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Abstract Background Galangin, a flavonoid compound, is derived from Alpinia officinarum Hance. Previous studies have shown that galangin can inhibit the proliferation of hepatocellular carcinoma (HCC), but its mechanism is still unclear. This study aims to investigate the potential targets and molecular mechanisms of galangin on HCC through network pharmacology, bioinformatics, molecular docking, and experimental in vitro validation. Methods In this study, network pharmacology was used to investigate the targets and mechanisms of galangin in the treatment of HCC. AutoDockTools software was used to simulate and calculate the binding of galangin to its core targets. GO and KEGG enrichment analyses were conducted in the DAVID database to explore the main biological functions and signaling pathways impacted by galangin intervention. In addition, bioinformatics was applied to examine the correlation between the differential expressions of the anti-HCC core targets of galangin and the survival of patients with HCC. Finally, the findings obtained from network pharmacology and bioinformatics were verified in cell experiments. Results A total of 67 overlapping target genes of galangin and HCC were identified. Through the analysis of the protein-protein interaction (PPI) network, 10 hub genes with the highest degree of freedom were identified, including SRC, ESR1, MMP9, CDK4, CCNB1, MMP2, CDK2, CDK1, CHK1, and PLK1. These genes were found to be closely related to the degradation of the extracellular matrix, signal transduction, and the cell cycle. GO and KEGG enrichment analyses revealed that galangin exerts an anti-HCC role by affecting various signaling pathways, including the cell cycle, pathways in cancer, and the PI3K-Akt signaling pathway. The results of molecular docking indicated a significant interaction between galangin and CCNB1, CDK4, CDK1, and PLK1. Bioinformatics analysis revealed that CCNB1, CDK4, CDK1, and PLK1 were upregulated in the liver of patients with HCC at both the mRNA and protein levels. Flow cytometry analysis showed that galangin induced G0/G1 phase arrest and cell apoptosis in HepG2 and Huh7 cells. Additionally, galangin suppressed the expression of key proteins and mRNAs involved in the cell cycle pathway. Conclusions These results suggest that galangin inhibits the growth of HCC cells by arresting the cell cycle at the G0/G1 phase.

Anthocyanins are plant secondary metabolites belonging to the polyphenol class of natural water-soluble phytopigments. The accumulation of anthocyanins in different plant tissues can improve plant survival under adverse conditions. In addition, plants with the resulting colorful morphology can be utilized as landscape plants. Triticum boeoticum (syn. Triticum monococcum ssp. aegilopoides, 2n=2x=14, AbAb) serves as a valuable genetic resource for the improvement of its close relative common wheat in terms of enhancing resilience to various biotic and abiotic stresses. In our previous study, the EMS-mutagenized mutant Z2921 with a red glume, stem, and rachis was generated from T. boeoticum G52, which has a green glume, stem, and rachis. In this study, the F1, F2, and F2:3 generations of a cross between mutant-type Z2921 and wild-type G52 were developed. A single recessive gene, tentatively designated RgM4G52, was identified in Z2921 via genetic analysis. Using bulked segregant exome capture sequencing (BSE-Seq) analysis, RgM4G52 was mapped to chromosome 6AL and was flanked by the markers KASP-58 and KASP-26 within a 3.40-cM genetic interval corresponding to 1.71-Mb and 1.61-Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Triticum boeoticum (TA299) reference genomes, respectively, in which seven and four genes related to anthocyanin synthesis development were annotated. Unlike previously reported color morphology-related genes, RgM4G52 is a recessive gene that can simultaneously control the color of glumes, stems, and rachis in wild einkorn. In addition, a synthetic Triticum dicoccum–T. boeoticum amphiploid Syn-ABAb-34, derived from the colchicine treatment of F1 hybrids between tetraploid wheat PI 352367 (T. dicoccum, AABB) and Z2921, expressed the red stems of Z2921. The flanking markers of RgM4G52 developed in this study could be useful for developing additional common wheat lines with red stems, laying the foundation for marker-assisted breeding and the fine mapping of RgM4G52.

BackgroundLarge-scale prospective cohort studies on diabetic foot ulcers risk factor screening in China are limited. Therefore, this prospective cohort study aimed to explore the predictive risk factors for diabetic foot ulcers to provide clinicians with concise and effective clinical indicators for identifying a high-risk diabetic foot and guiding the prevention of diabetic foot ulcers.MethodsPatients with diabetes who visited the Department of Endocrinology of Peking University First Hospital from October 2017 to December 2018 were selected as research participants by convenience sampling. A total of 968 patients were included. After enrollment, a dedicated person collected and recorded all baseline data. A dedicated telephone follow-up was conducted every 12–24 months to evaluate whether the endpoint event had occurred. All patients were followed up for an average of 61 (57–71) months, with 95% of them followed up for more than 60 months. According to the occurrence of endpoint events, they were divided into the DFU and non-DFU groups. The data between the two groups were analyzed using independent-sample t-test, Wilcoxon rank sum test, and chi square test. We used univariate and multivariate logistic regression analysis to analyze the factors that affected the occurrence of diabetic foot ulcers.Results and conclusionsAfter the 5-year follow-up, the incidence of diabetic foot was 25.83%. Multivariate logistic regression analysis revealed that body mass index (odds ratio: 1.046; 95% confidence interval: 1.001–1.093), abnormal pinprick sensation (odds ratio: 4.138; 95% confidence interval: 1.292–13.255), history of fungal foot infection (odds ratio: 2.287; 95% confidence interval: 1.517–3.448), abnormal 128-Hz tuning fork test (odds ratio: 2.628; 95% confidence interval: 1.098–6.294), and HbA1c≥ 8% (odds ratio: 1.522; 95% confidence interval: 1.014–2.284) were independent predictors of diabetic foot. Our study highlights clinically relevant indicators that may help to prevent the occurrence of diabetic foot and guide timely interventions.

Abstract Peptide toxins found in sea anemones venom have diverse properties that make them important research subjects in the fields of pharmacology, neuroscience and biotechnology. This study used high-throughput sequencing technology to systematically analyze the venom components of the tentacles, column, and mesenterial filaments of sea anemone Heteractis crispa, revealing the diversity and complexity of sea anemone toxins in different tissues. A total of 1049 transcripts were identified and categorized into 60 families, of which 91.0% were proteins and 9.0% were peptides. Of those 1049 transcripts, 416, 291, and 307 putative proteins and peptide precursors were identified from tentacles, column, and mesenterial filaments respectively, while 428 were identified when the datasets were combined. Of these putative toxin sequences, 42 were detected in all three tissues, including 33 proteins and 9 peptides, with the majority of peptides being ShKT domain, β-defensin, and Kunitz-type. In addition, this study applied bioinformatics approaches to predict the family classification, 3D structures, and functional annotation of these representative peptides, as well as the evolutionary relationships between peptides, laying the foundation for the next step of peptide pharmacological activity research.

Triticum boeoticum Boiss. (AbAb, 2n = 2x = 14) is a wheat-related species with the blue aleurone trait. In this study, 18 synthetic Triticum turgidum-Triticum boeoticum amphiploids were identified, which were derived from crosses between T. boeoticum and T. turgidum. Three probes (Oligo-pTa535, Oligo-pSc119.2, and Oligo-pTa713) for multicolor fluorescence in situ hybridization (mc-FISH) were combined with genomic in situ hybridization (GISH) to identify chromosomal composition. Seven nutritional indices (anthocyanins, protein, total essential amino acids TEAA, Fe, Zn, Mn and Cu) were measured, and the nutritional components of 18 synthetic amphiploids were comprehensively ranked by principal component analysis (PCA). The results showed that all three synthetic amphiploids used for cytological identification contained 42 chromosomes, including 14 A, 14 B, and 14 Ab chromosomes. The average anthocyanin content was 82.830 μg/g to 207.606 μg/g in the whole meal of the 17 blue-grained lines (Syn-ABAb-1 to Syn-ABAb-17), which was obviously higher than that in the yellow-grained line Syn-ABAb-18 (6.346 μg/g). The crude protein content was between 154.406 and 180.517 g/kg, and the EAA content was 40.193-63.558 mg/g. The Fe, Zn, Mn and Cu levels in the 17 blue-grained lines were 60.55 to 97.41 mg/kg, 60.55-97.41 mg/kg, 35.11 to 65.20 mg/kg and 5.74 to 7.22 mg/kg, respectively, which were higher than those in the yellow-grained line. The contribution of the first three principal components reached 84%. The first principal component was mainly anthocyanins, Fe, Zn and Mn. The second principal component contained protein and amino acids, and the third component contained only Cu. The top 5 Triticum turgidum-Triticum boeoticum amphiploids were Syn-ABAb-11, Syn-ABAb-17, Syn-ABAb-5, Syn-ABAb-8 and Syn-ABAb-4. These amphidiploids exhibited the potential to serve as candidates for hybridization with common wheat, as indicated by comprehensive score rankings, toward enhancing the nutritional quality of wheat.

Background: sex differences existed in animal behavioral adaption and activity rhythms when exposed to chronic disruption of the circadian rhythm. Whether these differences extend to cardiac performance has not been fully investigated by cardiac imaging technology. Methods: One hundred and thirty patients enrolled in this study. Patients were divided into the day shift (DS) group and the irregular shift (IRS) group based on whether involved in the night shift and the frequency of the night shift. Comparisons of clinical data and cardiac imaging parameters were performed to identify the sex difference in cardiac function in the participants with day shift work or irregular shifts. Results: The absolute value of GLS was significantly lower in male IRS group than in male DS group. In females, no significant difference was tested in left ventricular function between the two groups. In male participants, Weekly work hours (WWH) was positively correlated with HR (r = 0.51, p = 0.02) and QTc duration (r = 0.68, p

Abstract“Skin gambling” is a new form of online gambling that has gained significant popularity over the last decade in the People’s Republic of China. Drawing on government reports and business media, this study employed two case studies of three leading Chinese skin gambling businesses to investigate how these companies survived and thrived despite Chinese laws that regulate online gambling. The findings revealed that the industry used the division of online gambling into virtual “skin” items and the separate exchange of these items for cash to shield businesses from the crackdowns ordered on online cash gambling events. Further, the skin gambling businesses were found to operate under the cover of the “esports industry,” “predictive games in public forums,” and “virtual assets markets.” The study demonstrated the significance of cultural framing in negotiating the regulation of illicit market practices.

Abstract Background With advances in massive parallel sequencing (MPS) technology, whole-genome sequencing (WGS) has gradually evolved into the first-tier diagnostic test for genetic disorders. However, deployment practice and pipeline testing for clinical WGS are lacking. Methods In this study, we introduced a whole WGS pipeline for genetic disorders, which included the entire process from obtaining a sample to clinical reporting. All samples that underwent WGS were constructed using polymerase chain reaction (PCR)-free library preparation protocols and sequenced on the MGISEQ-2000 platform. Bioinformatics pipelines were developed for the simultaneous detection of various types of variants, including single nucleotide variants (SNVs), insertions and deletions (indels), copy number variants (CNVs) and balanced rearrangements, mitochondrial (MT) variants, and other complex variants such as repeat expansion, pseudogenes and absence of heterozygosity (AOH). A semiautomatic pipeline was developed for the interpretation of potential SNVs and CNVs. Forty-five samples (including 14 positive commercially available samples, 23 laboratory-held positive cell lines and 8 clinical cases) with known variants were used to validate the whole pipeline. Results In this study, a whole WGS pipeline for genetic disorders was developed and optimized. Forty-five samples with known variants (6 with SNVs and Indels, 3 with MT variants, 5 with aneuploidies, 1 with triploidy, 23 with CNVs, 5 with balanced rearrangements, 2 with repeat expansions, 1 with AOHs, and 1 with exon 7–8 deletion of SMN1 gene) validated the effectiveness of our pipeline. Conclusions This study has been piloted in test development, optimization, and validation of the WGS pipeline for genetic disorders. A set of best practices were recommended using our pipeline, along with a dataset of positive samples for benchmarking.

AHP-3a, a triple-helix acidic polysaccharide isolated from Alpinia officinarum Hance, was evaluated for its anticancer and antioxidant activities. The physicochemical properties and structure of AHP-3a were investigated through gel permeation chromatography, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. The weight-average molecular weight of AHP-3a was 484 kDa, with the molar percentages of GalA, Gal, Ara, Xyl, Rha, Glc, GlcA, and Fuc being 35.4%, 21.4%, 16.9%, 11.8%, 8.9%, 3.1%, 2.0%, and 0.5%, respectively. Based on the results of the monosaccharide composition analysis, methylation analysis, and NMR spectroscopy, the main chain of AHP-3a was presumed to consist of (1→4)-α-D-GalpA and (1→2)-α-L-Rhap residues, which is a pectic polysaccharide with homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) structural domains containing side chains. In addition, the results of the antioxidant activity assay revealed that the ability of AHP-3a to scavenge DPPH, ABTS, and OH free radicals increased with an increase in its concentration. Moreover, according to the results from the EdU, wound healing, and Transwell assays, AHP-3a can control the proliferation, migration, and invasion of HepG2 and Huh7 hepatocellular carcinoma cells without causing any damage to healthy cells. Thus, AHP-3a may be a natural antioxidant and anticancer component.

Sea anemone venom, abundant in protein and peptide toxins, serves primarily for predatory defense and competition. This study delves into the insulin-like peptides (ILPs) present in sea anemones, particularly focusing on their role in potentially inducing hypoglycemic shock in prey. We identified five distinct ILPs in Exaiptasia diaphana, exhibiting varied sequences. Among these, ILP-Ap04 was successfully synthesized using solid phase peptide synthesis (SPPS) to evaluate its hypoglycemic activity. When tested in zebrafish, ILP-Ap04 significantly reduced blood glucose levels in a model of diabetes induced by streptozotocin (STZ) and glucose, concurrently affecting the normal locomotor behavior of zebrafish larvae. Furthermore, molecular docking studies revealed ILP-Ap04’s unique interaction with the human insulin receptor, characterized by a detailed hydrogen-bonding network, which supports a unique mechanism for its hypoglycemic effects. Our findings suggest that sea anemones have evolved sophisticated strategies to activate insulin receptors in vertebrates, providing innovative insights into the design of novel drugs for the treatment of diabetes.

Background: Hashimoto’s thyroiditis (HT) can be divided into IgG4 HT and non-IgG4 HT based on IgG4 and IgG immunohistochemical staining. In clinical practice, it is often necessary to identify diseases such as primary thyroid lymphoma (PTL) and IgG4 HT when a patient presents with a rapidly enlarged thyroid. The aim of our study was to uncover the differential points between the two diseases. Methods: Clinical information from 19 IgG4 HT and 10 PTL patients was obtained from the patients’ medical records, including age, sex, main clinical manifestation, thyroid functional status, the presence of serum anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and thyroid ultrasonography results. Thyroid sections from all patients were collected to detect IgG4 and IgG expression by immunohistochemical staining. Results: The IgG4 HT patients were significantly younger than those in t he PTL group (39.68 ± 10.95 vs 66.20 ± 10.23 years, P < 0.001). There were no significant differences in the sex distribution or TgAb- or TPOAb-positive r ates. The PTL group had a higher prevalence of clinical hypothyroidism than the IgG4 HT group (P = 0.016). In the PTL group, thyroid lesions were more likely to exhibit hypoechogenicity (6/6 vs 1/19, P < 0.001) on ultrasound images. In the PTL group, two patients met the immunohistochemical cut-off value of the criteria for IgG4 HT. Conclusions: Simply relying on immunohistochemistry for IgG4 cannot diagnose IgG4 HT correctly when a patient presents with rapid thyroid enlargement. A combination of clinical and pathological analyses will help distinguish IgG4 HT from PTL which may be with abundant IgG4-positive plasma cells.

Abstract Objective The study aimed to investigate the attitudes of people with diabetes mellitus (DM) on COVID-19 vaccination and its influence on the glycemic control. Methods Data were collected from a consecutive series of adults (age > 18 years) with type 2 diabetes under regular follow-ups in the Integrated Care Diabetes Outpatient Clinic of Peking University First Hospital from December 1st to December 31st 2021. An online interview questionnaire was conducted, and demographic data including age, sex category, history of drug allergy, history of hypertension, the duration of diabetes, reasons for vaccine hesitancy (VH) and adverse reactions after each injection of vaccines was collected. Glucose levels were collected from medical records. Results Thirty-nine (22.9%) subjects experienced VH and 131 (77.1%) people living with diabetes received inactivated vaccine against COVID-19. Hesitant individuals had a higher proportion of female gender (vaccinated group vs. VH group, 62/131 vs. 26/39, p = 0.044), higher baseline glycosylated hemoglobin A1c (HbA1c) (vaccinated group vs. VH group, 6.56 ± 0.95% vs. 7.54 ± 2.01%, p

IntroductionAlpinia oxyphylla Miquel (A. oxyphylla), one of the “Four Famous South Medicines” in China, is an essential understory cash crop that is planted widely in the Hainan, Guangdong, Guangxi, and Fujian provinces. Particularly, A. oxyphylla from Hainan province is highly valued as the best national product for geo-herbalism and is an important indicator of traditional Chinese medicine efficacy. However, the molecular mechanism underlying the formation of its quality remains unspecified.MethodsTo this end, we employed a multi-omics approach to investigate the authentic quality formation of A. oxyphylla.ResultsIn this study, we present a high-quality chromosome-level genome assembly of A. oxyphylla, with contig N50 of 76.96 Mb and a size of approximately 2.08Gb. A total of 38,178 genes were annotated, and the long terminal repeats were found to have a high frequency of 61.70%. Phylogenetic analysis demonstrated a recent whole-genome duplication event (WGD), which occurred before A. oxyphylla’s divergence from W. villosa (~14 Mya) and is shared by other species from the Zingiberaceae family (Ks, ~0.3; 4DTv, ~0.125). Further, 17 regions from four provinces were comprehensively assessed for their metabolite content, and the quality of these four regions varied significantly. Finally, genomic, metabolic, and transcriptomic analyses undertaken on these regions revealed that the content of nootkatone in Hainan was significantly different from that in other provinces.DiscussionOverall, our findings provide novel insights into germplasm conservation, geo-herbalism evaluation, and functional genomic research for the medicinal plant A. oxyphylla.

Ammonia is an attractive clean fuel for its potential to reduce CO2 emission and fossil fuel consumption. However, ammonia combustion has been mainly discouraged by the low flammability and the high fuel NOx emissions. This study numerically investigates the effects of swirl intensity on combustion characteristics in swirl-stabilized ammonia/methane combustion. Large eddy simulation was performed by using OpenFOAM, and the accuracy of numerical results was validated by the experiment. The results show that swirl intensity will significantly affects the flow field and flame structure, and flame stability decreases with the swirl number increasing. The high swirl intensity leads to extinguishing at the flame root, while the low swirl intensity cannot generate the central recirculation zone to stabilize the flame. Selective non-catalytic reduction of NO (SNCR) is the key to controlling NO emission, the decrease of temperature will promote the reduction of NO, while the decrease of residence time will inhibit the reduction of NO. Meanwhile, SNCR will weaken the correlation between NO and OH in ammonia/methane combustion. NO emission will decrease with the swirl intensity increasing. In a word, medium swirl number (S ≈ 0.76) is proper to control NO emission and ensure flame stability.

Background: To investigate the clinical characteristics of Addison’s disease caused by adrenal tuberculosis in Tibet. After the anti-tuberculosis treatment, the clinical features between continuous glucocorticoid therapy and glucocorticoid withdrawal were analyzed. Methods: Clinical data of patients with Addison's disease caused by adrenal tuberculosis diagnosed in The People's Hospital of Tibet Autonomous Region from January 2015 to October 2021 were collected and analyzed. All patients were taking anti-tuberculosis and glucocorticoids replacement therapy, and the root cause of the disease was analyzed following prognosis observations. Results: There were 25 patients (24 Tibetan and 1 Han patient) with Addison's disease caused by adrenal tuberculosis, including 18 males and 7 females. A total of 21 cases were followed up successfully, of which 13 cases discontinued anti-tuberculosis drugs successfully, 6 cases discontinued glucocorticoid therapy among the rest, 6 cases continued anti-tuberculosis + glucocorticoid replacement therapy, and 2 cases died. Conclusion: Early diagnosis and proper anti-tuberculosis treatment can improve the prognosis of patients with adrenal tuberculosis. Moreover, screening and educating Tibetan people regarding the potential risk and adversities of adrenal tuberculosis is crucial for eradicating the disease.