ABSTRACT
BACKGROUND: This study aims to assess the recovery patterns and factors influencing outcomes in patients with common peroneal nerve (CPN) injury. METHODS: This retrospective study included 45 patients with CPN injuries treated between 2009 and 2019 in Jing'an District Central Hospital. The surgical interventions were categorized into three groups: neurolysis (group A; n = 34 patients), nerve repair (group B; n = 5 patients) and tendon transfer (group C; n = 6 patients). Preoperative and postoperative sensorimotor functions were evaluated using the British Medical Research Council grading system. The outcome of measures included the numeric rating scale, walking ability, numbness and satisfaction. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal time interval between injury and surgery for predicting postoperative foot dorsiflexion function, toe dorsiflexion function, and sensory function. RESULTS: Surgical interventions led to improvements in foot dorsiflexion strength in all patient groups, enabling most to regain independent walking ability. Group A (underwent neurolysis) had significant sensory function restoration (P < 0.001), and three patients in Group B (underwent nerve repair) had sensory improvements. ROC analysis revealed that the optimal time interval for achieving M3 foot dorsiflexion recovery was 9.5 months, with an area under the curve (AUC) of 0.871 (95% CI = 0.661-1.000, P = 0.040). For M4 foot dorsiflexion recovery, the optimal cut-off was 5.5 months, with an AUC of 0.785 (95% CI = 0.575-0.995, P = 0.020). When using M3 toe dorsiflexion recovery or S4 sensory function recovery as the gold standard, the optimal cut-off remained at 5.5 months, with AUCs of 0.768 (95% CI = 0.582-0.953, P = 0.025) and 0.853 (95% CI = 0.693-1.000, P = 0.001), respectively. CONCLUSIONS: Our study highlights the importance of early surgical intervention in CPN injury recovery, with optimal outcomes achieved when surgery is performed within 5.5 to 9.5 months post-injury. These findings provide guidance for clinicians in tailoring treatment plans to the specific characteristics and requirements of CPN injury patients.
Subject(s)
Peroneal Nerve , Peroneal Neuropathies , Humans , Retrospective Studies , Peroneal Nerve/surgery , Peroneal Nerve/injuries , Peroneal Neuropathies/surgery , Neurosurgical ProceduresABSTRACT
Itch is a complex aversive sensory and emotional experience. As a most upsetting symptom in many dermatological and systemic diseases, it lacks efficient treatments. The lateral habenula nucleus (LHb) encodes negative emotions in the epithalamus and has been implicated in pain and analgesia. Nevertheless, the role of the lateral habenula nucleus in the pruritic sensation and emotion remains elusive. Here we defined the crucial role of glutamatergic neurons within the lateral habenula nucleus (GluLHb) in itch modulation in mice. We established histamine-dependent and histamine-independent models of acute pruritus, as well as the acetone-ether-water (AEW) model of chronic pruritus. We first assessed the effects of pruritogen injection on neural activation in both medial and lateral divisions of LHb in vitro. We then demonstrated that the population activity of GluLHb neurons was increased during the acute itch and chronic itch-induced scratching behaviors in vivo. In addition, electrophysiological data showed that the excitability of GluLHb neurons was enhanced by chronic itch. Chemogenetic suppression of GluLHb neurons disrupted both acute and chronic itch-evoked scratching behaviors. Furthermore, itch-induced conditioned place aversion (CPA) was abolished by GluLHb neuronal inhibition. Finally, we dissected the LHb upstream brain regions. Together, these findings reveal the involvement of LHb in processing both the sensational and emotional components of pruritus and may shed new insights into itch therapy.
Subject(s)
Habenula , Mice , Animals , Histamine , Emotions , Sensation , PruritusABSTRACT
BACKGROUND: Gut microbiota plays a significant role in the colorectal cancer (CRC) process. Ectopic colonization of multiple oral bacteria is reportedly associated with CRC pathogenesis and progression, but the details remain unclear. METHODS: We enrolled a cohort of 50 CRC patients and 52 healthy controls from an East China population. Taxonomic and functional analysis of the fecal microbiota were performed using 16S rDNA (50 + 52 samples) and shotgun metagenomic sequencing (8 + 6 samples), respectively, with particular attention paid to gut-colonized oral bacteria. RESULTS AND CONCLUSIONS: The results showed more detected bacterial species but lower species evenness within the samples from CRC patients. To determine the specific bacteria enriched in each group, we analyzed their possible protective, carcinogenic, or opportunistic roles in the CRC process. Among the ectopic oral bacteria, we observed a significant increase in the abundance of Fusobacterium and decreased abundance of Prevotella and Ruminococcus in the CRC group. Main differences in the functional composition of these two groups were related to energy metabolism and biosynthesis, especially the glycolytic pathway. Furthermore, we validated the colonization of Fusobacterium nucleatum subsp. animalis within CRC tissues and studied its impact on the host intestinal epithelium and tumor cells. With high selectivity for cancerous tissues, this subspecies promoted CRC cell proliferation and induced potential DNA damage.
Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Microbiota , Humans , Colorectal Neoplasms/pathology , Bacteria/genetics , Microbiota/genetics , CarcinogenesisABSTRACT
In this study, we examined the prognostic factors affecting outcomes following nerve grafting in high radial nerve injuries. Thirty-three patients with radial nerve injuries at a level distal to the first branch to the triceps and proximal to the posterior interosseous nerve were retrospectively studied. After a follow-up of at least 1 year, 24 patients (73%) obtained M3+ wrist extension, 16 (48%) obtained M3+ finger extension and only ten (30%) obtained M3+ thumb extension. Univariate, multivariate and receiver operating characteristic analyses showed that a delay in the repair of less than 6 months, a defect length of less than 5 cm or when grafted with three or more donor nerve cables achieved better recovery. Number of cables used was related to muscle strength recovery but not time to reinnervation. Nerve grafting for high radial nerve injury achieved relatively good wrist extension but poor thumb extension and is affected by certain prognostic factors. Level of evidence: IV.
Subject(s)
Nerve Transfer , Radial Nerve , Humans , Radial Nerve/surgery , Radial Nerve/injuries , Retrospective Studies , Prognosis , Neurosurgical Procedures , Fingers/innervationABSTRACT
Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are leading causes of long-term disability. It is estimated that more than half of the survivors of severe unilateral injury are unable to use the denervated limb. Previous studies have focused on neuroprotective interventions in the affected hemisphere to limit brain lesions and neurorepair measures to promote recovery. However, the ability to increase plasticity in the injured brain is restricted and difficult to improve. Therefore, over several decades, researchers have been prompted to enhance the compensation by the unaffected hemisphere. Animal experiments have revealed that regrowth of ipsilateral descending fibers from the unaffected hemisphere to denervated motor neurons plays a significant role in the restoration of motor function. In addition, several clinical treatments have been designed to restore ipsilateral motor control, including brain stimulation, nerve transfer surgery, and brain-computer interface systems. Here, we comprehensively review the neural mechanisms as well as translational applications of ipsilateral motor control upon rehabilitation after CNS injuries.
Subject(s)
Spinal Cord Injuries , Stroke , Animals , Spinal Cord Injuries/therapy , Motor Neurons/physiology , Brain , Recovery of Function/physiologyABSTRACT
Greenhouse cover pollution with green shading composed of dust, microalgae and bacteria is a severe problem in tropical areas. The shading results in lower greenhouse indoor light intensity reducing the yield and quality of protected horticulture crops. However, few studies have focused on environmentally efficient ways to remove green shading to increase greenhouse production. In this study, five purified microalgae were isolated from the green shading of three greenhouse roofs and were identified using morphological and molecular assessments. The effects of Ultraviolet-C irradiation (UV-C, 254 nm) at doses of 100, 200 and 300 mJ cm-2 on the growth of GLY-1 microalgae were investigated. The results indicated that five purified microalgae all appeared to belong to the genus of Jaagichlorella. The purified microalgae cell density and chlorophyll content decreased respectively by 26.89-74.44 % and 42.02-77.31 % at 1-3 d after UV-C treatment with doses ranging from 100 to 300 mJ cm-2. The inhibition of the growth rate of microalgae was significantly positively correlated with the UV-C irradiation dose and significantly negatively correlated with treatment time. In summary, UV-C irradiation treatment at 300 mJ cm-2 and 3 d could substantially inhibit microalgae growth in green shading on greenhouse covers. UV-C irradiation could be an effective method for solving the problem of greenhouse cover pollution with microalgae.
Subject(s)
Microalgae , Ultraviolet Rays , Chlorophyll , Dust , LightABSTRACT
Disinfection byproducts (DBPs) are initially formed in the process of chlorination in the drinking water treatment plants (DWTPs), then further formed in the distribution system due to the presence of residual chlorine and reactive organic matters. However, in China, DBPs are monitored in the effluent from the DWTPs, but less is known about concentrations of DBPs in tap water since they are usually monitored once per half a year. The smart water service system is establishing real-time monitoring of water indices, although DBPs are an urgent need, they are difficult to monitor in real-time due to their diversity and complicated detection methods. If the correlation between DBP concentration and routinely real-time monitored water quality parameters (e.g., pH value, residual chlorine, ammonia) can be evaluated, the concentration of DBPs can be predicted, which will strengthen the control of tap water safety. This article comprehensively assessed the physicochemical parameters and the occurrence of DBP formation in the tap water with an 18-month investigation in Z city (China). DBP formation in tap water of different seasons and different water sources were compared. Based on the relationship between DBPs and physicochemical parameters, linear prediction and nonlinear prediction models of trihalomethanes (THMs), haloacetonitriles (HANs) and haloacetic acids (HAAs) were established, and the accuracy of these models was verified by measured data. Finally, the toxicity and carcinogenic and non-carcinogenic health risk assessment of DBPs in tap water were analyzed.
Subject(s)
Disinfectants , Drinking Water , Water Pollutants, Chemical , Water Purification , Ammonia , China , Chlorine , Disinfectants/analysis , Disinfection/methods , Halogenation , Humans , Trihalomethanes/analysis , Water Pollutants, Chemical/analysisABSTRACT
Restoring limb movements after central nervous system injury remains a substantial challenge. Recent studies proved that crossing nerve transfer surgery could rebuild physiological connectivity between the contralesional cortex and the paralyzed arm to compensate for the lost function after brain injury. However, the neural mechanism by which this surgery mediates motor recovery remains still unclear. Here, using a clinical mouse model, we showed that this surgery can restore skilled forelimb function in adult mice with unilateral cortical lesion by inducing cortical remapping and promoting corticospinal tract sprouting. After reestablishing the ipsilateral descending pathway, resecting of the artificially rebuilt peripheral nerve did not affect motor improvements. Furthermore, retaining the sensory afferent, but not the motor efferent, of the transferred nerve was sufficient for inducing brain remapping and facilitating motor restoration. Thus, our results demonstrate that surgically rebuilt sensory input triggers neural plasticity for accelerating motor recovery, which provides an approach for treating central nervous system injuries.
Subject(s)
Brain Injuries , Nerve Transfer , Animals , Brain Injuries/pathology , Forelimb , Mice , Neuronal Plasticity/physiology , Pyramidal Tracts/pathologyABSTRACT
Purpose: To establish and verify the ability of a radiomics prediction model to distinguish invasive adenocarcinoma (IAC) and minimal invasive adenocarcinoma (MIA) presenting as ground-glass nodules (GGNs). Methods: We retrospectively analyzed 118 lung GGN images and clinical data from 106 patients in our hospital from March 2016 to April 2019. All pathological classifications of lung GGN were confirmed as IAC or MIA by two pathologists. R language software (version 3.5.1) was used for the statistical analysis of the general clinical data. ITK-SNAP (version 3.6) and A.K. software (Analysis Kit, American GE Company) were used to manually outline the regions of interest of lung GGNs and collect three-dimensional radiomics features. Patients were randomly divided into training and verification groups (ratio, 7:3). Random forest combined with hyperparameter tuning was used for feature selection and prediction modeling. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate model prediction efficacy. The calibration curve was used to evaluate the calibration effect. Results: There was no significant difference between IAC and MIA in terms of age, gender, smoking history, tumor history, and lung GGN location in both the training and verification groups (P>0.05). For each lung GGN, the collected data included 396 three-dimensional radiomics features in six categories. Based on the training cohort, nine optimal radiomics features in three categories were finally screened out, and a prediction model was established. We found that the training group had a high diagnostic efficacy [accuracy, sensitivity, specificity, and AUC of the training group were 0.89 (95%CI, 0.73 - 0.99), 0.98 (95%CI, 0.78 - 1.00), 0.81 (95%CI, 0.59 - 1.00), and 0.97 (95%CI, 0.92-1.00), respectively; those of the validation group were 0.80 (95%CI, 0.58 - 0.93), 0.82 (95%CI, 0.55 - 1.00), 0.78 (95%CI, 0.57 - 1.00), and 0.92 (95%CI, 0.83 - 1.00), respectively]. The model calibration curve showed good consistency between the predicted and actual probabilities. Conclusions: The radiomics prediction model established by combining random forest with hyperparameter tuning effectively distinguished IAC from MIA presenting as GGNs and represents a noninvasive, low-cost, rapid, and reproducible preoperative prediction method for clinical application.
ABSTRACT
Promoter is a key DNA element located near the transcription start site, which regulates gene transcription by binding RNA polymerase. Thus, the identification of promoters is an important research field in synthetic biology. Nannochloropsis is an important unicellular industrial oleaginous microalgae, and at present, some studies have identified some promoters with specific functions by biological methods in Nannochloropsis, whereas few studies used computational methods. Here, we propose a method called DNPPro (DenseNet-Predict-Promoter) based on densely connected convolutional neural networks to predict the promoter of Nannochloropsis. First, we collected promoter sequences from six Nannochloropsis strains and removed 80% similarity using CD-HIT for each strain to yield a reliable set of positive datasets. Then, in order to construct a robust classifier, within-group scrambling method was used to generate negative dataset which overcomes the limitation of randomly selecting a non-promoter region from the same genome as a negative sample. Finally, we constructed a densely connected convolutional neural network, with the sequence one-hot encoding as the input. Compared with commonly used sequence processing methods, DNPPro can extract long sequence features to a greater extent. The cross-strain experiment on independent dataset verifies the generalization of our method. At the same time, T-SNE visualization analysis shows that our method can effectively distinguish promoters from non-promoters.
Subject(s)
Neural Networks, Computer , Synthetic Biology , Promoter Regions, GeneticABSTRACT
The ability to meet higher effluent quality requirements and the reduction of energy consumption are the biggest challenges in wastewater treatment worldwide. A large proportion of the energy generated during wastewater treatment processes is neglected and lost in traditional wastewater treatment plants. As a type of energy harvesting system, triboelectric nanogenerators (TENGs) can extensively harvest the microscale energies generated from wastewater treatment procedures and auxiliary devices. This harvested energy can be utilized to improve the removal efficiency of pollutants through photo/electric catalysis, which has considerable potential application value in wastewater treatment plants. This paper gives an overall review of the generated potential energies (e.g., water wave energy, wind energy, and acoustic energy) that can be harvested at various stages of the wastewater treatment process and introduces the application of TENG devices for the collection of these neglected energies during wastewater treatment. Furthermore, the mechanisms and catalytic performances of TENGs coupled with photo/electric catalysis (e.g., electrocatalysis, photoelectric catalysis) are discussed to realize higher pollutant removal efficiencies and lower energy consumption. Then, a thorough, detailed investigation of TENG devices, electrode materials, and their coupled applications is summarized. Finally, the intimate coupling of self-powered photoelectric catalysis and biodegradation is proposed to further improve removal efficiencies in wastewater treatment. This concept is conducive to improving knowledge about the underlying mechanisms and extending applications of TENGs in wastewater treatment to better solve the problems of energy demand in the future.
Subject(s)
Electric Power Supplies , Water Purification , Electricity , Electrodes , Nanotechnology/methodsABSTRACT
Distributions of halogenated disinfection byproducts (DBPs) in a two-source water distribution system (WDS) with enhanced chlorination were investigated. The WDS was divided into different sub-service areas based on different electrical conductivity of two water sources. Results clearly show that the principal halogenated DBPs were trihalomethanes (THMs) (5.06-82.69 µg/L), varying within the concentration range as 2-5 times as the levels of haloacetic acids (HAAs) (1.41-61.48 µg/L) and haloacetonitriles (HANs) (0.21-15.13 µg/L). Different water sources, treatment trains, and enhanced chlorination within the WDS had significant effects on seasonal and spatial variations of the DBP distributions over water conveyance. THM and HAA formation followed the sequence of summer > autumn > winter > spring. On the other hand, the DBP spatial distributions were visualized using the ArcGIS enabled Inverse distance weighting technique. The superposition of different DBP spatial distributions allowed for the identification of the high-risk THMs and HAAs areas based on the average values of THMs (27.49 µg/L) and HAAs (14.06 µg/L). Beyond the comprehensive analyses of DBP distribution in a municipal WDS, the project proposed and validated an innovative methodology to locate the DBP high-risk areas and to reveal the effects of different factors on DBPs distribution in a two-source WDS.
Subject(s)
Disinfectants , Drinking Water , Water Pollutants, Chemical , Water Purification , Chlorine , Disinfectants/analysis , Disinfection , Drinking Water/analysis , Halogenation , Trihalomethanes/analysis , Water Pollutants, Chemical/analysisABSTRACT
Crossing nerve transfer surgery has been a powerful approach for repairing injured upper extremities in patients with brachial plexus avulsion injuries. Recently, this surgery was creatively applied in the clinical treatment of brain injury and achieved substantial rehabilitation of the paralyzed arm. This functional recovery after the surgery suggests that peripheral sensorimotor intervention induces profound neuroplasticity to compensate for the loss of function after brain damage; however, the underlying neural mechanism is poorly understood. Therefore, an emergent clinical animal model is required. Here, we simulated clinical surgery to establish a protocol of direct anastomosis of bilateral brachial plexus nerves via the prespinal route in mice. Neuroanatomical, electrophysiological, and behavioral experiments helped identify that the transferred nerves of these mice successfully reinnervated the impaired forelimb and contributed to accelerating motor recovery after brain injury. Therefore, the mouse model revealed the neural mechanisms underlying rehabilitation upon crossing nerve transfer after central and peripheral nervous system injuries.
Subject(s)
Brachial Plexus Neuropathies , Brachial Plexus , Nerve Transfer , Anastomosis, Surgical , Animals , Brachial Plexus/injuries , Brachial Plexus/surgery , Humans , Mice , Nerve Transfer/methods , Neurosurgical ProceduresABSTRACT
Macrophages promote early host responses to infection by releasing pro-inflammatory cytokines, and they are crucial to combat amoebiasis, a disease affecting millions of people worldwide. Macrophages elicit pro-inflammatory responses following direct cell/cell interaction of Entamoeba histolytica, inducing NLRP3 inflammasome activation with high-output IL-1ß/IL-18 secretion. Here, we found that trophozoites could upregulate peroxiredoxins (Prx) expression and abundantly secrete Prxs when encountering host cells. The C-terminal of Prx was identified as the key functional domain in promoting NLRP3 inflammasome activation, and a recombinant C-terminal domain could act directly on macrophage. The Prxs derived from E. histolytica triggered toll-like receptor 4-dependent activation of NLRP3 inflammasome in a cell/cell contact-independent manner. Through genetic, immunoblotting or pharmacological inhibition methods, NLRP3 inflammasome activation was induced through caspase-1-dependent canonical pathway. Our data suggest that E. histolytica Prxs had stable and durable cell/cell contact-independent effects on macrophages following abundantly secretion during invasion, and the C-terminal of Prx was responsible for activating NLRP3 inflammasome in macrophages. This new alternative pathway may represent a potential novel therapeutic approach for amoebiasis, a global threat to millions.
Subject(s)
Entamoeba histolytica/enzymology , Inflammasomes/metabolism , Macrophages/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Peroxiredoxins/metabolism , Toll-Like Receptor 4/metabolism , Animals , Binding Sites , Cells, Cultured , Male , Mice , Mice, Inbred C57BL , Peroxiredoxins/analysis , Peroxiredoxins/geneticsABSTRACT
Objective To explore the feasibility of preheating in 41 â water bath for 30 minutes to correct the red blood cell parameters in the specimens containing high-titer cold agglutinins(CAs). Methods Two specimens containing high-titer CAs were selected during work,and the parameters of complete blood count at room temperature or after preheating in 37 â or 41 â water bath were compared.The smears were stained,and the distribution of red blood cells was observed with a microscope.Further,74 specimens without CAs were collected for complete blood count,and then the test results at room temperature and after preheating at 41 â were compared. Results At room temperature,the specimens containing high-titer CAs showed significantly reduced red blood cell count(RBC)and hematocrit(HCT),abnormally increased mean corpuscular hemoglobin(MCH)and mean cell hemoglobin concentration(MCHC),abnormal percents of hemoglobin(HGB)and RBC,and aggregation of a large number of red blood cells.After being preheated at 37 â for a certain time,the specimens demonstrated obviously improved parameters while still aggregation of a small number of red blood cells.After being preheated at 41 â for 30 minutes,the specimens showed significantly increased RBC,normal HCT,MCH,and MCHC,and evenly distributed red blood cells.The 74 specimens without CAs showed the comparability was ≥80% between room temperature and preheating at 41 â for 30 minutes or 60 minutes. Conclusion We can preheat the specimens containing high-titer CAs in a water bath at 41 â to obtain accurate red blood cell parameters.
Subject(s)
Erythrocytes , Cryoglobulins , Erythrocyte Count , Feasibility Studies , HematocritABSTRACT
Arecae Semen, as the first place among "Four South Medicines" in China, has great dual-use value of medicine and food. The research of Arecae Semen was mainly focused on the active ingredients and efficacy value, and its potential safety hazards were also concerned. Until now, there is still a lack of clear boundaries between medicine and food, resulting in its safety cannot be guaranteed. Therefore, it is of great significance to establish clear boundaries of medicine and food use and health risk assessment. In this paper, the differences of pretreatment and application methods of Arecae Semen were analyzed, and the research progress of Arecae Semen in chemical composition identification and toxicology research and safety evaluation were reviewed emphatically. Finally, the differences of quality control and safety evaluation of Arecae Semen in pharmacopoeias or standards were analyzed at home and abroad. It was expected to provide reference value for quality control, safety evaluation and international standardization research of Arecae Semen.
Subject(s)
Areca , Drugs, Chinese Herbal , Seeds , China , Drugs, Chinese Herbal/adverse effects , Seeds/chemistryABSTRACT
In recent years, obesity has become a global public health issue. It is closely associated with the occurrence of several chronic diseases, such as diabetes and cardiovascular diseases. Some edible and medicinal plants show anti-obesity activity, such as fruits, vegetables, spices, legumes, edible flowers, mushrooms, and medicinal plants. Numerous studies have indicated that these plants are potential candidates for the prevention and management of obesity. The major anti-obesity mechanisms of plants include suppressing appetite, reducing the absorption of lipids and carbohydrates, inhibiting adipogenesis and lipogenesis, regulating lipid metabolism, increasing energy expenditure, regulating gut microbiota, and improving obesity-related inflammation. In this review, the anti-obesity activity of edible and medicinal plants was summarized based on epidemiological, experimental, and clinical studies, with related mechanisms discussed, which provided the basis for the research and development of slimming products. Further studies should focus on the exploration of safer plants with anti-obesity activity and the identification of specific anti-obesity mechanisms.
Subject(s)
Anti-Obesity Agents , Plants, Medicinal , Energy Metabolism , Humans , Lipid Metabolism , Obesity/drug therapy , Obesity/prevention & control , Plants, EdibleABSTRACT
Diabetes mellitus has become a serious and growing public health concern. It has high morbidity and mortality because of its complications, such as diabetic nephropathy, diabetic cardiovascular complication, diabetic neuropathy, diabetic retinopathy, and diabetic hepatopathy. Epidemiological studies revealed that the consumption of tea was inversely associated with the risk of diabetes mellitus and its complications. Experimental studies demonstrated that tea had protective effects against diabetes mellitus and its complications via several possible mechanisms, including enhancing insulin action, ameliorating insulin resistance, activating insulin signaling pathway, protecting islet ß-cells, scavenging free radicals, and decreasing inflammation. Moreover, clinical trials also confirmed that tea intervention is effective in patients with diabetes mellitus and its complications. Therefore, in order to highlight the importance of tea in the prevention and management of diabetes mellitus and its complications, this article summarizes and discusses the effects of tea against diabetes mellitus and its complications based on the findings from epidemiological, experimental, and clinical studies, with the special attention paid to the mechanisms of action.
ABSTRACT
BACKGROUND: As RNA-seq becomes the assay of choice for measuring gene expression levels, differential expression analysis has received extensive attentions of researchers. To date, for the evaluation of DE methods, most attention has been paid on validity. Yet another important aspect of DE methods, stability, is overlooked and has not been studied to the best of our knowledge. RESULTS: In this study, we empirically show the need of assessing stability of DE methods and propose a stability metric, called Area Under the Correlation curve (AUCOR), that generates the perturbed datasets by a mixture distribution and combines the information of similarities between sets of selected features from these perturbed datasets and the original dataset. CONCLUSION: Empirical results support that AUCOR can effectively rank the DE methods in terms of stability for given RNA-seq datasets. In addition, we explore how biological or technical factors from experiments and data analysis affect the stability of DE methods. AUCOR is implemented in the open-source R package AUCOR, with source code freely available at https://github.com/linbingqing/stableDE .
Subject(s)
Gene Expression Profiling/statistics & numerical data , Sequence Analysis, RNA/statistics & numerical data , Area Under Curve , Computational Biology , Datasets as Topic , High-Throughput Nucleotide Sequencing/statistics & numerical dataABSTRACT
Medium-chain (C6-C10) chemicals are important components of fuels, commodities and fine chemicals. Numerous exciting achievements have proven reversed ß-oxidation cycle as a promising platform to synthesize these chemicals. However, under native central carbon metabolism, energetic and redox constraints limit the efficient operation of reversed ß-oxidation cycle. Current fermentative platform has to use different chemically and energetically inefficient ways for acetyl-CoA and NADH biosynthesis, respectively. The characteristics such as supplementation of additional acetate and formate or high ATP requirement makes this platform incompatible with large-scale production. Here, an artificial micro-aerobic metabolism for energy and carbon-efficient conversion of glycerol to MCFAs was constructed to present solutions towards these barriers. After evaluating numerous bacteria pathways under micro-aerobic conditions, one synthetic metabolic step enabling biosynthesis of acetyl-CoA and NADH simultaneously, without any energy cost and additional carbon requirement, and reducing loss of carbon to carbon dioxide-emitting reactions, was conceived and successfully constructed. The pyruvate dehydrogenase from Enterococcus faecalis was identified and biochemically characterized, demonstrating the most suitable characteristics. Furthermore, the carbon and energy metabolism in Escherichia coli was rewired by the clustered regularly interspaced short palindromic repeats interference system, inhibiting native fermentation pathways outcompeting this synthetic step. The present engineered strain exhibited a 15.7-fold increase in MCFA titer compared with that of the initial strain, and produced 15.67â¯g/L MCFAs from the biodiesel byproduct glycerol in 3-L bioreactor without exogenous feed of acetate or formate, representing the highest MCFA titer reported to date. This work demonstrates this artificial micro-aerobic metabolism has the potential to enable the cost-effective, large-scale production of fatty acids and other value-added reduced chemicals.