Study on fermentation preparation, physicochemical properties and biological activity of carboxymethylpachymaran with different degrees of substitution.

BACKGROUND: Carboxymethylpachymaran (CMP) is created by carboxymethylating pachyman (PM), which increases its water solubility and enhances a number of biological activities. Traditional polysaccharides modified by carboxymethylation employ strong chemical techniques. Carboxymethylcellulose (CMC) has been used previously for liquid fermentation to carboxymethyl modify bacterial polysaccharides. This theory can be applied to fungal polysaccharides because Poria cocos has the ability to naturally utilize cellulose. RESULTS: CMC with different degrees of substitution (DS) (0.7, 0.9 and 1.2) were added to P. cocos fermentation medium, and CMPs with different DS (0.38, 0.56 and 0.78, respectively) were prepared by liquid fermentation. The physical and chemical properties and biological activities of the CMPs were determined. Their structures were confirmed by Fourier transform infrared (FTIR) spectroscopy and monosaccharide composition. With the increase of DS, the viscosity and viscosity-average molecular weight of CMPs decreased, whereas polysaccharide content and water solubility increased, although the triple helix structure was not affected. The results of bioactivity assay showed that the higher the DS of CMPs, the higher the 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability, and the stronger the bacterial inhibition ability. CONCLUSION: The present study has developed a method for producing CMPs by P. cocos liquid fermentation. The results of the study confirm that enhancing the DS of CMP could effectively enhance its potential biological activity. The findings provide safe and reliable raw materials for creating CMP-related foods and encourage CMP application in the functional food industry. © 2024 Society of Chemical Industry.

Acupuncture for rheumatoid vasculitis complicated by refractory foot ulcer: A case report.

INTRODUCTION: Rheumatoid vasculitis (RV) is a frequently encountered complication of rheumatoid arthritis (RA), wherein skin vasculitis lesions are observed as a common clinical manifestation, encompassing skin purpura, erythema, vascular occlusion, ulcers, and gangrene. As a matter of fact, it marks the most severe extra-articular manifestation of RA. And the resultant ulcers tend to pose a greater challenge with regard to therapeutic interventions. We report a case of RV complicated by refractory foot ulcer that was successfully treated with puncture. CASE PRESENTATION: A 62-year-old man with RV caused by RA developed refractory foot ulcers. Despite the application of topical antibiotics, the wound gradually expanded and remained unhealed for 7 months. Consequently, the patient sought an integrated therapeutic approach involving Traditional Chinese Medicine and was subsequently treated with acupuncture. After 12 weeks of acupuncture, the foot ulcers healed completely. CONCLUSION: Acupuncture has the potential to facilitate wound healing and may serve as a viable alternative treatment modality for wounds unresponsive to traditional therapeutic interventions.

Knowledge mapping of extracellular vesicles in wound healing: A bibliometric analysis (2002-2022).

Extracellular vesicles in wound healing have become an active research field with substantial value and potential. Nevertheless, there are few bibliometric studies in this field. We aimed to visualise the research hot spots and trends of extracellular vesicles in wound healing using a bibliometric analysis to help understand the future development of basic and clinical research. The articles and reviews regarding extracellular vesicles in the wound healing were selected from the Web of Science Core Collection. VOSviewers, CiteSpace and R package "bibliometric" were used to conduct this bibliometric analysis. A total of 1225 articles from 56 countries led by China and the United States were included. The number of publications related to extracellular vesicles increased year by year. Shanghai Jiaotong University, Huazhong University of Science and Technology, Sun Yat-sen University and Central South University are the main research institutions. International Journal of Molecular Sciences is the most popular journal in this field, while Stem Cell Research & Therapy is the most frequently cited journal. These papers come from 7546 authors, among which Zhang Wei has published the most papers and Zhang Bin has the most cocited papers. The research on the treatment strategy of extracellular vesicles in the process of wound healing is the main topic in this field. "exosomes", "miRNA", "angiogenesis", "regenerative medicine", "inflammation" and "diabetic wound" are the main key words of emerging research hotspots. This is the first bibliometric study, which comprehensively summarises the research trend and development of extracellular vesicles and exocrine bodies in wound healing. These informations determine the latest research frontiers and hot directions, and provide reference for the study of extracellular vesicles and exosomes.

Gastrointestinal digestion, probiotic fermentation behaviors and immunomodulatory effects of polysaccharides from Sanghuangporus vaninii.

In this study, the crude polysaccharides (CSVP) and the preliminary purified polysaccharides (PSVP) from Sanghuangporus vaninii were obtained. The physicochemical properties, gastrointestinal digestion, and probiotic fermentation behaviors of CSVP and PSVP as well as the immunomodulatory effects of PSVP in cyclophosphamide-treated mice were investigated. The results showed that PSVP had higher total polysaccharides content and solubility, but lower radical scavenging activity than CSVP. Moreover, PSVP showed lower hydrolysis degree and better probiotic effects than CSVP. In immunosuppression mice model, PSVP supplement increased the body weight, spleen and thymus index, improved the release of cytokines IFN-γ, immunoglobulins IgM and IgG, and enhanced the lysozyme activity. Moreover, PSVP supplement significantly prevented the oxidative stress in vivo, increased the level of beneficial gut microbiota, especially Bacteroidaceae and Lactobscillsceae, as well as the content of short-chain fatty acids (SCFAs). These results indicated that PSVP could recover the immune response in cyclophosphamide-treated mice by regulating gut microbiota and intestinal barrier. The findings will lay a theoretical foundation for equitable utilization of S. vaninii resources as well as the product development.

Myotubularin functions through actomyosin to interact with the Hippo pathway.

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size by integrating diverse regulatory inputs, including actomyosin-mediated cytoskeletal tension. Despite established connections between the actomyosin cytoskeleton and the Hippo pathway, the upstream regulation of actomyosin in the Hippo pathway is less defined. Here, we identify the phosphoinositide-3-phosphatase Myotubularin (Mtm) as a novel upstream regulator of actomyosin that functions synergistically with the Hippo pathway during growth control. Mechanistically, Mtm regulates membrane phospholipid PI(3)P dynamics, which, in turn, modulates actomyosin activity through Rab11-mediated vesicular trafficking. We reveal PI(3)P dynamics as a novel mode of upstream regulation of actomyosin and establish Rab11-mediated vesicular trafficking as a functional link between membrane lipid dynamics and actomyosin activation in the context of growth control. Our study also shows that MTMR2, the human counterpart of Drosophila Mtm, has conserved functions in regulating actomyosin activity and tissue growth, providing new insights into the molecular basis of MTMR2-related peripheral nerve myelination and human disorders.

Zinc-Responsive Regulator Zur Regulates Zinc Homeostasis, Secondary Metabolism, and Morphological Differentiation in Streptomyces avermitilis.

Zinc is an essential cofactor for many metal enzymes and transcription regulators. Zn2+ availability has long been known to affect antibiotic production and morphological differentiation of Streptomyces species. However, the molecular mechanism whereby zinc regulates these processes remains unclear. We investigated the regulatory roles of the zinc-sensing regulator Zur in Streptomyces avermitilis. Our findings demonstrate that Zur plays an essential role in maintaining zinc homeostasis by repressing the expression of the zinc uptake system ZnuACB and alternative non-zinc-binding ribosomal proteins and promoting the expression of zinc exporter ZitB. Deletion of the zur gene resulted in decreased production of avermectin and oligomycin and delayed morphological differentiation, and these parameters were restored close to wild-type levels in a zur-complemented strain. Zur bound specifically to Zur box in the promoter regions of avermectin pathway-specific activator gene aveR, oligomycin polyketide synthase gene olmA1, and filipin biosynthetic pathway-specific regulatory genes pteR and pteF. Analyses by reverse transcription quantitative PCR and luciferase reporter systems indicated that Zur directly activates the transcription of these genes, i.e., that Zur directly activates biosynthesis of avermectin and oligomycin. Zur positively regulated morphological development by repressing the transcription of differentiation-related genes ssgB and minD2. Our findings, taken together, demonstrate that Zur in S. avermitilis directly controls zinc homeostasis, biosynthesis of avermectin and oligomycin, and morphological differentiation. IMPORTANCE Biosynthesis of secondary metabolites and morphological differentiation in bacteria are affected by environmental signals. The molecular mechanisms whereby zinc availability affects secondary metabolism and morphological differentiation remain poorly understood. We identified several new target genes of the zinc response regulator Zur in Streptomyces avermitilis, the industrial producer of avermectin. Zur was found to directly and positively control avermectin production, oligomycin production, and morphological differentiation in response to extracellular Zn2+ levels. Our findings clarify the regulatory functions of Zur in Streptomyces, which involve linking environmental Zn2+ status with control of antibiotic biosynthetic pathways and morphological differentiation.

Sleep quality and its influencing factors in senior high school students / 中国学校卫生

Objective@#To study the current situation of sleep quality of senior high school students and analyze the influencing factors, so as to provide a reference for targeted sleep quality improvement of high school students.@*Methods@#A total of 4 793 senior high school students of different grades were recruited from four different regions (Shanghai, Qinghai, Macao, Henan) in 2020. The information of demographic, sleep status, mental factors, living habits and other information were collected by questionnaire. Descriptive statistics and Logistic regression were used to analyze sleep quality and its influencing factors of the senior high school students.@*Results@#About 24.2% of senior high school students reported sleep problems and 71.4% slept less than 7 hours at night. Interpersonal sensitivity, depression, anxiety symptoms, learning, family and interpersonal stress had significant effects on sleep problems in senior high school students( χ 2=1 147.98, 1 228.35, 1 032.54, 371.05, 497.61, 475.39, P <0.01). Drinking coffee and tea, drinking alcohol, smoking (including secondhand smoke), long term use of electronic products, late sleep, bedtime diet, poor sleep environment, parents with sleep problems were the risk factors for sleep disorders of senior high school students, regular exercise was the protective factors for sleep disorders of senior high school students, the influence was significant ( χ 2=160.28, 127.73 , 108.02, 113.27, 470.91, 340.95, 72.02, 155.53, 116.30, 76.96, 28.75, 12.89, P <0.05).@*Conclusion@#The sleep quality of senior high school students needs to be improved. Schools and parents should pay attention to the mental health and living habits of senior high school students to help them improve their sleep quality and grow up smoothly.

An investigation of the intention and reasons of senior high school students in China to choose medical school.

BACKGROUND: Shortages of qualified health workers have been a global concern, especially in developing countries. China also faces this dilemma, which hinders the development of public health services. Senior high school students are a group who are considering their college majors and careers after graduation. They are also a potential and basic talent reserve for the health sector. This survey focused on senior high school students' intention to learn clinical medicine and explored potential influencing factors. METHODS: An anonymous questionnaire containing 20 items was distributed to 5344 senior high school students. The questions covered the following topics: students' intention to learn clinical medicine, personal and family information, understanding of medical education, cognition of doctors' working conditions, and doctor-patient relationships. Logistic regression and the chi-square test were used to compare students with and without a clear intention to learn clinical medicine to explore influencing factors. RESULTS: Only 5.6% of senior high school students had a clear intention to learn medicine (CILCM). Personal and family information had distinct impacts. Interest and anatomy course were also associated with students' choice. There was a positive correlation between understanding of medical education and students' intention Meanwhile, students' cognition of doctors, career prospects, and social status had significant impacts. The more optimistic students were about doctors' working conditions and doctor-patient relationships, the more likely they were to have a CILCM. CONCLUSION: To some extent, this survey reflects the shortage of medical talent in China and provides possible clues for solving this problem. In addition, these findings may provide a perspective for understanding the development of health services in developing countries.

Early evaluation of treatment response to transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The role of dynamic three-dimensional contrast-enhanced ultrasound.

BACKGROUND: Dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) with quantitative analysis is available in recent years. It can reduce the quantitative sampling error caused by the inconsistency of different sections in order to evaluate local treatment response of hepatocellular carcinoma (HCC) accurately. OBJECTIVE: To investigate the value of dynamic 3D-CEUS in evaluating the early response to transarterial chemoembolization (TACE) treatment in patients with advanced HCC lesions. METHODS: In this prospective study, both two-dimensional (2D) CEUS and dynamic 3D-CEUS were performed on 40 HCC patients who scheduled for TACE at baseline (T0) and 1-3 days (T1) after treatment. Tumor microvascular perfusion changes were assessed by CEUS time-intensity curve (TIC) and quantitative parameters. According to contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging 1 month after treatment results, patients were divided into responders and non-responders groups. The changes of perfusion parameters of both 2D-CEUS and 3D-CEUS were compared between responders and non-responders groups before and after TACE treatment. RESULTS: Before and after TACE treatment, no significant difference in maximum diameter of HCC lesions between the two groups could be found. There were more significant differences and ratios of perfusion parameters in 3D-CEUS quantitative analysis than in 2D-CEUS. The mutual significant differences and ratios of 2D-CEUS and 3D-CEUS included peak intensity (PI) difference, PI ratio, ratio of area under the curve (A), ratio of area under the wash-out part (AWO) and slope (S) difference. The former 4 corresponding parameters were better on 3D-CEUS than on 2D-CEUS. CONCLUSION: Dynamic 3D-CEUS can be used as a potential imaging method to evaluate early treatment response to TACE in advanced HCC patients.

SufR, a [4Fe-4S] Cluster-Containing Transcription Factor, Represses the sufRBDCSU Operon in Streptomyces avermitilis Iron-Sulfur Cluster Assembly.

Iron-sulfur (Fe-S) clusters are ubiquitous and versatile inorganic cofactors that are crucial for many fundamental bioprocesses in nearly all organisms. How cells maintain Fe-S cluster homeostasis is not well understood in Gram-positive bacteria. Genomic analysis showed that the Suf system, which is encoded by the sufRBDCSU operon, is the sole Fe-S cluster assembly system in the genus StreptomycesStreptomyces avermitilis is the industrial producer of avermectins, which are widely used as agricultural pesticides and antiparasitic agents. sufR (SAV6324) encodes a putative ArsR-family transcriptional regulator, which was characterized as a repressor of the sufRBDCSU operon in this investigation. Spectroscopy and mass spectrometry demonstrated that anaerobically isolated SufR contained an oxidation-sensitive [4Fe-4S] cluster and existed as a homodimer. Electrophoretic mobility shift assays (EMSAs) and DNase I footprinting analyses revealed that [4Fe-4S]-SufR bound specifically and tightly to a 14-bp palindromic sequence (CAAC-N6-GTTG) in the promoter region of the sufR operon, repressing expression of the sufRBDCSU operon. The presence of the [4Fe-4S] cluster is critical for the DNA-binding activity of SufR. Cys182, Cys195, and Cys223 in the C-terminal region of SufR are essential for [4Fe-4S] cluster coordination, but Cys178 is not. The fourth non-Cys ligand in coordination of the [4Fe-4S] cluster for SufR remains to be identified. The findings clarify the transcriptional control of the suf operon by [4Fe-4S] SufR to satisfy the various Fe-S cluster demands. SufR senses the intracellular Fe-S cluster status and modulates the expression of the sole Fe-S cluster assembly system via its Fe-S cluster occupancy.IMPORTANCE Fe-S clusters function as cofactors of proteins controlling diverse biological processes, such as respiration, photosynthesis, nitrogen fixation, DNA replication, and gene regulation. The mechanism of how Actinobacteria regulate the expression of the sole Fe-S cluster assembly system in response to the various Fe-S cluster demands remains to be elucidated. In this study, we showed that SufR functions as a transcriptional repressor of the sole Fe-S cluster assembly system in the avermectin producer S. avermitilis [4Fe-4S]-SufR binds to the promoter region of the suf operon and represses its expression. When Fe-S cluster levels are insufficient, SufR loses its [4Fe-4S] cluster and DNA-binding activity. Apo-SufR dissociates from the promoter region of suf operon, and the expression of the suf system is strongly increased by derepression to promote the synthesis of Fe-S clusters. The study clarifies how Streptomyces maintains its Fe-S cluster homeostasis through the activity of SufR to modulate the various Fe-S cluster demands.

AccR, a TetR Family Transcriptional Repressor, Coordinates Short-Chain Acyl Coenzyme A Homeostasis in Streptomyces avermitilis.

Malonyl coenzyme A (malonyl-CoA) and methylmalonyl-CoA are the most common extender units for the biosynthesis of fatty acids and polyketides in Streptomyces, an industrially important producer of polyketides. Carboxylation of acetyl- and propionyl-CoAs is an essential source of malonyl- and methylmalonyl-CoAs; therefore, acyl-CoA carboxylases (ACCases) play key roles in primary and secondary metabolism. The regulation of the expression of ACCases in Streptomyces spp. has not been investigated previously. We characterized a TetR family transcriptional repressor, AccR, that mediates intracellular acetyl-, propionyl-, methylcrotonyl-, malonyl-, and methylmalonyl-CoA levels by controlling the transcription of genes that encode the main ACCase and enzymes associated with branched-chain amino acid metabolism in S. avermitilis AccR bound to a 16-nucleotide palindromic binding motif (GTTAA-N6-TTAAC) in promoter regions and repressed the transcription of the accD1A1-hmgL-fadE4 operon, echA8, echA9, and fadE2, which are involved in the production and assimilation of acetyl- and propionyl-CoAs. Methylcrotonyl-, propionyl-, and acetyl-CoAs acted as effectors to release AccR from its target DNA, resulting in enhanced transcription of target genes by derepression. The affinity of methylcrotonyl- and propionyl-CoAs to AccR was stronger than that of acetyl-CoA. Deletion of accR resulted in increased concentrations of short-chain acyl-CoAs (acetyl-, propionyl-, malonyl-, and methylmalonyl-CoAs), leading to enhanced avermectin production. Avermectin production was increased by 14.5% in an accR deletion mutant of the industrial high-yield strain S. avermitilis A8. Our findings clarify the regulatory mechanisms that maintain the homeostasis of short-chain acyl-CoAs in StreptomycesIMPORTANCE Acyl-CoA carboxylases play key roles in primary and secondary metabolism. However, the regulation of ACCase genes transcription in Streptomyces spp. remains unclear. Here, we demonstrated that AccR responded to intracellular acetyl-, propionyl-, and methylcrotonyl-CoA availability and mediated transcription of the genes related to production and assimilation of these compounds in S. avermitilis When intracellular concentrations of these compounds are low, AccR binds to target genes and represses their transcription, resulting in low production of malonyl- and methylmalonyl-CoAs. When intracellular acetyl-, propionyl-, and methylcrotonyl-CoA concentrations are high, these compounds bind to AccR to dissociate AccR from target DNA, promoting the conversion of these compounds to malonyl- and methylmalonyl-CoAs. This investigation revealed how AccR coordinates short-chain acyl-CoA homeostasis in Streptomyces.

AveI, an AtrA homolog of Streptomyces avermitilis, controls avermectin and oligomycin production, melanogenesis, and morphological differentiation.

Streptomyces avermitilis is well known as the producer of anthelmintic agent avermectins, which are widely used in agriculture, veterinary medicine, and human medicine. aveI encodes a TetR-family regulator, which is the homolog of AtrA. It was reported that deletion of aveI caused enhanced avermectin production. In this study, we investigated the regulatory function of the AveI in S. avermitilis. By binding to the 15-nt palindromic sequence in the promoter regions, AveI directly regulates at least 35 genes. AveI represses avermectin production by directly regulating the transcription of the cluster-situated regulator gene aveR and structural genes aveA1, aveA3, and aveD. AveI represses oligomycin production by repressing the CSR gene olmRII and structural genes olmC. AveI activates melanin biosynthesis by activating the expression of melC1C2 operon. AveI activates morphological differentiation by activating the expression of ssgR and ssgD genes, repressing the expression of wblI gene. Besides, AveI regulates many genes involved in primary metabolism, including substrates transport, the metabolism of amino acids, lipids, and carbohydrates. Therefore, AveI functions as a global regulator in S. avermitilis, controls not only secondary metabolism and morphological differentiation, but also primary metabolism.

Altered Small-World Networks in First-Episode Schizophrenia Patients during Cool Executive Function Task.

At present, little is known about brain functional connectivity and its small-world topologic properties in first-episode schizophrenia (SZ) patients during cool executive function task. In this paper, the Trail Making Test-B (TMT-B) task was used to evaluate the cool executive function of first-episode SZ patients and electroencephalography (EEG) data were recorded from 14 first-episode SZ patients and 14 healthy controls during this cool executive function task. Brain functional connectivity between all pairs of EEG channels was constructed based on mutual information (MI) analysis. The constructed brain functional networks were filtered by three thresholding schemes: absolute threshold, mean degree, and a novel data-driven scheme based on orthogonal minimal spanning trees (OMST), and graph theory was then used to study the topographical characteristics of the filtered brain graphs. Results indicated that the graph theoretical measures of the theta band showed obvious difference between SZ patients and healthy controls. In the theta band, the characteristic path length was significantly longer and the cluster coefficient was significantly smaller in the SZ patients for a wide range of absolute threshold T. However, the cluster coefficient showed no significant changes, and the characteristic path length was still significantly longer in SZ patients when calculated as a function of mean degree K. Interestingly, we also found that only the characteristic path length was significantly longer in SZ patients compared with healthy controls after using the OMST scheme. Pearson correlation analysis showed that the characteristic path length was positively correlated with executive time of TMT-B for the combined SZ patients and healthy controls (r = 0.507, P = 0.006), but not for SZ patients alone (r = 0.072, P = 0.612). The above results suggested a less optimal organization of the brain network and could be useful for understanding the pathophysiologic mechanisms underlying cool executive dysfunction in first-episode SZ patients.

IdeR, a DtxR Family Iron Response Regulator, Controls Iron Homeostasis, Morphological Differentiation, Secondary Metabolism, and the Oxidative Stress Response in Streptomyces avermitilis.

Iron, an essential element for microorganisms, functions as a vital cofactor in a wide variety of key metabolic processes. On the other hand, excess iron may have toxic effects on bacteria by catalyzing the formation of reactive oxygen species through the Fenton reaction. The prevention of iron toxicity requires the precise control of intracellular iron levels in bacteria. Mechanisms of iron homeostasis in the genus Streptomyces (the producers of various antibiotics) are poorly understood. Streptomyces avermitilis is the industrial producer of avermectins, which are potent anthelmintic agents widely used in medicine, agriculture, and animal husbandry. We investigated the regulatory role of IdeR, a DtxR family regulator, in S. avermitilis In the presence of iron, IdeR binds to a specific palindromic consensus sequence in promoters and regulates 14 targets involved in iron metabolism (e.g., iron acquisition, iron storage, heme metabolism, and Fe-S assembly). IdeR also directly regulates 12 targets involved in other biological processes, including morphological differentiation, secondary metabolism, carbohydrate metabolism, and the tricarboxylic acid (TCA) cycle. ideR transcription is positively regulated by the peroxide-sensing transcriptional regulator OxyR. A newly constructed ideR deletion mutant (DideR) was found to be less responsive to iron levels and more sensitive to H2O2 treatment than the wild-type strain, indicating that ideR is essential for oxidative stress responses. Our findings, taken together, demonstrate that IdeR plays a pleiotropic role in the overall coordination of metabolism in Streptomyces spp. in response to iron levels.IMPORTANCE Iron is essential to almost all organisms, but in the presence of oxygen, iron is both poorly available and potentially toxic. Streptomyces species are predominantly present in soil where the environment is complex and fluctuating. So far, the mechanism of iron homeostasis in Streptomyces spp. remains to be elucidated. Here, we characterized the regulatory role of IdeR in the avermectin-producing organism S. avermitilis IdeR maintains intracellular iron levels by regulating genes involved in iron absorption and storage. IdeR also directly regulates morphological differentiation, secondary metabolism, and central metabolism. ideR is under the positive control of OxyR and is indispensable for an efficient response to oxidative stress. This investigation uncovered that IdeR acts as a global regulator coordinating iron homeostasis, morphological differentiation, secondary metabolism, and oxidative stress response in Streptomyces species. Elucidation of the pleiotropic regulation function of IdeR provides new insights into the mechanisms of how Streptomyces spp. adapt to the complex environment.

Redox-sensing regulator Rex regulates aerobic metabolism, morphological differentiation, and avermectin production in Streptomyces avermitilis.

The regulatory role of redox-sensing regulator Rex was investigated in Streptomyces avermitilis. Eleven genes/operons were demonstrated to be directly regulated by Rex; these genes/operons are involved in aerobic metabolism, morphological differentiation, and secondary metabolism. Rex represses transcription of target genes/operons by binding to Rex operator (ROP) sequences in the promoter regions. NADH reduces DNA-binding activity of Rex to target promoters, while NAD+ competitively binds to Rex and modulates its DNA-binding activity. Rex plays an essential regulatory role in aerobic metabolism by controlling expression of the respiratory genes atpIBEFHAGDC, cydA1B1CD, nuoA1-N1, rex-hemAC1DB, hppA, and ndh2. Rex also regulates morphological differentiation by repressing expression of wblE, which encodes a putative WhiB-family transcriptional regulator. A rex-deletion mutant (Drex) showed higher avermectin production than the wild-type strain ATCC31267, and was more tolerant of oxygen limitation conditions in regard to avermectin production.

OxyR is a key regulator in response to oxidative stress in Streptomyces avermitilis.

The role of the H2O2-sensing transcriptional regulator OxyR in oxidative stress responses in Streptomyces avermitilis was investigated. An oxyR deletion mutant was more sensitive to H2O2 and tert-butyl hydroperoxide than was the WT strain, indicating that OxyR mediates the defensive system against H2O2 and organic peroxide. Evidence presented herein suggests that in cells treated with exogenous H2O2, the oxidized form of OxyR activated expression of ahpCD by binding to a palindromic sequence of the promoter region. Oxidized OxyR also induced expression of other antioxidant enzymes (KatA1, KatA2, KatA3 and OhrB1) and oxidative stress regulators (CatR, OhrR and σR). The thiol-oxidative stress regulator gene sigR was regulated at the transcription level by OxyR. We conclude that OxyR is necessary to activate transcription of sigR from the σR-dependent promoter to express an unstable larger isoform of σR during oxidative stress. In response to oxidative stress, OxyR facilitates rapid production of H2O2-scavenging enzymes to repair oxidative damage through direct regulation and cascaded regulation of CatR, OhrR and σR.