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1.
Cancer Res Treat ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38726508

ABSTRACT

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: 75 patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and pre-operative and post-operative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher pre-operative positive rate than the tumor-agnostic assay (73.3% vs 57.3%). The pre-op ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined post-op ctDNA positivity was significantly associated with worse DFS (HR, 20.74, 95%CI 7.19-59.83; p<0.001), which was an independent predictor by multivariable analysis (HR, 28.57, 95%CI 7.10-114.9; p<0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest pre-operative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in post-op landmark (HR, 26.34, 95%CI, 6.01-115.57; p<0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04, 95%CI, 0.94-9.89; p=0.052). Conclusion: Our study confirmed the prognostic value of the ctDNA positivity at post-op day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

2.
Fish Shellfish Immunol ; 150: 109621, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38740230

ABSTRACT

This study aims to explore the effects of supplementing cholesterol in plant-based feed on intestinal barriers (including physical barrier, chemical barrier, immune barrier, biological barrier) of GIFT strain tilapia (Oreochromis niloticus). Four isonitrogenous and isolipidic diets were prepared as follows: plant-based protein diet (Con group) containing corn protein powder, soybean meal, cottonseed meal, and rapeseed meal, with the addition of cholesterol at a level of 0.6 % (C0.6 % group), 1.2 % (C1.2 % group), and 1.8 % (C1.8 % group), respectively. A total of 360 fish (mean initial weight of (6.08 ± 0.12) g) were divided into 12 tanks with 30 fish per tank, each treatment was set with three tanks and the feeding period lasted 9 weeks. Histological analysis revealed that both the C0.6 % and C1.2 % groups exhibited a more organized intestinal structure, with significantly increased muscle layer thickness compared to the Con group (P < 0.05). Furthermore, in the C1.2 % group, there was a significant up-regulation of tight junction-related genes (claudin-14, occludin, zo-1) compared to the Con group (P < 0.05). 5-ethynyl-2'-deoxyuridine staining results also demonstrated a notable enhancement in intestinal cell proliferation within the C1.2 % group (P < 0.05). Regarding the intestinal chemical barrier, trypsin and lipase activities were significantly elevated in the C1.2 % group (P < 0.05), while hepcidin gene expression was considerably down-regulated in this group but up-regulated in the C1.8 % group (P < 0.05). In terms of the intestinal immune barrier, inflammation-related gene expression levels (tnf-α, il-1ß, caspase 9, ire1, perk, atf6) were markedly reduced in the C1.2 % group (P < 0.05). Regarding the intestinal biological barrier, the composition of the intestinal microbiota indicated that compared to the Con group, both the 0.6 % and 1.2 % groups showed a significant increase in Shannon index (P < 0.05). Additionally, there was a significant increase in the abundance of Firmicutes and Clostridium in the C1.2 % group (P < 0.05). In summary, supplementation of 1.2 % cholesterol in the plant-based diet exhibits the potential to enhance intestinal tight junction function and improve the composition of intestinal microbiota, thereby significantly promoting tilapia's intestinal health.

3.
Nucleic Acids Res ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709873

ABSTRACT

Small ubiquitin-like modifiers (SUMOs) are tiny but important protein regulators involved in orchestrating a broad spectrum of biological processes, either by covalently modifying protein substrates or by noncovalently interacting with other proteins. Here, we report an updated server, GPS-SUMO 2.0, for the prediction of SUMOylation sites and SUMO-interacting motifs (SIMs). For predictor training, we adopted three machine learning algorithms, penalized logistic regression (PLR), a deep neural network (DNN), and a transformer, and used 52 404 nonredundant SUMOylation sites in 8262 proteins and 163 SIMs in 102 proteins. To further increase the accuracy of predicting SUMOylation sites, a pretraining model was first constructed using 145 545 protein lysine modification sites, followed by transfer learning to fine-tune the model. GPS-SUMO 2.0 exhibited greater accuracy in predicting SUMOylation sites than did other existing tools. For users, one or multiple protein sequences or identifiers can be input, and the prediction results are shown in a tabular list. In addition to the basic statistics, we integrated knowledge from 35 public resources to annotate SUMOylation sites or SIMs. The GPS-SUMO 2.0 server is freely available at https://sumo.biocuckoo.cn/. We believe that GPS-SUMO 2.0 can serve as a useful tool for further analysis of SUMOylation and SUMO interactions.

4.
Nat Commun ; 15(1): 3685, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693116

ABSTRACT

Sleep, locomotor and social activities are essential animal behaviors, but their reciprocal relationships and underlying mechanisms remain poorly understood. Here, we elicit information from a cutting-edge large-language model (LLM), generative pre-trained transformer (GPT) 3.5, which interprets 10.2-13.8% of Drosophila genes known to regulate the 3 behaviors. We develop an instrument for simultaneous video tracking of multiple moving objects, and conduct a genome-wide screen. We have identified 758 fly genes that regulate sleep and activities, including mre11 which regulates sleep only in the presence of conspecifics, and NELF-B which regulates sleep regardless of whether conspecifics are present. Based on LLM-reasoning, an educated signal web is modeled for understanding of potential relationships between its components, presenting comprehensive molecular signatures that control sleep, locomotor and social activities. This LLM-aided strategy may also be helpful for addressing other complex scientific questions.


Subject(s)
Behavior, Animal , Drosophila melanogaster , Locomotion , Sleep , Animals , Sleep/physiology , Sleep/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/physiology , Locomotion/physiology , Locomotion/genetics , Behavior, Animal/physiology , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Social Behavior , Male
5.
Development ; 151(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38722096

ABSTRACT

During embryonic development, lymphatic endothelial cell (LEC) precursors are distinguished from blood endothelial cells by the expression of Prospero-related homeobox 1 (Prox1), which is essential for lymphatic vasculature formation in mouse and zebrafish. Prox1 expression initiation precedes LEC sprouting and migration, serving as the marker of specified LECs. Despite its crucial role in lymphatic development, Prox1 upstream regulation in LECs remains to be uncovered. SOX18 and COUP-TFII are thought to regulate Prox1 in mice by binding its promoter region. However, the specific regulation of Prox1 expression in LECs remains to be studied in detail. Here, we used evolutionary conservation and chromatin accessibility to identify enhancers located in the proximity of zebrafish prox1a active in developing LECs. We confirmed the functional role of the identified sequences through CRISPR/Cas9 mutagenesis of a lymphatic valve enhancer. The deletion of this region results in impaired valve morphology and function. Overall, our results reveal an intricate control of prox1a expression through a collection of enhancers. Ray-finned fish-specific distal enhancers drive pan-lymphatic expression, whereas vertebrate-conserved proximal enhancers refine expression in functionally distinct subsets of lymphatic endothelium.


Subject(s)
Endothelial Cells , Enhancer Elements, Genetic , Gene Expression Regulation, Developmental , Homeodomain Proteins , Lymphatic Vessels , Tumor Suppressor Proteins , Zebrafish Proteins , Zebrafish , Animals , Homeodomain Proteins/metabolism , Homeodomain Proteins/genetics , Zebrafish/genetics , Zebrafish/embryology , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , Enhancer Elements, Genetic/genetics , Lymphatic Vessels/metabolism , Lymphatic Vessels/embryology , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Endothelial Cells/metabolism , Lymphangiogenesis/genetics , CRISPR-Cas Systems/genetics , Promoter Regions, Genetic/genetics , Mice
6.
J Hazard Mater ; 471: 134361, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38669924

ABSTRACT

Evaporative emissions release organic compounds comparable to gasoline exhaust in China. However, the measurement of intermediate volatility organic compounds (IVOCs) is lacking in studies focusing on gasoline evaporation. This study sampled organics from a real-world refueling procedure and analyzed the organic compounds using comprehensive two-dimensional gas chromatography coupled with a mass spectrometer (GC×GC-MS). The non-target analysis detected and quantified 279 organics containing 93 volatile organic compounds (VOCs, 64.9 ± 7.4 % in mass concentration), 182 IVOCs (34.9 ± 7.4 %), and 4 semivolatile organic compounds (SVOCs, 0.2 %). The refueling emission profile was distinct from that of gasoline exhaust. The b-alkanes in the B12 volatility bin are the most abundant IVOC species (1.9 ± 1.4 µg m-3) in refueling. A non-negligible contribution of 17.5 % to the ozone formation potential (OFP) from IVOCs was found. Although IVOCs are less in concentration, secondary organic aerosol potential (SOAP) from IVOCs (58.1 %) even exceeds SOAP from VOCs (41.6 %), mainly from b-alkane in the IVOC range. At the molecular level, the proportion of cyclic compounds in SOAP (12.1 %) indeed goes above its mass concentration (3.1 %), mainly contributed by cyclohexanes and cycloheptanes. As a result, the concentrations and SOAP of cyclic compounds (>50 %) could be overestimated in previous studies. Our study found an unexpected contribution of IVOCs from refueling procedures to both ozone and SOA formation, providing new insights into secondary pollution control policy.

8.
Nat Commun ; 15(1): 1809, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38418489

ABSTRACT

Further increasing the critical temperature and/or decreasing the stabilized pressure are the general hopes for the hydride superconductors. Inspired by the low stabilized pressure associated with Ce 4f electrons in superconducting cerium superhydride and the high critical temperature in yttrium superhydride, we carry out seven independent runs to synthesize yttrium-cerium alloy hydrides. The synthetic process is examined by the Raman scattering and X-ray diffraction measurements. The superconductivity is obtained from the observed zero-resistance state with the detected onset critical temperatures in the range of 97-141 K. The upper critical field towards 0 K at pressure of 124 GPa is determined to be between 56 and 78 T by extrapolation of the results of the electrical transport measurements at applied magnetic fields. The analysis of the structural data and theoretical calculations suggest that the phase of Y0.5Ce0.5H9 in hexagonal structure with the space group of P63/mmc is stable in the studied pressure range. These results indicate that alloying superhydrides indeed can maintain relatively high critical temperature at relatively modest pressures accessible by laboratory conditions.

9.
Sci Total Environ ; 917: 170378, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38280581

ABSTRACT

Reducing the differences between real-world and certificated NOx emission levels is an important element of in-use emission surveillance programs. Therefore, investigating the characteristics of the vehicles which have much higher NOx emissions (i.e., high-emitters) and determining a reasonable cut-off point to identify high-emitters with a low false detection rate is important. In this study, six diesel trucks were tested under different aftertreatment conditions. The results showed that the discrepancies of fuel-specific NOx emissions between vehicles with functioning and tampered selective catalytic reduction (SCR) systems occur mainly from medium- to high-speed modes. This is because the SCR systems were at low conversion efficiencies when the exhaust temperature was low, including cold-start and urban creep conditions. By using binary classification, we selected fuel-specific NOx cut-off points for high-emitters from China V and China VI diesel trucks. The false detection rate of high-emitters can decrease by 33 % and 95 %, if only NOx emissions from medium- to high-speed modes were used for the chosen cut-off points, respectively. This work highlights the importance of in-use emission compliance programs. It also suggests that high-emitters can be more accurately identified at medium- to high-speed modes if using instantaneous emission data.

10.
Fish Physiol Biochem ; 50(1): 225-237, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37594622

ABSTRACT

The aim of this study was to investigate the effect of dietary vitamin A on juvenile Chinese perch (Siniperca chuatsi). Chinese perch were fed with five experimental diets containing 0, 20, 40, 60, and 80 mg VA·kg-1 for 8 weeks. Results showed that dietary vitamin A significantly influenced the fish's growth, feed utilization, glucose and lipid metabolism, appetite, and antioxidant capacity. Vitamin A-supplemented groups had higher weight gain rate (WGR) and specific growth rate (SGR) compared to the control group. Feed conversion ratio (FCR) was also lower in the vitamin A-supplemented groups. Dietary vitamin A had no significant effect on the survival rate (SR). Compared to the control group, fish fed with vitamin A had increased feed intake (FI), and the expression of appetite-promoting genes (npy and agrp) was significantly higher in the 40 mg VA·kg-1 group. Vitamin A also enhanced the utilization of dietary protein by Chinese perch. The serum glucose content of the fish fed with 40 mg VA·kg-1 diet was significantly higher than that of the control group and 20 mg VA·kg-1 diet, indicating that the promoting effect of VA on gluconeogenesis was greater than that on glycolysis. Additionally, dietary vitamin A increased the expression of lipid metabolism-related genes (hl and fas) and antioxidant genes (nrf2 and gpx) in the fish. These results suggest that the optimal vitamin A requirement of juvenile Chinese perch bream was estimated to be 37.32 mg VA·kg-1 based on broken-line regression analysis of WGR. In conclusion, this study provides valuable insights into the potential benefits of dietary vitamin A on the growth, metabolism, and antioxidant capacity of Chinese perch.


Subject(s)
Antioxidants , Perches , Animals , Antioxidants/metabolism , Lipid Metabolism , Vitamin A/pharmacology , Vitamin A/metabolism , Appetite , Glucose/metabolism , Dietary Supplements/analysis , Diet/veterinary , Animal Feed/analysis
11.
Nat Prod Res ; : 1-11, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38126176

ABSTRACT

Alpha-Momorcharin (α-MMC), as one of the most important type I RIPs, has been reported to exert inhibitory effects against various tumour cells through its N-glycosidase activity. The present study was designed to propose an efficient purification strategy and explored its mechanism of apoptosis signalling pathway against human liver cancer cells SK-Hep-1. α-MMC can be successfully obtained by our purification strategy combining ion-exchange and gel-filtration chromatography. The functional studies revealed that α-MMC obviously increased the level of ROS and apoptosis rate, induced cell cycle arrest in the G1 phase, and depolarised MMP of SK-Hep-1 cells. To further confirm whether α-MMC could induce mitochondria involved apoptosis, we found that PARP-1, Caspase-3, Caspase-9, and BCL-2 were downregulated upon α-MMC. Taken together, these results suggested that this natural purified α-MMC can induce apoptosis involved mitochondria and may serve as a potential novel therapeutic drug in the treatment of human liver cancer in the future.

12.
J Phys Condens Matter ; 36(7)2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37918102

ABSTRACT

Clathrate hydrideFm3-m-LaH10has been proven as the most extraordinary superconductor with the critical temperatureTcabove 250 K upon compression of hundreds of GPa in recent years. A general hope is to reduce the stabilization pressure and maintain the highTcvalue of the specific phase in LaH10. However, strong structural instability distortsFm3-mstructure and leads to a rapid decrease ofTcat low pressures. Here, we investigate the phase stability and superconducting behaviors ofFm3-m-LaH10with enhanced chemical pre-compression through partly replacing La by Ce atoms from both experiments and calculations. For explicitly characterizing the synthesized hydride, we choose lanthanum-cerium alloy with stoichiometry composition of 1:1. X-ray diffraction and Raman scattering measurements reveal the stabilization ofFm3-m-La0.5Ce0.5H10in the pressure range of 140-160 GPa. Superconductivity withTcof 175 ± 2 K at 155 GPa is confirmed with the observation of the zero-resistivity state and supported by the theoretical calculations. These findings provide applicability in the future explorations for a large variety of hydrogen-rich hydrides.

13.
Fish Physiol Biochem ; 49(6): 1097-1114, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37855970

ABSTRACT

To explore the potential benefits of dietary phospholipids (PLs) in fish glucose metabolism and to promote feed culture of Chinese perch (Siniperca chuatsi), we set up six diets to feed Chinese perch (initial mean body weight 37.01 ± 0.20 g) for 86 days, including: Control diet (CT), 1% (SL1), 2% (SL2), 3% (SL3), 4% (SL4) soybean lecithin (SL) and 2% (KO2) krill oil (KO) supplemental diets (in triplicate, 20 fish each). Our study found that the SL2 significantly improved the weight gain rate and special growth rate, but the KO2 did not. In addition, the SL2 diet significantly improved feed intake, which is consistent with the mRNA levels of appetite-related genes (npy, agrp, leptin A). Additionally, in the CT and SL-added groups, leptin A expression levels were nearly synchronized with serum glucose levels. Besides, the SL2 significantly upregulated expression levels of glut2, gk, cs, fas and downregulated g6pase in the liver, suggesting that it may enhance glucose uptake, aerobic oxidation, and conversion to fatty acids. The SL2 also maintained the hepatic crude lipid content unchanged compared to the CT, possibly by significantly down-regulating the mRNA level of hepatic lipase gene (hl), and by elevating serum low-density lipoprotein (LDL) level and intraperitoneal fat ratio in significance. Moreover, the serum high-density lipoprotein levels were significantly increased by PL supplementation, and the SL2 further significantly increased serum total cholesterol and LDL levels, suggesting that dietary PLs promote lipid absorption and transport. Furthermore, dietary SL at 1% level could enhance non-specific immune capacity, with serum total protein level being markedly higher than that in the CT group. In conclusion, it is speculated that the promotion of glucose utilization and appetite by 2% dietary SL could be linked. We suggest a 1.91% supplementation of SL in the diet for the best growth performance in juvenile Chinese perch.


Subject(s)
Lecithins , Perches , Animals , Lecithins/pharmacology , Lecithins/metabolism , Glycine max , Leptin/metabolism , Diet/veterinary , Fatty Acids/metabolism , Lipid Metabolism , Glucose/pharmacology , Glucose/metabolism , RNA, Messenger/metabolism
14.
J Am Chem Soc ; 145(44): 24012-24020, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37903430

ABSTRACT

Understanding charge transport among metal particles with sizes of approximately 1 nm poses a great challenge due to the ultrasmall nanosize, yet it holds great significance in the development of innovative materials as substitutes for traditional semiconductors, which are insulative and unstable in less than ∼10 nm thickness. Herein, atomically precise gold nanoclusters with well-defined compositions and structures were investigated to establish a mathematical relation between conductivity and interparticle distance. This was accomplished using high-pressure in situ resistance characterizations, synchrotron X-ray diffraction (XRD), and the Murnaghan equation of state. Based on this precise correlation, it was predicted that the conductivity of Au25(SNap)18 (SNap: 1-naphthalenethiolate) solid is comparable to that of bulk silver when the interparticle distance is reduced to approximately 3.6 Å. Furthermore, the study revealed the coexisting, competing tunneling, and incoherent hopping charge transport mechanisms, which differed from those previously reported. The introduction of conjugation-structured ligands, tuning of the structures of metal nanoclusters, and use of high-pressure techniques contributed to enhanced conductivity, and thus, the charge carrier types were determined using Hall measurements. Overall, this study provides valuable insight into the charge transport in gold nanocluster solids and represents an important advancement in metal nanocluster semiconductor research.

15.
Front Endocrinol (Lausanne) ; 14: 1266985, 2023.
Article in English | MEDLINE | ID: mdl-37876537

ABSTRACT

The detection and quantification of hormones are important to assess the reproductive and stress status of experimental models and for the diagnosis of diseases in human and veterinary clinics. Traditionally, steroid, peptide, and protein hormones are analyzed in individual experiments using different extraction methodologies. With the new advancement on HPLC sorbents, the simultaneous measurement of hormones from different categories becomes possible. In this study, we present a novel sample processing strategy for the simultaneous extraction and detection of peptides, steroids, and proteins using high-resolution liquid chromatography tandem mass spectrometry. We demonstrate the sensitivity of our method for small tissues by acquiring data from brain, pituitary gland, and gonads of single zebrafish samples. This approach promises to shed light on the hormonal pathways and their interrelationships, providing knowledge on the integration of hormone systems.


Subject(s)
Tandem Mass Spectrometry , Zebrafish , Animals , Humans , Zebrafish/metabolism , Tandem Mass Spectrometry/methods , Steroids/metabolism , Hormones , Peptides
16.
Fish Physiol Biochem ; 49(5): 1017-1030, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37718352

ABSTRACT

An 84-day feeding experiment was conducted to investigate the effects of dietary Zn (zinc) on growth performance, food intake, and lipid metabolism of Chinese perch (Siniperca chuatsi). Five isonitrogenous and isolipidic diets with differential Zn contents (67, 100, 149, 230, and 410 mg/kg) were fed to 270 fish (35.47 ± 0.49 g). Results showed that fish growth and food intake increased markedly with the dietary 149 mg/kg Zn levels. Meanwhile, the food intake of 149 mg/kg group was significantly higher than that of other treatment groups after feeding for 8 weeks (P < 0.05). The qRT-PCR results showed that the expression of center appetite regulation factors in the hypothalamus was significantly regulated, and 149 mg/kg significantly increased mRNA expression of npy (neuropeptide Y) and decreased pomc (anorexigenic proopiomelanocortin) and cart (cocaine- and amphetamine-regulated transcript) gene expression. Meanwhile, the expressions of the main genes (such as leptin A and ghrelin) involved in peripheral appetite regulation factors were significantly up-regulated firstly and then reduced with the dietary Zn level increased, whereas the expression of cck (cholecystokinin) was significantly up-regulated. Serum AST (aspartate transaminase) and ALT (alanine transaminase) activities in fish fed the diets containing 230 and 410 mg/kg were significantly higher than that in other groups (P < 0.05). The lipid content of liver in 67 and 100 mg/kg groups was significantly higher than other groups (P < 0.05). Furthermore, dietary Zn significantly elevated the serum TG (triglyceride) and TCHO (total cholesterol) content levels (P < 0.05). Fish fed a high Zn diet (149, 230, and 410 mg/kg) dramatically down-regulated expression of srebp1 (sterol regulatory element binding proteins1c) and fas (fatty acid synthetase), but up-regulated expression of pparα (peroxisome proliferators-activated receptor-α) and cpt1 (carnitine palmitoyl transferase I) in the liver. The optimal dietary Zn inclusion level ranged from 146.69 to 152.86 mg/kg diet, based on two-slope broken-line regression analysis of WGR (weight gain rate) and FCR (feed conversion rate) for Chinese perch.


Subject(s)
Appetite , Perches , Animals , Lipid Metabolism/genetics , Diet/veterinary , Neuropeptide Y/genetics , Zinc
17.
Cancer Cell ; 41(10): 1749-1762.e6, 2023 10 09.
Article in English | MEDLINE | ID: mdl-37683638

ABSTRACT

We report a personalized tumor-informed technology, Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (PROPHET) using deep sequencing of 50 patient-specific variants to detect molecular residual disease (MRD) with a limit of detection of 0.004%. PROPHET and state-of-the-art fixed-panel assays were applied to 760 plasma samples from 181 prospectively enrolled early stage non-small cell lung cancer patients. PROPHET shows higher sensitivity of 45% at baseline with circulating tumor DNA (ctDNA). It outperforms fixed-panel assays in prognostic analysis and demonstrates a median lead-time of 299 days to radiologically confirmed recurrence. Personalized non-canonical variants account for 98.2% with prognostic effects similar to canonical variants. The proposed tumor-node-metastasis-blood (TNMB) classification surpasses TNM staging for prognostic prediction at the decision point of adjuvant treatment. PROPHET shows potential to evaluate the effect of adjuvant therapy and serve as an arbiter of the equivocal radiological diagnosis. These findings highlight the potential advantages of personalized cancer techniques in MRD detection.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cell-Free Nucleic Acids , Circulating Tumor DNA , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Circulating Tumor DNA/analysis , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/surgery , DNA, Neoplasm , Neoplasm, Residual/genetics , Biomarkers, Tumor/genetics , Neoplasm Recurrence, Local/genetics
18.
Plant Cell ; 35(11): 4066-4090, 2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37542515

ABSTRACT

Endosperm filling in maize (Zea mays), which involves nutrient uptake and biosynthesis of storage reserves, largely determines grain yield and quality. However, much remains unclear about the synchronization of these processes. Here, we comprehensively investigated the functions of duplicate NAM, ATAF1/2, and CUC2 (NAC)-type transcription factors, namely, ZmNAC128 and ZmNAC130, in endosperm filling. The gene-edited double mutant zmnac128 zmnac130 exhibits a poorly filled kernel phenotype such that the kernels have an inner cavity. RNA sequencing and protein abundance analysis revealed that the expression of many genes involved in the biosynthesis of zein and starch is reduced in the filling endosperm of zmnac128 zmnac130. Further, DNA affinity purification and sequencing combined with chromatin-immunoprecipitation quantitative PCR and promoter transactivation assays demonstrated that ZmNAC128 and ZmNAC130 are direct regulators of 3 (16-, 27-, and 50-kD) γ-zein genes and 6 important starch metabolism genes (Brittle2 [Bt2], pullulanase-type starch debranching enzyme [Zpu1], granule-bound starch synthase 1 [GBSS1], starch synthase 1 [SS1], starch synthase IIa [SSIIa], and sucrose synthase 1 [Sus1]). ZmNAC128 and ZmNAC130 recognize an additional cis-element in the Opaque2 (O2) promoter to regulate its expression. The triple mutant zmnac128 zmnac130 o2 exhibits extremely poor endosperm filling, which results in more than 70% of kernel weight loss. ZmNAC128 and ZmNAC130 regulate the expression of the transporter genes sugars that will eventually be exported transporter 4c (ZmSWEET4c), sucrose and glucose carrier 1 (ZmSUGCAR1), and yellow stripe-like2 (ZmYSL2) and in turn facilitate nutrient uptake, while O2 plays a supporting role. In conclusion, ZmNAC128 and ZmNAC130 cooperate with O2 to facilitate endosperm filling, which involves nutrient uptake in the basal endosperm transfer layer (BETL) and the synthesis of zeins and starch in the starchy endosperm (SE).


Subject(s)
Endosperm , Zein , Endosperm/genetics , Endosperm/metabolism , Zea mays/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Zein/genetics , Zein/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Starch/metabolism
19.
Fish Physiol Biochem ; 49(6): 1063-1078, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37542702

ABSTRACT

This study aimed to assess the effect of pyridoxine supplementation in the mandarin fish diet on growth performance, protein and lipid metabolism, and liver and intestinal histology. Mandarin fish were fed six diets with different levels of pyridoxine (2.67 mg/kg (control), 4.41 mg/kg, 6.57 mg/kg, 10.25 mg/kg, 17.93 mg/kg, 33.12 mg/kg diet) for 8 weeks, and samples were collected for analysis. The findings demonstrated that feeding mandarin fish a diet with 6.57 mg/kg pyridoxine led to a significant increase in weight gain rate (WGR), protein efficiency ratio (PER), whole-body crude protein, whole-body crude lipid, serum protein, cholesterol (CHO), triacylglycerol (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and alkaline phosphatase (ALP), as well as significantly lower serum glucose (GLU) and feed conversion ratio (FCR), compared to the control group (P < 0.05). Furthermore, we found a significant upregulation of the relative expression of genes associated with hepatic lipid oxidation and synthesis (hl, lpl, pparα, cpt1, cs, srebp1, and fas) and proteolysis (ast, alt, and gdh) in fish fed a diet containing 6.57 mg/kg pyridoxine (P < 0.05). Regarding the histological analysis, we observed a notable decrease in the quantity of intestinal mucus-secreting cells when the fish fed a diet containing 10.25 mg/kg pyridoxine (P < 0.05). These findings suggest that dietary pyridoxine supplementation promotes mandarin fish growth by improving the efficiency of protein and lipid utilization. Additionally, we used a broken-line regression analysis to estimate the optimal dietary pyridoxine requirement for mandarin fish in the range of 6.17-6.41 mg/kg based on WGR, FCR, and PER.


Subject(s)
Diet , Pyridoxine , Animals , Pyridoxine/pharmacology , Diet/veterinary , Triglycerides/metabolism , Fishes/metabolism , Cholesterol , Dietary Supplements , Animal Feed/analysis , Lipid Metabolism
20.
Phys Chem Chem Phys ; 25(29): 19606-19611, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37435704

ABSTRACT

In this work, we prepared a BiOBr powder sample by the coprecipitation method for in situ high-pressure AC impedance spectroscopy tests, in situ high-pressure Raman measurements and in situ high-pressure X-ray diffraction experiments to explore its structural properties and electrical transport processes under compression. Two pressure-driven isostructural phase transitions, T-T' and T'-T'' (T - tetragonal, T' - tetragonal 1 and T'' - tetragonal 2), were discovered at around 10.0 and 15.0 GPa, respectively. The pressure-induced changes in the crystal structure and electrical transport of BiOBr can provide a reference for explaining the mechanism of the isostructural phase transition of other similar compounds after compression.

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