Background: Antibiotics and antibiotic resistance genes (ARGs) used in intensive animal farming threaten human health worldwide; however, the common resistome, ARG mobility, and ARG host composition in different animal manures and mixed manure composts remain unclear. In the present study, metagenomic assembly and cross-sample mapping were used to comprehensively decipher the common resistome and its potential mobility and hosts in animal manure and composts. Results: In total, 201 ARGs were shared among different animal (layer, broiler, swine, beef cow, and dairy cow) manures and accounted for 86–99% of total relative abundance of ARGs. Except for multidrug, sulfonamide, and trimethoprim resistance genes, the relative abundance of most ARGs in composts was significantly lower than that in animal manure. Procrustes analysis indicated that antibiotic residues positively correlated with ARG composition in manure but not in composts. More than 75% ARG subtypes were shared between plasmids and chromosomes in our samples. Transposases could play a pivotal role in mediating the transfer of ARGs between different phyla in animal manure and composting. Cross-sample mapping to contigs carrying ARGs showed that the hosts of common resistome in manure had preference on animal species, and the dominant genus of ARG host shifted from Enterococcus in manure to Pseudomonas in composts. The broad host range and linking with diverse mobile genetic elements (MGEs) were two key factors for ARGs, such as sul1 and aadA, which could survive during composting. The multidrug resistance genes represented the dominant ARGs in pathogenic antibiotic-resistant bacteria in manure but could be effectively controlled by composting. Conclusions: Our experiments revealed the common resistome in animal manure, classified and relative quantified the ARG hosts, and assessed the mobility of ARGs. Composting can mitigate ARGs in animal manure by altering the bacterial hosts; however, persistent ARGs can escape from the removal because of diverse host range and MGEs. Our findings provide an overall background for source tracking, risk assessment, and control of livestock ARGs.

Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats. A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder. Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes. Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction.

Objective: To review studies on diabetic bladder dysfunction (DBD), a common and bothersome complication of diabetes mellitus. Data sources: We performed a search of the English literature through PubMed. The key words used were “diabetes” and “bladder dysfunction” or “cystopathy”. Our own data and perspective are included in the discussion. Study selection: Studies containing data relevant to DBD were selected. Because of the limited length of this article, we also referenced reviews that contain comprehensive amalgamations of relevant literature. Results: The classic symptoms of DBD are decreased bladder sensation, increased bladder capacity, and impaired bladder emptying with resultant elevated post-void residual urine. However, recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes. Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes, causing an early phase of compensatory bladder function and a later phase of decompensated bladder function. The pathophysiology of DBD is multifactorial, including disturbances of the detrusor, urothelium, autonomic nerves, and urethra. Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes. Polyuria causes significant bladder hypertrophy in the early stage of diabetes, whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function. Conclusions: DBD includes time-dependent and mixed manifestations. The pathological alterations include muscle, nerve, and urothelium. Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD. Treatments for DBD are limited. Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately. Animal studies of DBD in type 2 diabetes are needed, from the natural history to mechanisms. Further understanding of the molecular mechanisms of DBD will provide multiple potential targets for therapeutic intervention.

Aging and major chronic diseases are risk factors for lower urinary tract symptoms (LUTS). On the other hand, oxidative stress (OS) is one of the fundamental mechanisms of aging and the development of chronic diseases. Therefore, OS might be a candidate mechanism linking these two clinical entities. This article aims to summarize the studies on the prevalence of LUTS, the role of OS in aging and chronic diseases, and the potential mechanisms supporting the putative link. A comprehensive literature search was performed to identify recent reports investigating LUTS and OS in major chronic diseases. In addition, studies on the impact of OS on the lower urinary tract, including bladder, urethra, and prostate, were collected and summarized. Many studies showed LUTS are prevalent in aging and major chronic diseases, including obesity, metabolic syndrome, diabetes, cardiovascular disease, hypertension, obstructive sleep apnea, autoimmune diseases, Alzheimer’s disease, and Parkinson’s disease. At the same time, OS is a key component in the pathogenesis of those chronic diseases and conditions. Recent studies also provided evidence that exacerbated OS can cause functional and/or structural changes in the bladder, urethra, and prostate, leading to LUTS. The reviewed data support the concept that OS is involved in multiple risk factors-associated LUTS, although further studies are needed to confirm the causative relationship. The specific ROS/RNS and corresponding reactions/pathways involved in chronic diseases and associated LUTS should be identified in the future and could serve as therapeutic targets.

Drought stress is a major abiotic factor affecting tomato production and fruit quality. However, the genes and metabolites associated with tomato responses to water deficiency and rehydration are poorly characterized. To identify the functional genes and key metabolic pathways underlying tomato responses to drought stress and recovery, drought-susceptible and drought-tolerant inbred lines underwent transcriptomic and metabolomic analyses. A total of 332 drought-responsive and 491 rehydration-responsive core genes were robustly differentially expressed in both genotypes. The drought-responsive and rehydration-responsive genes were mainly related to photosynthesis–antenna proteins, nitrogen metabolism, plant–pathogen interactions, and the MAPK signaling pathway. Various transcription factors, including homeobox-leucine zipper protein ATHB-12, NAC transcription factor 29, and heat stress transcription factor A-6b-like, may be vital for tomato responses to water status. Moreover, 24,30-dihydroxy-12(13)-enolupinol, caffeoyl hawthorn acid, adenosine 5′-monophosphate, and guanosine were the key metabolites identified in both genotypes under drought and recovery conditions. The combined transcriptomic and metabolomic analysis highlighted the importance of 38 genes involved in metabolic pathways, the biosynthesis of secondary metabolites, the biosynthesis of amino acids, and ABC transporters for tomato responses to water stress. Our results provide valuable clues regarding the molecular basis of drought tolerance and rehydration. The data presented herein may be relevant for genetically improving tomatoes to enhance drought tolerance.