TRIM65 deficiency alleviates renal fibrosis through NUDT21-mediated alternative polyadenylation.

Chronic kidney disease (CKD) is a major global health concern and the third leading cause of premature death. Renal fibrosis is the primary process driving the progression of CKD, but the mechanisms behind it are not fully understood, making treatment options limited. Here, we find that the E3 ligase TRIM65 is a positive regulator of renal fibrosis. Deletion of TRIM65 results in a reduction of pathological lesions and renal fibrosis in mouse models of kidney fibrosis induced by unilateral ureteral obstruction (UUO)- and folic acid. Through screening with a yeast-hybrid system, we identify a new interactor of TRIM65, the mammalian cleavage factor I subunit CFIm25 (NUDT21), which plays a crucial role in fibrosis through alternative polyadenylation (APA). TRIM65 interacts with NUDT21 to induce K48-linked polyubiquitination of lysine 56 and proteasomal degradation, leading to the inhibition of TGF-ß1-mediated SMAD and ERK1/2 signaling pathways. The degradation of NUDT21 subsequently altered the length and sequence content of the 3'UTR (3'UTR-APA) of several pro-fibrotic genes including Col1a1, Fn-1, Tgfbr1, Wnt5a, and Fzd2. Furthermore, reducing NUDT21 expression via hydrodynamic renal pelvis injection of adeno-associated virus 9 (AAV9) exacerbated UUO-induced renal fibrosis in the normal mouse kidneys and blocked the protective effect of TRIM65 deletion. These findings suggest that TRIM65 promotes renal fibrosis by regulating NUDT21-mediated APA and highlight TRIM65 as a potential target for reducing renal fibrosis in CKD patients.

Phosphine-catalyzed dearomative [3+2] cycloaddition of 4-nitroisoxazoles with allenoates or Morita-Baylis-Hillman carbonates.

An efficient phosphine-catalyzed dearomative [3+2] annulation of 4-nitroisoxazoles with allenoates or Morita-Baylis-Hillman carbonates has been established for the convenient synthesis of bicyclic isoxazoline derivatives. This reaction approach showed a broad substrate scope, high functional group compatibility, and excellent regioselectivity and diastereoselectivity. Furthermore, the success at the gram-scale and synthetic applications of the obtained compound 3a demonstrate the great potential of this methodology for practical applications in organic synthesis.

Replacing soybean meal with fermented rapeseed meal in diets: potential effects on growth performance, antioxidant capacity, and liver and intestinal health of juvenile tilapia (Oreochromis niloticus).

This study aims to evaluate the effects of substituting soybean meal with fermented rapeseed meal (FRM) on growth, antioxidant capacity, and liver and intestinal health of the genetically improved farmed tilapia (GIFT, Oreochromis niloticus). A total of 450 tilapia (7.22 ± 0.15 g) were fed with five experimental diets, including a basal diet containing 40% soybean meal (CP0), which was subsequently replaced by 25% (CP25), 50% (CP50), 75% (CP75), and 100% (CP100) FRM in a recirculated aquiculture system for 9 weeks (30 fish per tank in triplicates). The results showed that the weight gain, specific growth rate, feed intake, feed efficiency, hepatosomatic index, and viscerosomatic index of fish in both CP75 and CP100 groups were significantly lower than those in CP0 group (P < 0.05). The fish in CP100 group had the lower content of muscle crude protein while the higher level of muscle crude lipid (P < 0.05). Activities of serum aspartate aminotransferase, alanine aminotransferase along with total triglyceride in CP100 group were significantly higher than those in CP0 group (P < 0.05). There were no significant differences in the contents of liver protease, amylase, and lipase among five groups (P > 0.05). The activities of liver total antioxidant capacity and superoxide dismutase exhibited the increased tendency with the increase of FRM replacement levels from 25 to 50% (P < 0.05), while then significantly decreased from 75 to 100% (P < 0.05). Histological morphology indicated that the fish in between CP75 and CP100 groups had poor liver and intestine health. Intestinal microbial diversity analysis showed that the relative abundance of Cetobacterium and Alcaligenaceae in both CP75 and CP100 groups were lower than that in other three groups. In conclusion, the maximum replacement level of soybean meal with FRM in the diet was determined to be 50% without compromising the growth performance, antioxidant status, and liver and intestinal health of tilapia under the current experimental conditions. The observed decrease in food intake and subsequent retarded growth performance in the CP75 and CP100 groups can be attributed directly to a reduction in feed palatability caused by FRM.

Phosphine-Catalyzed Ring-Opening Regioselective Addition of Cyclopropenones with Amides.

A series of amides, including α-bromo hydroxamates, N-alkoxyamides, and N-aryloxyamides, were subjected to phosphine-catalyzed ring-opening O-selective addition with cyclopropenones, producing various special α,ß-unsaturated esters containing oxime ether motif, in moderate to excellent yields, with high regioselectivity, and exclusive O-selectivity. The methodology is highly atom-economical, with simple operation procedures, and compatible with a wide substrate scope (more than 44 examples).

Dietary cholesterol intervention could alleviate the intestinal injury of Oreochromis niloticus induced by plant-based diet via the intestinal barriers.

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.

Acute promyelocytic leukemia with additional chromosome abnormalities in a patient positive for HIV: A case report and literature review.

Acute promyelocytic leukemia (APL), especially cases of high-risk with complex chromosomes (CK), is rare in individuals infected with human immunodeficiency virus (HIV), making the establishment of therapeutic approaches challenging; often the treatment is individualized. This report describes a 49-year-old female patient with HIV who was diagnosed with high-risk APL with a new CK translocation and presents a literature review. At diagnosis, the patient presented with typical t(15;17)(q24;q21) with additional abnormalities, including add(5)(q15), add(5)(q31), add(7)(q11.2) and add(12) (p13). The results of acute myeloid leukemia mutation analysis suggested positivity for calreticulin and lysine methyltransferase 2C genes. The patient received all-trans retinoic acid combined with arsenic trioxide and chemotherapy, with morphologically complete remission after the first cycle of chemotherapy. The present report provided preliminary data for future clinical research.

A networked iron and nitrogen-doped ZIF-8/MWCNTs heterostructure for oxygen reduction reaction.

Zeolitic Imidazolate Frameworks-8 (ZIF-8) is commonly used as an ideal precursor for non-noble metal catalysts because of its high specific surface area, ultra-high porosity, and N-rich content. Upon pyrolyzing ZIF-8 at 900 °C in Ar, the resulting material, referred to as Z8, displayed good activity toward the oxygen reduction reaction (ORR). Then the ZIF-8 was mixed with various conductive carbon materials, such as multiwall carbon nanotubes (MWCNTs), Acetylene black (ACET), Vulcan XC-72R (XC-72R), and Ketjenblack EC-600JD (EC-600JD), to form Z8 composites. The Z8/MWCNTs composite exhibited enhanced ORR activity owing to its network structure, meso-/microporous hierarchical porous structure, improved electrical conductivity, and graphitization. Subsequently, iron and nitrogen co-doping is achieved through the pyrolysis of a mixture comprising Fe, N precursor, and ZIF-8/MWCNTs, which is denoted as FeN-Z8/MWCNTs. The intrinsically high electrical conductivity of MWCNTs facilitated efficient electron transfer during the ORR, while the meso-/microporous hierarchical porous structure and network structure of Fe, N co-doped ZIF-8/MWCNTs promoted oxygen transport. The presence of Fe-containing species in the catalyst acted as activity centers for ORR. This strategy of preparing Z8 composites and modifying them with Fe, N co-doping offers an insightful approach to designing cost-effective electrocatalysts.

Enhancing growth, liver health, and bile acid metabolism of tilapia (Oreochromis niloticus) through combined cholesterol and bile acid supplementation in plant-based diets.

The present study aimed to compare the nutritional effects of cholesterol, bile acids, and combination of cholesterol with bile acids in plant-based diets on juvenile genetically improved farmed tilapia (GIFT; Oreochromis niloticus). The isonitrogenous (321 g/kg crude protein) and isolipidic (76 g/kg crude fat) diets (Con diet) were based on plant protein sources, which included corn gluten meal, soybean meal, cottonseed meal and rapeseed meal. The Con diet was supplemented with 12 g/kg cholesterol (CHO diet), 0.2 g/kg bile acids (BAs diet), a combination of 12 g/kg cholesterol and 0.2 g/kg bile acids (CHO-BAs diet), respectively. Each diet was fed to three tanks in an indoor recirculating aquaculture system for 9 weeks. Results showed that compared to the Con group, fish had a higher weight gain rate, hepatosomatic index, and a lower feed conversion ratio in the CHO-BAs group. The highest levels of whole-fish fat and ash were found in the Con group. Serum parameters, including activities of alanine aminotransferase (ALT) and aspartate transaminase (AST), along with levels of glucose (GLU) and triglyceride (TG) except for total cholesterol (TCHO), were lower in the CHO, BAs, and CHO-BAs groups than those in the Con group (P < 0.001). Histological examination revealed that fish in the Con group exhibited severe hepatocyte vacuolization and diminished hepatocyte proliferation. Gene expression analysis indicated that the transcriptional levels of bile acid metabolism-related genes (including fxr, fgf19, bsep) were up-regulated in the CHO-BAs group (P < 0.05), whereas cholesterol metabolism-related genes (acly and hmgcr) were down-regulated in both CHO and CHO-BAs groups (P < 0.001). Moreover, UPLC-MS/MS analysis revealed that the higher taurine-conjugated bile acids (T-BAs), followed by free bile acids (Free-BAs) and glycine (G-BAs) were determined in tilapia bile. Among these, taurochenodeoxycholic bile acid was the predominant bile acid. Dietary bile acids supplementation also increased the proportion of T-BAs (tauro ß-muricholic acid and taurodehydrocholic acid) while decreasing Free-BAs in the fish bile. In conclusion, the incorporation of cholesterol with bile acids into plant-based diets can effectively reduce cholesterol uptake, suppress bile acids synthesis, enhance bile acids efflux, and promote hepatocyte proliferation, which is helpful for maintaining the normal liver morphology in tilapia, and thus improving its growth performance.

Modified respiratory-triggered SPACE sequences for magnetic resonance cholangiopancreatography.

Background: Respiratory-triggered (RT) and breath-hold are the most common acquisition modalities for magnetic resonance cholangiopancreatography (MRCP). The present study compared the three different acquisition modalities for optimizing the use of MRCP in patients with diseases of the pancreatic and biliary systems. Materials and methods: Three MRCP acquisition modalities were used in this study: conventional respiratory-triggered sampling perfection with application-optimized contrasts using different flip evolutions (RT-SPACE), modified RT-SPACE, and breath-hold (BH)-SPACE. Fifty-eight patients with clinically suspected pancreatic and biliary system disease were included. All image data were acquired on a 1.5 T MR. Scan time and image quality were compared between the three acquisition modalities. Friedman test, which was followed by post-hoc analysis, was performed among triple-scan protocol. Results: There was a significant difference in the mean acquisition time among conventional RT-SPACE, modified RT-SPACE, and BH-SPACE (167.41±32.11 seconds vs 50.84±73.78 seconds vs 18.00 seconds, P <0.001). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were also significantly different among the three groups (P <0.001). The SNR and CNR were higher in the RT-SPACE group than in the BH-SPACE group (P <0.05). However, there were no statistically significant differences (P >0.05) among the 3 groups regarding quality of overall image, image clarity, background inhibition, and visualization of the pancreatic and biliary system. Conclusions: MRCP acquisition with the modified RT-SPACE sequence greatly shortens the acquisition time with comparable quality images. The MRCP acquisition modality could be designed based on the patient's situation to improve the examination pass rate and obtain excellent images for diagnosis.

Molecular cloning and gene expression of acc2 from grass carp (Ctenopharyngodon idella) and the regulation of glucose metabolism by ACCs inhibitor.

BACKGROUND: Acetyl-CoA carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to malonyl-CoA. Malonyl-CoA, which plays a key role in regulating glucose and lipid metabolism, is not only a substrate for fatty acid synthesis but also an inhibitor of the oxidation pathway. ACC exists as two isoenzymes that are encoded by two different genes. ACC1 in grass carp (Ctenopharyngodon idellus) has been cloned and sequenced. However, studies on the cloning, tissue distribution, and function of ACC2 in grass carp were still rare. METHODS AND RESULTS: The full-length cDNA of acc2 was 8537 bp with a 7146 bp open reading frame encoding 2381 amino acids. ACC2 had a calculated molecular weight of 268.209 kDa and an isoelectric point of 5.85. ACC2 of the grass carp shared the closest relationship with that of the common carp (Sinocyclocheilus grahami). The expressions of acc1 and acc2 mRNA were detected in all examined tissues.  The expression level of acc1 was high in the brain and fat but absent in the midgut and hindgut. The expression level of acc2 in the kidney was significantly higher than in other tissues, followed by the heart, brain, muscle, and spleen. ACCs inhibitor significantly reduced the levels of glucose, malonyl-CoA, and triglyceride in hepatocytes. CONCLUSIONS: This study showed that the function of ACC2 was evolutionarily conserved from fish to mammals. ACCs inhibitor inhibited the biological activity of ACCs, and reduced fat accumulation in grass carp.

A novel PGPR strain, Streptomyces lasalocidi JCM 3373T, alleviates salt stress and shapes root architecture in soybean by secreting indole-3-carboxaldehyde.

While soybean (Glycine max L.) provides the most important source of vegetable oil and protein, it is sensitive to salinity, which seriously endangers the yield and quality during soybean production. The application of Plant Growth-Promoting Rhizobacteria (PGPR) to improve salt tolerance for plant is currently gaining increasing attention. Streptomycetes are a major group of PGPR. However, to date, few streptomycetes has been successfully developed and applied to promote salt tolerance in soybean. Here, we discovered a novel PGPR strain, Streptomyces lasalocidi JCM 3373T, from 36 strains of streptomycetes via assays of their capacity to alleviate salt stress in soybean. Microscopic observation showed that S. lasalocidi JCM 3373T does not colonise soybean roots. Chemical analysis confirmed that S. lasalocidi JCM 3373T secretes indole-3-carboxaldehyde (ICA1d). Importantly, IAC1d inoculation alleviates salt stress in soybean and modulates its root architecture by regulating the expression of stress-responsive genes GmVSP, GmPHD2 and GmWRKY54 and root growth-related genes GmPIN1a, GmPIN2a, GmYUCCA5 and GmYUCCA6. Taken together, the novel PGPR strain, S. lasalocidi JCM 3373T, alleviates salt stress and improves root architecture in soybean by secreting ICA1d. Our findings provide novel clues for the development of new microbial inoculant and the improvement of crop productivity under salt stress.

Ferric Chloride-Mediated Transacylation of N-Acylsulfonamides.

Transacylation of N-acylsulfonamides, which replaces the N-acyl group with a new one, is a challenging and underdeveloped fundamental transformation. Herein, a general method for transacylation of N-acylsulfonamides is presented. The transformation is enabled by coincident catalytic reactivities of FeCl3 for nonhydrolytic deacylation of N-acylsulfonamides and subsequent acylation of the resultant sulfonamides and can be conducted either stepwise or in a one-pot manner. GaCl3 and RuCl3·xH2O are similarly effective for the reaction. This method is mild, efficient, and operationally simple. A variety of functional groups such as halogeno, keto, nitro, cyano, ether, and ester are well tolerated, providing the transacylation products in good to excellent yields.

Dietary Cholesterol Requirements of Large Red Swamp Crayfish (Procambarus clarkii).

To investigate the dietary cholesterol requirements of large red swamp crayfish (Procambarus clarkii), crayfish (initial body weight: 13.49 ± 0.22 g) were hand-fed six diets containing 2.47 (C0), 4.27 (C1), 6.80 (C2), 8.77 (C3), 11.74 (C4), and 14.24 (C5) g/kg cholesterol. After 8 weeks of feeding, the maximum weight gain rate and specific growth rate occurred in group C4. The lowest feed conversion ratio was observed in group C3. Total flesh percentage increased significantly by 15.33% in group C2 compared to group C0. The increase in dietary cholesterol resulted in significant quadratic trends in concentrations of crude protein and lipid in muscle and whole body; cholesterol and free fatty acid in hemolymph, hepatopancreas, and muscle; activities of lipase and amylase in hepatopancreas and intestine; and total antioxidant capacity and catalase activity in hepatopancreas. Group C3 experienced a noteworthy increase in hemolymph glucose and total protein content compared to group C0. Additionally, malondialdehyde content and superoxide dismutase activity in hepatopancreas displayed significant linear and quadratic trends. The optimal dietary cholesterol level for large P. clarkii is between 7.42 and 10.93 g/kg, as revealed by the quadratic regression analysis.

Preliminary Study to Assess the Impact of Dietary Rutin on Growth, Antioxidant Capacity, and Intestinal Health of Yellow Catfish, Pelteobagrus fulvidraco.

This research aimed to examine the effects of dietary rutin supplementation on growth, body composition, serum biochemical indexes, liver enzyme activities and antioxidant-related genes expression, intestinal morphology, and microbiota composition of juvenile yellow catfish (Pelteobagrus fulvidraco). Rutin was added to the basal diets at doses of 0 (control), 100 mg/kg, and 500 mg/kg. Each diet was fed randomly into three tanks, each tank containing 30 fish with an initial body mass of (10.27 ± 0.62) g. The feeding trial was conducted in an indoor recirculating aquiculture system at 28 °C for 56 days. According to the findings, the inclusion of 100 mg/kg rutin significantly improved the growth performance of yellow catfish and reduced the feed conversion ratio; however, the growth promotion effect was diminished when the diet was supplemented with 500 mg/kg of rutin. The inclusion of 500 mg/kg rutin in the diet significantly reduced the level of crude lipid and protein of the whole fish. Serum activities of alkaline phosphatase, albumin, and total protein were all significantly increased when fish were fed the diet supplemented with 500 mg/kg rutin, while serum glucose was significantly lower compared to the control group. Meanwhile, dietary rutin at a concentration of 500 mg/kg significantly induced the hepatic mRNA expressions of antioxidant-related genes (including Cu/Zn-SOD, Mn-SOD, CAT, GPx) and inflammatory-associated genes (including TNFα, IL-10, LYZ). Incorporating rutin at doses of 100 mg/kg and 500 mg/kg into the diets resulted in a notable increase in superoxide dismutase (SOD) activity, while simultaneously reducing malondiadehyde (MDA) content in the liver and intestine. Intestinal villus height, villus width, muscular thickness, and lumen diameter were significantly increased with the administration of 500 mg/kg of dietary rutin. Gut microbial diversity analysis indicated that supplementing diets with 100 mg/kg and 500 mg/kg rutin significantly enhanced the abundance of Cetobacterium while decreasing Plesiomonas richness. In conclusion, dietary rutin levels at 100 mg/kg could enhance the growth, antioxidant capability, and intestinal health of yellow catfish under present experimental conditions.

Zeaxanthin Combined with Tocopherol to Improve the Oxidative Stability of Chicken Oil.

Chicken oil is prone to oxidation due to the high content of unsaturated fatty acids. The interaction of antioxidants was affected by their concentration, ratio, and reaction system. In this article, mixtures of zeaxanthin and tocopherols (α-tocopherol and γ-tocopherol) were chosen to enhance the oxidative stability of chicken oil. The antioxidation of zeaxanthin with tocopherols was analyzed using the Rancimat test, the free radical scavenging capacity and the Schaal oven test (the variation of antioxidant content, PV and shelf life prediction). The optimal concentration of zeaxanthin determined by Rancimat in chicken oil was 20 mg/kg. The binary mixtures have a strong synergistic effect in the ABTS experiment, and the clearance rate was up to 99%, but antagonistic effect in ORAC. The degree of synergism between zeaxanthin and tocopherols was determined by ratio. The interaction between zeaxanthin and α-tocopherol was synergistic, while the types of interaction between zeaxanthin and γ-tocopherol were affected by concentration. The main synergistic interaction mechanism was the regeneration of tocopherol by zeaxanthin. Synergistic combinations of zeaxanthin with α-tocopherol and γ-tocopherol played a key role in the primary oxidation stage of the lipid. The best synergistic combination was A3 (zeaxanthin+α-tocopherol: 15+50 23 mg/kg), which could extend the shelf life of chicken oil (92.46 d) to 146.93 days. This work provides a reference for zeaxanthin and tocopherol to improve the oxidative stability of animal fat.

The probiotic effects of host-associated Bacillus velezensis in diets for hybrid yellow catfish (Pelteobagrus fulvidraco ♀ × Pelteobagrus vachelli ♂).

This study was to evaluate the potential of a host-associated Bacillus velezensis as a probiotic for hybrid yellow catfish (Pelteobagrus fulvidraco ♀ × Pelteobagrus vachelli ♂). Diets (B0 to B5) containing 0, 0.90 × 108, 0.80 × 109, 0.85 × 1010, 0.90 × 1011, 0.83 × 1012 CFU/kg B. velezensis YFI-E109 were fed to the fish with initial weight (3.07 ± 0.08 g) in a recirculating aquaculture system for six weeks with three replicates, respectively. Probiotic effects were analyzed based on growth, body composition, liver and gut morphology, gut microbiome, and liver metabolome. Analysis of the bacterial genome has shown that the most abundant genes in B. velezensis YFI-E109 were distributed in carbohydrate and amino acid metabolism. Fish in groups B3 and B4 had better growth performance, and higher intestinal amylase (AMS) and lipase (LPS) activities compared with other groups (P < 0.05). Fish in groups B0 and B5 showed significant liver damage, while this status improved in group B3. The liver malondialdehyde (MDA) content in group B3 was lower than that in other groups (P < 0.05). The abundance of Mycoplasma, Ralstonia and Acinetobacter was significantly reduced in B3 and B5 compared to B0. The amino acid and carbohydrate metabolism pathways were enriched in group B3 compared with group B0. In conclusion, dietary B. velezensis YFI-E109 supplementation has the potential to improve growth, liver metabolism, and liver and gut health, and reshape the gut microbiome of hybrid yellow catfish. Excessive B. velezensis YFI-E109 reduced the prebiotic effects. The recommended dietary supplementation of B. velezensis YFI-E109 is 0.31 × 1010 to 0.77 × 1011 CFU/kg for hybrid yellow catfish according to the quadratic regression method by plotting specific growth rate (SGR), feed conversion ratio (FCR), MDA and activities of AMS against dietary B. velezensis YFI-E109 levels.

Transcriptomic response for revealing the molecular mechanism of oat flowering under different photoperiods.

Proper flowering is essential for the reproduction of all kinds of plants. Oat is an important cereal and forage crop; however, its cultivation is limited because it is a long-day plant. The molecular mechanism by which oats respond to different photoperiods is still unclear. In this study, oat plants were treated under long-day and short-day photoperiods for 10 days, 15 days, 20 days, 25 days, 30 days, 40 days and 50 days, respectively. Under the long-day treatment, oats entered the reproductive stage, while oats remained vegetative under the short-day treatment. Forty-two samples were subjected to RNA-Seq to compare the gene expression patterns of oat under long- and short-day photoperiods. A total of 634-5,974 differentially expressed genes (DEGs) were identified for each time point, while the floral organ primordium differentiation stage showed the largest number of DEGs, and the spikelet differentiation stage showed the smallest number. Gene Ontology (GO) analysis showed that the plant hormone signaling transduction and hormone metabolism processes significantly changed in the photoperiod regulation of flowering time in oat. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Mapman analysis revealed that the DEGs were mainly concentrated in the circadian rhythm, protein antenna pathways and sucrose metabolism process. Additionally, transcription factors (TFs) involved in various flowering pathways were explored. Combining all this information, we established a molecular model of oat flowering induced by a long-day photoperiod. Taken together, the long-day photoperiod has a large effect at both the morphological and transcriptomic levels, and these responses ultimately promote flowering in oat. Our findings expand the understanding of oat as a long-day plant, and the explored genes could be used in molecular breeding to help break its cultivation limitations in the future.

Development of machine learning prognostic models for overall survival of prostate cancer patients with lymph node-positive.

Prostate cancer (PCa) patients with lymph node involvement (LNI) constitute a single-risk group with varied prognoses. Existing studies on this group have focused solely on those who underwent prostatectomy (RP), using statistical models to predict prognosis. This study aimed to develop an easily accessible individual survival prediction tool based on multiple machine learning (ML) algorithms to predict survival probability for PCa patients with LNI. A total of 3280 PCa patients with LNI were identified from the Surveillance, Epidemiology, and End Results (SEER) database, covering the years 2000-2019. The primary endpoint was overall survival (OS). Gradient Boosting Survival Analysis (GBSA), Random Survival Forest (RSF), and Extra Survival Trees (EST) were used to develop prognosis models, which were compared to Cox regression. Discrimination was evaluated using the time-dependent areas under the receiver operating characteristic curve (time-dependent AUC) and the concordance index (c-index). Calibration was assessed using the time-dependent Brier score (time-dependent BS) and the integrated Brier score (IBS). Moreover, the beeswarm summary plot in SHAP (SHapley Additive exPlanations) was used to display the contribution of variables to the results. The 3280 patients were randomly split into a training cohort (n = 2624) and a validation cohort (n = 656). Nine variables including age at diagnosis, race, marital status, clinical T stage, prostate-specific antigen (PSA) level at diagnosis, Gleason Score (GS), number of positive lymph nodes, radical prostatectomy (RP), and radiotherapy (RT) were used to develop models. The mean time-dependent AUC for GBSA, RSF, and EST was 0.782 (95% confidence interval [CI] 0.779-0.783), 0.779 (95% CI 0.776-0.780), and 0.781 (95% CI 0.778-0.782), respectively, which were higher than the Cox regression model of 0.770 (95% CI 0.769-0.773). Additionally, all models demonstrated almost similar calibration, with low IBS. A web-based prediction tool was developed using the best-performing GBSA, which is accessible at https://pengzihexjtu-pca-n1.streamlit.app/ . ML algorithms showed better performance compared with Cox regression and we developed a web-based tool, which may help to guide patient treatment and follow-up.