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The increasing prevalence of depression is a major societal burden. The etiology of depression involves multiple mechanisms. Thus, the outcomes of the currently used treatment for depression are suboptimal. The anti-depression effects of traditional Chinese medicine (TCM) formulations have piqued the interest of the scientific community owing to their multi-ingredient, multi-target, and multi-link characteristics. According to the TCM theory, the functioning of the kidney is intricately linked to that of the brain. Clinical observations have indicated the therapeutic potential of the kidney-tonifying formula Erxian Decoction (EXD) in depression. This review aimed to comprehensively search various databases to summarize the anti-depression effects of EXD, explore the underlying material basis and mechanisms, and offer new suggestions and methods for the clinical treatment of depression. The clinical and preclinical studies published before 31 August 2023, were searched in PubMed, Google Scholar, China National Knowledge Infrastructure, and Wanfang Database. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical studies have demonstrated that EXD exhibits therapeutic properties in patients with menopausal depression, postpartum depression, and maintenance hemodialysis-associated depression. Meanwhile, preclinical studies have reported that EXD and its special chemical markers exert anti-depression effects by modulating monoamine neurotransmitter levels, inhibiting neuroinflammation, augmenting synaptic plasticity, exerting neuroprotective effects, regulating the hypothalamic-pituitary-adrenal axis, promoting neurogenesis, and altering cerebrospinal fluid composition. Thus, the anti-depression effects of EXD are mediated through multiple ingredients, targets, and links. However, further clinical and animal studies are needed to investigate the anti-depression effects of EXD and the underlying mechanisms and offer additional evidence and recommendations for its clinical application. Moreover, strategies must be developed to improve the quality control of EXD. This review provides an overview of EXD and guidance for future research direction.

BackgroundEpilepsy is one of the most common serious chronic neurological disorders, which can have a serious negative impact on individuals, families and society, and even death. With the increasing application of machine learning techniques in medicine in recent years, the integration of machine learning with epilepsy has received close attention, and machine learning has the potential to provide reliable and optimal performance for clinical diagnosis, prediction, and precision medicine in epilepsy through the use of various types of mathematical algorithms, and promises to make better parallel advances. However, no bibliometric assessment has been conducted to evaluate the scientific progress in this area. Therefore, this study aims to visually analyze the trend of the current state of research related to the application of machine learning in epilepsy through bibliometrics and visualization.MethodsRelevant articles and reviews were searched for 2004–2023 using Web of Science Core Collection database, and bibliometric analyses and visualizations were performed in VOSviewer, CiteSpace, and Bibliometrix (R-Tool of R-Studio).ResultsA total of 1,284 papers related to machine learning in epilepsy were retrieved from the Wo SCC database. The number of papers shows an increasing trend year by year. These papers were mainly from 1,957 organizations in 87 countries/regions, with the majority from the United States and China. The journal with the highest number of published papers is EPILEPSIA. Acharya, U. Rajendra (Ngee Ann Polytechnic, Singapore) is the authoritative author in the field and his paper “Deep Convolutional Neural Networks for Automated Detection and Diagnosis of Epileptic Seizures Using EEG Signals” was the most cited. Literature and keyword analysis shows that seizure prediction, epilepsy management and epilepsy neuroimaging are current research hotspots and developments.ConclusionsThis study is the first to use bibliometric methods to visualize and analyze research in areas related to the application of machine learning in epilepsy, revealing research trends and frontiers in the field. This information will provide a useful reference for epilepsy researchers focusing on machine learning.

Pneumococcal infections continue to pose a significant global health concern, necessitating the development of effective vaccines. Despite the progress shown by pneumococcal polysaccharide and conjugate vaccines, their limited coverage and the emergence of non-vaccine serotypes have highlighted the need for alternative approaches. Protein-based pneumococcal vaccines, targeting conserved surface proteins of Streptococcus pneumoniae, have emerged as a promising strategy. In this review, we provide an overview of the advancements made in the development of pneumococcal protein vaccines. We discuss the key protein vaccine candidates, highlight their vaccination results in animal studies, and explore the challenges and future directions in protein-based pneumococcal vaccine.

ObjectivesX-linked adrenoleukodystrophy (ALD) is a peroxisomal disease caused by mutations in the ABCD1 gene. Childhood cerebral ALD (CCALD) is characterized by inflammatory demyelination, rapidly progressing, often fatal. Hematopoietic stem cell transplant only delays disease progression in patients with early-stage cerebral ALD. Based on emergency humanitarianism, this study aims to investigate the safety and efficacy of sirolimus in the treatment of patients with CCALD.MethodsThis was a prospective, single-center, one-arm clinical trial. We enrolled patients with CCALD, and all enrolled patients received sirolimus treatment for three months. Adverse events were monitored and recorded to evaluate the safety. The efficacy was evaluated using the neurologic function scale (NFS), Loes score, and white matter hyperintensities.ResultsA total of 12 patients were included and all presented with CCALD. Four patients dropped out and a total of eight patients in the advanced stage completed a 3-month follow-up. There were no serious adverse events, and the common adverse events were hypertonia and oral ulcers. After sirolimus treatment, three of the four patients with an initial NFS > 10 showed improvements in their clinical symptoms. Loes scores decreased by 0.5–1 point in two of eight patients and remained unchanged in one patient. Analysis of white matter hyperintensities revealed a significant decrease in signal intensity (n = 7, p = 0.0156).ConclusionsOur study suggested that autophagy inducer sirolimus is safe for CCALD. Sirolimus did not improve clinical symptoms of patients with advanced CCALD significantly. Further study with larger sample size and longer follow-up is needed to confirm the drug efficacy.Clinical Trial registration:https://www.chictr.org.cn/historyversionpuben.aspx, identifier ChiCTR1900021288.

Studies of biogeographic patterns of fungi have long been behind those of plants and animals. The presence of worldwide species, the lack of systematic sampling design and adequate sampling effort, and the lack of research units are responsible for this status. This study investigates the biogeographical patterns of Arthrobotrys oligospora, the most widespread globally distributed nematode-trapping fungi (NTF), by stratified collecting and analyzing 2,250 samples from 228 sites in Yunnan Province, China. The A. oligospora was isolated, and 149 strains were subjected to ITS, TUB, TEF and RPB2 gene sequencing and multi-gene association phylogeographic analysis. The results show that at population level A. oligospora is randomly distributed throughout Yunnan Province and has no biogeographical distribution pattern. At the genetic level, the phylogenetic tree of A. oligospora diverges into five major evolutionary clades, with a low degree of gene flow between the five clades. However, the correlation between the phylogenetic diversity of A. oligospora and geographical factors was low. There was no clear pattern in the phylogenetic clades distribution of A. oligospora either without dividing the study unit or when the grid was used as the study unit. When watersheds were used as the study unit, 67.4%, 63.3%, 65.9%, 83.3%, and 66.7% of clade 1–5 strains were distributed in the Jinsha river, Red river, Peal river, Lancang river, and Nujiang-Irawaddy river watersheds, respectively. The clades distribution of A. oligospora was highly consistent with the watersheds distribution. Training predictions of the clades distributions using randomly generated polygons were also less accurate than watersheds. These results suggest that watersheds are key to discovering the biogeographic distribution patterns of A. oligospora. The A. oligospora populations are blocked by mountains in the watershed, and gene flow barriers have occurred, which may have resulted in the formation of multiple cryptic species. Watersheds are also ideal for understanding such speciation processes, explaining factors affecting biodiversity distribution and coupling studies of plant and animal and microbial diversity.

Dispersal is one of the key processes determining biodiversity. The passive sampling hypothesis, which emphasizes dispersal processes, suggests that larger habitats receive more species from the species pool as the main mechanism leading to more species in larger habitats than in smaller habitats (i.e., species-area relationships). However, the specific mechanisms by which dispersion shapes biodiversity still need to be discovered due to the difficulties of quantifying dispersal and the influence of multiple factors. Solving the above problem with a designed experiment is necessary to test the passive sampling hypothesis. This study designed a passive sampling experiment using sterile filter paper to quantify the microbial diffusion process, excluding the effects of pure sampling effects, habitat heterogeneity, and extinction processes. The results of high-throughput sequencing showed that a larger filter paper could receive more colonists, and the passive sampling hypothesis of SAR was confirmed. Dispersal shaped SAR by increasing species richness, especially rare species, and increasing the species replacement rate between habitats. These two processes are the mechanisms by which dispersal shapes biodiversity patterns. Compared with the results of this study, the commonly used mathematical model of passive sampling was able to predict the richness of non-rare species accurately but underestimated the richness of rare species. Underestimating rare species by mathematical models of passive sampling is more severe in small habitats. These findings provide new insights into the study of dispersal processes and the mechanism of species-area relationships.

ObjectiveTo investigate clinical characteristics, radiological features and biomarkers of pancreatic metastases of small cell lung carcinoma (PM-SCLC), and establish a convenient nomogram diagnostic predictive model to differentiate PM-SCLC from pancreatic ductal adenocarcinomas (PDAC) preoperatively.MethodsA total of 299 patients with meeting the criteria (PM-SCLC n=93; PDAC n=206) from January 2016 to March 2022 were retrospectively analyzed, including 249 patients from hospital 1 (training/internal validation cohort) and 50 patients from hospital 2 (external validation cohort). We searched for meaningful clinical characteristics, radiological features and biomarkers and determined the predictors through multivariable logistic regression analysis. Three models: clinical model, CT imaging model, and combined model, were developed for the diagnosis and prediction of PM-SCLC. Nomogram was constructed based on independent predictors. The receiver operating curve was undertaken to estimate the discrimination.ResultsSix independent predictors for PM-SCLC diagnosis in multivariate logistic regression analysis, including clinical symptoms, CA199, tumor size, parenchymal atrophy, vascular involvement and enhancement type. The nomogram diagnostic predictive model based on these six independent predictors showed the best performance, achieved the AUCs of the training cohort (n = 174), internal validation cohort (n = 75) and external validation cohort (n = 50) were 0.950 (95%CI, 0.917-0.976), 0.928 (95%CI, 0.873-0.971) and 0.976 (95%CI, 0.944-1.00) respectively. The model achieved 94.50% sensitivity, 83.20% specificity, 86.80% accuracy in the training cohort and 100.00% sensitivity, 80.40% specificity, 86.70% accuracy in the internal validation cohort and 100.00% sensitivity, 88.90% specificity, 87.50% accuracy in the external validation cohort.ConclusionWe proposed a noninvasive and convenient nomogram diagnostic predictive model based on clinical characteristics, radiological features and biomarkers to preoperatively differentiate PM-SCLC from PDAC.

BackgroundAmelioration of depression in patients with post-stroke depression (PSD) remains challenging.ObjectiveThe primary vision was to explore the effect of transcranial magnetic stimulation (TMS) in combination with citalopram on patients with PSD.MethodsOne hundred eligible patients who were diagnosed with PSD were recruited and randomly assigned to the control group (n = 50) or the TMS group (n = 50). The controls were given citalopram (10 mg/d for consecutive 8 weeks), while, in addition to citalopram, patients in the TMS group were also given TMS at 5 Hz once a workday for 8 weeks. The primary outcome was patient depression status as reflected by 17-item Hamilton Rating Scale for Depression (HAMD-17) score, and the secondary outcome was patient neuropsychological score determined by Mini-Mental State Examination (MMSE) and Wisconsin Card Sorting Test (WCST).ResultsPatients treated with TMS in combination with citalopram had a drastic decrease in HAMD-17 score during treatment. Bigger changes in HAMD-17 score between baseline and 2 weeks as well as between baseline and 8 weeks in the TMS group were observed (P < 0.01). Patients in both groups had increased MMSE scores after treatment. Data of WCST revealed patients with TMS treatment completed more categories (P < 0.01) and had a lower RPP in comparison to patients in the control group (P < 0.0001). Additionally, TMS in combination with citalopram strikingly improved patients' MMSE scores when compared with those taking citalopram alone. Last, there was no striking difference in side effects between the two groups (P > 0.05).ConclusionOur study found TMS in combination with citalopram is conducive to improving depression status and neuropsychological function, which holds great promise for treating PSD.

ObjectiveSCN1A, encoding the alpha 1 subunit of the sodium channel, is associated with a range of related epilepsy. This study aims to assess saliva and urine pH in children with SCN1A-related epilepsy.MethodsA prospective controlled observational study with a 1:1 ratio was conducted on seven patients with SCN1A-related epilepsy and seven healthy children of the same family, gender, and age but without a history of seizures. The pH of saliva and urine was measured by pH test paper. Parents of patients with epilepsy recorded seizures to compare the relationship between pH and seizures.ResultsThe fourteen participants were all males, aged 1 to 14 years. Seven patients had different pathogenic SCN1A variants. The pH of saliva and urine was monitored for 21–95 days. The pH of saliva and urine was higher in patients with SCN1A-related epilepsy than in the healthy group. The urine pH in Dravet syndrome patients was high compared with other epilepsy patients. The urine pH in patients with seizures was higher than that in patients without seizures, which occurred during the study.ConclusionsThe pH of saliva and urine was chronically high in patients with SCN1A-related epilepsy, and urine pH was higher in patients with seizures and with Dravet syndrome.

ObjectiveTo use structural magnetic resonance imaging (3D-MRI) to evaluate the abnormal development of the cerebral cortex in infants with global developmental delay (GDD).MethodsThe GDD group includes 67 infants aged between 112 and 699 days with global developmental delay and who underwent T1-weighted MRI scans in Shanxi Children's Hospital from December 2019 to March 2022. The healthy control (HC) group includes 135 normal developing infants aged between 88 and 725 days in Shanxi Children's Hospital from September 2020 to August 2021. Whole-brain T1-weighted MRI scans were carried out with a 3.0-T magnetic resonance scanner, which was later processed using InfantSurfer to perform MR image processing and cortical surface reconstruction. Two morphological features of the cortical surface of the 68 brain regions were computed, i.e., the cortical thickness (CT) and cortical surface area (SA), and compared between the GDD and HC groups.ResultsWith regard to the CT, the HC group showed a rapid decrease at first and then a slow increase after birth, and the CT of the GDD group decreased slowly and then became relatively stable. The GDD group showed bilaterally higher hemispherical average CT than those in the HC group. In detail, for the left hemisphere, except in the entorhinal and temporal poles in which the average CT values of the two brain regions were lower than those of the HC group, the CT of the 26 brain regions in the GDD group was higher than those of the HC group (p < 0.05). For the right hemisphere, the CT of the entorhinal in the GDD group was lower than that in the HC group. Otherwise, the CT of the remaining 28 brain regions was higher than those in the HC group (p < 0.05). With regard to the SA, both groups showed a rapid increase after birth till 23 months and remained quite stable afterward. The GDD group shows lower SA bilaterally than that in the HC group. In detail, SA in the GDD group was lower in most cortical regions of both hemispheres than in the HC group (p < 0.05), except for the right temporal pole and entorhinal. When testing for brain asymmetry, we found that the HC group showed obvious asymmetry of CT and SA, while only a few cortical regions in the GDD group showed asymmetry.

Streptococcus pyogenes is one of the main pathogenic bacteria that causes disease in humans. It is reported that over 18 million cases of S. pyogenes disease occurred in the world, and more than 500,000 deaths occur annually worldwide. An effective vaccine is widely regarded as the most reliable way to control and prevent streptococcal infections. However, there is currently no approved vaccine for S. pyogenes. In this study, we evaluated the potential of lipoprotein FtsB as a new vaccine candidate to prevent S. pyogenes infection. Mice vaccinated with purified FtsB protein elicited high titers of IgG, IgG1 and IgG2a antibodies in mouse serum. Vaccinated with FtsB can reduce bacterial systemic dissemination in the blood, heart, and spleen and reduce organ damage in the mouse bacteremia model. In addition, active immunization with FtsB protected against streptococcal abscess formation. Furthermore, immunization with FtsB was efficient in inducing a mixed cellular immune response and promoting the maturation of dendritic cells in mice. The lipoprotein HtsA was served as a positive control because it has been reported to protect mice from S. pyogenes infection in both active and passive immunization. These findings demonstrated that lipoprotein FtsB may serve as a candidate vaccine for the prevention of S. pyogenes infection.

In most bacteria, iron plays an important role in the survival of bacteria and the process of infection to the host. Streptococcus pneumoniae (S. pneumoniae) evolved three iron transporters (i.e., PiaABC, PiuABC, and PitABC) responsible for the transportation of three kinds of iron (i.e., ferrichrome, hemin, and ferric ion). Our previous study showed that both mRNA and protein levels of SPD_0090 were significantly upregulated in the ΔpiuA/ΔpiaA/ΔpitA triple mutant, but its detailed biological function is unknown. In this study, we constructed spd_0090 knockout and complement strain and found that the deletion of spd_0090 hinders bacterial growth. SPD_0090 is located on the cell membrane and affects the hemin utilization ability of S. pneumoniae. The cell infection model showed that the knockout strain had stronger invasion and adhesion ability. Notably, knockout of the spd_0090 gene resulted in an enhanced infection ability of S. pneumoniae in mice by increasing the expression of virulence factors. Furthermore, iTRAQ quantitative proteomics studies showed that the knockout of spd_0090 inhibited carbon metabolism and thus suppressed bacterial growth. Our study showed that SPD_0090 negatively regulates the virulence of S. pneumoniae.

Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children.Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-μg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 μg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 μg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 μg and 100 μg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3.Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 μg, whereas the Fabs was tolerated to only 28.9%–32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%–89.0%. A severe adverse event was found in Part 2. In Part 3 (100 μg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly.Conclusion: Using the optimized nasal spray method, a single dose of 20/100 μg of the test drug was safe and tolerable, and 100 μg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value.

Pathogenic streptococcal species are responsible for a broad spectrum of human diseases ranging from non-invasive and localized infections to more aggressive and life-threatening diseases, which cause great economic losses worldwide. Streptococci possess a dozen two-component systems (TCSs) that play important roles in the response to different environmental changes and adjust the expression of multiple genes to successfully colonize and infect host cells. In this review, we discuss the progress in the study of a conserved TCS named CiaRH in pathogenic or opportunistic streptococci including Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus mutans, Streptococcus gordonii, Streptococcus sanguinis, and Streptococcus suis, focusing on the function and regulatory networks of CiaRH, which will provide a promising strategy for the exploration of novel antistreptococcal therapies. This review highlights the important role of CiaRH and provides an important basis for the development of antistreptococcal drugs and vaccines.

Objectives: The aim of this research was to investigate the clinical and microbiological characteristics of a case of community-acquired carbapenem-resistant Escherichia coli isolated from a patient with a bloodstream infection in China.Methods:Escherichia coli Huamei202001 was recovered from the first blood culture from a patient hospitalised in China. An antimicrobial susceptibility test was performed, and the genome was sequenced on an Illumina HiSeq X 10 platform with a 150-bp paired-end approach. The generated sequence reads were assembled using Unicycler, and the whole genome sequence data were analysed using bioinformatics tools. Moreover, the patient and her main family members obtained a faecal sample screening test for CRE, the positive strain was further isolated and the identification and antimicrobial susceptibility testing was performed.Results:Escherichia coli Huamei202001 belonged to sequence type 410. In addition, a blaNDM-5-encoding IncX3-type plasmid was responsible for the spreading of carbapenem resistance. Only the patient was detected as having a positive faecal sample screening test for CRE. Strain Fec01 was identified as E. coli, and the antibiotic susceptibility profile was the same as that of E. coli Huamei202001.Conclusions:Escherichia coli Huamei202001 is defined as community-acquired carbapenem-resistant Enterobacteriaceae. The clone ST410 that harbours the blaNDM-5-encoding IncX3-type plasmid is causing new high-risk clones globally. Thus, infection control measures should be strengthened to curb the dissemination of IncX3.

In most bacteria, iron plays a vital role in pathogenesis processes. To support survival and infection, Streptococcus pneumoniae has evolved three ABC transporters, PiaABC, PiuABC, and PitABC. Moreover, indirect evidence supports that operon 804 may be a novel ABC transporter in S. pneumoniae. We have recently described the identification of lipoprotein SPD_1609 in operon 804; however, whether the SPD_1609 protein affects the virulence of S. pneumoniae has not yet been studied. In the present work, alignment analysis showed that lipoprotein SPD_1609 is conserved in a variety of gram-positive bacteria, and deletion of the spd_1609 gene led to a reduction in adherence and invasion of S. pneumoniae to host cells. RT-qPCR assays indicated that deletion of the spd_1609 gene resulted in decreased expression of genes involved in colonization. Furthermore, decreased virulence in a mouse bacteremia infection model caused by the loss of the lipoprotein encoded by spd_1609 was also demonstrated. Overall, these data provide insights into the functional role of lipoprotein SPD_1609 in pneumococcal pathogenesis, suggesting its possibility to be developed as a novel S. pneumoniae vaccine candidate.

The NLRP3 inflammasome, a multiprotein cytosolic complex that activates the IL-1 family of cytokines, plays an important role in atherosclerosis (AS). High-sensitivity c-reactive protein (hs-CRP) is widely recognized as a major cardiovascular risk predictor and recent studies name NLRP3 as a predictor of CRP levels. Mounting evidence has indicated that subendothelial retention of apolipoprotein B100-containing lipoproteins, such as low-density lipoprotein (LDL), is the initial step of atherogenesis, and is usually termed the “response to retention hypothesis.” We previously reported that CRP promotes AS by directly increasing LDL transcytosis across endothelial cells (ECs). The present study aims to investigate the effects of CRP on NLRP3 inflammasome activation and the role of the NLRP3 inflammasome in CRP-induced LDL transcytosis. We found that CRP upregulated NF-κB activity, the NF-κB inhibitor (BAY-11-7082) and Fcγ receptors (FcγRs) inhibitor (CD32/64Ab) blocked CRP-induced NF-κB activation. CRP also induced expression of pro-IL-1β and NLRP3, while BAY and CD32/64 Ab suppressed CRP-mediated expression of NLRP3 and pro-IL-1β. Moreover, CRP activated the NLRP3 inflammasome in ECs. NADPH oxidase inhibitor, diphenylene iodonium (DPI) and dithiothreitol (DTT), a broad-spectrum P2 receptor inhibitor, oxidized ATP (oATP), and a broad inhibitor of cysteine proteases, E-64d, inhibited CRP-induced NLRP3 inflammasome activation. Furthermore, NLRP3 siRNA and caspase-1 inhibitor blocked CRP-mediated LDL transcytosis across ECs. In conclusion, NLRP3 inflammasome activation was shown to be involved in CRP-mediated LDL transcytosis across ECs. CRP not only increased the expression of pro-IL-1β and NLRP3 via the FcγRs/NF-κB pathway, but also promoted NLRP3 inflammasome activation and IL-1β maturation by upregulation of reactive oxygen species (ROS) levels, purinergic receptor signaling, and activation of cysteine proteases.

Streptococcus pneumoniae (S.pneumoniae) is a major human pathogen causing morbidity and mortality worldwide. Efficiently acquiring iron from the environment is critical for S. pneumoniae to sustain growth and cause infection. There are only three known iron-uptake systems in Streptococcal species responsible for iron acquisition from the host, including ABC transporters PiaABC, PiuABC, and PitABC. Besides, no other iron-transporting system has been suggested. In this work, we employed our newly established translating mRNA analysis integrated with proteomics to evaluate the possible existence of novel iron transporters in the bacterium. We simultaneously deleted the iron-binding protein genes of the three iron-uptake systems to construct a piaA/piuA/pitA triple mutant (Tri-Mut) of S. pneumoniae D39, in which genes and proteins related to iron transport should be regulated in response to the deletion. With ribosome associated mRNA sequencing-based translatomics focusing on translating mRNA and iTRAQ quantitative proteomics based on the covalent labeling of peptides with tags of varying mass, we indeed observed a large number of genes and proteins representing various coordinated biological pathways with significantly altered expression levels in the Tri-Mut mutant. Highlighted in this observation is the identification of several new potential iron-uptake ABC transporters participating in iron metabolism of Streptococcus. In particular, putative protein SPD_1609 in operon 804 was verified to be a novel iron-binding protein with similar function to PitA in S. pneumoniae. These data derived from the integrative translatomics and proteomics analyses provided rich information and insightful clues for further investigations on iron-transporting mechanism in bacteria and the interplay between Streptococcal iron availability and the biological metabolic pathways. [ABSTRACT FROM AUTHOR]