Predictors for Failed Removal of Nasogastric Tube in Patients With Brain Insult.

Objective: To construct a prognostic model for unsuccessful removal of nasogastric tube (NGT) was the aim of our study. Methods: This study examined patients with swallowing disorders receiving NGT feeding due to stroke or traumatic brain injury in a regional hospital. Clinical data was collected, such as age, sex, body mass index (BMI), level of activities of daily living (ADLs) dependence. Additionally, gather information regarding the enhancement in Functional Oral Intake Scale (FOIS) levels and the increase in food types according to the International Dysphagia Diet Standardization Initiative (IDDSI) after one month of swallowing training. A stepwise logistic regression analysis model was employed to predict NGT removal failure using these parameters. Results: Out of 203 patients, 53 patients (26.1%) had experienced a failed removal of NGT after six months of follow-up. The strongest predictors for failed removal were age over 60 years, underweight BMI, total dependence in ADLs, and ischemic stroke. The admission prediction model categorized patients into high, moderate, and low-risk groups for removal failure. The failure rate of NGT removal was high not only in the high-risk group but also in the moderate-risk groups when there was no improvement in FOIS levels and IDDSI food types. Conclusion: Our predictive model categorizes patients with brain insults into risk groups for swallowing disorders, enabling advanced interventions such as percutaneous endoscopic gastrostomy for high-risk patients struggling with NGT removal, while follow-up assessments using FOIS and IDDSI aid in guiding rehabilitation decisions for those at moderate risk.

Increasing structure diversity of farnesylated chalcones by a fungal aromatic prenyltransferase.

Farnesylated chalcones were favored by researchers due to their different biological activities. However, only five naturally occurring farnesylated chalcones were described in the literature until now. Here, the farnesylation of six chalcones by the Aspergillus terreus aromatic prenyltransferase AtaPT was reported. Fourteen monofarnesylated chalcones (1F1-1F5, 2F1-2F3, 3F1, 3F2, 4F1, 4F2, 5F1, 6F1, and 6F2) and a difarnesylated product (2F3) were obtained, enriching the diversity of natural farnesylated chalcones significantly. Ten of them are C-farnesylated products, which complement O-farnesylated chalcones by chemical synthesis. Fourteen products have not been reported prior to this study. Nine of the produced compounds (1F2-1F5, 2F1-2F3, 5F1, and 6F1) exhibited inhibitory effect on α-glucosidase with IC50 values ranging from 24.08 ± 1.44 to 190.0 ± 0.28 µM. Among them, compounds 2F3 with IC50 value at 24.08 ± 1.44 µM and 1F4 with IC50 value at 30.09 ± 0.59 µM showed about 20 times stronger than the positive control acarbose with an IC50 at 536.87 ± 24.25 µM in α-glucosidase inhibitory assays.

Stimulus-Induced Dynamic Behavior Regulation of Flexible Crystals through the Tuning of Module Rigidity.

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

Intraoperative transcutaneous electroacupoint stimulation on early postoperative fatigue in patients with Parkinson's disease undergoing deep brain stimulation surgery.

Background: In this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Methods: A total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6-15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. Results: Fifty-nine patients' datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. Conclusions: Intraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

The Promiscuous Flavin-Dependent Monooxygenase PboD from Aspergillus ustus Increases the Structural Diversity of Hydroxylated Pyrroloindoline Diketopiperazines.

The potential of natural products as pharmaceutical and agricultural agents is based on their large structural diversity, resulting in part from modifications of the backbone structure by tailoring enzymes during biosynthesis. Flavin-dependent monooxygenases (FMOs), as one such group of enzymes, play an important role in the biosynthesis of diverse natural products, including cyclodipeptide (CDP) derivatives. The FMO PboD was shown to catalyze C-3 hydroxylation at the indole ring of cyclo-l-Trp-l-Leu in the biosynthesis of protubonines, accompanied by pyrrolidine ring formation. PboD substrate promiscuity was investigated in this study by testing its catalytic activity toward additional tryptophan-containing CDPs in vitro and biotransformation in Aspergillus nidulans transformants bearing a truncated protubonine gene cluster with pboD and two acetyltransferase genes. High acceptance of five CDPs was detected for PboD, especially of those with a second aromatic moiety. Isolation and structure elucidation of five pyrrolidine diketopiperazine products, with two new structures, proved the expected stereospecific hydroxylation and pyrrolidine ring formation. Determination of kinetic parameters revealed higher catalytic efficiency of PboD toward three CDPs consisting of aromatic amino acids than of its natural substrate cyclo-l-Trp-l-Leu. In the biotransformation experiments with the A. nidulans transformant, modest formation of hydroxylated and acetylated products was also detected.

Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds.

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.

Fungal Prenyltransferase AnaPT and Its F265 Mutants Catalyze the Dimethylallylation at the Nonaromatic Carbon of Phloretin.

Phloretin is widely found in fruit and shows various biological activities. Here, we demonstrate the dimethylallylation, geranylation, and farnesylation, particularly the first dimethylallylation at the nonaromatic carbon of phloretin (1) by the fungal prenyltransferase AnaPT and its mutants. F265 was identified as a key amino acid residue related to dimethylallylation at the nonaromatic carbon of phloretin. Mutants AnaPT_F265D, AnaPT_F265G, AnaPT_F265P, AnaPT_F265C, and AnaPT_F265Y were discovered to generally increase prenylation activity toward 1. AnaPT_F265G catalyzes the O-geranylation selectively at the C-2' hydroxyl group, which involves an intramolecular hydrogen bond with the carbonyl group of 1. Seven products, 1D5, 1D7-1D9, 1G2, 1G4, and 1F2, have not been reported prior to this study. Twelve compounds, 1D3-1D9, 1G1-1G3, and 1F1-1F2, exhibited potential inhibitory effects on α-glucosidase with IC50 values ranging from 11.45 ± 0.87 to 193.80 ± 6.52 µg/mL. Among them, 1G1 with an IC50 value of 11.45 ± 0.87 µg/mL was the most potential α-glucosidase inhibitor, which is about 30 times stronger than the positive control acarbose with an IC50 value of 346.63 ± 15.65 µg/mL.

[Factors influencing the occurrence of small for gestational age at different degrees]. / ä¸åŒç¨‹åº¦å°äºŽèƒŽé¾„å„¿å‘ç”Ÿçš„å½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. METHODS: Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. RESULTS: A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). CONCLUSIONS: Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.

Interleukin-2 enhancer binding factor 2 negatively regulates the replication of duck hepatitis A virus type 1 by disrupting the RNA-dependent RNA polymerase activity of 3D polymerase.

The interaction between viral components and cellular proteins plays a crucial role in viral replication. In a previous study, we showed that the 3'-untranslated region (3'-UTR) is an essential element for the replication of duck hepatitis A virus type 1 (DHAV-1). However, the underlying mechanism is still unclear. To gain a deeper understanding of this mechanism, we used an RNA pull-down and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay to identify new host factors that interact with the 3'-UTR. We selected interleukin-2 enhancer binding factor 2 (ILF2) for further analysis. We showed that ILF2 interacts specifically with both the 3'-UTR and the 3D polymerase (3Dpol) of DHAV-1 through in vitro RNA pull-down and co-immunoprecipitation assays, respectively. We showed that ILF2 negatively regulates viral replication in duck embryo fibroblasts (DEFs), and that its overexpression in DEFs markedly suppresses DHAV-1 replication. Conversely, ILF2 silencing resulted in a significant increase in viral replication. In addition, the RNA-dependent RNA polymerase (RdRP) activity of 3Dpol facilitated viral replication by enhancing viral RNA translation efficiency, whereas ILF2 disrupted the role of RdRP in viral RNA translation efficiency to suppress DHAV-1 replication. At last, DHAV-1 replication markedly suppressed the expression of ILF2 in DEFs, duck embryo hepatocytes, and different tissues of 1 day-old ducklings. A negative correlation was observed between ILF2 expression and the viral load in primary cells and different organs of young ducklings, suggesting that ILF2 may affect the viral load both in vitro and in vivo.

Asperustins A-J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856.

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.

A linker selective retention strategy to construct hierarchical porous metal-organic frameworks with high catalytic activity for oxidative desulfurization.

In order to improve the oxidative desulfurization (ODS) performance of MOF materials, an effective way is to convert a microporous MOF into a hierarchical porous MOF (HP-MOF) by utilizing the linker selective retention strategy. Herein, UiO-66 with the introduction of an unstable linker ligand (dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate, dhtz) can selectively remove dhtz ligands to form HP-MOF (HP-UiO-66-dhtz) through heat treatment at high temperature. While maintaining the original structure of UiO-66, HP-UiO-66-dhtz features mesopores and abundant Lewis acid sites, showing excellent ODS performance for diphenylthiophene (DBT).

Biosynthesis of Epipyrone A Reveals a Highly Specific Membrane-Bound Fungal C-Glycosyltransferase for Pyrone Galactosylation.

Epipyrone A is a unique C-galactosylated 4-hydroxy-2-pyrone derivative with an antifungal potential from the fungus Epicoccum nigrum. We elucidated its biosynthesis via heterologous expression and characterized an unprecedented membrane-bound pyrone C-glycosyltransferase biochemically. Molecular docking and mutagenesis experiments suggested a possible mechanism for the heterocyclic C-glycosylation and the importance of a transmembrane helix for its catalysis. These results expand the repertoire of C-glycosyltransferases and provide new insights into the formation of C-glycosides in fungi.

Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan.

BACKGROUND: Cancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population. METHODS: Exome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHRmut, including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy. RESULTS: Overall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0-43.7), the median overall survival (OS) was not significantly different among patients with gHRmut, non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHRmut. Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7-33.7) versus 9.6 months (95% CI 5.9-17.6), P = 0.001. However, the median OS of patients without gHRmut was 14.5 months (95% CI 13.2-16.9) and 12.6 months (95% CI 10.8-14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis. CONCLUSIONS: Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

Downregulation of transcription 1 hinders the replication of Dabie bandavirus by promoting the expression of TLR7, TLR8, and TLR9 signaling pathway.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS, with a case fatality rate of up to 30 %. The innate immune system plays a crucial role in the defense against SFTSV; however, the impact of viral propagation of STFSV on the innate immune system remains unclear. Although proteomics analysis revealed that the expression of the downregulator of transcription 1 (DR1) increased after SFTSV infection, the specific change trend and the functional role of DR1 during viral infection remain unelucidated. In this study, we demonstrate that DR1 was highly expressed in response to SFTSV infection in HEK 293T cells using qRT-PCR and Western blot analysis. Furthermore, viral replication significantly increased the expression of various TLRs, especially TLR9. Our data indicated that DR1 positively regulated the expression of TLRs in HEK 293T cells, DR1 overexpression highly increased the expression of numerous TLRs, whereas RNAi-mediated DR1 silencing decreased TLR expression. Additionally, the myeloid differentiation primary response gene 88 (MyD88)-dependent or TIR-domain-containing adaptor inducing interferon-ß (TRIF)-dependent signaling pathways were highly up- and downregulated by the overexpression and silencing of DR1, respectively. Finally, we report that DR1 stimulates the expression of TLR7, TLR8, and TLR9, thereby upregulating the TRIF-dependent and MyD88-dependent signaling pathways during the SFTSV infection, attenuating viral replication, and enhancing the production of type I interferon and various inflammatory factors, including IL-1ß, IL-6, and IL-8. These results imply that DR1 defends against SFTSV replication by inducing the expression of TLR7, TLR8, and TLR9. Collectively, our findings revealed a novel role and mechanism of DR1 in mediating antiviral responses and innate immunity.

Four new steroidal glycosides from Lilium lancifolium Thunb. and their antitumor activity.

Four new steroidal glycosides (1-4), including two steroidal saponins named lililancifoloside B and C (1-2), one pregnane glycoside named lililancifoloside D (3), and one C22-steroidal lactone glycoside named lililancifoloside E (4), together with five known ones (5-9), were isolated from the bulbs of Lilium lancifolium Thunb. By using spectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS, the structures of 1-4 were elucidated. All isolates were tested for their cytotoxic potential against the MCF-7, MDA-MB-231, HepG2, and A549 cell lines. Compound 6 distinguished out among them, IC50 values of 3.31, 5.23, 1.78, and 1.49 µM against the four cell lines, respectively. Other compounds such as compound 3, 5, and 9 have also shown specific cytotoxic activity. Next, studies showed that compound 6 might cause HepG2 cells to undergo a cell cycle arrest during the G2/M phase and apoptosis.

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Neonatal lupus erythematosus (NLE) is caused by the transmission of maternal anti-Ro/SSA antibodies, anti-La/SSB antibodies, and other autoantibodies to the fetus through the placenta. Usually, with the disappearance of autoantibodies in the children's body, abnormal changes in the mucocutaneous, blood system, and digestive system can spontaneously subside, but the damage to various systems caused by autoantibodies may persist for a long time. This article provides a comprehensive review of the manifestations and prognosis of NLE in various systems, including mucocutaneous, blood system, circulatory system, nervous system, digestive system, respiratory system, aiming to provide reference for clinical work.

Exploring NK-Cell molecules that impact the immune response and microenvironment in head and neck squamous cell carcinoma.

NK cells play a role in various cancers, but their role in head and neck squamous cell carcinoma (HNSCC) still needs to be explored. All public data are obtained from the Cancer Genome Atlas Program (TCGA) database. All analysis was performed using specific packages in R software. In our study, we quantified the immune microenvironment of HNSCC through multiple algorithms. Next, we identified NK cell-associated genes by quantifying NK cells, including SSNA1, TRIR, PAXX, DPP7, WDR34, EZR, PHLDA1 and ELOVL1. Then, we explored the single-cell expression pattern of these genes in the HNSCC microenvironment. Univariate Cox regression analysis indicated that the EZR, PHLDA1 and ELOVL1 were related to the prognosis of HNSCC patients. Following this, we selected EZR for further analysis. Our results showed that the patients with high EZR expression might have a poor prognosis and worse clinical features. Biological enrichment analysis showed that EZR is associated with many oncogenic pathways and a higher tumour stemness index. Meanwhile, we found that EZR can remodel the immune microenvironment of HNSCC. Moreover, we noticed that EZR could affect the immunotherapy and specific drug sensitivity, making it an underlying clinical target. In summary, our results can improve the understanding of NK cell in HNSCC. Meanwhile, we identified EZR as the underlying clinical target of HNSCC.

Genome-wide characterization of microsatellites in cobia Rachycentron canadum (Linnaeus, 1766): Survey and analysis of their abundance and diversity.

The cobia Rachycentron canadum, mainly distributed in the warm waters of tropical and subtropical regions around the world, remains a fish of considerable economic importance. Detailed diversity and the number of microsatellite sequences in the cobia genome are still unintelligible. The primary aim of this work was to identify and quantify the miscellaneous SSR sequences in the cobia genome. More than 280,000 sequences were sequenced and screened using next-generation sequencing technology and microsatellite identification. Perfect mononucleotide repeats, dinucleotide microsatellites, and trinucleotide microsatellites contain (A)10 /(T)10 , (AC)6 /(TG)6 , and (AAT)5-32 as the largest number of motifs in each type of microsatellite, respectively. The tetranucleotide and pentanucleotide microsatellites (TTM and PTM) consist of the largest number of motifs of both (ATCT)5-32 and (TCAT)5-31 in TTMs, and (CTCTC)5-9 in PTMs, whereas the hexanucleotide microsatellites are rarely observed in the cobia genome. All c. 38000 sequences of composite microsatellites are extremely diverse, including compound (11.71%), interrupted compound (71.77%), complex (0.45%), and interrupted complex (16.07%). In this study, we developed a convenient and useful recording system for writing down and categorizing diverse composite microsatellite types. This system will provide great support for exploring repeat origins, evolutionary mechanisms, and the application of polymorphic microsatellites.

Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway.

Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata, is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.