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Two new species; Lobothallia crenulata Lun Wang & Y. Y. Zhang, L. lobulata Lun Wang & Y. Y. Zhang and one new variety; L. subdiffracta var. rimosa Lun Wang & Y. Y. Zhang, are reported from China and described, based on morphological, chemical and molecular characters. Phylogenetic analyses showed that these new taxa form monophyletic groups. Lobothallia crenulata and L. lobulata, together with L. hydrocharis, L. radiosa and L. recedens, form a well-supported clade, whereas L. subdiffracta var. rimosa is nested within the samples of L. subdiffracta. Lobothallia crenulata is characterised by its placodioid thallus, thickly pruinose upper surface with a rimose appearance, aspicilioid to lecanorine apothecia with a crenate thalline margin and concave, black and pruinose discs. Lobothallia lobulata is characterised by its placodioid thallus, pruinose upper surface with lobules, aspicilioid when immature, lecanorine to zeorine apothecia at maturity and concave to plane, dark brown, shiny and epruinose discs. Lobothallia subdiffracta var. rimosa is characterised by its areolate thallus, rimose and pruinose upper surface, lecanorine apothecia and slightly concave to plane, black and pruinose discs. Secondary metabolites were not detected in the two new species nor the new variety. A key is provided for the species of Lobothallia in China.

Abstract Broomcorn millet (Panicum miliaceum L.), known for its traits of drought resistance, adaptability to poor soil, short growth period, and high photosynthetic efficiency as a C4 plant, represents one of the earliest domesticated crops globally. This study reports the telomere-to-telomere (T2T) gap-free reference genome for broomcorn millet (AJ8) using PacBio high-fidelity (HiFi) long reads, Oxford Nanopore long-read technologies and high-throughput chromosome conformation capture (Hi-C) sequencing data. The size of AJ8 genome was approximately 834.7 Mb, anchored onto 18 pseudo-chromosomes. Notably, 18 centromeres and 36 telomeres were obtained. The assembled genome showed high quality in terms of completeness (BUSCO score: 99.6%, QV: 61.7, LAI value: 20.4). In addition, 63,678 protein-coding genes and 433.8 Mb (~52.0%) repetitive sequences were identified. The complete reference genome for broomcorn millet provides a valuable resource for genetic studies and breeding of this important cereal crop.

Abstract Background LncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC). Method qRT-PCR and Immunofluorescence were used to analyze Arg-1, IL-10, CD163, CCL-18, CD206, and CRNDE expression in HCC tissues and macrophages. Western Blotting was used to analyze ERK and p-ERK expression. Edu assay, transwell assay and xenograft experiments were carried out to study cell viability, migrated and invasive capability. Immunohistochemical staining was used to evaluate Ki67 expression. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for macrophages metabolites analysis. Results Arg-1, IL-10, CD163, CD206, and CRNDE were significantly up-regulated in HCC tissues, M2 macrophage and M0 macrophage with CRNDE overexpressed (OV-CRNDE-M0), which downregulated in M0 macrophage with CRNDE knockdown (sh-CRNDE-M0). The conditioned medium (CM) of M2 cells and OV-CRNDE-M0 cells promoted cell viability, invasion, and migration of HCC cells, the effect was reversed by sh-CRNDE-M0 cells CM. OV-CRNDE-M0 cells promoted tumor growth, Ki67 and CD206 expression in xenograft model. 61 metabolites were detected, of which 18 metabolites changed significantly in OV-CRNDE-M0 group compared to M0 group, with 9 upregulated and 9 downregulated. KEGG analysis showed the enrichment pathways were biosynthesis, glyoxylate and dicarboxylate metabolism. SMPDB analysis showed the enrichment pathways were hypoacetylaspartia, canavan disease, and aspartate metabolism. Conclusion CRNDE regulated the metabolic reprogramming of M2 macrophage via ERK pathway, which thereby contributed to HCC proliferation, migration, and invasion.

Abstract This study aimed to retrospectively analyze the perioperative and postoperative follow-up data of patients with super obesity who had undergone RYGB, SG, BPD/DS, and SADI-S. A retrospective observational study was conducted to analyze the perioperative and postoperative follow-up data of 60 patients with super obesity who had undergone bariatric surgery. A total of 34 men and 26 women were included in this study. The participants had an average preoperative BMI of 53.81 ± 3.25 kg/m2. The body weight and BMI of all four patient groups decreased significantly at 3, 6, and 12 months postoperatively compared with the preoperative values. Additionally, the TWL (%) and EWL (%) of all four groups increased gradually over the same period. Compared with the preoperative values, the systolic and diastolic blood pressure, glycosylated hemoglobin, uric acid, triglycerides, and total cholesterol decreased to varying degrees in the four groups 1 year postoperatively. RYGB, SG, BPD/DS, and SADI-S are all safe and effective in treating super obese patients and improving their metabolic diseases to a certain extent.

Virus-induced gene silencing (VIGS) and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) systems are effective technologies for rapid and accurate gene function verification in modern plant biotechnology. However, the investigation of gene silencing and editing in radish remains limited. In this study, a bleaching phenotype was generated through the knockdown of RsPDS using tobacco rattle virus (TRV)- and turnip yellow mosaic virus (TYMV)-mediated gene silencing vectors. The TYMV-mediated gene silencing efficiency was higher than the TRV-based VIGS system in radish. The expression level of RsPDS was significantly inhibited using VIGS in ‘NAU-067’ radish leaves. The rootless seedlings of ‘NAU-067’ were infected with Agrobacterium rhizogenes using the 2300GN-Ubi-RsPDS-Cas9 vector with two target sequences. Nine adventitious roots were blue with GUS staining, and four of these adventitious roots were edited at target sequence 1 of the RsPDS gene as indicated by Sanger sequencing. Furthermore, albino lines were generated with A. tumefaciens-mediated transformation of radish cotyledons. Five base substitutions and three base deletions occurred at target sequence 2 in Line 1, and three base insertions and three base substitutions occurred at target sequence 1 in Line 2. This study shows that VIGS and CRISPR/Cas9 techniques can be employed to precisely verify the biological functions of genes in radish, which will facilitate the genetic improvement of vital horticultural traits in radish breeding programs.

Abstract To evaluate the efficacy and nutrition of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in Chinese obese patients in the first postoperative year. Clinical data of 66 obese patients who underwent SADI-S surgery at China-Japan Union Hospital of Jilin University from November 2018 to May 2022 were retrospectively collected. The weight, body mass index (BMI), percentage of excess weight loss (%EWL), and percentage of total weight loss (%TWL) were recorded at 3, 6, and 12 months after surgery. Moreover, metabolic disease remission and nutrient deficiencies were assessed at 1 year postoperatively. Overall, 66 patients (38 males and 28 females) were recruited, with a mean age of 35 (18–61) years and an average preoperative BMI of 42.94 kg/m2. Before surgery, 38 patients had type 2 diabetes mellitus (T2DM), 46 patients had hyperuricemia (HUA), 45 patients had hypertension (HTN), 35 patients had hyperlipidemia, 12 patients had hypercholesterolemia, 12 patients had hyper-low-density lipoproteinemia, and 14 patients had gastroesophageal reflux disease symptoms (GERD). All patients had undergone a DaVinci robotic or laparoscopic SADI-S surgery, and none converted to laparotomy or died. Four patients developed postoperative complications and were cured and discharged after conservative treatment or surgical treatment. At 3, 6 and 12 months, the average %EWL was 62.07 ± 26.56, 85.93 ± 27.92, and 106.65 ± 29.65%, %TWL was 22.67 ± 4.94, 32.10 ± 5.18, and 40.56 ± 7.89%, respectively. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), uric acid (UA), triglycerides (TG), blood pressure (BP), and other indexes were significantly lower after one year post-surgery compared with the preoperative period (P

Background: Dysferlinopathy is an autosomal recessive disorder caused by mutations in the DYSF gene. This study reported two homozygous adjacent missense mutations in the DYSF gene, presenting clinically with bilateral lower limb weakness and calf swelling. Two homozygous adjacent missense mutations in the DYSF gene may be associated with the development of dysferlinopathy, but the exact mechanism needs further investigation.Methods: A retrospective analysis of clinical data from a dysferlinopathy-affected family was conducted. Peripheral blood samples were collected from members of this family for whole-exome sequencing (WES) and copy number variation analysis. Sanger sequencing was employed to confirm potential pathogenic variants. The Human Splicing Finder, SpliceAI, and varSEAK database were used to predict the effect of mutations on splicing function. The pathogenic mechanism of aberrant splicing in dysferlinopathy due to two homozygous adjacent missense mutations in the DYSF gene was determined by an in vivo splicing assay and an in vitro minigene assay.Results: The proband was a 42-year-old woman who presented with weakness of the lower limbs for 2 years and edema of the lower leg. Two homozygous DYSF variants, c.5628C>A p. D1876E and c.5633A>T p. Y1878F, were identified in the proband. Bioinformatics databases suggested that the mutation c.5628C>A of DYSF had no significant impact on splicing signals. Human Splicing Finder Version 2.4.1 suggested that the c.5633A>T of DYSF mutation caused alteration of auxiliary sequences and significant alteration of the ESE/ESS motif ratio. VarSEAK and SpliceAI suggested that the c.5633A>T of DYSF mutation had no splicing effect. Both an in vivo splicing assay and an in vitro minigene assay showed two adjacent mutations: c.5628C>A p. D1876E and c.5633A>T p. Y1878F in the DYSF gene leading to an Exon50 jump that resulted in a 32-aa amino acid deletion within the protein. Point mutation c.5628C>A p. D1876E in the DYSF gene affected splicing in vitro, while point mutation c.5633A>T p. Y1878F in the DYSF gene did not affect splicing function.Conclusion: This study confirmed for the first time that two homozygous mutations of DYSF were associated with the occurrence of dysferlinopathy. The c.5628C>A p. D1876E mutation in DYSF affected the splicing function and may be one of the contributing factors to the pathogenicity.

In this study, two new species, Rhizoplaca adpressa Y. Y. Zhang & Li S. Wang and R. auriculata Y. Y. Zhang, Li S. Wang & Printzen, are described from Southwest China, based on their morphology, phylogeny and chemistry. In phylogeny, the two new species are monophyletic, and sister to each other within Rhizoplaca chrysoleuca-complex. Rhizoplaca adpressa is characterized by its placodioid and closely adnate thallus, pale green and heavily pruinose upper surface, narrow (ca. 1 mm) and white free margin on the lower surface of marginal squamules, the absence of a lower cortex, and its basally non-constricted apothecia with orange discs that turn reddish-brown at maturity. Rhizoplaca auriculata is characterized by its squamulose to placodioid thallus, yellowish green and marginally pruinose squamules, wide (1−3 mm) and bluish-black free margin on the lower surface of marginal squamules, the absence of a lower cortex, and its basally constricted apothecia with persistently orange discs. Rhizoplaca adpressa and R. auriculata share the same secondary metabolites of usnic and placodiolic acids.

Abstract Aminoacyl-tRNA synthetase (aaRS) is a core component for genetic code expansion (GCE), a powerful technique that enables the incorporation of noncanonical amino acids (ncAAs) into a protein. The aaRS with polyspecificity can be exploited in incorporating additional ncAAs into a protein without the evolution of new, orthogonal aaRS/tRNA pair, which hence provides a useful tool for probing the enzyme mechanism or expanding protein function. A variant (N346A/C348A) of pyrrolysyl-tRNA synthetase from Methanosarcina mazei (MmPylRS) exhibited a wide substrate scope of accepting over 40 phenylalanine derivatives. However, for most of the substrates, the incorporation efficiency was low. Here, a MbPylRS (N311A/C313A) variant was constructed that showed higher ncAA incorporation efficiency than its homologous MmPylRS (N346A/C348A). Next, N-terminal of MbPylRS (N311A/C313A) was engineered by a greedy combination of single variants identified previously, resulting in an IPE (N311A/C313A/V31I/T56P/A100E) variant with significantly improved activity against various ncAAs. Activity of IPE was then tested toward 43 novel ncAAs, and 16 of them were identified to be accepted by the variant. The variant hence could incorporate nearly 60 ncAAs in total into proteins. With the utility of this variant, eight various ncAAs were then incorporated into a lanthanide-dependent alcohol dehydrogenase PedH. Incorporation of phenyllactic acid improved the catalytic efficiency of PedH toward methanol by 1.8-fold, indicating the role of modifying protein main chain in enzyme engineering. Incorporation of O-tert-Butyl-L-tyrosine modified the enantioselectivity of PedH by influencing the interactions between substrate and protein. Enzymatic characterization and molecular dynamics simulations revealed the mechanism of ncAAs affecting PedH catalysis. This study provides a PylRS variant with high activity and substrate promiscuity, which increases the utility of GCE in enzyme mechanism illustration and engineering. Graphical Abstract

The epigenetic variation in protoplast regeneration is a topic that has attracted interest recently. To elucidate the role of DNA methylation in the regeneration of protoplasts from the ponkan (Citrus reticulata), this study employs the methylation-sensitive amplification polymorphism (MSAP) molecular marker technique to analyze changes in DNA methylation levels and patterns during the isolation and culture of protoplasts from ponkan and tobacco. Additionally, differential DNA methylation fragments are cloned, sequenced, and subjected to bioinformatics analysis. The results reveal that, for non-regenerable ponkan mesophyll protoplasts, DNA methylation levels increase by 3.98% after isolation and then show a trend of initial decrease followed by an increase during culture. In contrast, for regenerable ponkan callus protoplasts and tobacco mesophyll protoplasts, DNA methylation levels decrease by 1.75% and 2.33%, respectively, after isolation. During culture, the DNA methylation levels of ponkan callus protoplasts first increase and then decrease, while those of tobacco mesophyll protoplasts show an opposite trend of initial decrease followed by an increase. Regarding DNA methylation patterns, ponkan mesophyll protoplasts exhibit primarily hypermethylation changes accompanied by a small amount of gene demethylation, whereas ponkan callus protoplasts are dominated by demethylation changes with some genes undergoing hypermethylation. The methylation exhibits dynamic changes in protoplast isolation regeneration. By recovering, cloning, sequencing, and performing BLASTn alignment analysis on specific methylation modification sites in the ponkan, 18 DNA sequences with high homology are identified which are found to be involved in various biological functions, thereby establishing a foundational basis for genetic editing in protoplasts.

Ascorbate oxidase (AAO) plays an important role in maintaining cellular redox homeostasis, thereby influencing plant growth, development, and responses to both biotic and abiotic stresses. However, there has been no systematic characterization of AAO genes in Citrus, especially their roles in response to cold stress. In the present study, nine AAO genes were identified in C. sinensis through bioinformatics analyses, exhibiting uneven distribution across four chromosomes. All CsAAOs possessed three conserved domains and were predicted to localize in the apoplast. The CsAAO gene family displayed varied intron–exon patterns. Phylogenetic analysis categorized the CsAAO family into three main clades (Clade A–C), suggesting distinct biological functions. Collinearity and Ka/Ks analysis revealed three duplicate gene pairs within the CsAAO gene family, with all duplicated CsAAOs primarily evolving under purifying selection. Analysis of cis-acting elements showed the presence of multiple hormone response elements and stress response elements within the CsAAO promoters. The computational analysis of microRNA target transcripts suggested that CsAAO9 may be a target of csi-miR156. RNA-Seq data demonstrated high expression levels of CsAAOs in roots and young fruits, while qRT-PCR analysis showed significant upregulation of six CsAAOs in response to cold treatment. Furthermore, the activities of CsAAOs exhibited a pattern of initial decrease followed by an increase after exposure to low temperatures. These findings offer important insights into the role of CsAAOs in response to cold stress. Furthermore, AAOs could be target genes for breeding crops with better cold resistance.

BackgroundBariatric and metabolic surgery often leads to significant changes in gut microbiota composition, indicating that changes in gut microbiota after bariatric and metabolic surgery might play a role in ameliorating type 2 diabetes (T2D). However, the effects of single-anastomosis duodenal–ileal bypass with sleeve gastrectomy (SADI-S) on gut microbiota in T2D remain unclear.ObjectivesTo investigate the effects of SADI-S on gut microbiota and glucose metabolism in T2D rats.MethodsNineteen T2D rats were randomly divided into the SADI-S group (n = 10) and the sham operation with pair-feeding group (sham-PF, n = 9). Fecal samples were collected to analyze the gut microbiota composition with 16S ribosomal DNA gene sequencing. The fasting blood glucose and glycated hemoglobin were measured to evaluate the effects of SADI-S on glucose metabolism.ResultsThe Chao and ACE index results indicated the richness of the gut microbial community. The ACE and Chao index values were significantly lower in the SADI-S group than in the sham-PF group, indicating that indicating that species richness was significantly lower in the SADI-S group than in the sham-PF group (p < 0.05). Shannon and Simpson indices were used to estimate the species diversity of the gut microbiota. Compared with the sham-PF group, the SADI-S group showed significantly lower Shannon index and higher Simpson index values, indicating that the species diversity was significantly lower in the SADI-S group than in the sham-PF group (p < 0.05). At the genus level, SADI-S significantly changed the abundances of 33 bacteria, including the increased anti-inflammatory bacteria (Akkermansia and Bifidobacterium) and decreased pro-inflammatory bacteria (Bacteroides). SADI-S significantly decreased the fasting blood glucose and glycated hemoglobin levels. The blood glucose level of rats was positively correlated with the relative abundances of 12 bacteria, including Bacteroides, and negatively correlated with the relative abundances of seven bacteria, including Bifidobacterium.ConclusionSADI-S significantly altered the gut microbiota composition of T2D rats, including the increased anti-inflammatory bacteria (Akkermansia and Bifidobacterium) and decreased pro-inflammatory bacteria (Bacteroides). The blood glucose level of rats was positively correlated with the abundances of 12 bacteria, including Bacteroides, but negatively correlated with the relative abundance of 7 bacteria, including Bifidobacterium. These alternations in gut microbiota may be the mechanism through which SADI-S improved T2D. More studies should be performed in the future to validate these effects.

Backgrounds: Ferroptosis, an iron-dependent cell death characterized by lethal lipid peroxidation, has been involved in the pathogenesis of various diseases, such as ischemia/reperfusion injury, neurodegenerative diseases, and inflammatory disorders. Pharmacological inhibition of ferroptosis represents a promising strategy for the treatment of the above diseases. Flavonoids, a class of natural products found in medicinal plants and functional foods, are known for numerous activities, especially the newly discovered anti-ferroptotic activity. Objectives: Our review aims to expand our understanding of flavonoids’ anti-ferroptotic activity on multiple biological systems and to highlight the importance of utilizing flavonoids in ferroptosis-associated diseases. Material and Method: A systematic literature search was conducted using Google Scholar, PubMed, Web of Science, ScienceDirect, and Springer Link. The search was conducted using the following keywords: flavonoids, natural products, ferroptosis, mechanism, ischemia/reperfusion injury, neurodegenerative diseases, and inflammatory diseases. The available information was comprehensively studied and compiled. Results: We review the recent advances in molecular mechanisms of ferroptosis and its multiple roles in diverse diseases. We further systematically summarize the inhibitory roles and underlying mechanisms of flavonoids on ferroptosis, and suggest that inhibition of lipid ROS accumulation and labile Fe2+ availability as well as activation of Nrf2 signaling are responsible for ferroptosis inhibition. We also discuss their clinical applications in ferroptosis-related diseases. Conclusion: Taken together, natural flavonoids exhibit a promising treatment prospect for ferroptosis-associated diseases. This review is also expected to not only facilitate the design and development of flavonoid-based ferroptosis inhibitors, but also and the treatment of ferroptosis-related diseases using flavonoid-based therapies.

This study aimed to elucidate responses of the bacterial structure and diversity of the rhizosphere in flowering broomcorn millet after rehydration following drought stress. In this study, the broomcorn millet varieties ‘Hequ red millet’ (A1) and ‘Yanshu No.10′ (A2), known for their different drought tolerance levels, were selected as experimental materials. The plants were subjected to rehydration after drought stress at the flowering stage, while normal watering (A1CK and A2CK) served as the control. Soil samples were collected at 10 days (A11, A21, A1CK1, and A2CK1) and 20 days (A12, A22, A1CK2, and A2CK2) after rehydration. High-throughput sequencing technology was employed to investigate the variations in bacterial community structure, diversity, and metabolic functions in the rhizosphere of the broomcorn millet at different time points following rehydration. The findings indicated that the operational taxonomic units (OTUs) of bacteria in the rhizosphere of broomcorn millet were notably influenced by the duration of treatment, with a significant decrease in OTUs observed after 20 days of rehydration. However, bacterial Alpha diversity was not significantly impacted by rehydration following drought stress. The bacterial community in the rhizosphere of broomcorn millet was mainly composed of Actinobacteria and Proteobacteria. After rewatering for 10 to 20 days after drought stress, the abundance of Sphingomonas and Aeromicrobium in the rhizosphere soil of the two varieties of broomcorn millet decreased gradually. Compared with Yanshu No.10, the abundance of Pseudarthrobacter in the rhizosphere of Hequ red millet gradually increased. A Beta diversity analysis revealed variations in the dissimilarities of the bacterial community which corresponded to different rehydration durations. The relative abundance of bacterial metabolic functions in the rhizosphere of broomcorn millet was lower after 20 days of rehydration, compared to measurements after 10 days of rehydration. This observation might be attributed to the exchange of materials between broomcorn millet and microorganisms during the initial rehydration stage to repair the effects of drought, as well as to the enrichment of numerous microorganisms to sustain the stability of the community structure. This study helps to comprehend the alterations to the bacterial structure and diversity in the rhizosphere of broomcorn millet following drought stress and rehydration. It sheds light on the growth status of broomcorn millet and its rhizosphere microorganisms under real environmental influences, thereby enhancing research on the drought tolerance mechanisms of broomcorn millet.

IntroductionWe tried to apply a new surgical method to treat obesity combined with pancreatic pseudocyst and achieved satisfactory results.Case and presentationWe report a case of a severely obese patient with pancreatic pseudocyst who underwent robotic-assisted sleeve gastrectomy, while the pseudocyst was incised and cyst-jejunostomy was performed. The operation was successful, and the patient was discharged on the 8th day after the procedure. There were no complications during the perioperative period. After 12 months of follow-up examinations, the patient's pancreatic pseudocyst disappeared. Additionally, there was a significant decrease in body weight, body mass index, and other indicators. As a result, obesity and related metabolic diseases were completely relieved.ConclusionsThis case summarizes and presents the experience of using robotic bariatric surgery for the treatment of pancreatic pseudocyst. This case report indicates that this surgical procedure is both safe and effective for patients with pancreatic pseudocyst who also have obesity and related metabolic diseases.

The prefrontal cortex is involved in cocaine abuse disorders. Here, the authors show that cocaine suppresses frontal association cortex (FrA) in awake mice and induces locomotor sensitization through a dopamine dependent VTA-vmPFC-FrA pathway.

Background: Bariatric surgery is the most effective treatment for obese T2D. As one of the most effective bariatric surgeries, SADI-S was recently introduced in China, and there is limited evidence of its efficacy and safety in the treatment of obese T2D. The aim of this study is to investigate the safety and efficacy of SADI-S in the treatment of obese T2D in China. Methods: The clinical data of 32 obese T2D patients who underwent SADI-S was included in this study. Changes in weight-related indicators, diabetes-related indicators, and patient nutritional outcomes were analyzed. Results: SADI-S was conducted successfully in all of the 32 cases without conversion to laparotomy or death. The incidence of surgical complications was 15.6% (5/32). The major complication rate was 6.3% (2/32). At 1 year after surgery, the BMI (kg/m2) significantly decreased from 40.8 ± 7.4 to 23.9 ± 2.9 (P

Three new compounds (1, 11, and 12), together with 32 known ones, were isolated from the root bark of Morus alba L. using various chromatographic methods. The structures of the undescribed compounds were elucidated based on 1D, 2D NMR, and HRESIMS dataanalysis, while the known ones were identified by comparison of their spectroscopic data with those reported in the literature. All the isolates were evaluated for their cytotoxic activities against human gastric cancer HGC27 cells by CCK-8 assay. Among them, compounds 5, 8, 10, and 30 exhibited cytotoxic activities on HGC27 cells with IC50 values of 33.76 ± 2.64 μM, 28.94 ± 0.72 μM, 6.08 ± 0.34 μM, and 10.24 ± 0.89 μM, respectively. Furthermore, compound 10 was confirmed to reduce proliferation ability, increase apoptosis rate, and inhibit cell migration pathway by annexin V/PI double staining experiment, transwell experiment, and Western blot analysis.

Background: The effect of laparoscopic sleeve gastrectomy (LSG) in the treatment of type 2 diabetes (T2D) patients with body mass index (BMI is calculated by dividing weight in kilograms by height in meters squared) higher than 25 kg/m2 but lower than 32.5 kg/m2, especially in East Asian population characterized by abdominal obesity, are still unclear. This study aims to explore the effect of LSG in T2D patients with BMI higher than 25 kg/m2 but lower than 32.5 kg/m2. Methods: A total of 49 T2D patients with BMI(25–32.5 kg/m2) treated successfully with LSG were included in our study. The effect of LSG on T2D remission outcomes at 12 and 24 months after operation was analyzed. Results: All patients were treated successfully with LSG without conversion. The mean preoperative body weight,BMI, fasting plasma glucose, glycosylated hemoglobin (A1c) and fasting C-peptide were 81.7 ± 10.0 kg, 29.1 ± 2.4 kg/m2, 10.4 ± 3.9 mmol/L,8.2 ± 1.5%, and 2.3 ± 1.1 nmol/L,respectively.The age, duration of diabetes and ABCD score were 48.6 ± 9.6 years,6.6 ± 5.1 years, and 2.9 ± 1.5. The mean fasting plasma glucose,A1c, and C-peptide levels were significantly decreased at 12 and 24 months after operation. At postoperative 24 months, 18 out of 49 patients (36.7%) reached diabetes complete remission (A1c levels≤6.0%).14 out of 49 patients (28.6%) reached partial remission (6.0%

The kinase domain is highly conserved among protein kinases 'in terms of both sequence and structure. Conformational rearrangements of the kinase domain are affected by the phosphorylation of residues and the binding of kinase inhibitors. Interestingly, the conformational rearrangement of the active pocket plays an important role in kinase activity and can be used to design novel kinase inhibitors. We characterized the conformational plasticity of the active pocket when bosutinib was bound to salt-inducible kinase 2 (SIK2) using homology modeling and molecular dynamics simulations. Ten different initial complex models were constructed using the Morph server, ranging from open to closed conformations of SIK2 binding with bosutinib. Our simulation showed that bosutinib binds SIK2 with up or down conformations of the P-loop and with all the conformations of the activation loop. In addition, the αC-helix conformation was induced by the conformation of the activation loop, and the salt bridge formed only with its open conformation. The binding affinity of the models was also determined using the molecular mechanics generalized Born surface area method. Bosutinib was found to form a strong binding model with SIK2 and hydrophobic interactions were the dominant factor. This discovery may help guide the design of novel SIK2 inhibitors.

BackgroundBiliopancreatic diversion with duodenal switch (BPD-DS) is a bariatric procedure used in the treatment of obesity and related metabolic disorders. However, to date, the data on BPD-DS among Chinese patients with obesity is completely lacking.ObjectiveThis is the first study to evaluate the safety and efficacy of BPD-DS in the treatment of Chinese patients with obesity.MethodsData from 12 patients undergoing BPD-DS between September 2019 and March 2020 were analyzed retrospectively to evaluate complications, weight loss, comorbidity resolution, and nutritional status.ResultsAll patients completed the 1-year follow-up. There was no conversion to laparotomy or death. Mean operative time was 257.08 ± 29.27 min. The median length of stay was 7 days (ranging from 4–38 days). Complications occurred in three patients. The 1-year body mass index was 25.13 ± 4.71 kg/m2 with a mean excess weight loss of 100.11 ± 33.29% and a mean total weight loss of 43.22 ± 7.71%. Remission was achieved in 100% (7/7 cases) for type 2 diabetes, in 83.3% (10/12 cases) for hypertension, and in 62.5% (5/8 cases) for hyperuricemia. At 1 year after BPD-DS, the prevalence of albumin deficiency was 16.7%, for iron deficiency was 16.7%, and for zinc deficiency was 50%. There were 8.3% of the patients who were anemic. High deficiency rates for vitamins were presented mainly in vitamin A and vitamin E: vitamin A in 58.3% of the patients and vitamin E in 50% of the patients. The prevalence of asymptomatic gallstones increased significantly from 0% preoperatively to 41.7% postoperatively.ConclusionBPD-DS had excellent weight loss and resolution of comorbidities among Chinese patients with obesity. However, high rates of nutritional deficiencies and complications were found after BPD-DS, especially for vitamin A and vitamin E.

The start-up period is the most difficult period for enterprises to survive and innovate. How will government subsidies affect the innovation efficiency of enterprises in the start-up period? And, is there any heterogeneity? The academic research is still relatively preliminary and controversial. This study adopts the cash flow method to screen a sample of start-ups from Chinese GEM, STAR Market and SME board-listed companies from 2010 to 2020 for empirical research. The study found that financial subsidies can generally promote the innovation efficiency of start-ups, but there is also significant heterogeneity by industry, region and whether the subsidies are sustainable. Financial subsidies generally have a signaling effect that facilitates startups to attract external capital, and this effect is most significant in the industrial sector. Overall, fiscal decentralization negatively regulates the effect of subsidies on the innovation efficiency of start-ups, especially in the public utilities and industrial sectors. The government subsidies are relatively insignificant to improve the innovation efficiency of start-up enterprises in non-first-tier cities, especially in small and medium-sized cities, and the multiplier effect is relatively small. The effect of non-sustainable subsidies is not significant because they cannot produce a long-term mechanism and thus are difficult to influence future expectations and decisions. The subsidy effect is not significant in other industries outside the industrial sector, and the lower the level of industry competition, the weaker the signaling effect of enterprise credit, the less conducive to its access to external innovation resources to enhance innovation efficiency through the signaling effect of government subsidies. Moreover, financial decentralization does not improve the innovation efficiency of government subsidies as expected, but weakens the innovation efficiency of fiscal subsidies for start-up enterprises in general. The study proposed that the government (especially the small and medium-sized city government) should optimize the business environment and financial capital allocation, change the supervision and management mechanism, improve the efficiency of capital utilization and reduce the crowding out effect. The government’s subsidy policy should be further standardized and refined.

BackgroundSingle-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is one of the most effective bariatric procedures in the treatment of type 2 diabetes mellitus (T2DM). However, the mechanisms by which SADI-S improves T2DM are not well-known.ObjectiveTo explore the effects of SADI-S on metabolites in the stool of rats with T2DM.MethodsTwenty rats were fed on high-fat diet and administered with a low-dose (30mg/kg) of streptozotocin to establish T2DM models. The rats were then randomly assigned to the SADI-S group (n=10) and sham operation group (n=9). Stool samples were collected from all rats at 8 weeks after surgery and stored at -80 °C. Metabolomics analysis was performed to identify differential metabolites through ultra- performance liquid chromatography-mass spectrometry.ResultsAt 8-week after surgery, rats of the SADI-S group showed significantly decreased fasting blood glucose, glucose tolerance test 2-hour, glycated haemoglobin, and body weight compared with those of the sham group. A total of 245 differential metabolites were identified between the two groups, among which 8 metabolites were detectable under both the positive ion model and negative ion model. Therefore, a total of 237 differential metabolites were identified in our study which were mainly involved in tryptophan metabolism; cysteine and methionine metabolism; phenylalanine metabolism; phenylalanine; tyrosine and tryptophan biosynthesis; arginine biosynthesis; alanine, aspartate and glutamate metabolism; Arginine and proline metabolism; glyoxylate and dicarboxylate metabolism; alpha-Linolenic acid metabolism; Linoleic acid metabolism; riboflavin metabolism; nicotinate and nicotinamide metabolism; pyrimidine metabolism; porphyrin and chlorophyll metabolism.ConclusionSADI-S significantly improved the glucose metabolism in T2DM rats. In addition, SADI-S significantly changed the composition of metabolites in T2DM rats which were involved in tryptophan metabolism pathway, linoleic acid metabolism pathway and so on. This may be the mechanism by which SADI-S improved T2DM.

SWEET (Sugars Will Eventually be Exported Transporter) genes play essential roles in various biological processes, including phloem loading, sugar efflux, plant development and stress response. In this study, a total of 33 RsSWEET gene members were identified in the radish genome. They could be divided into four subfamilies and are distributed on eight radish chromosomes. Cis-acting regulatory element analysis indicated that these RsSWEET genes were potentially involved in the radish growth and development and stress response process, including circadian control and light response and responses to numerous stresses, including low-temperature and drought stress. Transcriptome data analysis revealed that a number of RsSWEET genes exhibited specific expression patterns in different tissues and developmental stages of radish. Moreover, several RsSWEET genes (e.g., RsSWEET2a, RsSWEET3a, RsSWEET16b and RsSWEET17) showed differential expression profiles under various abiotic stresses, including cold, heat, salt, Cd and Pb stress. Remarkably, the RsSWEET17 was specifically expressed in the cambium of radish. RsSWEET17 was heterologously expressed in yeast strain EBY.VW4000, which suggested that it has the ability to transport sugar. Notably, RsSWEET17-overexpressing Arabidopsis plants exhibited excessive root length, greater fresh weight and higher soluble sugar content (SSC) accumulation compared with wild-type (WT) plants, indicating that RsSWEET17 might positively regulate radish taproot development by strategically manipulating sugar accumulation. Collectively, these results clarify the molecular mechanisms underlying RsSWEET-mediated sugar accumulation and root growth and development in radish.

To identify optimal mating combinations for Litopenaeus vannamei, a linear mixed model was used to estimate the general combining ability (GCA) and specific combining ability (SCA) for growth and multiple stress tolerance [high salt (35‰), low pH (6 ± 0.1), and high ammonia nitrogen (70 mg/L) co-stress] traits in 47 combinations of L. vannamei. The results showed that the SCA in the parents played a dominant role in the offspring traits. The highest GCAs were observed for females of strain O and males of strain B (0.602 and 8.889, respectively), indicating that the dams of strain O and sires of strain B could be used as maternal and paternal lines to increase multiple stress resistance in the next generation. The growth traits of the hybrid combination strain G♂ × strain H♀ exhibited the highest degree of heterosis (9.838%–46.518%) and a generally high SCA (0.643–8.596) among all mating combinations. The SCA was the highest for the strain N♂ × strain O♀ multiple stress tolerance (30.131), while the heterosis for that combination strain was the third-highest. The combinations of strain G♂ × strain H♀ and strain N♂ × strain O♀ can be used as candidate combinations for rapid growth and multiple stress tolerance, respectively.

BackgroundThe robotic surgical system is being used in various bariatric procedures. However, only a few studies with very small sample size are present on robotic single-anastomosis duodenal–ileal bypass with sleeve gastrectomy (SADI-S). Moreover, to date, the learning curve of robotic SADI-S has been poorly evaluated yet.ObjectiveThis retrospective study aimed to estimate the learning curve of robotic SADI-S.Methods102 consecutive patients who underwent robotic SADI-S between March 2020 and December 2021 were included. Textbook outcome standard was performed to comprehensively evaluate clinical outcome of robotic SADI-S. Based on the textbook outcome, we evaluated the learning curve of robotic SADI-S by the cumulative sum (CUSUM) method.ResultsThe mean operative time was 186.13 ± 36.91 min. No conversion to laparotomy or deaths occurred during the study period. The rate of complications was 6.9% (n = 7), of which major complications were identified in 2.9% (n = 3), including 2 gastric leakages and 1 respiratory failure. A total of 60 patients reached the textbook outcome standard. The rate of textbook outcome was positive and was steadily increasing after the number of surgical cases accumulated to the 58th case. Taking the 58th case as the boundary, all the patients were divided into the learning stage group (the first 58 patients) and mastery stage group (the last 44 patients). The rate of complications, proportion of abdominal drainage tubes and postoperative hospital stay were significantly higher in the learning stage group compared with the mastery stage group (P

Due to the complexity and uncertainty of decision-making circumstances, it is difficult to provide an accurate compensation cost in strategic weight manipulation, making the compensation cost uncertain. Simultaneously, the change in the attribute weight is also accompanied by risk, which brings a greater challenge to manipulators’ decision making. However, few studies have investigated the risk aversion behavior of manipulators in uncertain circumstances. To address this research gap, a robust risk strategic weight manipulation approach is proposed in this paper. Firstly, mean-variance theory (MVT) was used to characterize manipulators’ risk preference behavior, and a risk strategic weight manipulation model was constructed. Secondly, the novel robust risk strategic weight manipulation model was developed based on the uncertainty caused by the estimation error of the mean and covariance matrix of the unit compensation cost. Finally, a case of emergency facility location was studied to verify the feasibility and effectiveness of the proposed method. The results of the sensitivity analysis and comparative analysis show that the proposed method can more accurately reflect manipulators’ risk preference behavior than the deterministic model. Meanwhile, some interesting conclusions are revealed.

Abstract Background The anterior chest wall (ACW) involvement is characteristic of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, yet little research has focused on its magnetic resonance imaging (MRI) findings. Purpose To characterize the MRI features of the ACW in patients with SAPHO syndrome. Methods Seventy-one patients with SAPHO syndrome and ACW involvement evidenced by bone scintigraphy were recruited in this cross-sectional study. The ACW region was scanned using sagittal, axial, and oblique coronal Dixon T2-weighted sequences and axial Dixon T1-weighted sequences. The characteristics of both active inflammatory and chronic structural lesions were evaluated. Results The ACW lesions exhibited an asymmetrical distribution and a predilection for the sternocostoclavicular region (93.0%). Notably, 91.5% of the patients had lesions in the area of the anterior first ribs. Bone marrow edema (BME) was observed in 63 (88.7%) patients, which mainly affected the sternocostal joints (87.3%) and the manubrium sterni (84.5%). All of the BMEs were distributed under the articular surface or the bone cortex, consistent with the distribution of the ligaments and joint capsules. Synovitis was detected in 64 (90.1%) patients, with a predilection for the sternoclavicular joints (76.1%). A soft tissue mass or infiltration was found in all the patients who had bone marrow edema. Thirteen (18.3%) patients showed venous stenosis. Structural changes included bone bridge formation (80.3%), hyperostosis (43.7%), and fat infiltration (39.4%). Four common patterns of involvement were observed: the first rib area, the sternoclavicular area, the sternal angle area, and the areas of the second to sixth sternocostal joints. Conclusion The ACW lesions of SAPHO syndrome demonstrated a triad of enthesitis, synovitis, and osteitis, suggesting complex interactions among the ligaments, synovium, and bones in the region. The inflammatory changes in the first rib area were highlighted in SAPHO syndrome.

Objective: Angiogenesis plays a vital role in tumor growth and metastasis. Here, we aimed to find novel efficient antiangiogenic molecules targeting vascular endothelial growth factor A (VEGFA ) at the transcriptional level to treat triple-negative breast cancer (TNBC). Methods: We used a cell-based seryl tRNA synthetase (SerRS) promoter-driven dual-luciferase reporter system to screen an in-house library of 384 naturally occurring small molecules and their derivatives to find candidate molecules that could upregulate the expression of SerRS, a potent transcriptional repressor of VEGFA. The levels of SerRS and VEGFA were examined by quantitative RT-PCR (qRT-PCR), western blotting, and/or ELISAs in TNBC cells after candidate molecule administration. Zebrafish, the Matrigel plug angiogenesis assay in mice, the TNBC allograft, and xenograft mouse models were used to evaluate the in vivo anti-angiogenic and anti-cancer activities. Furthermore, the potential direct targets of the candidates were identified by proteomics and biochemical studies. Results: We found the most active compound was 3-(4-methoxyphenyl) quinolin-4(1H)-one (MEQ), an isoflavone derivative. In TNBC cells, MEQ treatment resulted in increased SerRS mRNA (P < 0.001) and protein levels and downregulated VEGFA production. Both the vascular development of zebrafish and Matrigel plug angiogenesis in mice were inhibited by MEQ. MEQ also suppressed the angiogenesis in TNBC allografts and xenografts in mice, resulting in inhibited tumor growth and prolonged overall survival (P < 0.05). Finally, we found that MEQ regulated SerRS transcription by interacting with MTA2 (Metastasis Associated 1 Family Member 2). Conclusions: Our findings suggested that the MTA2/SerRS/VEGFA axis is a drug-treatable anti-angiogenic target, and MEQ is a promising anti-tumor molecule that merits further investigation for clinical applications.

Abstract. Objective:. To review the latest progress on the pathogenic mechanism and management of rheumatoid arthritis (RA)-associated coronary artery disease (CAD), and propose advice on future management optimization as well as prospects for research and development of new therapeutic regimen. Data sources:. This study was based on data obtained from PubMed up to May 2019 using various search terms and their combinations, including coronary artery disease, myocardial ischemia, cardiovascular diseases, RA, rheumatic diseases, treatment, therapy, strategies, immunotherapy, inflammation, and anti-inflammation. Study selection:. All retrieved literature was scrutinized, most relevant articles about the pathogenic mechanism and clinical management, especially anti-inflammatory therapy of RA-associated CAD were reviewed. Results:. RA is an immune-mediated chronic inflammatory disease which has a great social disease burden. In addition to typical arthritic manifestations, RA also affects extra-articular tissues and organs, within which the involvement of the cardiovascular system, especially incorporating CAD, is the leading cause of death for patients with RA. Recently, numerous basic and clinical studies have been carried out on the mechanism of CAD development and progression under the inflammatory cascade of RA. The effect of traditional RA drugs on CAD risk management has been gradually clarified, and more emerging biologic agents are being explored and studied, which have also achieved satisfactory outcomes. Furthermore, with the success of the CANTOS clinical trial, novel anti-inflammatory therapy for the prevention of cardiovascular disease is believed to have a broad prospect. Conclusions:. RA is an independent risk factor for CAD, which mainly results from the underlying inflammatory cascade; therefore, anti-inflammatory therapy, especially the emerging novel biologic drugs, is important for CAD management in patients with RA and may also be a promising approach among the general population.

In most higher plants, sucrose is the significant form of carbohydrate for long-distance transportation. Sucrose transporters/sucrose carriers (SUTs/SUCs) are involved in the loading and unloading of sucrose in phloem and play an important role in the growth and development of plants. In this study, 12 RsSUC genes were first identified from the radish genome, and their phylogenetic relationships, gene structure, and conserved motifs were further analyzed. RT-qPCR results indicated that RsSUC genes exhibited various expression patterns in different tissues and development stages of the radish. Overexpression of RsSUC1b in Arabidopsis significantly improved the uptake efficiency of exogenous sucrose, and promoted leaves and lateral root growth. In addition, the transgenic plants flowered significantly earlier than wild-type (WT) plants, and the soluble sugar contents (SSCs) including sucrose, glucose, and fructose in the mature leaves and pods were increased. It could be inferred that RsSUC1b is a plasma membrane sucrose transporter and plays a vital role in sucrose transportation and sugar accumulation during plant growth and development. These findings provided novel insights into the biological function of RsSUC genes and facilitate dissecting the molecular mechanism underlying sugar transport during radish development.

In this study, systematic separation and subsequent pharmacological activity studies were carried out to identify cytotoxic natural products from the dried stems of Millettia pachyloba Drake. Five previously undescribed isoflavones, pachyvones A–E; one previously undescribed xanthone, pachythone A; and twenty-two known compounds were obtained. The structures of these compounds were assigned on the basis of 1D/2D NMR data and high-resolution electrospray ionization mass spectroscopy analysis. Preliminary activity screening with HeLa and MCF-7 cells showed that ten compounds (3–5, 9, 12, 17–19, 24, and 25) had potential cytotoxicity. Further in-depth activity studies with five cancer cell lines (HeLa, HepG2, MCF-7, Hct116, and MDA-MB-231) and one normal cell line (HUVEC) revealed that these ten compounds showed specific cytotoxicity in cancer cells, with IC50 values ranging from 5 to 40 μM, while they had no effect on normal cell lines. To investigate whether the cytotoxicity of these ten compounds was associated with autophagy, their autophagic effects were evaluated in GFP-LC3-HeLa cells. The results demonstrated that compound 9 (durmillone) significantly induced autophagy in a concentration-dependent manner and had the best activity as an autophagy inducer among all of the compounds. Therefore, compound 9 was selected for further study. The PI/Annexin V double staining assay and Western blotting results revealed that compound 9 also induced obvious apoptosis in HeLa and MCF-7 cells, which suggests that it mediates cytotoxic activity through activation of both apoptosis and autophagy. Taken together, this study identified ten natural cytotoxic products from the dried stems of Millettia pachyloba Drake, of which compound 9 induced apoptosis and autophagy and could be an anticancer drug candidate. Keywords: Millettia pachyloba, Leguminosae, Isoflavones, Cytotoxicity, Autophagy, Apoptosis

Background: The leaves and roots of Panax ginseng are rich in ginsenosides. However, the chemical compositions of the leaves and roots of P. ginseng differ, resulting in different medicinal functions. In recent years, the aerial parts of members of the Panax genus have received great attention from natural product chemists as producers of bioactive ginsenosides. The aim of this study was the isolation and structural elucidation of novel, minor ginsenosides in the leaves of P. ginseng and evaluation of their antiinflammatory activity in vitro. Methods: Various chromatographic techniques were applied to obtain pure individual compounds, and their structures were determined by nuclear magnetic resonance and high-resolution mass spectrometry, as well as chemical methods. The antiinflammatory effect of the new compounds was evaluated on lipopolysaccharide-stimulated RAW 264.7 cells. Results and conclusions: Two novel, minor triterpenoid saponins, ginsenoside LS1 (1) and 5,6-didehydroginsenoside Rg3 (2), were isolated from the leaves of P. ginseng. The isolated compounds 1 and 2 were assayed for their inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 cells, and Compound 2 showed a significant inhibitory effect with IC50 of 37.38 μM compared with that of NG-monomethyl-L-arginine (IC50 = 90.76 μM). Moreover, Compound 2 significantly decreased secretion of cytokines such as prostaglandin E2 and tumor necrosis factor-α. In addition, Compound 2 significantly suppressed protein expression of inducible nitric oxide synthase and cyclooxygenase-2. These results suggested that Compound 2 could be used as a valuable candidate for medicinal use or functional food, and the mechanism is warranted for further exploration. Keywords: Antiinflammatory activity, Panax ginseng, Triterpenoid saponins

Broomcorn millet is one of the oldest crops cultivated by human that has strong abiotic stress tolerance. To facilitate genome assisted breeding of this and related species, the authors report its genome assembly and conduct comparative genome structure and evolution analyses with foxtail millet.

Objective: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disorder and the underlying pathogenesis is unclear. In this study, 88 SAPHO patients and 118 healthy controls were recruited to investigate the role of serum-derived extracellular vesicles (SEVs) in SAPHO syndrome. Methods: Quantitative proteomics was applied for SEVs proteome identification, and ELISA and Western blotting was performed to verify the results of mass spectrum data. In vitro osteoclastogenesis and osteogenesis assay was used to confirm the effects of SEVs on bone metabolism. Results: Tandem mass tagging-based quantitative proteomic analysis of SAPHO SEVs revealed differential expressed proteins involved in bone metabolism. Of these, serum amyloid A-1 (SAA1) and C-reactive protein (CRP) were upregulated. Higher SAA1 levels in SAPHO patients were confirmed by ELISA. In addition, SAA1 levels were positively correlated with CRP, an inflammatory marker related to the condition of patients. In vitro celluler studies confirmed that SAPHO SEVs inhibited osteoclastogenesis in patients mainly in the active phase of the disease. Further analysis demonstrated that Nucleolin was upregulated in osteoclasts of active-phase patients under SAPHO SEVs stimulation. Conclusion: In this study, we identified SAA1 as an additional inflammation marker that can potentially assist the diagnosis of SAPHO syndrome, and speculated that Nucleolin is a key regulator of osteoclastogenesis in active-phase patients.

Catalysis covers almost all the chemical reactions or processes aiming for many applications. Sonochemistry has emerged in designing and developing the synthesis of nano-structured materials, and the latest progress mainly focuses on the synthetic strategies, product properties as well as catalytic applications. This current review simply presents the sonochemical effects under ultrasound irradiation, roughly describes the ultrasound-synthesized inorganic nano-materials, and highlights the sonochemistry applications in the inorganics-based catalysis processes including reduction, oxidation, degradation, polymerization, etc. Or all in all, the review hopes to provide an integrated understanding of sonochemistry, emphasize the great significance of ultrasound-assisted synthesis in structured materials as a unique strategy, and broaden the updated applications of ultrasound irradiation in the catalysis fields.

Herein, TKP-2-1, a water-soluble polysaccharide with a weight-average molecular weight of 1693 kDa, was isolated from the seed kernels of Tamarindus indica L. UV, FT-IR, GC–MS and 1D, 2D-NMR data analysis revealed that TKP-2-1 is chiefly composed of a (1 → 4)-β-D-glucan backbone with side chains of α-D-xylopyranosyl, α-D-xylopyranosyl-(1 → 4)-β-D-galactopyranosyl and β-D-galactopyranosyl-(1 → 2)-α-D-xylopyranosyl sugar moieties linked to the C-6 positions of the glucose residues. Furthermore, TKP-2-1 exhibited a potent immunostimulatory activity through enhancing phagocytosis and NO production, as well as the expression of iNOS, IL-1β, IL-6, and TNF-α in RAW264.7 macrophages. Mechanistically, TKP-2-1 caused the degradation of IκBα and nuclear translocation of NF-κB p65, and phosphorylation of ERK, JNK and p38 MAPK in RAW264.7 cells. Specific inhibitors of NF-κB, ERK, JNK, and p38 MAPK obviously abolished TKP-2-1-induced NO production in RAW264.7 cells, respectively. Thus, TKP-2-1 from the seed kernels of T. indica might potentially be used as a natural immunomodulator in functional foods.

Substantial controversies exist in the exploration of the molecular mechanism of heart failure (HF) and pose challenges to the diagnosis of HF and the discovery of specific drugs for the treatment. Recently, cardiac transthyretin (TTR) amyloidosis is becoming recognized as one of major causes of underdiagnosed HF. The investigation and modulation of TTR misfolding and amyloidal aggregation open up a new revenue to reveal the molecular mechanisms of HF and provide new possibilities for the treatment of HF. The aim of this review is to briefly introduce the recent advances in the study of TTR native and misfolding structures, discuss the correlation between the genotype and phenotype of cardiac TTR amyloidosis, and summarize the therapeutic applications of TTR structural stabilizers in the treatment of TTR amyloidosis-associated HF.

Background: Time-restricted feeding, also known as intermittent fasting, can confer various beneficial effects, especially protecting against obesity, and related metabolic disorders, but little is known about the underlying mechanisms. Therefore, the present study aims to investigate the effects of time-restricted feeding on the circadian rhythm of gut microbiota and hepatic metabolism.Methods: Eight-week-old male Kunming mice received either a normal diet ad libitum, a high-fat diet ad libitum, or a high-fat diet restricted to an 8-h temporal window per day for an experimental period of 8 weeks. Weight gain and calorie intake were measured weekly. Serum metabolites, hepatic sections and lipid metabolites, gut microbiota, and the hepatic expression of Per1, Cry1, Bmal1, SIRT1, SREBP, and PPARα were measured at the end of the experimental period. The composition of gut microbiota and the expression of hepatic genes were compared between four timepoints.Results: Mice that received a time-restricted high-fat diet had less weight gain, milder liver steatosis, and lower hepatic levels of triglycerides than mice that received a high-fat diet ad libitum (p < 0.05). The numbers of Bacteroidetes and Firmicutes differed between mice that received a time-restricted high-fat diet and mice that received a high-fat diet ad libitum (p < 0.05). Mice fed a time-restricted high-fat diet showed distinct circadian rhythms of hepatic expression of SIRT1, SREBP, and PPARα compared with mice fed a normal diet ad libitum, as well as the circadian rhythm of the abundance of Bacteroidetes and Firmicutes.Conclusions: Time-restricted feeding is associated with better metabolic conditions, perhaps owing to alterations in gut microbiota and the circadian pattern of molecules related to hepatic lipid metabolism, which were first to report.

Hereditary transthyretin amyloid cardiomyopathy is cardiac involvement in systemic transthyretin amyloidosis. For the first time, we generated induced pluripotent stem cell (iPSC) line of hATTR-CM carrying the TTR mutation p.Asp38Asn. We isolated peripheral blood mononuclear cells from the patient’s peripheral blood. The reprogramming of PBMCs achieved a pluripotent state by the transfection of non-integrated episomal vectors. We demonstrated pluripotency with the presence of cell surface markers, the expression of pluripotency-related genes and the ability to form teratoma composed of three germ layers in vivo. This iPSC line is a useful model for studying the pathogenic mechanism of TTR p.Asp38Asn mutation.

In December 2019, Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2, occurred in China and has currently led to a global pandemic. In addition to respiratory involvement, COVID-19 was also associated with significant multiple organ dysfunction syndrome (MODS). Cardiovascular impairment has been observed and is now drawing growing attention. Cardiovascular protective strategies are urgent and of great significance to the overall prognosis of COVID-19 patients. Direct viral infection, cytokine storm, and aggravation of existing cardiovascular diseases were recognized as possible mechanisms of cardiovascular impairment in COVID-19. Hyperactivated inflammation plays an important role in all three mechanisms and is considered to be fundamental in the development of cardiovascular impairment and MODS in COVID-19. Therefore, in addition to conventional cardiovascular treatment, anti-inflammatory therapy is a reasonable strategy for severe cases to further enhance cardiovascular protection and potentially mitigate MODS. We reviewed the inflammatory features and current promising treatments of COVID-19 as well as cardiovascular anti-inflammatory therapies that have been verified in previous clinical trials with positive outcomes. We believe that targeting the central pathway (IL-1β, TNF-α, IL-6), balancing the Th1 and Th2 response, and administering long-term anti-inflammatory therapy might be promising prospects to reduce cardiovascular impairment and even MODS during the acute and recovery phases of COVID-19. The cardiovascular anti-inflammatory therapies might be of great application value to the management of COVID-19 patients and we further propose an algorithm for the selection of anti-inflammatory therapy for COVID-19 patients with or at high risk of cardiovascular impairment. We recommend to take the experiences in cardiovascular anti-inflammatory therapy as references in the management of COVID-19 and conduct related clinical trials, while the clinical translation of novel treatments from preclinical studies or in vitro drug screening should proceed with caution due to unguaranteed efficacy and safety profiles.

Abstract Epimedium brevicornum Maxim has a long history of use in the treatment of estrogen deficiency-related diseases. However, the chemical constituents and mechanism of action of this medicinal plant are not fully understood. In the present study, we isolated four new isoprenylated flavonoid glycosides, as well as 16 known flavonoids (13 isoprenylated flavonoids), from this plant. The chemical structures of the new flavonoid glycosides were elucidated by extensive spectroscopic analysis. The new compounds 1–4 were potent promoters of estrogen biosynthesis in human ovarian granulosa-like KGN cells. ZW1, an isoprenylated flavonoid analogue and a specific inhibitor of phosphodiesterase 5 (PDE5), was synthesized and used to explore the mechanism of the isoprenylated analogues on estrogen biosynthesis. ZW1 treatment increased estrogen production by upregulation of aromatase mRNA and protein expression. ZW1 increased the phosphorylation of cAMP response element-binding protein (CREB). Further study showed that the inhibition of PDE5 by ZW1 increased estrogen biosynthesis partly through suppression of phosphodiesterase 3 (PDE3). Our results suggested that the isoprenylated flavonoids from E. brevicornum may produce beneficial health effects through the promotion of estrogen biosynthesis. PDE5 warrants further investigation as a new therapeutic target for estrogen biosynthesis in the prevention and treatment of estrogen-deficiency related diseases.

Panicum miliaceum is the most important and ancient domesticated crops in the world. The complete chloroplast genome of P. miliaceum was sequenced using the Illumina Hiseq platform (Illumina Inc., San Diego, CA). The chloroplast genome of P. miliaceum was 139,929 bp in length, with 38.60% GC content. It contains a pair of inverted repeats (IRs) (22,723 bp) which were separated by a large single copy (LSC) (81,918 bp) and a small single copy region (SSC) (12,565 bp). A total of 132 genes were annotated, which included 84 protein coding genes, 40 tRNA genes and eight rRNA genes. The neighbour-joining (NJ) phylogenetic analysis with the reported chloroplast genomes showed that P. miliaceum chloroplasts are most closely related to those of the Gramineae family.