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As Charles Darwin anticipated, living fossils provide excellent opportunities to study evolutionary questions related to extinction, competition, and adaptation. Ginkgo ( Ginkgo biloba L.) is one of the oldest living plants and a fascinating example of how people have saved a species from extinction and assisted its resurgence. By resequencing 545 genomes of ginkgo trees sampled from 51 populations across the world, we identify three refugia in China and detect multiple cycles of population expansion and reduction along with glacial admixture between relict populations in the southwestern and southern refugia. We demonstrate multiple anthropogenic introductions of ginkgo from eastern China into different continents. Further analyses reveal bioclimatic variables that have affected the geographic distribution of ginkgo and the role of natural selection in ginkgo’s adaptation and resilience. These investigations provide insights into the evolutionary history of ginkgo trees and valuable genomic resources for further addressing various questions involving living fossil species. Ginkgo is one of the living fossils from the plant kingdom. Here, authors conduct population genomics analyses to reveal its refugia and demographic history, and provide evidence of multiple anthropogenic introductions of ginkgo from eastern China into different continents.

We aimed to evaluate the performance of the newly developed deep learning Radiomics of elastography (DLRE) for assessing liver fibrosis stages. DLRE adopts the radiomic strategy for quantitative analysis of the heterogeneity in two-dimensional shear wave elastography (2D-SWE) images. A prospective multicentre study was conducted to assess its accuracy in patients with chronic hepatitis B, in comparison with 2D-SWE, aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors, by using liver biopsy as the reference standard. Its accuracy and robustness were also investigated by applying different number of acquisitions and different training cohorts, respectively. Data of 654 potentially eligible patients were prospectively enrolled from 12 hospitals, and finally 398 patients with 1990 images were included. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the optimal area under the ROC curve (AUC) for cirrhosis (F4), advanced fibrosis (≥F3) and significance fibrosis (≥F2). AUCs of DLRE were 0.97 for F4 (95% CI 0.94 to 0.99), 0.98 for ≥F3 (95% CI 0.96 to 1.00) and 0.85 (95% CI 0.81 to 0.89) for ≥F2, which were significantly better than other methods except 2D-SWE in ≥F2. Its diagnostic accuracy improved as more images (especially ≥3 images) were acquired from each individual. No significant variation of the performance was found if different training cohorts were applied. DLRE shows the best overall performance in predicting liver fibrosis stages compared with 2D-SWE and biomarkers. It is valuable and practical for the non-invasive accurate diagnosis of liver fibrosis stages in HBV-infected patients. NCT02313649; Post-results.

Organic emitters with persistent phosphorescence have shown potential application in optoelectronic devices. However, rational design and phosphorescence tuning are still challenging. Here, a series of metal-free luminophores without heavy atoms and carbonyl groups from commercial/lab-synthesized carbazole and benzene were synthesized to realize tunable molecular emission from fluorescence to phosphorescence by simply substituent variation. All the molecules emit blue fluorescence in both solution and solid state. Upon removal of excitation source, the fluorinated luminophores show obvious phosphorescence. The lab-synthesized carbazole based molecules exhibit a huge lifetime difference to the commercially purchased ones due to the existence of isomer in the latter samples. The small energy gap between singlet and triplet state and low reorganization energy help enhance intersystem crossing to contribute to a more competitive radiative process from triplet to ground state. Blue and white organic light-emitting devices are fabricated by using fluorinated luminophore as emitting layer. Though organic emitters with room temperature phosphorescence (RTP) are attractive for various applications, realizing highly efficient and long lifetime emission remains a challenge. Here, the authors report the role of push-pull electronic effects on emission for organic RTP emitters.

One new bisabolane sesquiterpene, bisabolan-1,10,11-triol (1), one new norbisabolane sesquiterpene, 12-nor-11-acetoxybisabolen-3,6,7-triol (2), two new naturally occurring monoterpenes, (7S)- and (7R)-1-hydroxy-3-p-menthen-9-oic acids (3 and 4), one new naturally occurring trichodenone, dechlorotrichodenone C (5), one new chlorine-containing trichodenone, 3-hydroxytrichodenone C (6), one new diketopiperazine, methylcordysinin A (7), and one new naturally occurring oxazole derivative, 4-oxazolepropanoic acid (8), were isolated from the culture of a marine brown alga-endophytic strain (cf44-2) of Trichoderma asperellum. Their structures and relative configurations were determined by extensive 1D/2D NMR and mass spectrometric data, and the absolute configurations of 3–6 were assigned by analysis of the ECD spectra aided by quantum chemical computations. Compounds 1, 2, 5, and 6 showed growth inhibition of some marine phytoplankton species and pathogenic bacteria.

Aims/Introduction The purpose of the present study was to evaluate the validation and application of the 2019 International Working Group on the Diabetic Foot (IWGDF) risk stratification system among Chinese patients with diabetes. Materials and Methods A retrospective cohort study was carried out with 254 patients with diabetes, but without an active diabetic foot (DF) ulcer. Patients hospitalized from January to May 2017 were enrolled, and the follow‐up period was from January to May 2020. Patients were stratified into four risk groups based on the 2019 IWGDF risk stratification system. Results Of the 254 patients, four of 31 patients at risk 1 were diagnosed with DF within 3 years, whereas 12 of 26 patients at risk 2 and 16 of 20 patients at risk 3 developed DF. The area under the curve was 0.919 (P < 0.01, 95% confidence interval 0.893–0.945). Because DF risk 2 and greater (risk 2 + risk 3) was the optimal cut‐off point, we simplified the risk stratification system by using two tiers, namely, low risk (risk 0 + 1) and high risk (risk 2 + 3). For the simplified risk stratification system, the sensitivity, specificity, positive likelihood ratio, percent agreement, positive predictive value and negative predictive value were 87.5%, 91.8%, 10.607, 91.3%, 60.8% and 98.1%, respectively. The χ2‐test showed that the odds ratio of the high‐risk group (risk 2 + 3) was 29.33‐fold that of the low‐risk group (risk 0 + 1). Conclusions The 2019 IWGDF risk stratification system showed high validity and primary screening value in Chinese patients with diabetes. Thus, a simplified, two‐tiered IWGDF stratification might be more efficient and cost‐effective for predicting DF ulcers. The 2019 International Working Group on the Diabetic Foot risk stratification system showed high validity and primary screening value in Chinese patients with diabetes. We found that a simplified International Working Group on the Diabetic Foot stratification system might be more efficient and cost‐effective at predicting diabetic foot ulcers than the original risk strategy. We suggest using two‐tiered risk stratification for high‐risk diabetic foot ulcers during the primary screening of diabetes patients in routine clinical practice.

Galectin-9 (Gal-9) induces adhesion and aggregation of certain cell types and inhibits the metastasis of tumor cells. T-cell immunoglobulin-and mucin domain-3-containing molecule 3 (TIM-3) plays a pivotal role in immune regulation. The aim of this study is to investigate Gal-9 and TIM-3 alterations in gastric cancer and their prognostic values. Gal-9 and Tim-3 expression was evaluated using a tissue microarray immunohistochemistry method in 305 gastric cancers, of which 84 had paired adjacent normal samples. Cell lines SGC-7901, BGC-823, MGC-803, MKN45 and GES-1 were also stained. Correlations were analyzed between expression levels of Gal-9 and Tim-3 protein and tumor parameters or clinical outcomes. Gal-9 and Tim-3 stained positive on tumor cells in 86.2% (263/305), and 60.0% (183/305) patients with gastric cancer, respectively. Gal-9 expression was significantly higher in cancer than in normal mucosa (P<0.001). Reduced Gal-9 expression was associated with lymph-vascular invasion, lymph node metastasis, distant metastasis and worse TNM staging (P = 0.034, P = 0.009, P = 0.002 and P = 0.043, respectively). In contrast, Tim-3 expression was significantly lower in cancer than in control mucosa (P<0.001). Patients with lymph-vascular invasion had higher expression levels of Tim-3 (P<0.001). Moreover, multivariate analysis shows that both high Gal-9 expression and low Tim-3 expression were significantly associated with long overall survival (P = 0.002, P = 0.010, respectively); the combination of Gal-9 and Tim-3 expression was an independent prognostic predictor for patients with gastric cancer (RR: 0.43; 95%CI: 0.20-0.93). H.pylori infection status was not associated with Gal-9 and Tim-3 expression (P = 0.102, P = 0.565). The results suggest that expression of Gal-9 and Tim-3 in tumor cells may be a potential, independent prognostic factor for patients with gastric cancer. Gal-9 and TIM-3 may play an important part in the gastric carcinogenesis.

Background Pyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis. Methods We performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1β ELISA were used to analysis pyroptosis between hydrogen-supplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation. Results We observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosis-related proteins, and increased the number of PI- and TUNEL-positive cells, as well as the release of LDH and IL-1β, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway. Conclusions This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.

The Majorana fermion, which is its own antiparticle and obeys non-Abelian statistics, plays a critical role in topological quantum computing. It can be realized as a bound state at zero energy, called a Majorana zero mode (MZM), in the vortex core of a topological superconductor, or at the ends of a nanowire when both superconductivity and strong spin orbital coupling are present. A MZM can be detected as a zero-bias conductance peak (ZBCP) in tunneling spectroscopy. However, in practice, clean and robust MZMs have not been realized in the vortices of a superconductor because of contamination from impurity states or other closely packed Caroli–de Gennes-Matricon (CdGM) states, which hampers further manipulations of MZMs. Here, using scanning tunneling spectroscopy, we show that a ZBCP well separated from the other discrete CdGM states exists ubiquitously in the cores of free vortices in the defect-free regions of(Li0.84Fe0.16)OHFeSe, which has a superconducting transition temperature of 42 K. Moreover, a Dirac-cone-type surface state is observed by angle-resolved photoemission spectroscopy, and its topological nature is confirmed by band calculations. The observed ZBCP can naturally be attributed to a MZM arising from the chiral topological surface state of a bulk superconductor. Thus,(Li0.84Fe0.16)OHFeSeprovides an ideal platform for studying MZMs and topological quantum computing.

Abstract Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-β. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.

Background The health literacy of staff in preschool childcare institution is an important issue to consider in providing healthcare for children aged 3–6 years, which could contribute to reducing incidence of diseases and accidental injuries as well as maintaining children’s good health. Seldom instruments have been designed to measure health literacy across this group. This research aims to develop a health literacy scale for staff in preschool childcare institutions and validate its psychometric properties. Methods The scale was developed through four phases. In Phase 1, an item pool was developed mainly based on literature review and kindergarten work; In Phase 2, the initial items were reviewed by fifteen experts and content validity analysis was conducted; In Phase 3, a pilot study was conducted involving 30 kindergarten staff, which aimed to further modify the scale; In Phase 4, a psychometric validation study involving 466 kindergarten staff was conducted through a cross-sectional survey in May 2023. Item analysis was performed through critical ration, correlation analysis, and Cronbach’s alpha if item deleted. Construct validity was performed through exploratory ( n  = 190) and confirmatory factor analyses ( n  = 276). Convergent and discriminant validity were evaluated. Reliability was evaluated through internal consistency, split-half reliability, and test-retest reliability. Results The final Health Literacy Scale consisted of 28 items, including dimensions of Basic Health Knowledge (11 items), Functional Health Literacy Skills (3 items), Communicative Health Literacy (5 items), and Critical Health Literacy (9 items). Principal component analysis revealed a four-factor structure that explained 80.092% of the total variance. The goodness-of-fit indices signified an adequate model fit (χ 2 /df = 2.093, RMSEA = 0.063, RMR = 0.031, GFI = 0.852, CFI = 0.958, NFI = 0.923, IFI = 0.958, TLI = 0.953, PCFI = 0.844). Cronbach’s alpha showed a good internal consistency reaching a value of 0.921. The split-half reliability was 0.805, and the test-retest reliability was good with an intraclass correlation coefficient of 0.885 ( P  < 0.001). Conclusions The Health Literacy Scale developed in this research focuses on health literacy issues related to children aged 3–6 years. The scale is demonstrated to be valid and reliable for assessing the health literacy of staff in preschool childcare institutions. It could potentially be used as an effective instrument for targeted development of health literacy intervention.