Knowledge of protein function is important for biological, medical and therapeutic studies, but many proteins are still unknown in function. There is a need for more improved functional prediction ...methods. Our SVM-Prot web-server employed a machine learning method for predicting protein functional families from protein sequences irrespective of similarity, which complemented those similarity-based and other methods in predicting diverse classes of proteins including the distantly-related proteins and homologous proteins of different functions. Since its publication in 2003, we made major improvements to SVM-Prot with (1) expanded coverage from 54 to 192 functional families, (2) more diverse protein descriptors protein representation, (3) improved predictive performances due to the use of more enriched training datasets and more variety of protein descriptors, (4) newly integrated BLAST analysis option for assessing proteins in the SVM-Prot predicted functional families that were similar in sequence to a query protein, and (5) newly added batch submission option for supporting the classification of multiple proteins. Moreover, 2 more machine learning approaches, K nearest neighbor and probabilistic neural networks, were added for facilitating collective assessment of protein functions by multiple methods. SVM-Prot can be accessed at http://bidd2.nus.edu.sg/cgi-bin/svmprot/svmprot.cgi.
Boletaceae, the largest family in Boletales, has been attracted by mycologists in the world due to its diverse morphology and complex history of evolution. Although considerable work has been done in ...the past decades, novel taxa are continually described. The current study aimed to introduce three new taxa and one new record of Boletaceae from China. The morphological descriptions, color photographs, phylogenetic trees to show the positions of the taxa, and comparisons with allied taxa are provided. The new genus
is unique in the
group, and
was introduced as the type species. It can be distinguished by its bluing basidioma when injured, a decurrent hymenophore, a stipe covered with distinct reticulations, and a fertile stipitipellis.
is characterized by its pileipellis consisting of broadly concatenated cells and thin-walled caulocystidia in
. In
,
can be distinguished by its hymenophores that change to blue when injured and yellow basal mycelium.
, as a new record, is first reported in Northern China. Internal transcribed spacer (ITS), 28S rDNA (28S), translation elongation factor 1-alpha (tef1-α), RNA polymerase II subunit 1 (rpb1), and RNA polymerase II subunit 2 (rpb2) were employed to execute phylogenetic analyses.
Organic heterostructures (OHTs) with the desired geometry organization on micro/nanoscale have undergone rapid progress in nanoscience and nanotechnology. However, it is a significant challenge to ...elucidate the epitaxial-growth process for various OHTs composed of organic units with a lattice mismatching ratio of > 3%, which is unimaginable for inorganic heterostructures. Herein, we have demonstrated a vivid visualization of the morphology evolution of epitaxial-growth based on a doped interfacial-layer, which facilitates the comprehensive understanding of the hierarchical self-assembly of core-shell OHT with precise spatial configuration. Significantly, the barcoded OHT with periodic shells obviously illustrate the shell epitaxial-growth from tips to center parts along the seeded rods for forming the core-shell OHT. Furthermore, the diameter, length, and number of periodic shells were modulated by finely tuning the stoichiometric ratio, crystalline time, and temperature, respectively. This epitaxial-growth process could be generalized to organic systems with facile chemical/structural compatibility for forming the desired OHTs.
In this article, two undescribed amides (1-2) with an unusual (2-formyl-5- hydroxymethyl)-pyrroyl-butylamine moiety were obtained from the Physochlainae Radix. Comprehensive spectroscopic ...studies, including NMR and HRESIMS, coupling with spectroscopic data comparisons were used to determine structures. Anti-inflammatory assay results showed that new amides possessed significant inhibitory activities of the NO production of LPS-induced RAW 264.7 cells, with IC50 values of 17.52 ± 1.68 μM and 20.37 ± 2.42 μM, respectively.
The presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor ...T-cell (CAR-T) therapy in patients with MRD is currently unclear.
We conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission.
A total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8%
51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group 77.8% (95% CI, 64.8-90.7%)
68.7% (95% CI, 47.7-89.6%), P = 0.575 and had a significantly higher 3-year LFS than those in the intensified chemotherapy group 77.8% (95% CI, 64.8-90.7%)
28.6% (95% CI, 4.9-52.3%), P = 0.001. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion.
Our findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.
The infiltration of tumor-associated macrophages (TAMs) is associated with tumor progression and poor prognosis in endometrial cancer (EC). Collagen triple helix repeat containing 1 (CTHRC1), a ...secreted ECM protein, has been reported to have important roles in promoting cancer invasion and metastasis, but the functional role of CTHRC1 and its association with TAMs in EC remain unclear. Here we report that, in EC patients, CTHRC1 expression was up-regulated in endometrial cancer tissues compared with normal endometrium (P < 0.0001), and is positively correlated with tumor grade and depth of myometrial invasion (P = 0.024 and P = 0.0002, respectively). Meanwhile, CTHRC1 expression was positively correlated with an increased number of infiltrating TAMs, especially M2-like TAMs (P = 0.003, P = 0.001). In the tumor microenvironment of EC, CTHRC1 not only promoted myometrial invasion by interacting with Integrin β3-Akt signaling pathway, but also promoted infiltration of M2-like TAMs by upregulating Fractalkine chemokine receptor (CX3CR1) expression in macrophages. Changing levels of recombinant CTHRC1 protein (rCTHRC1) promoted tumor migration and invasion via enhancing macrophage recruitment in vitro. In summary, our findings eventually provided a novel role for CTHRC1 in remodeling the tumor immune microenvironment to promote tumor metastasis in EC patients.
To probe the differences of gut microbiota among major depressive disorder (MDD), bipolar disorder with current major depressive episode (BPD) and health participants.
Thirty one MDD patients, thirty ...BPD patients, and thirty healthy controls (HCs) were recruited. All the faecal samples were analyzed by shotgun metagenomics sequencing. Except for routine analyses of alpha diversity, we specially designed a new indicator, the Gm coefficient, to evaluate the inequality of relative abundances of microbiota for each participant.
The Gm coefficients are significant decreased in both MDD and BPD groups. The relative abundances of increased phyla Firmicutes and Actinobacteria and decreased Bacteroidetes were significantly in the MDD and BPD groups. At genus level, four of top five enriched genera (Bacteroides, Clostridium, Bifidobacterium, Oscillibacter and Streptococcus) were found increased significantly in the MDD and BPD groups compared with HCs. The genera Escherichia and Klebsiella showed significant changes in abundances only between the BPD and HC groups. At the species level, compared with BPD patients, MDD patients had a higher abundance of Prevotellaceae including Prevotella denticola F0289, Prevotella intermedia 17, Prevotella ruminicola, and Prevotella intermedia. Furthermore, the abundance of Fusobacteriaceae, Escherichia blattae DSM 4481 and Klebsiella oxytoca were significantly increased, whereas the Bifidobacterium longum subsp. infantis ATCC 15697 = JCM 1222 was significantly reduced in BPD group compared with MDD group.
Our study suggested that gut microbiota may be involved in the pathogenesis of both MDD and BPD patients, and the nuances of bacteria may have the potentiality of being the biomarkers of MDD and BPD.
Abstract The recurrence of breast cancer is associated with drug-resistance of cancer stem cells (CSCs), while overexpression of cell membrane ATP-binding cassette (ABC) transporters and resistance ...of mitochondrial apoptosis-related proteins are responsible for the drug-resistance of CSCs. The targeting berberine liposomes were developed to modulate the resistant membrane and mitochondrial proteins of breast CSCs for the treatment and prevention of breast cancer relapse. Evaluations were performed on human breast CSCs and CSC xenografts in nude mice. The targeting berberine liposomes were shown to cross the CSC membrane, inhibit ABC transporters (ABCC1, ABCC2, ABCC3, ABCG2) and selectively accumulate in the mitochondria. Furthermore, the pro-apoptotic protein Bax was activated while the anti-apoptotic protein Bcl-2 was inhibited resulting in opening of the mitochondrial permeability transition pores, release of cytochrome c , and activation of caspase-9/caspase-3 enzymes. Significant efficacy of the administrations in mice was observed, indicating that the targeting berberine liposomes are a potential therapy for the treatment and prevention of breast cancer relapse arising from CSCs.
Understanding the bacterial dynamics in aquaculture ponds is imperative for the assessment of disinfection efficiency and regulation of subsequent pond ecosystems. In this study, the objective was to ...evaluate the impact of trichloroisocyanuric acid (TCCA) (0.135 mg/L, LG; 0.405 mg/L, HG) on the water quality index, heterotrophic bacteria, microbial community and ecological function. Nine separated artificial customized tanks were inserted into the pond sediment to form relatively independent pond bodies with similar environments. 16S rRNA gene amplicon sequencing was used to evaluate the dynamics of bacterial relative abundance within 192 h. Furthermore, the functional composition of the microbial community was inferred. The results indicated that both doses of TCCA had little influence on water quality. The residual chlorine was lower than the detection limit (0.03 mg/L) in the both LG and HG within 30 min. The bacterial inactivation rate was 65.04% in the HG compared with the control group within 1 h., whereas the number of heterotrophic bacteria increased to 1.26 × 105 cfu/mL at 24 h. and 4.53 × 105 cfu/mL at 48 h., 6.03 and 6.38 times higher than the CG (P < 0.05), respectively. The TCCA in the HG significantly decreased the microbial diversity and changed the relative abundance of the pond at 24 h. and 48 h. There were 28 and 35 significantly different genera between the CG and HG (P < 0.05), and the relative abundance of Bacillariophyta in the HG was significantly higher than that in the CG at 24 h. and 48 h. (P < 0.05).There were 7 and 4 significantly different functions (except other function) between the HG and CG (P < 0.05) at 24 h. and 48 h., respectively. The results indicated that the active chlorine disappeared immediately after using TCCA, 0.405 mg/L active chlorine had a strong influence on the heterotrophic bacteria, microbial community and function, and the effect lasted for 96 h., whereas 0.135 mg/L TCCA usage had little influence on the pond water.
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•Nine nonexchange tanks were used to evaluate the efficiency of aquaculture pond water after using disinfectant.•Total bacteria increased 6 times after using 0.405 mg/L trichloroisocyanuric acid at 24 h. and 48 h.•The microbial community and ecological function changed strongly after using 0.405 mg/L trichloroisocyanuric acid.•Effect of 0.405 mg/L trichloroisocyanuric acid lasted for 96 h.
Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma of the lung associated with early metastasis and an exceptionally poor prognosis. Little progress has been made in ...developing efficacious targeted therapy for this recalcitrant disease. Herein, we showed that H3.3, encoded by two genes (H3F3A and H3F3B), was prominently overexpressed in SCLC. Darinaparsin (ZIO-101), a derivative of arsenic trioxide, dose- and time-dependently inhibited the viability of SCLC cells in an H3.3-dependent manner. More importantly, ZIO-101 treatment resulted in substantial accumulation of H3.3 and PARP1 besides induction of G
/M cell cycle arrest and apoptosis in SCLC cells. Through integrative analysis of the RNA-seq data from Cancer Cell Line Encyclopedia dataset, JNCI and Genomics of Drug Sensitivity in Cancer 2 datasets, we found that H3F3A expression was negatively correlated with the IC
values of PARP inhibitors (PARPi). Furthermore, co-targeting H3.3 and PARP1 by ZIO-101 and BMN673/olaparib achieved synergistic growth inhibition against SCLC in vitro and in vivo. In conclusion, it is feasible to target H3.3 by ZIO-101 to potentiate the response rate of PARPi in SCLC patients.
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