Identification, Purification, and Characterization of Kunitz-Type Protease Inhibitors from White-Fleshed Dragon Fruit (Selenicereus undatus) and Red-Fleshed Dragon Fruit (Selenicereus costaricensis) Seeds as Novel Food Allergens.

There have been clinical reports of allergies to dragon fruits. However, little is known about the allergens that trigger these reactions. This study aimed to investigate novel allergens in dragon fruits. The peptide mass fingerprints of two purified natural allergens were identified by LC-MS/MS with chymotrypsin proteolysis. The complete amino acid sequences of the allergens were deduced from cDNA amplicon sequences. The coding sequences of two allergens were inserted in the expression vector pColdI, and recombinant allergens were produced in Escherichia coli. Circular dichroism was performed to analyze the secondary structures of natural and recombinant allergens. Our results identified two novel allergens as Kunitz-type protease inhibitors. Recombinant allergens exhibited well-folded structures, predominantly composed of ß-sheets, similar to their natural counterparts. IgE reactivity analysis with sera from ten patients primarily sensitized to dragon fruit indicated that Kunitz-type protease inhibitors are major allergens in dragon fruits. These results improve our understanding of allergen sources and provide important insights into the allergenicity of proteins from different species.

Prenatal p25-activated Cdk5 induces pituitary tumorigenesis through MCM2 phosphorylation-mediated cell proliferation.

Aberrant expression of cyclin-dependent kinase 5 (Cdk5) has been reported in pituitary adenomas. However, the role of Cdk5 in the tumorigenesis remains unclear. We show that prenatal p25-activated Cdk5 phosphorylates minichromosome maintenance protein 2 (Mcm2), enhancing minichromosome maintenance (MCM) family proteins and driving intermediate lobe-located melanotrope-originated pituitary tumorigenesis. In a mouse model with CaMKII promoter-driven transgenic induction of p25, we observed intermediate lobe-originated pituitary adenoma producing non-functional proopiomelanocortin (POMC)-derived peptides under persistent p25 overexpression. Single-cell RNA sequencing revealed Mcm2 may play an important role during tumor progression. Subsequently, Mcm2 was identified as a potential phosphorylated substrate of Cdk5, mediating the tumorous proliferation of melanotrope cells. Silencing Cdk5 or Mcm2 suppressed cell proliferation and colony formation in the 293T cell lines. Therefore, our findings provide a new mouse model of intermediate lobe-originated pituitary adenoma induced by p25/Cdk5 and unveil a previously unappreciated role of Cdk5 and Mcm2 in pituitary adenoma tumorigenesis.

Elucidating the Role of SlBBX31 in Plant Growth and Heat-Stress Resistance in Tomato.

Heat stress inhibits plant growth and productivity. Among the main regulators, B-box zinc-finger (BBX) proteins are well-known for their contribution to plant photomorphogenesis and responses to abiotic stress. Our research pinpoints that SlBBX31, a BBX protein harboring a conserved B-box domain, serves as a suppressor of plant growth and heat tolerance in tomato (Solanum lycopersicum L.). Overexpressing (OE) SlBBX31 in tomato exhibited yellowing leaves due to notable reduction in chlorophyll content and net photosynthetic rate (Pn). Furthermore, the pollen viability of OE lines obviously decreased and fruit bearing was delayed. This not only affected the fruit setting rate and the number of plump seeds but also influenced the size of the fruit. These results indicate that SlBBX31 may be involved in the growth process of tomato, specifically in terms of photosynthesis, flowering, and the fruiting process. Conversely, under heat-stress treatment, SlBBX31 knockout (KO) plants displayed superior heat tolerance, evidenced by their improved membrane stability, heightened antioxidant enzyme activities, and reduced accumulation of reactive oxygen species (ROS). Further transcriptome analysis between OE lines and KO lines under heat stress revealed the impact of SlBBX31 on the expression of genes linked to photosynthesis, heat-stress signaling, ROS scavenging, and hormone regulation. These findings underscore the essential role of SlBBX31 in regulating tomato growth and heat-stress resistance and will provide valuable insights for improving heat-tolerant tomato varieties.

Revascularization of superior mesenteric artery occlusion via the arc of Buhler: A case report and literature review.

BACKGROUND: To report revascularization of a superior mesenteric artery (SMA) ostial occlusion via the Arc of Buhler. CASE REPORT: A 62-year-old female presented with 2 months of recurrent abdominal distension and postprandial pain. Computed tomography angiography (CTA) revealed ostial occlusion of the SMA with distal perfusion via the Arc of Buhler (connecting the celiac trunk and SMA). Conventional endovascular techniques failed. A 0.014 guidewire was passed retrograde through the occlusion via the Arc of Buhler. The guidewire was captured from the femoral sheath and balloon angioplasty with stent placement was performed. The patient had complete symptom resolution post-procedure. CONCLUSIONS: Retrograde revascularization via the Arc of Buhler is an effective method for treating the initial segment occlusion of the SMA.

Near-Infrared-II Photoactivated Iron(III) Complexes for Highly Efficient RNS and ROS Synergistic Therapy.

Reactive nitrogen species (RNS) are more lethal than reactive oxygen species (ROS), which gives them a very promising future in the field of cancer treatment. However, there are still a few drugs available for RNS generation. In this work, two 5th-order nonlinear optical materials, FB-Fe(III)/SNP@PEG and FB-Fe(II)-FB/SNP@PEG, are synthesized. The outstanding nonlinear optical properties of FB-Fe(III)/SNP@PEG help to achieve generation of bounteous superoxide anions (O2•-) in deep tissues, while sodium nitroprusside (SNP) provides NO in the body, both of which are prerequisites for RNS generation. Meanwhile, type I and type II ROS were also generated under irradiation of a 1600 nm laser. Based on the synergistic effect of ROS and RNS, FB-Fe(III)/SNP@PEG induced mitochondrial damage and DNA fragmentation and inhibited tumor cells through apoptosis, possessing better therapeutic effects than FB-Fe(II)-FB/SNP@PEG. This work put forward an innovative strategy to achieve the cooperative release of RNS and ROS in deep tissues, which provides insights and ideas for applying nonlinear optical materials to RNS therapy.

Chaiqin chengqi decoction treatment mitigates hypertriglyceridemia-associated acute pancreatitis by modulating liver-mediated glycerophospholipid metabolism.

BACKGROUND: The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing globally and more so in China. The characteristics of liver-mediated metabolites and related key enzymes are rarely reported in HTG-AP. Chaiqin chengqi decoction (CQCQD) has been shown to protect against AP including HTG-AP in both patients and rodent models, but the underlying mechanisms in HTG-AP remain unexplored. PURPOSE: To assess the characteristics of liver-mediated metabolism and the therapeutic mechanisms of CQCQD in HTG-AP. METHODS: Male human apolipoprotein C3 transgenic (hApoC3-Tg; leading to HTG) mice or wild-type littermates received 7 intraperitoneal injections of cerulein (100 µg/kg) to establish HTG-AP and CER-AP, respectively. In HTG-AP, some mice received CQCQD (5.5 g/kg) gavage at 1, 5 or 9 h after disease induction. AP severity and related liver injury were determined by serological and histological parameters; and underlying mechanisms were identified by lipidomics and molecular biology. Molecular docking was used to identify key interactions between CQCQD compounds and metabolic enzymes, and subsequently validated in vitro in hepatocytes. RESULTS: HTG-AP was associated with increased disease severity indices including augmented liver injury compared to CER-AP. CQCQD treatment reduced severity and liver injury of HTG-AP. Glycerophospholipid (GPL) metabolism was the most disturbed pathway in HTG-AP in comparison to HTG alone. In HTG-AP, the mRNA level of GPL enzymes involved in phosphocholine (PC) and phosphatidylethanolamine (PE) synthesis (Pcyt1a, Pcyt2, Pemt, and Lpcat) were markedly upregulated in the liver. Of the GPL metabolites, lysophosphatidylethanolamine LPE(16:0) in serum of HTG-AP was significantly elevated and positively correlated with the pancreas histopathology score (r = 0.65). In vitro, supernatant from Pcyt2-overexpressing hepatocytes co-incubated with LPE(16:0) or phospholipase A2 (a PC- and PE-hydrolyzing enzyme) alone induced pancreatic acinar cell death. CQCQD treatment downregulated PCYT1a and PCYT2 enzyme levels in the liver. Hesperidin and narirutin were identified top two CQCQD compounds with highest affinity docking to PCYT1a and PCYT2. Both hesperidin and narirutin reduced the level of some GPL metabolites in hepatocytes. CONCLUSION: Liver-mediated GPL metabolism is excessively activated in HTG-AP with serum LPE(16:0) level correlating with disease severity. CQCQD reduces HTG-AP severity partially via modulating key enzymes in GPL metabolism pathway.

Advanced superhydrophobic polylactic acid fibers with high porosity and biodegradability for efficient solvent recovery.

The conventional oil-absorbing materials utilized for addressing oil and organic solvent pollution are plagued by the issue of secondary pollution. In this study, biodegradable porous polylactic acid (PLA) fiber materials were prepared using centrifugal spinning technology, with PLA and polyvinyl butyral (PVB) as raw materials. PVB was utilized as a pore-forming agent to fabricate multi-layered porous PLA fiber materials. When the content of PVB in the spinning solution was 14 %, the porous PLA fibers exhibited the maximum specific surface area of 60.7 m2/g and a porosity of up to 85.4 %, interior of the fiber contained numerous mesopores. Additionally, the porous PLA fibers demonstrated excellent superhydrophobic oil absorption properties, with a water static contact angle of 137.8° and oil or organic solvent absorption capacities ranging from 10 to 17.7 g/g. Furthermore, porous PLA fiber materials exhibited outstanding biodegradability, with a degradation mass loss rate of 42.3-45.1 %. Therefore, superhydrophobic and oleophilic biomass-based PLA fiber materials prepared in centrifugal spinning show promising applications in the recovery of organic solvents and oily substances.

Dynamic Adsorption of Mn2+ from Acid Mine Drainage by Highly Active Immobilized Particles with Fe0/Fe2+ Enhanced SRB.

Bioremediation of acid mine drainage (AMD) was often challenged by poor tolerance of sulfate-reducing bacteria (SRB) to heavy metals and low bioactivity. The highly active immobilized particles with Fe0/Fe2+ enhanced SRB (Fe0/2+-SRB) were prepared by the microorganism immobilization technique. Three dynamic columns were constructed to investigate the adsorption capacity of Fe0/2+-SRB for Mn2+ under varying adsorption layer heights, inflow velocity, and initial Mn2+ concentrations. The role of each matrix material in the immobilized particles was explored, the mechanism of AMD remediation by Fe0/2+-SRB was revealed, and the adaptability of Fe0/2+-SRB to AMD under various initial conditions was investigated. The results showed that the prepared Fe0/2+-SRB exhibited a well-developed surface pore structure. When the adsorption layer height was 200 mm, the influent flow rate was 5 × 10-5 m3/s, and the initial manganese ion concentration was 10 mg/L, the maximum dynamic adsorption capacities (qe) of Mn2+ for each dynamic column were 7.8430, 4.7627, and 8.7677 mg/g, respectively. Compared to dynamic columns 1# and 2#, dynamic column 3# showed the best performance in treating AMD, and the Thomas model effectively described the adsorption kinetics of Mn2+ by Fe0/2+-SRB(3#). Microstructural analysis indicated that chemical adsorption, ion exchange, dissimilation-reduction reaction, and surface complexation occurred between the various matrix materials in Fe0/2+-SRB(3#). Mn2+ was primarily removed in the form of metal sulfide (MnS), and Fe0/Fe2+ could promote the dissimilatory reduction of SO42- by SRB to form S2-. Fe0/2+-SRB(3#) was able to adapt to AMD with initial conditions of pH was 2~4, SO42- < 2500 mg/L, and Mn2+ < 20 mg/L. The research results provide new insights into the remediation of AMD, using a combined microbial-adsorption technology.

Effect of Lactiplantibacillus and sea buckthorn pomace on the fermentation quality and microbial community of paper mulberry silage.

Background: Paper mulberry is a promising alternative fodder source due to its high protein and the abundance of active components. However, paper mulberry often faces susceptibility to contamination during silage fermentation, and there is a need to improve the quality of silage fermentation of paper mulberry through exotic additives. Sea buckthorn pomace (BP) is a feed additive containing antimicrobial and antioxidant substances that help to enhance silage fermentation. Therefore, the objective of this study was to evaluate the effects of BP and Lactiplantibacillus as additives on silage fermentation and bacterial community of paper mulberry. Results: The results showed that BP and Lactiplantibacillus significantly reduced the pH and ammonium nitrogen content of paper mulberry silage (P < 0.05) and significantly increased the content of lactic acid and acetic acid (P < 0.05), resulting in more residual water-soluble carbohydrate and crude protein contents and less fiber content relative to the control. The key microorganisms in paper mulberry silage fermentation are Lactiplantibacillus pentosus and Weissella cibaria. Among these, Lactiplantibacillus favored a rapid increase in Lactiplantibacillus pentosus abundance during the pre-silage fermentation period, whereas BP favored the promotion of Lactiplantibacillus pentosus growth, resulting in higher contents of lactic and acetic acid than those of the control. Conclusions: Simultaneously adding Lactiplantibacillus and BP can effectively improve the quality of paper mulberry silage and increase the abundance of beneficial microorganisms in paper mulberry silage.

Amino acid-sulphur decomposition in agricultural soil profile along a long-term recultivation chronosequence.

The significance of sulphur (S) availability for crop yield and quality is highlighted under the global S deficiency scenario. However, little is known about the temporal trend in belowground organic S mineralisation when restoring land to productive agricultural systems, particularly for the deeper soil parts. Therefore, we investigated the decomposition of 35S-labelled methionine in surface (0-30 cm) and subsurface soil (30-60 cm and 60-90 cm) over a 48-year recultivation chronosequence (sampled after1, 8, 14, 24 and 48 years). Soil total sulphur (TS) significantly (p < 0.05) increased in surface soil but not in subsurface soils after 48 years of recultivation. Overall, the immobilisation of 35S-methionine (35S-MB) in subsurface soils relative to year 1 significantly decreased over the chronosequence but did not change in the surface samples. The 35S-MB values in subsurface soils were positively corrected with soil carbon (C) stoichiometry (Pearson correlation, p < 0.05), suggesting the immobilisation of methionine was likely constrained by microbial C demand in deep soil. Compared to year 1, 35S-SO42- released from 35S-methionine significantly declined throughout the older (≥ 8 years) soil profiles. Significant (p < 0.05) changes in the organic 35S partition (35S immobilisation and 35S released as sulphate) were observed in year 8 after the soil was recultivated with N-fixing alfalfa or fertilisers. Whereas, after that (≥ 14 years), soil organic S partition remained affected when conventional tillage and agricultural crops dominated this site. Indicating that the effect of recultivation on organic S decomposition depends on the manner of recultivation management. Our study contributes to an improved understanding of amino acid S and organic S mineralisation under severe anthropogenic disturbance.

A cucurbit[6]uril-based fluorescence supramolecular assembly for information encryption and visualization detection of nitro compounds and antibiotics.

A novel CB[6]-based supramolecular assembly [K(ANS)(CB[6])2(DMF)2(H2O)0.5] (1) (CB[6] = cucurbit[6]uril, ANS- = 8-amino-1-naphthalene sulfonic acid ion) was successfully synthesized under solvothermal condition. Performance studies have shown that 1 exhibited excellent chemical stability and recycling performance. Meanwhile, 1 exhibited remarkable potential as a fluorescence sensor for the detection of 2,4,6-trinitrophenol (TNP), 4-nitrophenol (4-NP), and rifampicin (RFP) in both aqueous environments and practical samples. This sensing capability is achieved through fluorescence quenching, which offers fast response times and exceptional sensitivity, with detection limits of 0.19 µM for both TNP and 4-NP, and 0.21 µM for RFP. Even more remarkably, an anti-counterfeiting ink based on 1 and a portable test hydrogel were devised for encrypting information and visually detecting using a smartphone application. This work has the potential to expand the utilization of CB[6]-based materials in optical applications.

Phosphorus fertilization enhanced overwintering, root system and forage yield of late-seeded alfalfa in sodic soils.

Sowing date and soil fertility are very important factors in the overwintering and production performance of alfalfa (Medicago sativa L.), yet there's a knowledge gap in knowledge on how late-seeded alfalfa responds to phosphorus (P) fertilization. A field study was conducted in Inner Mongolia from 2020 to 2022 using a split-plot design. The main plots consisted of five sowing dates (31 July, 8, 16, and 24 August, and 1 September), while the subplots involved five P application rates (0, 40, 70, 100, and 130 kg P2O5 ha-1). Throughout the growing seasons, the overwintering rate, root traits, forage yield, and yield components were measured. The results revealed a consistent decrease in overwintering ability and productivity with the delayed sowing. This reduction in overwintering rate was mainly due to diminished root traits, while the decrease in forage yield was largely associated with a reduction in plants per square meter. However, P fertilizer application to late-seeded alfalfa demonstrated potential in enhancing the diameter of both the crown and taproot, thus strengthening the root system and improving the overwintering rate, the rate of increase ranges from 11.6 to 49%. This adjustment could also improve the shoots per square meter and mass per shoot, increasing by 9.4-31.3% and 15.0-27.1% respectively in 2 years, which can offset the decline in forage yield caused by late sowing and might even increase the forage yield. Regression and path analysis indicated that alfalfa forage yield is primarily affected by mass per shoot rather than shoots per square meter. This study recommended that the sowing of alfalfa in similar regions of Inner Mongolia should not be later than mid-August. Moreover, applying P fertilizer (P2O5) at 70.6-85.9 kg ha-1 can enhance the forage yield and persistence of late-seeded alfalfa. Therefore, appropriate late sowing combined with the application of P fertilizer can be used as an efficient cultivation strategy for alfalfa cultivation after a short-season crop harvest in arid and cold regions.

Genome-Wide Identification of B-Box Family Genes and Their Potential Roles in Seed Development under Shading Conditions in Rapeseed.

B-box (BBX) proteins, a subfamily of zinc-finger transcription factors, are involved in various environmental signaling pathways. In this study, we conducted a comprehensive analysis of BBX family members in Brassica crops. The 482 BBX proteins were divided into five groups based on gene structure, conserved domains, and phylogenetic analysis. An analysis of nonsynonymous substitutions and (Ka)/synonymous substitutions (Ks) revealed that most BBX genes have undergone purifying selection during evolution. An analysis of transcriptome data from rapeseed (Brassica napus) organs suggested that BnaBBX3d might be involved in the development of floral tissue-specific RNA-seq expression. We identified numerous light-responsive elements in the promoter regions of BnaBBX genes, which were suggestive of participation in light signaling pathways. Transcriptomic analysis under shade treatment revealed 77 BnaBBX genes with significant changes in expression before and after shading treatment. Of these, BnaBBX22e showed distinct expression patterns in yellow- vs. black-seeded materials in response to shading. UPLC-HESI-MS/MS analysis revealed that shading influences the accumulation of 54 metabolites, with light response BnaBBX22f expression correlating with the accumulation of the flavonoid metabolites M46 and M51. Additionally, BnaBBX22e and BnaBBX22f interact with BnaA10.HY5. These results suggest that BnaBBXs might function in light-induced pigment accumulation. Overall, our findings elucidate the characteristics of BBX proteins in six Brassica species and reveal a possible connection between light and seed coat color, laying the foundation for further exploring the roles of BnaBBX genes in seed development.

Selenate simultaneously alleviated cadmium and arsenic accumulation in rice (Oryza sativa L.) via regulating transport genes.

Cadmium (Cd) and arsenic (As) have contrasting biogeochemical behaviors in paddy soil, which posed an obstacle for reducing their accumulation in rice (Oryza sativa L.) simultaneously. In this study, selenate exhibited a more effective ability than selenite on simultaneous alleviation of Cd and As accumulation in rice under Cd-As co-exposure, and the mechanisms need to be further investigated. The results showed that selenate significantly decreased the root Cd and As contents by 59%-83% and 43%-72% compared to Cd-As compound exposure, respectively. Correspondingly, it significantly down-regulated the expression of uptake-related genes OsNramp5 (87.1%) and OsLsi1 (95.5%) in rice roots. Decreases in Cd (64.5%) and As (16.2%) contents in shoots were also found after selenate addition. Moreover, selenate may promoted the reduction of As(V) to As(Ⅲ) and As(III) efflux to the external medium, resulting in decreased As accumulation and As(Ⅲ) proportion in rice shoots and roots. In addition, selenate could promote the binding of Cd (by 14%-24%) and As (by 9%-15%) in the cell wall, and significantly reduced the oxidative stress by elevating levels of antioxidant enzymes (by 10%-105%) and thiol compounds (by 6%-210%). Additionally, selenate significantly down-regulated the expression of OsNramp1 (49.3%) and OsLsi2 (82.1%) associated with Cd and As transport in rice. These findings suggest selenate has the potential to be an effective material for the simultaneous reduction of Cd and As accumulation in rice under Cd-As co-contamination.

Targeted delivery of activatable 131I-radiopharmaceutical for sustained radiotherapy with improved pharmacokinetics.

Targeted radionuclide therapy (TRT) is an effective treatment for tumors. Self-condensation strategies can enhance the retention of radionuclides in tumors and enhance the anti-tumor effect. Considering legumain is overexpressed in multiple types of human cancers, a 131I-labeled radiopharmaceutical ([131I]MAAN) based on the self-condensation reaction between 2-cyanobenzothiazole (CBT) and cysteine (Cys) was developed by us recently for treating legumain-overexpressed tumors. However, liver enrichment limits its application. In this study, a new radiopharmaceutical [131I]IM(HE)3AAN was designed and synthesized by introducing a hydrophilic peptide sequence His-Glu-His-Glu-His-Glu ((HE)3) into [131I]MAAN to optimize the pharmacokinetics. Upon activation by legumain under a reducing environment, hydrophilic [131I]IM(HE)3AAN could react with its precursor to form heterologous dimer [131I]H-Dimer that is highly hydrophobic. Cerenkov imaging revealed that [131I]IM(HE)3AAN displayed superior tumor selectivity and longer tumor retention time as compared with [131I]MAAN, with a significant reduction in the liver uptake. After an 18-day treatment with [131I]IM(HE)3AAN, the tumor proliferation was obviously inhibited, while no obvious injury was observed in the normal organs. These findings suggest that [131I]IM(HE)3AAN could serve as a promising drug candidate for treating legumain-overexpressed tumors.

The natural compound sinometumine E derived from Corydalis decumbens promotes angiogenesis by regulating HIF-1/ VEGF pathway in vivo and in vitro.

The rhizome of Corydalis decumbens is a traditional Chinese medicine commonly utilized in the clinical treatment of acute ischemic stroke. Numerous phytochemical and biological investigations have demonstrated that protoberberine alkaloids from C. decumbens exhibit diverse pharmaceutical activities against various diseases. Sinometumine E (SE), a protoberberine alkaloid isolated from C. decumbens for the first time, is characterized by a complex 6/6/6/6/6/6 hexacyclic skeleton. In the current study, we investigated the protective effects of SE on endothelial cell injury and its angiogenesis effects in zebrafish. The results suggested that SE showed significant anti-ischemic effects on OGD/R-induced HBEC-5i and HUVECs cell ischemia/reperfusion injury model. Furthermore, it promoted angiogenesis in PTK787-induced, MPTP-induced, and atorvastatin-induced vessel injury models of zebrafish, while also suppressing hypoxia-induced locomotor impairment in zebrafish. Transcriptome sequencing analysis provided a sign that SE likely to promotes angiogenesis through the HIF-1/VEGF signaling pathway to exert anti-ischemic effects. Consistently, SE modulated several genes related to HIF-1/VEGF signal pathway, such as hif-1, vegf, vegfr-2, pi3k, erk, akt and plcγ. Molecular docking analysis revealed that VEGFR-2 exhibited high binding affinity with SE, and western blot analysis confirmed that SE treatment enhanced the expression of VEGFR-2. In conclusion, our study profiled the angiogenic activities of SE in vitro and in vivo. The key targets and related pathways involved in anti-ischemic effects of SE, shedding light on the pharmacodynamic components and mechanisms of Corydalis decumbens, and provides valuable insights for identifying effective substances for the treatment of ischemic stroke.

A novel artificial intelligence network to assess the prognosis of gastrointestinal cancer to immunotherapy based on genetic mutation features.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized gastrointestinal cancer treatment, yet the absence of reliable biomarkers hampers precise patient response prediction. Methods: We developed and validated a genomic mutation signature (GMS) employing a novel artificial intelligence network to forecast the prognosis of gastrointestinal cancer patients undergoing ICIs therapy. Subsequently, we explored the underlying immune landscapes across different subtypes using multiomics data. Finally, UMI-77 was pinpointed through the analysis of drug sensitization data from the Genomics of Drug Sensitivity in Cancer (GDSC) database. The sensitivity of UMI-77 to the AGS and MKN45 cell lines was evaluated using the cell counting kit-8 (CCK8) assay and the plate clone formation assay. Results: Using the artificial intelligence network, we developed the GMS that independently predicts the prognosis of gastrointestinal cancer patients. The GMS demonstrated consistent performance across three public cohorts and exhibited high sensitivity and specificity for 6, 12, and 24-month overall survival (OS) in receiver operating characteristic (ROC) curve analysis. It outperformed conventional clinical and molecular features. Low-risk samples showed a higher presence of cytolytic immune cells and enhanced immunogenic potential compared to high-risk samples. Additionally, we identified the small molecule compound UMI-77. The half-maximal inhibitory concentration (IC50) of UMI-77 was inversely related to the GMS. Notably, the AGS cell line, classified as high-risk, displayed greater sensitivity to UMI-77, whereas the MKN45 cell line, classified as low-risk, showed less sensitivity. Conclusion: The GMS developed here can reliably predict survival benefit for gastrointestinal cancer patients on ICIs therapy.

The effects of high-intensity interval training/moderate-intensity continuous training on the inhibition of fat accumulation in rats fed a high-fat diet during training and detraining.

BACKGROUND: Compared with moderate-intensity continuous training (MICT), high-intensity interval training (HIIT) has at least a comparable effect on inhibiting an increase in fat. However, few studies have been conducted to examine the effects of detraining on body fat in rats fed a high-fat diet. The present study aimed to compare the effects of 10 weeks of HIIT or MICT as well as 6 weeks of detraining on body fat in rats fed a high-fat diet. METHODS: After being fed a high-fat diet for 8 weeks, 54 female rats were randomly assigned to six groups: (1) CON-10, sedentary control for 10 weeks; (2) MICT-10, 10 weeks of MICT; (3) HIIT-10, 10 weeks of HIIT; (4) CON-16, sedentary control for 16 weeks; (5) MICT-16, 10 weeks of MICT followed by 6 weeks of training cessation; and (6) HIIT-16, 10 weeks of HIIT followed by 6 weeks of training cessation. The training was performed 5 days/week. The subcutaneous adipose tissue (inguinal; SCAT), visceral adipose tissue (periuterine; VAT) and serum lipid profile were analysed after 10 or 16 weeks. Adipose tissue triglyceride lipase (ATGL) protein expression in VAT was assessed by western blotting. RESULTS: HIIT-10 and MICT-10 prevented the increase in SCAT, VAT and serum lipid levels seen in the CON group. During the 6-week detraining period, HIIT continued to prevent the increase in adipose tissue mass observed in the CON group, whereas MICT at least maintained this inhibition. The inhibition of fat mass increase was mainly the result of preventing adipocyte hypertrophy. The HIIT-10 and HIIT-16 groups showed the highest ATGL protein expression. CONCLUSIONS: HIIT has a comparable effect to MICT on inhibiting fat accumulation in female rats; however, the inhibition of SCAT and VAT increase by HIIT is superior to MICT after short-term training cessation.

Comparative structure and evolution of the organellar genomes of Padina usoehtunii (Dictyotales) with the brown algal crown radiation clade.

BACKGROUND: Organellar genomes have become increasingly essential for studying genetic diversity, phylogenetics, and evolutionary histories of seaweeds. The order Dictyotales (Dictyotophycidae), a highly diverse lineage within the Phaeophyceae, is long-term characterized by a scarcity of organellar genome datasets compared to orders of the brown algal crown radiation (Fucophycidae). RESULTS: We sequenced the organellar genomes of Padina usoehtunii, a representative of the order Dictyotales, to investigate the structural and evolutionary differences by comparing to five other major brown algal orders. Our results confirmed previously reported findings that the rate of structural rearrangements in chloroplast genomes is higher than that in mitochondria, whereas mitochondrial sequences exhibited a higher substitution rate compared to chloroplasts. Such evolutionary patterns contrast with land plants and green algae. The expansion and contraction of the inverted repeat (IR) region in the chloroplast correlated with the changes in the number of boundary genes. Specifically, the size of the IR region influenced the position of the boundary gene rpl21, with complete rpl21 genes found within the IR region in Dictyotales, Sphacelariales and Ectocarpales, while the rpl21 genes in Desmarestiales, Fucales, and Laminariales span both the IR and short single copy (SSC) regions. The absence of the rbcR gene in the Dictyotales may indicate an endosymbiotic transfer from the chloroplast to the nuclear genome. Inversion of the SSC region occurred at least twice in brown algae. Once in a lineage only represented by the Ectocarpales in the present study and once in a lineage only represented by the Fucales. Photosystem genes in the chloroplasts experienced the strongest signature of purifying selection, while ribosomal protein genes in both chloroplasts and mitochondria underwent a potential weak purifying selection. CONCLUSIONS: Variations in chloroplast genome structure among different brown algal orders are evolutionarily linked to their phylogenetic positions in the Phaeophyceae tree. Chloroplast genomes harbor more structural rearrangements than the mitochondria, despite mitochondrial genes exhibiting faster mutation rates. The position and the change in the number of boundary genes likely shaped the IR regions in the chloroplast, and the produced structural variability is important mechanistically to create gene diversity in brown algal chloroplast.

Electrospun nanofibers-based thin film microextraction for enrichment of phthalate esters in biodegradable plastics.

In this work, a novel electrospun nanofiber (PAN/TpBD; 2,4,6-triformylphloroglucinol [Tp] and benzidine [BD]; polyacrylonitrile [PAN]) was fabricated via a facile electrospinning method and utilized as adsorbent in thin film microextraction (TFME) of phthalate esters (PAEs) (dimethyl phthalate, diethyl phthalate, diallyl phthalate, dibutyl phthalate, and dioctyl phthalate) in biodegradable plastics. The prepared PAN/TpBD combines the strong stability of nanofibers with increased exposure sites for covalent organic frameworks and enhanced interactions with the target, thus improving the enrichment effect on the target. The extraction efficiency of PAN/TpBD reached above 80%. Based on PAN/TpBD, a TFME-high-performance liquid chromatography method was established, and the experimental parameters were optimized. Under the optimal extraction conditions, the PAEs of this method varied linearly in the range of 10-10 000 µg/L with low detection limits (0.69-2.72 µg/L). The intra-day and inter-day relative standard deviation values of the PAEs were less than 8.04% and 8.73%, respectively. The adsorbent can achieve more than 80% recovery of the five targets after six times reuse. The developed method was successfully applied for the determination of trace PAEs in biodegradable plastics with recoveries ranging from 80.1% to 113.4% and relative standard deviations were less than 9.45%. The as-synthesized PAN/TpBD adsorbent exhibited great potential in PAE analysis.