Multi-genome evolutionary study of the ABC1 gene family and identification of the pleiotropic effects of OsABC1-13 in rice development

In four rice genomes,85 ABC1-family genes were identified by comparative genomics,evolution,genetics,and physiology.One,OsABC1-13,was shown by knockdown and knockout experiments to affect plant height,grain size,and photosynthetic capability.

Detecting the distribution of and public attitudes to charismatic alien species based on media coverage

Charismatic species are often reported by the media,providing information for detecting population status and public perception.To identify the number and distribution of free-living Black Swan(Cygnus atratus),a charismatic alien species in Chinese mainland and to detect the public and the media attitudes to the species,we analyzed the reports and emotional tendency from media coverage in 2000-2022 using manual reading,crawler extraction and latent Dirichlet allocation.A total of 6654 Black Swans were reported at 711 sites,including 147 individuals at 30 nature reserves.Successful breeding was reported at one-fourth of the total sites,including five nature reserves.The proportion of positive emotional tendency to Black Swans was overwhelming in the reports and was higher than that to alien species in general,suggesting that the public and the media are unaware of the risk of biological invasion.Effective management of invasive species requires the media clarifies the invasion risk of charismatic alien species.Promoting the unity between the harmfulness of abstract concept of alien species and the charisma of a specific alien species among the public help effective management.

Individual consistency in spatiotemporal characteristics of migratory Whimbrels in the East Asian-Australasian Flyway

Many migratory birds exhibit interannual consistency in migration schedules,routes and stopover sites.Detecting the interannual consistency in spatiotemporal characteristics helps understand the maintenance of migration and enables the implementation of targeted conservation measures.We tracked the migration of Whimbrel(Numenius phaeopus)in the East Asian-Australasian Flyway and collected spatiotemporal data from individuals that were tracked for at least two years.Wilcoxon non-parametric tests were used to compare the interannual variations in the dates of departure from and arrival at breeding/nonbreeding sites,and the inter-annual variation in the longitudes when the same individual across the same latitudes.Whimbrels exhibited a high degree of consistency in the use of breeding,nonbreeding,and stopover sites between years.The variation of arrival dates at nonbreeding sites was significantly larger than that of the departure dates from nonbreeding and breeding sites.Repeatedly used stopover sites by the same individuals in multiple years were concentrated in the Yellow Sea coast during northward migration,but were more widespread during southward migration.The stopover duration at repeatedly used sites was significantly longer than that at sites used only once.When flying across the Yellow Sea,Whimbrels breeding in Sakha(Yakutia)exhibited the highest consistency in migration routes in both autumn and spring.Moreover,the consistency in migration routes of Yakutia breeding birds was generally higher than that of birds breeding in Chukotka.Our results suggest that the northward migration schedule of the Whimbrels is mainly controlled by endogenous factors,while the southward migration schedule is less affected by endogenous factors.The repeated use of stopover sites in the Yellow Sea coast suggests this region is important for the migration of Whimbrel,and thus has high conservation value.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Direct interaction between Rab5a and Rab4a enhanced epidermal growth factor-stimulated proliferation of gastric cancer cells

BACKGROUND Gastric cancer(GC)is one of the leading causes of cancer-related death worldwide.Although targeted therapies such as antibodies against human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have been widely used in the treatment of metastatic cancer,the overall outcomes are poor.Therefore,elucidation of the mechanism underlying cancer progression is important to improve prognosis.Overexpression of the Rab5a gene has been confirmed to correlate with tumorigenesis of many cancers,but the mechanism underling,especially of GC,is still unclear.AIM To investigate the effects of Rab5a overexpression on the tumorigenesis of GC.METHODS First,the expression levels of Rab5a and Rab4a in primary tumorous tissues of GC patients diagnosed between 2015 and 2018 were analyzed.Then we constructed HGC-27 cell lines overexpressing green fluorescent protein-Rab5a or red fluorescent protein-Rab4a and investigated the interaction between Rab5a or Rab4a using Western blotting,co-immunoprecipitation,confocal microscopy,and colocalization analysis.Finally,epidermal growth factor-stimulated proliferation of these cell lines was analyzed using cell counting kit-8 cell viability assay.RESULTS Compared with normal gastric tissues,the expression levels of Rab5a and Rab4a increased progressively both in paracancerous tissues and in advanced cancerous tissues.Epidermal growth factor could promote the proliferation of HGC-27 cells,especially Rab5a-overexpressing HGC-27 cells.Notably,Rab5a and Rab4a cooverexpression promoted the proliferation of HGC-27 cells to the greatest extent.Further analysis identified a direct interaction between Rab5a and Rab4a in HGC-27 cells.CONCLUSION Co-overexpression of Rab5a and Rab4a in GC may promote the endosomal recycling of epidermal growth factor receptor,which in turn contributes to poor prognosis and tumor progression in GC patients.Inhibition of Rab5a or Rab4a expression might be a promising therapy for refractory GC.

Road of no return——loss of TP53 paves a defined evolution path from gastric preneoplasia-to-cancer

Gastric cancer(GC),the fifth-and fourth-leading causes of morbidity and mortality worldwide,still lacks effective diagnoses and treatment.Moreover,China accounts for nearly 50%of the newly diagnosed and death cases of GC globally1.Being directly exposed to external food intake,extremely acidic content,and microorganisms,such as Helicobacter pylori and Epstein-Barr virus(EBV),stomach homeostasis is easily perturbed and disrupted.Importantly,the gastric epithelium is composed of multiple cell types,including chief,parietal,pit,and stem cells.The lineages of these gastric epithelial cells are rather plastic,giving rise to a high degree of GC heterogeneity.

A Case Report of Diabetic Foot Ulcer Treated by Herbal Food Homology Therapy

Diabetic foot ulcer (DFU) is a common and severe complication among patients with diabetes. There are hundreds of natural products derived from herbs that have been identified and proven to be effective for glucose-lowering and wound-healing effects, such as flavones. In this case study, we reported that a 76-year-old male patient with severe traumatic DFU was cured after drinking yellow tea (dehydrogenated Camellia sinensis) as a postprandial auxiliary treatment for six months. Previously, the patient was required to be hospitalized, but the wound deteriorated after five months. The patient drank yellow tea at approximately 12:30 pm (the active time of heart meridian) after lunch every day. Five grams of yellow tea were boiled in one liter of water and covered above 70°C for approximately 30 minutes. He experienced profuse sweating on his back after drinking yellow tea, with no other adverse effects. His lifestyle and healthcare remained constant except for replacing green tea with yellow tea. After six months, the ulcer had completely healed, and after one year of follow-up, no new abnormalities or side effects were found. This self-controlled case study indicates that flavone-enriched yellow tea or other herbs may be an auxiliary therapy for diabetes and its complications.

A digital microfluidic single-cell manipulation systemoptimized by extending-depth-of-field device

Microfuidic systems have been widely utilized in high-throughput biology analysis,but thedificulties in iquid manipulation and cell cultivation limit its application.This work has developed a new digital microfluidic(DMF)system for on-demand droplet control.By adopting anextending-depth-of-field(EDoF)phase modulator to the optical system,the entire depth of themicrofluidic channel can be covered in one image without any refocusing process,ensuring that 95%of the particles in the droplet are captured within three shots together with shaking pro-cesses.With this system,suspension droplets are generated and droplets containing only oneyeast cll can be recognized,then each single cell is cultured in the array of the chip.Byobservingtheir growth in cell numbers and the green fluorescence protein(GFP)production via fluorescence imaging,the single cell with the highest production can be identified.The results haveproved the heterogeneity of yeast cells,and showed that the combined system can be applied forrapid single-cell sorting,cultivation,and analysis.

Ginsenoside compound-K attenuates OVX-induced osteoporosis via the suppression of RANKL-induced osteoclastogenesis and oxidative stress

Osteoporosis(OP),a systemic and chronic bone disease,is distinguished by low bone mass and destruction of bone microarchitecture.Ginsenoside Compound-K(CK),one of the metabolites of ginsenoside Rb1,has anti-aging,anti-inflammatory,anti-cancer,and hypolipidemic activities.We have demonstrated CK could promote osteogenesis and fracture healing in our previous study.However,the contribution of CK to osteoporosis has not been examined.In the present study,we investigated the effect of CK on osteoclastogenesis and ovariectomy(OVX)-induced osteoporosis.The results showed that CK inhibited receptor activator for nuclear factor-κB ligand(RANKL)-mediated osteoclast differentiation and reactive oxygen species(ROS)activity by inhibiting the phosphorylation of NF-κB p65 and oxidative stress in RAW264.7 cells.In addition,we also demonstrated that CK could inhibit bone resorption using bone marrow-derived macrophages.Furthermore,we demonstrated that CK attenuated bone loss by suppressing the activity of osteoclast and alleviating oxidative stress in vivo.Taken together,these results showed CK could inhibit osteoclastogenesis and prevent OVX-induced bone loss by inhibiting NF-κB signaling pathway.

Blocking of N-acetylglucosaminyltransferase V induces cellular endoplasmic reticulum stress in human hepatocarcinoma 7721 cells

N-acetylglucosaminyltransferase V （GnT-V） is an important tumorigenesis and metastasis-associated enzyme. To study its biofunction, the GnT-V stably suppressed cell line （GnT-V-AS/7721） was constructed from 7721 hepatocarcinoma cells in previous study. In this study, cDNA array gene expression profiles were compared between GnT-V-AS/7721 and parental 7721 cells. The data indicated that GnT-V-AS/7721 showed a characteristic expression pattern consistent with the ER stress. The molecular mechanism of the ER stress was explored in GnT-V-AS/7721 by the analysis on key molecules in both two unfolded protein response （UPR） pathways. For ATF6 and Irel/XBP-1 pathway, it was evidenced by the up-regulation of BIP at mRNA and protein level, and the appearance of the spliced form ofXBP-1. As for PERK/eIF2α pathway, the activation of ER eIF2α kinase PERK was observed. To confirm the results from GriT-V-AS/7721 cells, the key molecules in the UPR were examined again in 7721 cells interfered with the GnT-V by the specific RNAi treatment. The results were similar with those from GnT-V-AS/7721, indicating that blocking of GnT-V can specifically activate ER stress in 7721 cells. Rate of 3H-Man incorporation corrected with rate of 3H-Leu incorporation in GnT-V-AS/7721 was down-regulated greatly compared with the control, which demonstrated the deficient function of the enzyme synthesizing N-glycans after GnT-V blocking. Moreover, the faster migrating form of chaperone GRP94 associated with the underglycosylation, and the extensively changed N-glycans structures of intracellular glycoproteins were also detected in GnT-V-AS/7721. These results supported the mechanism that blocking of GnT-V expression impaired functions of chaperones and N-glycan-synthesizing enzymes, which caused UPR in vivo.

Functional conservation of the meiotic genes SDS and RCK in male meiosis in the monocot rice

The Arabidopsis SDS （SOLO DANCERS） and RCK （ROCK-N-ROLLERS） genes are important for male meiosis, but it is still unknown whether they represent conserved functions in plants. We have performed phylogenetic analyses of SDS and RCK and their respective homologs, and identified their putative orthologs in poplar and rice. Quantitative real-time RT-PCR analysis indicated that rice SDS and RCK are expressed preferentially in young flowers, and transgenic RNAi rice lines with reduced expression of these genes exhibited normal vegetative development, but showed significantly reduced fertility with partially sterile flowers and defective pollens. SDS deficiency also caused a decrease in pollen amounts. Further cytological examination of male meiocytes revealed that the SDS deficiency led to defects in homolog interaction and bivalent formation in meiotic prophase I, and RCK deficiency resulted in defective meiotic crossover formation. These results indicate that rice SDS and RCK genes have similar functions to their Arabidopsis orthologs. Because rice and Arabidopsis, respectively, are members of monocots and eudicots, two largest groups of flowering plants, our results suggest that the functions of SDS and RCK are likely conserved in flowering plants.

Oral vaccination of mice against rodent malaria with recombinant Lactococcus lactis expressing MSP-1_(19)

AIM： To construct the recombinant Lactococcus/actis as oral delivery vaccination against malaria. METHODS： The C-terminal 19-ku fragments of MSP1 （MSP-119） of Plasmodium yoelii265-BY was expressed in L. lactis and the recombinant L. lact/s was administered orally to BALB/c and C57BL/6 mice. After seven interval vaccinations within 4 wk, the mice were challenged with P. yoelii 265-BY parasites of erythroo/tic stage. The protective efficacy of recombinant L. lactiswas evaluated. RESULTS： The peak parasitemias in average for the experiment groups of BALB/c and C57BL/6 mice were 0.8± 0.4% and 20.8±26.5%, respectively, and those of their control groups were 12.0±0.8% and 60.8±9.6%, respectively. None of the BALB/c mice in both experimental group and control group died during the experiment. However, all the C57BL/6 mice in the control group died within 23 d and all the vaccinated mice survived well. CONCLUSION： The results imply the potential of recombinant L. lactis as oral delivery vaccination against malaria.

Twelve years of GWAS discoveries for osteoporosis and related traits: advances, challenges and applications

Osteoporosis is a common skeletal disease,affecting-200 million people around the world.As a complex disease,osteoporosis is influenced by many factors,including diet(e.g.calcium and protein intake),physical activity,endocrine status,coexisting diseases and genetic factors.In this review,we first summarize the discovery from genome-wide association studies(GWASs)in the bone field in the last 12 years.To date,GWASs and meta-analyses have discovered hundreds of loci that are associated with bone mineral density(BMD),osteoporosis,and osteoporotic fractures.However,the GWAS approach has sometimes been criticized because of the small effect size of the discovered variants and the mystery of missing heritability,these two questions could be partially explained by the newly raised conceptual models,such as omnigenic model and natural selection.Finally,we introduce the clinical use of GWAS findings in the bone field,such as the identification of causal clinical risk factors,the development of drug targets and disease prediction.Despite the fruitful GWAS discoveries in the bone field,most of these GWAS participants were of European descent,and more genetic studies should be carried out in other ethnic populations to benefit disease prediction in the corresponding population.

Influence of heme oxygenase-1 gene transfer on the viability and function of rat islets in in vitro culture

AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene （Ad- HO-1） or enhanced green fluorescent protein gene （Ad- EGFP）, and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index （SI） was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS： After seven days culture, the viability of cultured rat islets decreased significantly （92% ± 6% vs 52% ± 13%, P 〈 0.05）, and glucose-stimulated insulin release also decreased significantly （6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets（71% ± 15% vs 52% ± 13%, P 〈 0.05）. There was no significant difference in insulin release upon low glucose stimulation （2.8 mmol/L） among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group （P 〉 0.05）, while when stimulated by high glucose （16.7 mmol/L） solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively （12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively （2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05）. CONCLUSION： The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.

Genome sequencing and population genomics modeling provide insights into the local adaptation of weeping forsythia

Understanding the genetic basis underlying the local adaptation of nonmodel species is a fundamental goal in evolutionary biology.In this study,we explored the genetic mechanisms of the local adaptation of Forsythia suspensa using genome sequence and population genomics data obtained from specific-locus amplified fragment sequencing.We assembled a high-quality reference genome of weeping forsythia(Scaffold N50=7.3 Mb)using ultralong Nanopore reads.Then,genome-wide comparative analysis was performed for 15 natural populations of weeping forsythia across its current distribution range.Our results revealed that candidate genes associated with local adaptation are functionally correlated with solar radiation,temperature and water variables across heterogeneous environmental scenarios.In particular,solar radiation during the period of fruit development and seed drying after ripening,cold,and drought significantly contributed to the adaptive differentiation of F.suspensa.Natural selection exerted by environmental factors contributed substantially to the population genetic structure of F.suspensa.Our results supported the hypothesis that adaptive differentiation should be highly pronounced in the genes involved in signal crosstalk between different environmental variables.Our population genomics study of F.suspensa provides insights into the fundamental genetic mechanisms of the local adaptation of plant species to climatic gradients.

Different expression patterns of duplicated PHANTASTICA-like genes in Lotus japonicus suggest their divergent functions during compound leaf development

Recent studies on leaf development demonstrate that the mechanism on the adaxial-abaxial polarity pattern formation could be well conserved among the far-related species, in which PHANTASTICA （PAHN）-Iike genes play important roles. In this study, we explored the conservation and diversity on functions of PHAN-Iike genes during the compound leaf development in Lotusjaponicus, a papilionoid legume. Two PHAN-Iike genes in L. japonicus, LjPHANa and LjPHANb, were found to originate from a gene duplication event and displayed different expression patterns during compound leaf development. Two mutants, reduced leafletsl （rell） and reduced leaflets3 （rel3）, which exhibited decreased adaxial identity of leaflets and reduced leaflet initiation, were identified and investigated. The expression patterns of both LjPHANs in rel mutants were altered and correlated with abnormalities of compound leaves. Our data suggest that LjPHANa and LjPHANb play important but divergent roles in regulating adaxial-abaxial polarity of compound leaves in L. japonicus.

Visual functional changes during acute elevation of intraocular pressure

Glaucoma is closely related to elevation of intraocular pressure （IOP）. Many studies have done on the effect of chronic elevation of lOP on the retina and optic nerve, but less attention was paid to the effect of acute elevated lOP. Here we briefly review experimental studies on functional changes of the visual system from the retina to the visual cortex under acute elevated lOP condition, which is similar to that of acute primary angle-closure glaucoma.

Chemical composition and phytotoxic activity of the volatile oil of invasive Xanthium italicum Moretti from Xinjiang,China

Aerial parts of Xanthium italicum in an air tight container greatly inhibited root elongation of radish, implying that this invasive plant could release biologically active volatile organic compounds （VOCs） into the environment to affect other plants＇ growth. This phenomenon was further studied by evaluating the phytotoxic effects of X. italicum essential oil against two dicot plants, amaranth （Amaranthus mangostanus L.） and lettuce （Lectuca sativa L.）, and two monocot plants, wheat （Triticum aestivum Linn） and ryegrass （Lolium multiforum）, and analyzing the chemical composition of the oil. Among the 4 test species, amaranth was the most sensitive plant, 0.5μl/mL essential oil application resulted in a 50% reduction on root elongation, and 2.5 μl/mL essential oil almost completely inhibited its seedling growth. Wheat was the least sensitive species, whose root growth was reduced to 36% of control by 5 μl/mL essential oil. The essential oil exerted moderate inhibitory effect on both lettuce and ryegrass. Compared to a commercial herbicide-Harness, X. italicum oil exhibited stronger phytotoxicity on amaranth, lettuce and wheat, but weaker activity on ryegrass. The chemical composition of the essential oil isolated by hydrodistillation from the aerial parts of X. italicum Moretti was analyzed by GC/MS. Thirty two compounds were identified, representing 94.89% of total oil, which was found to be rich in monoterpene hydrocarbons （60.71%）. The main constituents of the oil were limonene （51.61%）, germacrene B （6.98%）, 6-cadinol （5.94%）, β-pinene （5.23%）, α-caryophyllene （5.1%） and bornyl acetate （3.15%）. Bioassay revealed the dominant constituent-limonene, was unlikely the responsible phytotoxic compound due to its low biological activity; rather, there might be other oil constituent（s） that either act alone, or work together, and possibly assisted by synergistic effect, to display the phytotoxic activity. Our results suggested that X. italicum might produce allelopathic VOCs to facilitate its invasion success. This is the first report on the phytotoxic activity and the chemical composition of the essential oil of X. itaficum Moretti from China.

Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism

Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimyco- bacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10 236 715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9 228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel ＇quasicore＇ with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.

Impacts of exercise interventions on different diseases and organ functions in mice

Background'. In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This reviewsummarizes the exercise interventions used in studies involving mice as they are related to special diseases or physiological status. To furtherunderstand the effects of exercise interventions in treating or preventing diseases, it is important to establish a template for exercise interventionsthat can be used in future exercise-related studies.Methods'. PubMed was used as the data resource for articles. To identify studies related to the effectiveness of exercise interventions for treatingvarious diseases and organ functions in mice, we used the following search language: (exercise [Title] OR training [Title] OR physical activity[Title]) AND (mice [title/abstract] OR mouse [title/abstract] OR mus [title/abstract]). To limit the range of search results, we included 2 filters:one that limited publication dates to "in 10 years,^ and one that sorted the results as "best match^^. Then we grouped the commonly used exercisemethods according to their similarities and differences. We then evaluated the effectiveness of the exercise interventions for their impact on diseasesand organ functions in 8 different systems.Results'. A total of 331 articles were included in the analysis procedure. The articles were then segmented into 8 systems for which the exerciseinterventions were used in targeting and treating disorders: motor system (60 studies), metabolic system (45 studies), cardio-cerebral vascularsystem (58 studies), nervous system (74 studies), immune system (32 studies), respiratory system (7 studies), digestive system (1 study), and thesystem related to the development of cancer (54 studies). The methods of exercise interventions mainly involved the use of treadmills, voluntarywheel-running, forced wheel-running, swimming, and resistance training. It was found that regardless of the specific exercise method used, mostof them demonstrated positive effects on various systemic diseases and organ functions. Most diseases were remitted with exercise regardless ofthe exercise method used, although some diseases showed the best remission effects when a specific method was used.Conclusion-. Our review strongly suggests that exercise intervention is a cornerstone in disease prevention and treatment in mice. Because exerciseinterventions in humans typically focus on chronic diseases, national fitness, and body weight loss, and typically have low intervention com・pliance rates, it is important to use mice models to investigate the molecular mechanisms underlying the health benefits from exerciseinterventions in humans.