Machine-learning-based classification of diffuse large B-cell lymphoma patients by a 7-mRNA signature enriched with immune infiltration and cell cycle / Clasificación basada en aprendizaje automático de pacientes con linfoma difuso de células B grandes mediante una firma de 7 ARNm enriquecida con infiltración inmune y ciclo celular

Background: Diffuse large B-cell lymphoma (DLBCL) exhibits remarkable heterogeneity but still remains undiagnosed in identifying the subpopulation of DLBCL to predict the prognosis and guide clinical treatment. Methods: Molecular subgroups were identified in gene expression data from GSE10846 by a consensus clustering algorithm. And gene set enrichment analysis, immune infiltration, and the proposed cell cycle algorithm were applied to explore the biological functions of different subtypes. Meanwhile, univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of DLBCL. Finally, the prognostic model, including some key genes screened by Lasso regression, Random Forest algorithm, and point-biserial correlation, was constructed by an optimal classifier from seven machine learning algorithms and validated by another three external datasets (GSE34171, GSE87371, GSE31312). Results: Comprehensive genomic analysis of 1,143 DLBCL samples identify 2 molecularly, prognostically relevant subtypes: immune-enriched (IME) and cell-cycle-enriched (CCE). Then a new predictive model including seven key genes (SERPING1, TIMP2, NME1, DCTPP1, RFC4, POLE2, and SNRPD1) was developed with high prediction accuracy (88.6%) and strong predictive power (AUC = 0.973) based on the Support Vector Machine (SVM) algorithm in 414 patients from GSE10846. The predictive power was similar in another three testing sets (HR > 1.400, p < 0.05). Conclusion: This model could evaluate survival independently with strong predictive power compared with other clinical risk factors. Our study constructed a reliable model to predict two new subtypes of DLBCL patients, which could guide the implementation of individualized treatment.(AU)

Machine-learning-based classification of diffuse large B-cell lymphoma patients by a 7-mRNA signature enriched with immune infiltration and cell cycle.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) exhibits remarkable heterogeneity but still remains undiagnosed in identifying the subpopulation of DLBCL to predict the prognosis and guide clinical treatment. METHODS: Molecular subgroups were identified in gene expression data from GSE10846 by a consensus clustering algorithm. And gene set enrichment analysis, immune infiltration, and the proposed cell cycle algorithm were applied to explore the biological functions of different subtypes. Meanwhile, univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of DLBCL. Finally, the prognostic model, including some key genes screened by Lasso regression, Random Forest algorithm, and point-biserial correlation, was constructed by an optimal classifier from seven machine learning algorithms and validated by another three external datasets (GSE34171, GSE87371, GSE31312). RESULTS: Comprehensive genomic analysis of 1,143 DLBCL samples identify 2 molecularly, prognostically relevant subtypes: immune-enriched (IME) and cell-cycle-enriched (CCE). Then a new predictive model including seven key genes (SERPING1, TIMP2, NME1, DCTPP1, RFC4, POLE2, and SNRPD1) was developed with high prediction accuracy (88.6%) and strong predictive power (AUC = 0.973) based on the Support Vector Machine (SVM) algorithm in 414 patients from GSE10846. The predictive power was similar in another three testing sets (HR > 1.400, p < 0.05). CONCLUSION: This model could evaluate survival independently with strong predictive power compared with other clinical risk factors. Our study constructed a reliable model to predict two new subtypes of DLBCL patients, which could guide the implementation of individualized treatment.

Accelerating water oxidation - a mixed Co/Fe polyoxometalate with improved turnover characteristics.

Water oxidation is a bottleneck reaction for the establishment of solar-to-fuel energy conversion systems. Earth-abundant metal-based polyoxometalates are promising heterogeneous water oxidation catalysts that can operate in a wide pH range. However, detailed structure-reactivity relationships are not yet comprehensively understood, hampering the design and synthesis of more effective polyoxometalate-based oxidation catalysts. Here we report the synthesis of an ordered, mixed-metal cobalt-iron Weakley archetype [CoII2(H2O)2FeIII2(CoIIW9O34)2]14- (Co2Fe2-WS), which unexpectedly highlights the strong influence of the central, coordinatively saturated metal ions on the catalytic water oxidation characteristics. The resulting species exhibits catalytic turnover frequencies which are up to 4× higher than those of the corresponding archetype tetracobalt-oxo species [CoII2(H2O)2CoII2(PW9O34)2]10- (Co4-WS). It is further striking that the system becomes catalytically inactive when one of the central positions is occupied by a WVI ion as demonstrated by [CoII2(H2O)2CoIIWVI(CoIIW9O34)2]12- (Co3W-WS). Importantly, this study demonstrates that coordinatively saturated metal ions in this central position, which at first glance appear insignificant, do not solely have a structural role but also impart a distinctive structural influence on the reactivity of the polyoxometalate. These results provide unique insights into the structure-reactivity relationships of polyoxometalates with improved catalytic performance characteristics.

Integrative analysis identifies two molecular and clinical subsets in Luminal B breast cancer.

Comprehensive multiplatform analysis of Luminal B breast cancer (LBBC) specimens identifies two molecularly distinct, clinically relevant subtypes: Cluster A associated with cell cycle and metabolic signaling and Cluster B with predominant epithelial mesenchymal transition (EMT) and immune response pathways. Whole-exome sequencing identified significantly mutated genes including TP53, PIK3CA, ERBB2, and GATA3 with recurrent somatic mutations. Alterations in DNA methylation or transcriptomic regulation in genes (FN1, ESR1, CCND1, and YAP1) result in tumor microenvironment reprogramming. Integrated analysis revealed enriched biological pathways and unexplored druggable targets (cancer-testis antigens, metabolic enzymes, kinases, and transcription regulators). A systematic comparison between mRNA and protein displayed emerging expression patterns of key therapeutic targets (CD274, YAP1, AKT1, and CDH1). A potential ceRNA network was developed with a significantly different prognosis between the two subtypes. This integrated analysis reveals a complex molecular landscape of LBBC and provides the utility of targets and signaling pathways for precision medicine.

A 5-Pathway Signature Predicts Prognosis Based on Immune-Derived lncRNAs in Patients with Breast Cancer.

Background: Currently, predictive models were not developed based on the signaling pathway signatures of immune-related lncRNAs in breast cancer (BRCA) patients. Methods: We selected unsupervised hierarchical clustering algorithm to classify patients with BRCA based on the significant immune-derived lncRNAs from the TCGA dataset. And different methods including ESTIMATE, ImmuneCellAI, and CIBERSORT were performed to evaluate the immune infiltration of tumor microenvironment. Using Lasso regression algorithm, we filtered the significant signaling pathways enriched by GSEA, GSVA, or PPI analysis to develop a prognostic model. And a nomogram integrated with clinical factors and significant pathways was constructed to predict the precise probability of overall survival (OS) of BRCA patients in the TCGA dataset (n = 1,098) and another two testing sets (n = 415). Results: BRCA patients were stratified into the PC (n = 571) and GC (n = 527) subgroup with significantly different prognosis with 550 immune-related lncRNAs in the TCGA dataset. Integrated analysis revealed different immune response, oncogenic signaling, and metabolic reprograming pathways between these two subgroups. And a 5-pathway signature could predict the prognosis of BRCA patients between these two subgroups independently in the TCGA dataset, which was confirmed in another two cohorts from the GEO dataset. In the TCGA dataset, 5-year OS rate was 78% (95% CI: 73-84) vs. 82% (95% CI: 77-87) for the PC and GC group (HR = 1.63 (95% CI: 1.17-2.28), p = 0.004). The predictive power was similar in another two testing sets (HR > 1.20, p < 0.01). Finally, a nomogram is developed for clinical application, which integrated this signature and age to accurately predict the survival probability in BRCA patients. Conclusion: This 5-pathway signature correlated with immune-derived lncRNAs was able to precisely predict the prognosis for patients with BRCA and provided a rich source characterizing immune-related lncRNAs and further informed strategies to target BRCA vulnerabilities.

Dietary supplementation with selenomethionine enhances antioxidant capacity and selenoprotein gene expression in layer breeder roosters.

This study's objective was to investigate the effects of dietary Se (in the form of selenomethionine) on the antioxidant activity and selenoprotein gene expressions in layer breeder roosters. One hundred and eighty, 36-wk-old Jingfen layer breeder roosters were randomly allocated to one of 5 dietary treatments (0, 0.25, 0.5, 1, or 2 mg/kg Se) for 6 wk on a corn-soybean meal-based diet. Antioxidant parameters and selenoprotein gene expressions were assessed at the end of the experiment. The results showed that Se supplementation significantly increased the activity of T-SOD, CAT, GSH-Px, and superoxide anion scavenging ability in plasma (P ≤ 0.05), and activities of T-SOD, CAT, GSH-Px, superoxide anion scavenging ability, and hydroxyl radical scavenging ability in the liver, kidney, and testis (P < 0.05). Moreover, MDA levels were significantly reduced in plasma, liver, kidney, and testis (P < 0.01), compared to the control group. Furthermore, the dietary administration of Se significantly increased TrxR2 and GPx4 mRNA levels in kidney and testis, and ID1 mRNA levels in liver and kidney. Most of the antioxidant parameters and selenoprotein-related gene expressions significantly increased, and MDA significantly decreased at dietary supplementation with 0.5 mg/kg Se. Whereas a higher dose of Se level (1 or 2 mg/kg) inhibited the activities of some of the antioxidant enzymes and selenoprotein-related gene expressions in selected tissues. In conclusion, dietary Se supplementation with 0.5 mg/kg significantly improved roosters' antioxidant status and selenoprotein-related gene expression in liver, kidney, and testis, while higher doses led to inhibit these; dietary Se might increase reproductive performance by enhancing their antioxidant status in roosters.

Acid/alkali pretreatment enhances the formation of vivianite during anaerobic fermentation of waste activated sludge.

Phosphorus (P) recovery from waste activated sludge (WAS) of wastewater treatment plants is significant in the world suffering from P shortage. Recently, vivianite crystallization has been regarded as an essential method of recovering P from anaerobic fermentation (AF) of WAS. This study performed acid/alkali pretreatment (pH 3/pH 10) on AF of WAS to improve iron reduction and vivianite formation. The results showed that the maximum iron reduction rate (Rmax) in the pH 3 and pH 10 groups was increased by 1.9 and 1.7 times compared with that in the Control-Fe group, and the iron reduction efficiency (EFe) was increased by 17.5% and 12.0% respectively. The Fe bound P (Fe-P) proportion in the sludge in the pH 3 and pH 10 groups increased by 50.0% and 33.7%, respectively. Furthermore, the relative abundance of the iron-reducing bacteria Clostridium_sensusensu in the pH 3 group was higher; and the Fe-P proportion in the sludge and the size of vivianite crystal after AF were larger. With these results, pH 3 pretreatment was preferred for promoting Fe2+ release and vivianite formation during AF.

Flavonoid-enriched extract from Millettia speciosa Champ prevents obesity by regulating thermogenesis and lipid metabolism in high-fat diet-induced obese C57BL/6 mice.

Millettia speciosa (M. speciosa) Champ is a medicinal and edible plant. The roots are rich in flavonoids, which possess multiple biological activities, including lipid-lowering effects. This study aimed to explore the effect of flavonoid-enriched extract from M. speciosa (FMS) on obesity. The UPLC-Q-TOF-MS analysis and chromatographic analysis were adopted to identify flavonoid compounds in FMS. Male C57BL/6J mice were fed with a high-fat diet for 3 months and were then treated with FMS (50 or 100 mg/kg/d) or Orlistat (10 mg kg-1 d-1) for another 8 weeks. A total of 35 flavonoids were identified in the extract of M. speciosa root. FMS reduced body weight gain, liver weight gain, white adipose tissue, lipid accumulation, and blood glucose. The levels of TG, ALT, AST, and inflammatory-related adipokines (TNF-α and IL-6) in serum were also reduced by FMS. In addition, FMS promoted thermogenesis in brown adipose tissue and induced the activation of lipolysis, fatty acid oxidation, and oxidative phosphorylation in white adipose tissues. In summary, long-term administration of FMS could ameliorate high-fat diet-induced obesity by stimulating adipose thermogenesis and lipid metabolism.

A second species of Pseuduvaria in China: the identity of the enigmatic species Meiogyne kwangtungensis.

Meiogyne kwangtungensis is a rare species endemic to Hainan, China, known just from two fruiting collections made in the 1930s. Although it was published under the name Meiogyne in 1976, it was suggested that it might be better placed within Pseuduvaria or Mitrephora. For decades, this species was never collected again, thus its true generic affinity remained unresolved due to the lack of flowers. During a field exploration in Hainan, we re-discovered this species and collected a flowering specimen for the first time. The flower immediately confirmed its affinity with Pseuduvaria. Phylogenetic analyses of five chloroplast regions (psbA-trnH, trnL-F, matK, rbcL, and atpB-rbcL; ca. 4.2 kb, 70 accessions) also unambiguously placed Meiogyne kwangtungensis in the Pseuduvaria clade (PP = 1.00, ML BS = 99%). Morphologically, it is most similar to P. multiovulata which is endemic to Myanmar and Thailand, both with often-paired flowers, long pedicels and short peduncles, and often 1-2 monocarps. However, it differs in having smaller flowers with kidney-shaped glands on the inner petals, fewer stamens and carpels, smaller ovoid monocarps with an apicule and fewer seeds. On the basis of the combined molecular phylogenetic and morphological data, we propose a new combination, Pseuduvaria kwangtungensis (P.T.Li) Qing L.Wang & B.Xue. A full description including floral characters and a color plate are provided here for this species. A key to species in the genus Pseuduvaria in China is also provided.

In situ growth of luminescent perovskite fibers in natural hollow templates.

Natural hollow fibers were used as templates to in situ produce thin Cs4PbX6 nanosheets on the inner walls, forming luminescent fibers that integrated the advantages of the large length of fibers and the emission tunability of perovskites, and exhibited great robustness as well for multiple applications like warning signs, anti-counterfeiting and fashion.

[Present situation and development strategy of Alpinia oxyphylla].

Alpinia oxyphylla is mainly produced in Hainan,and also one of the four famous traditional Chinese medicines in South China with increasing importance in traditional Chinese medicine industry. Field surveys and literatures show that A. oxyphylla has widely used as a medicinal and edible plant,it is an important raw material for many Chinese patent medicines,health products and food,with a long history of artificial cultivation and application. The future development is prospected on health market. But A. oxyphylla industry has faced a lot of problems,including unreasonable planting layout,lack of good varieties,imperfect seed breeding system,low level of standardization,inconsistent quality of medicinal materials,low level of industry,and so on. The suggestions for sustainable development are listed below.First,it is essential to strengthen the research on the basis and application technology of A. oxyphylla,speed up the selection and breeding of improved varieties,and popularize standardized cultivation techniques. Secondly,it is important to strengthen the research on quality standards,improve the quality evaluation system of medicinal materials. Thirdly,it is necessary to take full advantage of the functional components to develop functional products with Hainan characteristics,find out the unique product characteristics of A. oxyphylla,build a famous brand and improve the product competitiveness in the market. It is also important to strengthen policy support and industrial supervision,promote the healthy and rapid development of A. oxyphylla industry.

Light-harvesting, 3rd generation RuII/CoII MOF with a large, tubular channel aperture.

A photoactive, hetero-metallic CoII/RuII-based metal-organic framework (MOF) with a large channel aperture, ca. 21 Å, is reported. The photophysical properties of the MOF are derived from the RuII nodes giving rise to emission centred at ca. 620 nm and relatively long triplet 3MLCT lifetimes. In addition to the optical attributes, the 1H-imidazo [4,5-f][1,10]-phenanthroline ligand imparts structural functionality to the MOF which is composed of alternating CoII- and RuII-based nodes of Δ and Λ helicity. The framework maintains its integrity upon activation and shows gas sorption behaviour that is characteristic of mesoporous materials promoting high CO2 sorption capacities and selectivities over N2.

The v-DECAF score can predict 90-day all-cause mortality in patients with COPD exacerbation requiring invasive mechanical ventilation.

INTRODUCTION: The DECAF score is a simple and effective tool for predicting mortality in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (AECOPD); however, the DECAF score has not been validated in AECOPD patients requiring invasive mechanical ventilation (IMV). We devised the ventilator (v)-DECAF score, in which "anemia" replaces "acidaemia," for use in AECOPD patients requiring IMV. The objective of this study was to compare the predictive efficacy of the v-DECAF score and the DECAF score. METHODS: This study prospectively recruited 112 consecutive AECOPD patients requiring IMV from a single center. The clinical endpoint was 90-day all-cause mortality. Demographic and clinical data were recorded, as well as APACHE II, GCS, CURB-65, BAP-65 and DECAF scores, and the newly devised v-DECAF score. The discriminatory value of the scoring systems in predicting 90-day all-cause mortality was determined using the area under the receiver operating characteristic (AUROC) curve. RESULTS: In multivariate logistic regression analysis, the v-DECAF score was an independent predictor of 90-day all-cause mortality (odds ratio 3.004, 95% CI 1.658-5.445, P < 0.001). The AUROC of the v-DECAF and DECAF scores were 0.852 (95% CI 0.766-0.938) and 0.777 (95%CI: 0.676-0.878), respectively. The v-DECAF score had a better predictive value for 90-day all-cause mortality compared to the DECAF score (Z = 2.338, P = 0.019). CONCLUSION: The v-DECAF score had good discriminatory power in predicting 90-day all-cause mortality in AECOPD patients requiring IMV.

Present situation and development strategy of Alpinia oxyphylla / 中国中药杂志

@#Alpinia oxyphylla is mainly produced in Hainan,and also one of the four famous traditional Chinese medicines in South China with increasing importance in traditional Chinese medicine industry. Field surveys and literatures show that A. oxyphylla has widely used as a medicinal and edible plant,it is an important raw material for many Chinese patent medicines,health products and food,with a long history of artificial cultivation and application. The future development is prospected on health market. But A. oxyphylla industry has faced a lot of problems,including unreasonable planting layout,lack of good varieties,imperfect seed breeding system,low level of standardization,inconsistent quality of medicinal materials,low level of industry,and so on. The suggestions for sustainable development are listed below.First,it is essential to strengthen the research on the basis and application technology of A. oxyphylla,speed up the selection and breeding of improved varieties,and popularize standardized cultivation techniques. Secondly,it is important to strengthen the research on quality standards,improve the quality evaluation system of medicinal materials. Thirdly,it is necessary to take full advantage of the functional components to develop functional products with Hainan characteristics,find out the unique product characteristics of A. oxyphylla,build a famous brand and improve the product competitiveness in the market. It is also important to strengthen policy support and industrial supervision,promote the healthy and rapid development of A. oxyphylla industry.

Near-saturated red emitters: four-coordinate copper(i) halide complexes containing 8-(diphenylphosphino)quinoline and 1-(diphenylphosphino)naphthalene ligands.

Recently, highly emissive neutral copper halide complexes have received much attention. Here, a series of four-coordinate mononuclear Cu(i) halide complexes, [CuX(dpqu)(dpna)] (dpqu = 8-(diphenylphosphino)quinoline, dpna = 1-(diphenylphosphino)naphthalene, X = I (1), Br (2) and Cl (3)), were synthesized, and their molecular structures and photophysical properties were investigated. These complexes exhibit near-saturated red emission in the solid state at room temperature and have peak emission wavelengths at 669-691 nm with microsecond lifetimes (τ = 0.46-1.80 µs). Small S1-T1 energy gaps in the solid state indicate that the emission occurs from a thermally activated excited singlet state at ambient temperature. The emission of the complexes 1-3 mainly originates from MLCT transition. The solution-processed devices of complex 1 exhibit stable red emission with a CIE(x, y) of (0.62, 0.38) for a doped device and (0.63, 0.37) for a non-doped device.

Limonoids from the roots of Trichilia sinensis and their cytotoxicities.

Six new compounds (1-4, 8, 10), along with six known limonoids (5-7, 9, 11, 12), were isolated from the roots of Trichilia sinensis. Their structures were elucidated on the basis of extensive spectroscopic methods including 1H NMR, 13C NMR, DEPT, HSQC, HMBC, 1H-1H COSY and ROESY experiments, as well as by comparison with the literature. All the compounds were evaluated for cytotoxicities against K562, SGC-7901 and BEL-7402 cell lines. Compounds 2, 7, 10, 11, and 12 showed weak inhibitory activity to the selected cell lines.

Mexicanolide-Type Limonoids from the Roots of Trichilia sinensis.

Four new mexicanolide-type limonoids 1-4, along with two known limonoids 5-6, were isolated from the ethanolic extracts of roots of the Traditional Chinese Medicine Trichilia sinensis. Their structures were unambiguously determined by analysis of spectroscopic data, including 1D and 2D NMR as well as MS, and by comparison with literature data. In addition, the acetylcholinesterase (AChE) inhibitory activity of compounds 1-6 was evaluated by the Ellman method. All these compounds showed weak AChE inhibitory activity, with the inhibition percentages ranging from 18.5% to 27.8%.

[Simulation Study of Dynamic Color Modulation Based on Tunable Micro/Nano-Structure Array].

With the development of nanotechnology, it has been accessible to display colors by artificial micro/nano-structure, and then the study of structure coloring has become a hot subject, opening a new space for inkless printing. In this paper, a dynamic color modulation method based on tunable micro/nano-structure array is proposed. To tune colors on the same device, a periodic micro/nano-structure array is designed with functional material inside, which could alter the height difference between up and bottom surface precisely by applying an external voltage. It is modeled, and simulated by the Finite Difference Time Domain (FDTD) method in this work. In simulations, perpendicular incident linearly polarized light source is applied, and parameters of surface height difference and period are swept. Series reflective spectra of the devices are obtained, and their corresponding colors are calculated and marked on the CIE 1931 chromaticity diagram. Simulation results demonstrate that when the period is in the range of 100-300 nm, full-color modulation could be realized by varying the height of functional material film via applied voltage, and the peak intensities of reflective spectra are at about 60%, having high energy efficiency. This method is innovative and provides a theoretical basis for the dynamic color modulation micro/nano device, which is quite promising in fields like inkless printing and display technology.

Osteopontin deficiency does not prevent but promotes alcoholic neutrophilic hepatitis in mice.

UNLABELLED: Alcoholic hepatitis (AH) is a distinct spectrum of alcoholic liver disease (ALD) with intense neutrophilic (polymorphonuclear; PMN) inflammation and high mortality. Although a recent study implicates osteopontin (SPP1) in AH, SPP1 is also shown to have protective effects on experimental ALD. To address this unsettled question, we examined the effects of SPP1 deficiency in male mice given 40% calories derived from ad libitum consumption of the Western diet high in cholesterol and saturated fat and the rest from intragastric feeding of alcohol diet without or with weekly alcohol binge. Weekly binge in this new hybrid feeding model shifts chronic ASH with macrophage inflammation and perisinusoidal and pericellular fibrosis to AH in 57% (15 of 26) of mice, accompanied by inductions of chemokines (Spp1, Cxcl1, and interleukin [Il]-17a), progenitor genes (Cd133, Cd24, Nanog, and epithelial cell adhesion molecule), PMN infiltration, and clinical features of AH, such as hypoalbuminemia, bilirubinemia, and splenomegaly. SPP1 deficiency does not reduce AH incidence and inductions of progenitor and fibrogenic genes, but rather enhances the Il-17a induction and PMN infiltration in some mice. Furthermore, in the absence of SPP1, chronic ASH mice without weekly binge begin to develop AH. CONCLUSION: These results suggest that SPP1 has a protective, rather than causal, role for experimental AH reproduced in our model.