretion, similar mantle heterogeneities caused by impacts may also exist in the interiors of other planetary bodies.

Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Cancer cells exhibit heterogenous metastatic potential, and high metastatic subclones can enhance metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogenous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration and invasion of CRA cells. Interestingly, high metastatic CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit NF1, thereby activate the RAS-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided the evidence that colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

A Tunable Threshold Colorimetric DNA Logic Gate for Intuitive Assessment of Chemical Contaminant Exceedance.

Current molecular logic gates are predominantly focused on the qualitative assessment of target presence, which has certain limitations in scenarios requiring quantitative assessment, such as chemical contaminant monitoring. To bridge this gap, we have developed a novel DNA logic gate featuring a tunable threshold, specifically tailored to the limits of contaminants. At the core of this logic gate is a DNA-gold nanoparticle (AuNP) hybrid film that incorporates aptamer sequences to selectively bind to acetamiprid (ACE) and atrazine (ATR). Upon interaction with these contaminants, the film degrades, releasing AuNPs that, in the presence of Hg2+, catalyze the oxidation of TMB, resulting in a visible blue coloration on test paper. This aptamer-enabled process effectively establishes an OR logic gate, with ACE and ATR as inputs and the appearance of blue color as the output. A key innovation of our system is its tunable input threshold. By adjusting the concentration of Hg2+, we can fine-tune the color mutation points to match the input threshold to predefined limits, such as Maximum Residue Limits (MRLs). This alignment allows semiquantitative assessment of contaminant levels, providing intuitive visual feedback of contaminant exceedance. Validation experiments with spiked samples confirm its accuracy and reliability by closely matching HPLC results. Therefore, our colorimetric DNA logic gate is emerging as a promising tool for easy and semiquantitative monitoring of chemical contaminants across diverse applications.

Performance of LWIR to VLWIR barrier photodetectors based on M-structure superlattices.

Antimonide superlattice materials with tunable energy bands, high electron mobility, and easy attainment of good uniformity in large-area materials, are considered to be the material of choice for third-generation infrared photodetectors. Based on energy band engineering, this paper designs a series of long-wave infrared(LWIR) to very-long-wave infrared(VLWIR) photodetectors by employing M-structure superlattice(M-SL) as both absorber layer and barrier layer. The photodetectors' performances at different temperatures are simulated in this manuscript. At 77K, while minimizing the lattice mismatch, effectively suppresses the dark current of the device which can be as low as 1× 10-8A/cm2, with a quantum efficiency reaching 20.85% and normalized detectivity achieves 4.78×1011 cm·Hz1/2/W for LWIR photodetector with a cutoff wavelength of 11.1 µm. For the VLWIR photodetector with a cutoff wavelength of 16.7 µm, the corresponding figures are 1×10-6A/cm2, 16.77% and 3.09×1010 cm·Hz1/2/W, respectively.

Bioleaching of Cd from contaminated Helianthus annuus L. stalk and the safe utilization of its byproducts by Aspergillus niger.

Disposal and recycling of heavy metal-enriched biomass is the key to measure the success of phytoremediation. This study employed innovative approach to use Aspergillus niger (A. niger) for the treatment of Cd-contaminated Helianthus annuus L. (sunflower) stalk after phytoremediation. Single-factor results showed that the removal of Cd at an initial pH of 3 was superior to sucrose and inoculation amount. 67.67% of Cd was removed by A. niger leaching system after 11 days based on response surface methodology optimum conditions (sucrose: 76.266 g L-1; inoculation amount: 10%; initial pH: 3), while the concentrations of nitrogen, phosphorus and potassium (N, P and K) of sunflower stalk were unaffected. While physicochemical pretreatment effectively enhanced the bioleaching efficiency, it also resulted in significant loss of P and K elements, thereby reducing the value of biomass for recycling and utilization. Therefore, the direct A. niger leaching method without pretreatment is more advantageous for the safe treatment and recycling of Cd-contaminated sunflower stalks.

Knockdown of the UL-16 binding protein 1 promotes osteoblast differentiation of human mesenchymal stem cells by activating the SMAD2/3 pathway.

Osteoporosis is caused by the imbalance of osteoblasts and osteoclasts. The regulatory mechanisms of differentially expressed genes (DEGs) in pathogenesis of osteoporosis are of significant and needed to be further investigated. GSE100609 dataset downloaded from Gene Expression Omnibus (GEO) database was used to identified DEGs in osteoporosis patients. KEGG analysis was conducted to demonstrate signaling pathways related to enriched genes. Osteoporosis patients and the human mesenchymal stem cells (hMSCs) were obtained for in vivo and in vitro resaerch. Lentivirus construction and viral infection was used to knockdown genes. mRNA expression and protein expression were detected via qRT-PCR and western blot assay separately. Alkaline phosphatase (ALP) activity detection, alizarin Red S (ARS) staining, and expression of bone morphogenetic protein 2 (BMP2), osteocalcin (OCN) and Osterix were evaluated to determine osteoblast differentiation capacity. UL-16 binding protein 1 (ULBP1) gene was upregulated in osteoporosis and downregulated in differentiated hMSCs. Knockdown of ULBP1 increased ALP activity, mineralization ability evaluated by ARS staining, expression of BMP2, OCN and Osterix in differentiated hMSCs. Furthermore, rescue experiment demonstrated that suppressed ULBP1 boosted osteoblast differentiation by activating TNF-ß signaling pathway. Knockdown of ULBP1 gene could promoted osteoblast differentiation by activating TNF-ß signaling pathway in differentiated hMSCs. ULBP1 may be a the Achilles' heel of osteoporosis, and suppression of ULBP1 could be a promising treatment for osteoporosis.

Autophagy regulates bone loss via the RANKL/RANK/OPG axis in an experimental rat apical periodontitis model.

AIM: Autophagy is involved in human apical periodontitis (AP). However, it is not clear whether autophagy is protective or destructive in bone loss via the receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) axis. This study aimed to investigate the involvement of autophagy via the RANKL/RANK/OPG axis during the development of AP in an experimental rat model. METHODOLOGY: Twenty-four female Sprague-Dawley rats were divided into control, experimental AP (EAP) + saline, and EAP + 3-methyladenine (An autophagy inhibitor, 3-MA) groups. The control group did not receive any treatment. The EAP + saline group and the EAP + 3-MA group received intraperitoneal injections of saline and 3-MA, respectively, starting 1 week after the pulp was exposed. Specimens were collected for microcomputed tomography (micro-CT) scanning, histological processing, and immunostaining to examine the expression of light chain 3 beta (LC3B), RANK, RANKL, and OPG. Data were analysed using one-way analysis of variance (p < .05). RESULTS: Micro-CT showed greater bone loss in the EAP + 3-MA group than in the EAP + saline group, indicated by an elevated trabecular space (Tb.Sp) (p < .05). Inflammatory cell infiltration was observed in the EAP + saline and EAP + 3-MA groups. Compared with EAP + saline group, the EAP + 3-MA group showed weaker expression of LC3B (p < .01) and OPG (p < .05), more intense expression of RANK (p < .01) and RANKL (p < .01), and a higher RANKL/OPG ratio (p < .05). CONCLUSION: Autophagy may exert a protective effect against AP by regulating the RANKL/RANK/OPG axis, thereby inhibiting excessive bone loss.

Feasibility and impact of three-dimensional (3D) printing technology in simulated teaching of congenital malformations.

AIMS: This study aimed to investigate the feasibility and effectiveness of utilizing three-dimensional (3D) printing technology in the simulation teaching of congenital malformations. METHODS: We conducted a comparative analysis between an experimental group that received traditional teaching supplemented with 3D printing model demonstrations and hands-on model operation, and a control group that received traditional teaching methods. Various parameters, including classroom interest, classroom interaction, learning enthusiasm, disease awareness, teaching satisfaction, and independent operation confidence, were assessed, along with theoretical and practical tests. RESULTS: The results showed no significant difference in theoretical test scores between the two groups (91.92 ± 15.04 vs. 89.44 ± 14.89), but the practical test revealed a significantly higher number of qualified trainees in the experimental group compared to the control group (23 vs. 8). In terms of classroom engagement, both groups exhibited similar levels of interest (8.08 ± 1.52 vs. 8.74 ± 0.984), classroom interaction (7.88 ± 1.97 vs. 8.7 ± 1.33), learning enthusiasm (8.81 ± 1.021 vs. 8.52 ± 1.189), and disease awareness (8.58 ± 0.99 vs. 8.58 ± 0.99). However, the experimental group demonstrated significantly higher teaching satisfaction (8.81 ± 1.06 vs. 9.19 ± 0.96) and greater operation confidence (7.67 ± 2.56 vs. 5.5 ± 2.79) than the control group. CONCLUSION: 3D printing technology can be effectively utilized to create surgical teaching models, enhancing the confidence of standardized training doctors and improving teaching outcomes.

Does prenatal diagnosis of meconium peritonitis have the better recovery? A single-center over 10 years of experience.

OBJECTIVE: To evaluate whether infants with prenatal diagnosis of meconium peritonitis (MP) have a poorer prognosis. METHODS: A retrospective analysis of data from infants treated with surgery from January 2008 to December 2020 was conducted. The patients were divided into prenatal diagnosis group and postnatal diagnosis group based on the timing of diagnosis. The intraoperative and postoperative parameters of the two groups of patients were compared. RESULTS: A total of 71 cases of MP were included in the study, with 48 cases in the prenatal diagnosis group and 23 cases in the postnatal diagnosis group. The comparison of preoperative indicators between the two groups of patients showed no statistically significant differences in baseline (p > 0.05). Intraoperative indicators, including blood loss, anastomosis, retained intestinal tube length and excised intestinal tube length, showed no statistically significant differences between the two groups (p > 0.05). However, the postnatal diagnosis group had a significantly shorter operation time than the prenatal diagnosis group (p < 0.05). Postoperative indicators, including fasting time, albumin usage, complications, and abandonment or mortality rates, show no difference (p > 0.05). Nevertheless, the postnatal diagnosis group exhibited significantly shorter hospital stay and time to first bowel movement compared to the prenatal diagnosis group (p < 0.05). CONCLUSION: Prenatal diagnosis of meconium peritonitis is associated with increased surgical complexity, prolonged hospital stay, and delayed recovery of intestinal function. However, there is no evidence of higher mortality or more complications compared to infants diagnosed postnatally, and there is no significant difference in long-term prognosis.

Recognition and evaluation of mental workload in different stages of perceptual and cognitive information processing using a multimodal approach.

This study explores the effects of different perceptual and cognitive information processing stages on mental workload by assessing multimodal indicators of mental workload such as the NASA-TLX, task performance, ERPs and eye movements. Repeated measures ANOVA of the data showed that among ERP indicators, P1, N1 and N2 amplitudes were sensitive to perceptual load (P-load), P3 amplitude was sensitive to P-load only in the prefrontal region during high cognitive load (C-load) states, and P3 amplitude in the occipital and parietal regions was sensitive to C-load. Among the eye movement indicators, blink frequency was sensitive to P-load in all C-load states, but to C-load in only low P-load states; pupil diameter and blink duration were sensitive to both P-load and C-load. Based on the above indicators, the k-nearest neighbours (KNN) algorithm was used to propose a classification method for the four different mental workload states with an accuracy of 97.89%.Practitioner summary: Based on the results of this study, it is possible to implement the monitoring of mental workload states and optimise brain task allocation in operations involving high mental workload, such as human-computer interaction.

Interactive effects of users' openness and robot reliability on trust: evidence from psychological intentions, task performance, visual behaviours, and cerebral activations.

Although trust plays a vital role in human-robot interaction, there is currently a dearth of literature examining the effect of users' openness personality on trust in actual interaction. This study aims to investigate the interaction effects of users' openness and robot reliability on trust. We designed a voice-based walking task and collected subjective trust ratings, task metrics, eye-tracking data, and fNIRS signals from users with different openness to unravel the psychological intentions, task performance, visual behaviours, and cerebral activations underlying trust. The results showed significant interaction effects. Users with low openness exhibited lower subjective trust, more fixations, and higher activation of rTPJ in the highly reliable condition than those with high openness. The results suggested that users with low openness might be more cautious and suspicious about the highly reliable robot and allocate more visual attention and neural processing to monitor and infer robot status than users with high openness.

The study could deepen practitioners' understanding of the effect of openness on trust in robots by examining the psychological intention, task performance, visual behaviours, and physiological activations. Moreover, the interaction effect could provide guidelines for designing robots adaptive to users' personalities, and the multimodal method would be practical for measuring trust in interaction.

Application of personalized templates in minimally invasive management of coronal dens invaginatus: a report of two cases.

BACKGROUND: Treating the coronal dens invaginatus (CDI) with pulp infection commonly involves the removal of invagination, which increases the risk of perforation and fracture, and compromises the tooth structure. Minimally invasive endodontic management of CDI is highly recommended. This report describes two cases of type II CDI with the application of personalized templates. CASE PRESENTATION: Two cases of type II CDI, affecting the main root canal in a maxillary canine and a lateral incisor, were diagnosed. A guided endodontics (GE) approach was applied. Cone-beam computed tomography and intraoral scans were imported and aligned in a virtual planning software to design debridement routes and templates. The MICRO principle (which involves the aspects of Mechanical (M) debridement, Irrigation (I), Access cavities (C), Rectilinear routes (R), and Obstruction (O)) was proposed for designing optimal debridement routes for future applications. The templates were innovatively personalized and designed to preserve the tooth structure maximally while effectively debriding the root canal. Root canal treatment with supplementary disinfection was then performed. The follow-up of the two patients revealed favorable clinical and radiographic outcomes. CONCLUSIONS: The GE approach could be a feasible method for preserving healthy dental structure while effectively debriding the root canal, thereby achieving successful and minimally invasive endodontic treatment for CDI.

Geographical variation in functional traits of leaves of Caryopteris mongholica and the role of climate.

BACKGROUND: Quantifying intra-specific variation in leaf functional traits along environmental gradients is important for understanding species' responses to climate change. In this study, we assessed the degree of among and within populations variation in leaf functional traits and explored leaf response to geographic and climate change using Caryopteris mongholica as material, which has a wide range of distribution environments. RESULTS: We selected 40 natural populations of C. mongholica, measured 8 leaf functional traits, analyzed the extent of trait variation among and within populations, and developed geographic and climatic models to explain trait variation between populations. Our results showed that the variation in leaf functional traits of C. mongholica was primarily lower within populations compared to among populations. Specifically, the leaf area (LA) exhibited higher variability both among and within populations, whereas leaf carbon content (LC) exhibited lower variation within populations but greater variation among populations. We observed a specific covariation pattern among traits and a strong linkage between morphological, economic, and mechanical traits. Increasing minimum temperature, precipitation of month, and seasonal precipitation differences all limited the growth and development of C. mongholica. However, it was observed that an increase in mean annual precipitation positively influenced the morphological development of its leaf. CONCLUSIONS: These results demonstrate the response of intra-specific trait variation to the environment and provide valuable insights into the adaptation of intra-specific leaf functional traits under changing climatic conditions.

In vitro and in vivo analyses on anti-NSCLC activity of apatinib: rediscovery of a new drug target V600E mutation.

BACKGROUND: Apatinib (YN968D1) is the first small-molecule-targeting drug with anti-tumor activity created in China for the treatment of advanced gastric cancer (GC) and hepatocellular carcinoma (HCC). It showed significant variation in the efficacy for treating cancers, including advanced non-squamous non-small-cell lung cancer (NSCLC). Whether its efficacy could be optimized by subgrouping patients with certain genetic variation remains elusive. METHODS: Here, we firstly used kinase screening to identify any possible target of apatinib against 138 kinases. The effects of apatinib on proliferation rates, cell cycle, cell apoptosis, and cell migration on cancer cell lines were analyzed; the in vitro potential pathways of apatinib on cancer cell lines were screened. The effect of apatinib on mouse cancer models in vivo was also analyzed. RESULTS: Based on HCC364 cells with BRAF V600E mutation, we have shown that apatinib could inhibit their growth, migration, cell cycle, and induce their apoptosis. Based on mice with transplanted HCC364 cells, we have also shown that apatinib could inhibit the tumor growth. Based on immunohistochemistry, we have demonstrated that apatinib could suppress the phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase and extracellular regulated protein kinases. This may account at least part of the apatinib's inhibitory effect on HCC364 cancer cells. CONCLUSIONS: BRAF V600E protein kinase is a target of apatinib by kinase screening. We have demonstrated that apatinib can effectively inhibit tumor cells with BRAF V600E mutation by in vitro and in vivo experiments. Our results have demonstrated that targeting BRAF V600E mutation, apatinib appears to be effective and safe for treating NSCLC and possibly other cancers with the same mutation.

SERPINB8 and furin regulate ITGAX expression and affect the proliferation and invasion of melanoma cells.

In the past 10 years, the systemic treatment of advanced melanoma has undergone tremendous changes through the development of targeted therapy. However, there is still a long way to go. This study aims to characterize the function and interaction of ITGAX, SERPINB8 and furin in BRAF V600E mutant melanoma. Differentially expressed genes related to BRAF V600E mutation and BRAFi treatment were obtained by analysing GSE141484 and GSE22838. two kinds of BRAFi (Vemurafenib, 10 µM; Dabrafenib, 1 µM) were used to treat A375 and 1205Lu cells, respectively. The expression of ITGAX, SERPINB8 and Furin in A375 and 1205Lu cells was down-regulated by specific siRNAs, and cell proliferation, clone formation and invasion were detected by CCK-8, colony formation and transwell assays. The physical binding of furin and SERPINB8 was detected by immunoprecipitation. BRAFi treatment down-regulated the ITGAX and SERPINB8 expression and did not change furin expression. Knockdown of ITGAX and SERPINB8 both inhibited the proliferation and invasion of A375 and 1205Lu cells. Knocking down SERPINB8 down-regulated the expression of ITGAX. Furin knockdown and inhibitors all up-regulated the protein level of ITGAX. SERPINB8 can physically bind to furin. In summary, SERPINB8 and furin regulate the expression of ITGAX in melanoma cells, and ITGAX significantly promotes the proliferation and invasion of melanoma cells.

Real-world practice of conversion surgery for unresectable hepatocellular carcinoma - a single center data of 26 consecutive patients.

AIM: To understand the proportion of uHCC (unresectable hepatocellular carcinoma) patients who achieve successful conversion resection in a high-volume setting with state of the art treatment options. METHODS: We retrospectively reviewed all HCC patients hospitalized to our center from June 1st, 2019 to June 1st, 2022. Conversion rate, clinicopathological features, response to systemic and/or loco-regional therapy and surgical outcomes were analyzed. RESULTS: A total of 1,904 HCC patients were identified, with 1672 patients receiving anti-HCC treatment. 328 patients were considered up-front resectable. Of the remaining 1344 uHCC patients, 311 received loco-regional treatment, 224 received systemic treatment, and the remainder (809) received combination systemic plus loco-regional treatment. Following treatment, one patient from the systemic group and 25 patients from the combination group were considered to have resectable disease. A high objective response rate (ORR) was observed in these converted patients (42.3% under RECIST v1.1 and 76.9% under mRECIST criteria). The disease control rate (DCR) reached 100%. 23 patients underwent curative hepatectomy. Major post-operative morbidity was equivalent in the both groups (P=0.76). Pathologic complete response (pCR) was 39.1%. During conversion treatment, grade 3 or higher treatment-related adverse events (TRAEs) were observed in 50% of patients. The median follow-up time was 12.9 months (range, 3.9~40.6) from index diagnosis and 11.4 months (range, 0.9~26.9) from resection. Three patients experienced disease recurrence following conversion surgery. CONCLUSIONS: By intensive treatment, a small sub-group of uHCC patients (2%) may potentially be converted to curative resection. Loco-regional combined with systemic modality was relative safe and effective in the conversion therapy. Short-term outcomes are encouraging, but long-term follow-up in a larger patient population are required to fully understand the utility of this approach.

Nonporous versus Mesoporous Bioinspired Polydopamine Nanoparticles for Skin Drug Delivery.

The use of polydopamine-based bioinspired nanomaterials has shed new light on advanced drug delivery arising from their efficient surface functionalization. More recently, the polydopamine self-assemblies formed in two different modalities, i.e., nonporous and mesoporous nanoparticles, have begun to attract attention due to their expedient and versatile properties. However, their possibility for use in dermal drug delivery for local therapy, as well as their interaction with the skin, has not yet been demonstrated. Our study aimed to compare and explore the feasibility of the self-assembled nonporous polydopamine nanoparticles (PDA) and mesoporous polydopamine nanoparticles (mPDA) for local skin drug delivery. The formation of the PDA and mPDA structures was confirmed by the UV-vis-NIR absorption spectrum, the Fourier transform infrared spectroscopy, and the nitrogen adsorption/desorption isotherms. Using retinoic acid (RA) as the model drug, their effects on drug loading, release, photostability, skin penetration, and radical scavenging were investigated. Laser scanning confocal microscopy (LSCM) and hematoxylin and eosin (H&E) were introduced to probe their delivery routes and possible interaction with the skin. The results indicated that both PDA and mPDA could reduce the photodegradation of RA, and mPDA showed significantly better radical scavenging activity and drug loading capacity. The ex vivo permeation study revealed that both PDA and mPDA significantly enhanced the delivery of RA into the deep skin layers by comparison with the RA solution, in which follicular and intercellular pathways existed, and alteration in the structure of stratum corneum was observed. In light of drug loading capacity, size controllability, physical stability, as well as radical scavenging activity, mPDA was more preferable due to the improvement of these factors. This work demonstrated the feasibility and promising application of PDA and mPDA nanoparticles for dermal drug delivery, and the comparative concept of these two types of biomaterials can provide implications for their use in other fields.

Perspective of sodium reduction based on endogenous proteases via the strategy of sodium replacement in conjunction with mediated-curing.

NaCl is the main curing agent in dry-cured meat products, and a large amount of NaCl addition leads to high salt content of final products. Salt content and composition are important factors affecting the activity of endogenous proteases, which in turn could affect proteolysis as well as the quality of dry-cured meat products. With the increasing emphasis on the relationship between diet and health, reducing sodium content without sacrificing quality and safety of products is a great challenge for dry-cured meat industry. In this review, the change of endogenous proteases activity during processing, the potential relationship between sodium reduction strategy, endogenous proteases activity, and quality were summarized and discussed. The results showed that sodium replacement strategy and mediated-curing had a complementary advantage in influencing endogenous proteases activity. In addition, mediated-curing had the potential to salvage the negative effects of sodium substitution by affecting endogenous proteases. Based on the results, a sodium reduction strategy that sodium replacement in conjunction with mediated-curing based on endogenous proteases was proposed for the future perspective.

Purple Rehmannia: Investigation of the activation of R2R3-MYB transcription factors involved in anthocyanin biosynthesis.

Engineering anthocyanin biosynthesis in herbs could provide health-promoting foods for improving human health. Rehmannia glutinosa is a popular medicinal herb in Asia, and was a health food for the emperors of the Han Dynasty (59 B.C.). In this study, we revealed the differences in anthocyanin composition and content between three Rehmannia species. On the 250, 235 and 206 identified MYBs in the respective species, six could regulate anthocyanin biosynthesis by activating the ANTHOCYANIDIN SYNTHASE (ANS) gene expression. Permanent overexpression of the Rehmannia MYB genes in tobacco strongly promoted anthocyanin content and expression levels of NtANS and other genes. A red appearance of leaves and tuberous/roots was observed, and the total anthocyanin content and the cyanidin-3-O-glucoside content were significantly higher in the lines overexpressing RgMYB41, RgMYB42, and RgMYB43 from R. glutinosa, as well as RcMYB1 and RcMYB3 in R. chingii and RhMYB1 from R. henryi plants. Knocking out of RcMYB3 by CRISPR/Cas9 gene editing resulted in the discoloration of the R. chingii corolla lobes, and decreased the content of anthocyanin. R. glutinosa overexpressing RcMYB3 displayed a distinct purple color in the whole plants, and the antioxidant activity of the transgenic plants was significantly enhanced compared to WT. These results indicate that Rehmannia MYBs can be used to engineer anthocyanin biosynthesis in herbs to improve their additional value, such as increased antioxidant contents.

Adjuvant chemotherapy improves long-term survival in pathologic stage III rectal mucinous adenocarcinoma after pre-operative chemoradiotherapy.

PURPOSE: The benefits of adjuvant chemotherapy remain debated rectal mucinous adenocarcinoma (MC). Our study aims to delve into the efficacy of adjuvant chemotherapy in pathologic stage III rectal MC by a large population-based database. METHODS: The Chi-square test was performed to examine the parameters between treatment groups. The overall survival (OS) and cancer-specific survival (CSS) of treatment groups were conducted by using the Kaplan-Meier method. The impact of factors on survival was assessed using Cox regression analyses. To balance the covariates and reduce the selection bias, we employed propensity score matching (PSM) to narrow the differences between treatment groups. RESULTS: The median follow-up time for overall patients was 80 months. In the pre-operative chemoradiotherapy (pre-CRT) group, patients who received adjuvant chemotherapy had significantly better 5-year OS and CSS. Multivariate analyses found that adjuvant chemotherapy was associated with better OS (p < 0.001, HR (95% CI): 0.66 (0.51-0.86)) and CSS (p = 0.012, HR (95% CI): 0.71 (0.54-0.93)). However, adjuvant chemotherapy was not an independent prognosis factor in both OS (p = 0.149, HR (95% CI): 0.76 (0.53-1.1); Supplement Table 1) and CSS (p = 0.183, HR (95% CI): 0.74 (0.48-1.15)) in patients who did not receive pre-CRT. After PSM, similar results were found in the pre-CRT and the no pre-CRT groups. CONCLUSION: In conclusion, our population-based retrospective cohort study indicates that the effects of adjuvant chemotherapy were associated with the pre-CRT status in patients with stage III rectal MC. In patients who underwent pre-CRT, the receipt of adjuvant chemotherapy was associated with better survival outcomes. Conversely, adjuvant chemotherapy does not seem to confer significant survival benefits to patients without pre-CRT.