Tropical rainforests play important roles in carbon sequestration and are hot spots for biodiversity. Tropical forests are being replaced by rubber (Hevea brasiliensis) plantations, causing widespread concern of a crash in biodiversity. Such changes in aboveground vegetation might have stronger impacts on belowground biodiversity. We studied tropical rainforest fragments and derived rubber plantations at a network of sites in Xishuangbanna, China, hypothesizing a major decrease in diversity with conversion to plantations. We used metabarcoding of the 18S rRNA gene and recovered 2313 OTUs, with a total of 449 OTUs shared between the two land-use types. The most abundant phyla detected were Annelida (66.4% reads) followed by arthropods (15.5% reads) and nematodes (8.9% reads). Of these, only annelids were significantly more abundant in rubber plantation. Taken together, α- and β-diversity were significantly higher in forest than rubber plantation. Soil pH and spatial distance explained a significant portion of the variability in phylogenetic community structure for both land-use types. Community assembly was primarily influenced by stochastic processes. Overall it appears that forest replacement by rubber plantation results in an overall loss and extensive replacement of soil micro- and mesofaunal biodiversity, which should be regarded as an additional aspect of the impact of forest conversion.

The multifunctional protein Y-box binding protein 1 (YBX1), is a critical regulator of transcription and translation, and is widely recognized as an oncogenic driver in several solid tumors, including colorectal cancer (CRC). However, very little is known about the upstream or downstream factors that underlie YBX1's regulation and involvement in CRC. Previously, we demonstrated that YBX1 overexpression correlated with potent activation of nuclear factor κB (NF-κB), a well-known transcription factor believed to be crucial in CRC progression. Here, we report a novel interaction between NF-κB, YBX1 and protein arginine methyltransferase 5 (PRMT5). Our findings reveal for the first time that PRMT5 catalyzes methylation of YBX1 at arginine 205 (YBX1-R205me2), an event that is critical for YBX1-mediated NF-κB activation and its downstream target gene expression. Importantly, when WT-YBX1 is overexpressed, this methylation exists under basal (unstimulated) conditions and is further augmented upon interleukin-1β (IL-1β) stimulation. Mechanistically, co-immunoprecipitation studies reveal that the R205 to alanine (A) mutant of YBX1 (YBX1-R205A) interacted less well with the p65 subunit of NF-κB and attenuated the DNA binding ability of p65. Importantly, overexpression of YBX1-R205A significantly reduced cell growth, migration and anchorage-independent growth of CRC cells. Collectively, our findings shed important light on the regulation of a novel PRMT5/YBX1/NF-κB axis through PRMT5-mediated YBX1-R205 methylation. Given the fact that PRMT5, YBX1 and NF-κB are all among top crucial factors in cancer progression, pharmacological disruption of this pivotal axis could serve as the basis for new therapeutics for CRC and other PRMT5/YBX1/NF-κB-associated cancers.

The association and potential role of the protein hormone adiponectin in autoimmune diseases causing musculoskeletal disorders, including rheumatoid arthritis (RA), are controversial. Conflicting results may arise from the influences of confounding factors linked to genetic backgrounds, disease stage, disease-modifying anti-rheumatic drugs and patients' metabolic characteristics. Here, we examined serum level of adiponectin and its relationship with disease activity score 28 with erythrocytes sedimentation rate (DAS28[ESR]) and Sharp score in a treatment-naïve Han Chinese RA population. This cross-sectional study enrolled 125 RA patients. Serum level of total adiponectin was assessed by enzyme-linked immunosorbent assay (ELISA). Other important clinical and laboratory parameters were collected from the hospital database. DAS28(ESR) was calculated according to the equation previously published. Sharp score was evaluated based on hands radiographs by an independent radiologist. The correlation between serum adiponectin level and DAS28(ESR) or the Sharp score was investigated by univariate and multivariable linear regression analyses, respectively. Multiple imputation by chained equations was used to account for missing data. Univariate analyses showed a significant positive correlation between DAS28(ESR) and age or C-reactive protein (CRP) (both p = 0.003), while serum adiponectin level was negatively correlated with DAS28(ESR) (p = 0.015). The negative correlation between adiponectin level and DAS28(ESR) remained true in multivariable analyses adjusted for confounders. In addition, the univariate analyses revealed positive correlations of Sharp score to disease duration (p < 0.001), CRP (p = 0.023) and ESR (p < 0.001). In the multivariable model adjusted for confounders, adiponectin was negatively correlated with Sharp score (p = 0.013). In this single-institution cross-sectional study, serum adiponectin level in treatment-naive RA patients is negatively correlated with DAS28(ESR) and the Sharp score after adjustment for prominent identified confounders. Serum adiponectin may be potentially useful for assessing disease activity and radiographic progression of RA.

Geldanamycin and elaiophylin are co-produced in several Streptomyces strains. However, the regulation of their biosynthesis is not fully understood yet. Herein the function of a TetR family regulator GdmRIII, which is located in the biosynthetic gene cluster of geldanamycin, was studied to understand the regulatory mechanism of geldanamycin biosynthesis in Streptomyces autolyticus CGMCC0516. The production of geldanamycin decreased substantially in a ΔgdmRIII mutant and the yield of three compounds which were thought to be geldanamycin congeners greatly increased. Surprisingly, the structural elucidation of these compounds showed that they were elaiophylin and its analogues, which implied that GdmRIII not only played a positive regulatory role in the biosynthesis of geldanamycin, but also played a negative role in elaiophylin biosynthesis. GdmRIII affected the expression of multiple genes in both gene clusters, and directly regulated the expression of gdmM, gdmN, and elaF by binding to the promoter regions of these three genes. A conserved non-palindromic sequence was found among the binding sites of elaF. Our findings suggested that the biosynthetic pathways of geldanamycin and elaiophylin were connected through GdmRIII, which might provide a way for Streptomyces to coordinate the biosynthesis of these compounds for better adapting to environment changes.

Major progress has been made clinically in inhibiting the programmed death receptor 1 (PD-1)/PD-L1 interaction to enhance T cell-mediated immune function, yet the effectiveness of anti-PD-L1/PD-1 agents in enhancing natural killer (NK) cell's function remains largely unknown. Susceptibilities of cisplatin-resistant A549CisR and H157CisR cells vs. parental cells to the cytotoxic action of NK cells were examined. We found cisplatin-resistant cells more resistant to NK cell cytotoxicity than parental cells. There were constitutively higher expressions of PD-L1 in A549CisR and H157CisR cells than in parental cells in vitro, as well as in H157CisR cell-derived tumors than H157P cell-derived tumors. In contrast, we observed that the expression of PD-1 in NK cells was induced after co-culture with cisplatin-resistant cells. We also observed increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity when neutralizing antibody of PD-1 or PD-L1 was added. Further, we found that the NK group 2, member D (NKG2D) ligand levels were lower in A549CisR and H157CisR cells than in parental cells. Meanwhile, we discovered that the MEK/Erk signaling pathway played a significant role in this regulation, and the addition of a MEK/Erk pathway inhibitor significantly enhanced the PD-L1 Ab effect in enhancing NK cell cytotoxicity to cisplatin-resistant cells.

A generic intelligent tomato classification system based on DenseNet-201 with transfer learning was proposed and the augmented training sets obtained by data augmentation methods were employed to train the model. The trained model achieved high classification accuracy on the images of different quality, even those containing high levels of noise. Also, the trained model could accurately and efficiently identify and classify a single tomato image with only 29 ms, indicating that the proposed model has great potential value in real-world applications. The feature visualization of the trained models shows their understanding of tomato images, i.e., the learned common and high-level features. The strongest activations of the trained models show that the correct or incorrect target recognition areas by a model during the classification process will affect its final classification accuracy. Based on this, the results obtained in this study could provide guidance and new ideas to improve the development of intelligent agriculture.

Alzheimer's disease (AD) is the most common type of age-related dementia. Inhibition of butyrylcholinesterase (BChE) emerge as an effective therapeutic target for AD. A series of new substituted acetamide derivatives were designed, synthesized and evaluated for their ability to inhibit BChE. The bioassay results revealed that several compounds displayed attractive inhibition against BChE). Among them, compound 8c exhibited the highest BChE inhibition with IC50 values of 3.94 μM. Lineweaver Burk plot indicated that 8c acted as a mixed-type BChE inhibitor. In addition, docking studies confirmed the results obtained through in vitro experiments, and showed that 8c bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE active site. Meanwhile, its ADME parameters were approximated using in silico method. Molecular dynamics simulation studies on the complex of 8c-BChE were performed, RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds were calculated as well. These results implied that 8c could serve as appropriate lead molecule for the development of BChE inhibitor.

FOLFIRINOX has been one of the first-line options for advanced pancreatic cancer, even though it induces significant adverse effects. Several institutions have begun using modified FOLFIRINOX to decrease its side effects and increase its tolerability. We systematically investigated the outcome from patients who initially received modified FOLFIRINOX as a chemotherapy regimen for advanced pancreatic cancer. We used the random-model generic inverse variance method to analyse the binary data with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis with 563 total patients. The 6-month and 1-year overall survival (OS) rates of locally advanced pancreatic cancer (LAPC) were 90.9% and 76.2%. The 6-month and 1-year progression-free survival (PFS) rates of LAPC were 81.5% and 48.5%. The 6-month and 1-year OS rates of metastatic pancreatic cancer (MPC) were 79.7% and 47.6%. The 6-month and 1-year PFS rates of MPC were 56.3% and 20.6%. The following rates were also calculated: complete response rate (CR): 2.9%; partial response rate (PR): 35.9%; stable disease rate (SD): 41.2%; overall response rate (OR): 34.6%; disease control rate (DCR): 76.7%; progressive disease: 23.1%; and grade III/IV adverse events (AEs): neutropenia 23.1%, febrile neutropenia 4.8%, thrombocytopenia 4.8%, anaemia 5.7%, fatigue 11.5%, nausea 9.1%, diarrhoea 10.1%, vomiting 5.7%, neuropathy 3.8%, and increased ALT 5.7%. In conclusion, modified FOLFIRINOX could provide comparative survival benefits with fewer adverse events compared to the conventional dosage.

Bearings are very important components in mechanical equipment, and detecting bearing failures helps ensure healthy operation of mechanical equipment and can prevent catastrophic accidents. Most of the well-established detection methods do not take into account the correlation between signals and are difficult to accurately identify those fault samples that have a low degree of failure. To address this problem, we propose a graph neural network-based bearing fault detection (GNNBFD) method. The method first constructs a graph using the similarity between samples; secondly the constructed graph is fed into a graph neural network (GNN) for feature mapping, and the samples outputted by the GNN network fuse the feature information of their neighbors, which is beneficial to the downstream detection task; then the samples mapped by the GNN network are fed into base detector for fault detection; finally, the results determined by the integrated base detector algorithm are determined, and the top n samples with the highest outlier scores are the faulty samples. The experimental results with five state-of-the-art algorithms on publicly available datasets show that the GNNBFD algorithm improves the AUC by 6.4% compared to the next best algorithm, proving that the GNNBFD algorithm is effective and feasible.

Ocular neovascular diseases including neovascular age-related macular degeneration (nvAMD) are widespread causes of blindness. Patients' non-responsiveness to currently used biologics that target vascular endothelial growth factor (VEGF) poses an unmet need for novel therapies. Here, we identify protein arginine methyltransferase 5 (PRMT5) as a novel therapeutic target for nvAMD. PRMT5 is a well-known epigenetic enzyme. We previously showed that PRMT5 methylates and activates a proangiogenic and proinflammatory transcription factor, the nuclear factor kappa B (NF-κB), which has a master role in tumor progression, notably in pancreatic ductal adenocarcinoma and colorectal cancer. We identified a potent and specific small molecule inhibitor of PRMT5, PR5-LL-CM01, that dampens the methylation and activation of NF-κB. Here for the first time, we assessed the antiangiogenic activity of PR5-LL-CM01 in ocular cells. Immunostaining of human nvAMD sections revealed that PRMT5 is highly expressed in the retinal pigment epithelium (RPE)/choroid where neovascularization occurs, while mouse eyes with laser induced choroidal neovascularization (L-CNV) showed PRMT5 is overexpressed in the retinal ganglion cell layer and in the RPE/choroid. Importantly, inhibition of PRMT5 by PR5-LL-CM01 or shRNA knockdown of PRMT5 in human retinal endothelial cells (HRECs) and induced pluripotent stem cell (iPSC)-derived choroidal endothelial cells (iCEC2) reduced NF-κB activity and the expression of its target genes, such as tumor necrosis factor α (TNF-α) and VEGF-A. In addition to inhibiting angiogenic properties of proliferation and tube formation, PR5-LL-CM01 blocked cell cycle progression at G1/S-phase in a dose-dependent manner in these cells. Thus, we provide the first evidence that inhibition of PRMT5 impedes angiogenesis in ocular endothelial cells, suggesting PRMT5 as a potential therapeutic target to ameliorate ocular neovascularization.