Antibiotic resistance genes (ARGs) have accelerated microbial threats to human health in the last decade. Many genes can confer resistance, but evaluating the relative health risks of ARGs is complex. Factors such as the abundance, propensity for lateral transmission and ability of ARGs to be expressed in pathogens are all important. Here, an analysis at the metagenomic level from various habitats (6 types of habitats, 4572 samples) detects 2561 ARGs that collectively conferred resistance to 24 classes of antibiotics. We quantitatively evaluate the health risk to humans, defined as the risk that ARGs will confound the clinical treatment for pathogens, of these 2561 ARGs by integrating human accessibility, mobility, pathogenicity and clinical availability. Our results demonstrate that 23.78% of the ARGs pose a health risk, especially those which confer multidrug resistance. We also calculate the antibiotic resistance risks of all samples in four main habitats, and with machine learning, successfully map the antibiotic resistance threats in global marine habitats with over 75% accuracy. Our novel method for quantitatively surveilling the health risk of ARGs will help to manage one of the most important threats to human and animal health.

The excessive accumulation of iron in deep gray structures is an important pathological characteristic in patients with Alzheimer's disease (AD). Quantitative susceptibility mapping (QSM) is more specific than other imaging-based iron measurement modalities and allows noninvasive assessment of tissue magnetic susceptibility, which has been shown to correlate well with brain iron levels. This study aimed to investigate the correlations between the magnetic susceptibility values of deep gray matter nuclei and the cognitive functions assessed by mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) in patients with mild and moderate AD. Thirty subjects with mild and moderate AD and 30 age- and sex-matched healthy controls were scanned with a 3.0 T magnetic resonance imaging (MRI) scanner. The magnetic susceptibilities of the regions of interest (ROIs), including caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), red nucleus (Rn), substantia nigra (Sn), and dentate nucleus (Dn), were quantified by QSM. We found that the susceptibility values of the bilateral Cd and Pt were significantly higher in AD patients than the controls ( P < 0.05). In contrast, bilateral Rn had significantly lower susceptibility values in AD than the controls. Regardless of gender and age, the increase of magnetic susceptibility in the left Cd was significantly correlated with the decrease of MMSE scores and MoCA scores ( P < 0.05). Our study indicated that magnetic susceptibility value of left Cd could be potentially used as a biomarker of disease severity in mild and moderate AD.

Under phosphate (Pi ) starvation, plants increase the secretion of purple acid phosphatases (PAPs) into the rhizosphere to scavenge organic phosphorus (P) for plant use. To date, only a few members of the PAP family have been characterized in crops. In this study, we identified a novel secreted PAP in rice, OsPAP10c, and investigated its role in the utilization of external organic P. OsPAP10c belongs to a monocotyledon-specific subclass of Ia group PAPs and is specifically expressed in the epidermis/exodermis cell layers of roots. Both the transcript and protein levels of OsPAP10c are strongly induced by Pi starvation. OsPAP10c overexpression increased acid phosphatase (APase) activity by more than 10-fold in the culture media and almost fivefold in both roots and leaves under Pi -sufficient and Pi -deficient conditions. This increase in APase activity further improved the plant utilization efficiency of external organic P. Moreover, several APase isoforms corresponding to OsPAP10c were identified using in-gel activity assays. Under field conditions with three different Pi supply levels, OsPAP10c-overexpressing plants had significantly higher tiller numbers and shorter plant heights. This study indicates that OsPAP10c encodes a novel secreted APase that plays an important role in the utilization of external organic P in rice.

The aim of this study was to investigate the changes in hepatic oxidative phosphorylation (OXPHOS) complexes (COs) in patients and cows with non‐alcoholic steatohepatitis (NASH) and to investigate the mechanism that links mitochondrial dysfunction and hepatic insulin resistance induced by non‐esterified fatty acids (NEFAs). Patients and cows with NASH displayed high blood NEFAs, TNF‐α and IL‐6 concentrations, mitochondrial dysfunction and insulin resistance. The protein levels of peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α), mitofusin‐2 (Mfn‐2) and OXPHOS complexes (human: COI and COIII; cow: COI‐IV) were significantly decreased in patients and cows with NASH. NEFA treatment significantly impaired mitochondrial function and, increased reactive oxygen species (ROS) production, and excessive ROS overactivated the JNK and p38MAPK pathways and induced insulin resistance in cow hepatocytes. PGC‐1α and Mfn‐2 overexpression significantly decreased the NEFA‐induced ROS production and TNF‐α and IL‐6 mRNA expressions, reversed the inhibitory effect of NEFAs on mitochondrial function and attenuated the overactivation of the ROS‐JNK/p38MAPK pathway, alleviated insulin resistance induced by NEFAs in cow hepatocytes and HepG2 cells. These findings indicate that NEFAs induce mitochondrial dysfunction and insulin resistance mediated by the ROS‐JNK/p38MAPK pathway. PGC‐1α or Mfn‐2 overexpression reversed the lipotoxicity of NEFAs on mitochondrial dysfunction and insulin resistance. Our study clarified the mechanism that links hepatic mitochondrial dysfunction and insulin resistance in NASH.

Immunoglobulin like transcript (ILT) 4, a negative regulator of immune response in allograft rejection, autoimmunity and infectious diseases, has recently been determined to serve important roles in tumor development. In the present study, the co expression of ILT4 and human leukocyte antigen G (HLA-G) in tissues of human primary colorectal cancer (CRC) was revealed, and its association with older age, advanced stage, regional lymph node involvement and poor overall survival time was identified. In CRC cell lines, ILT4 and HLA-G co expression and their autocrine regulation was demonstrated. ILT4 interference affected HLA-G expression and regulated the cell proliferation, invasion and migration of CRC. HLA-G fusion protein treatment also increased ILT4 expression in a dose dependent manner, thereby activating protein kinase B (AKT) and extracellular signal regulated kinase (ERK) signaling, and facilitating the proliferation, migration and invasion of CRC cells. Additionally, the AKT and ERK activation, and CRC cell malignant characteristics induced by HLA-G may be suppressed by blocking ILT4. The present results indicated that the interaction of ILT4 and its ligand HLA-G promotes CRC progression through AKT and ERK signal activation, providing a novel strategy of blocking ILT4/HLA-G for the treatment of CRC.