[Identification and functional analysis of jasmonic acid signaling repressor McJAZ8 gene in Mentha canadensis].

Mentha canadensis, as a plant with medicinal and culinary uses, holds significant economic value. Jasmonic acid signaling repressor JAZ protein has a crucial role in regulating plant response to adversity stresses. The M. canadensis McJAZ8 gene is cloned and analyzed for protein characterization, protein interactions, and expression patterns, so as to provide genetic resources for molecular breeding of M. canadensis for stress tolerance. This experiment will analyze the protein structural characteristics, subcellular localization, protein interactions, and gene expression of McJAZ8 using bioinformatics, yeast two-hybrid(Y2H), transient expression in tobacco leaves, qRT-PCR, and other technologies. The results show that:(1)The full length of the McJAZ8 gene is 543 bp, encoding 180 amino acids. The McJAZ8 protein contains conserved TIFY and Jas domains and exhibits high homology with Arabidopsis thaliana AtJAZ1 and AtJAZ2.(2)The McJAZ8 protein is localized in the nucleus and cytoplasm.(3)The Y2H results show that McJAZ8 interacts with itself or McJAZ1/3/4/5 proteins to form homologous or heterologous dimers.(4)McJAZ8 is expressed in different tissue, with the highest expression level in young leaves. In terms of leaf sequence, McJAZ8 shows the highest expression level in the fourth leaf and the lowest expression level in the second leaf.(5) In leaves and roots, the expression of McJAZ8 is upregulated to varying degrees under methyl jasmonate(MeJA), drought, and NaCl treatments. The expression of McJAZ8 shows an initial upregulation followed by a downregulation pattern under CdCl_2 treatment. In leaves, the expression of McJAZ8 tends to gradually decrease under CuCl_2 treatment, while in roots, it initially decreases and then increases before decreasing again. In both leaves and roots, the expression of McJAZ8 is downregulated to varying degrees under AlCl_(3 )treatment. This study has enriched the research on jasmonic acid signaling repressor JAZ genes in M. canadensis and provided genetic resources for the molecular breeding of M. canadensis.

[Cloning and expression pattern analysis of abscisic acid receptor gene McPYL4 in Mentha canadensis].

Mentha canadensis is a traditional Chinese herb with great medicinal and economic value. Abscisic acid(ABA) receptor PYLs have important roles in plant growth and development and response to adversity. The M. canadensis McPYL4 gene was cloned, and its protein characteristics, gene expression, and protein interactions were analyzed, so as to provide genetic resources for genetic improvement and molecular design breeding for M. canadensis resistance. Therefore, the protein characteristics, subcellular localization, gene expression pattern, and protein interactions of McPYL4 were analyzed by bioinformatics analysis, transient expression of tobacco leaves, RT-qPCR, and yeast two-hybrid(Y2H) techniques. The results showed that the McPYL4 gene was 621 bp in length, encoding 206 amino acids, and its protein had the conserved structural domain of SRPBCC and was highly homologous with Salvia miltiorrhiza SmPYL4. McPYL4 protein was localized to the cell membrane and nucleus. The McPYL4 gene was expressed in all tissue of M. canadensis, with the highest expression in roots, followed by leaves, and it showed a pattern of up-regulation followed by down-regulation in leaves 1-8. In both leaves and roots, the McPYL4 gene responded to the exogenous hormones ABA, MeJA, and the treatments of drought, AlCl_3, NaCl, CdCl_2, and CuCl_2. Moreover, McPYL4 was up-regulated for expression in both leaves and roots under the MeJA treatment, as well as in leaves treated with AlCl_3 stress for 1 h, whereas McPYL4 showed a tendency to be down-regulated in both leaves and roots under other treatments. Protein interactions showed that McPYL4 interacted with AtABI proteins in an ABA-independent manner. This study demonstrated that McPYL4 responded to ABA, JA, and several abiotic stress treatments, and McPYL4 was involved in ABA signaling in M. canadensis and thus in the regulation of leaf development and various abiotic stresses in M. canadensis.

[Improvement effect of cinnamaldehyde on reserpine-induced Parkinson's disease rat model].

In order to study the neuroprotective mechanism of cinnamaldehyde on reserpine-induced Parkinson's disease(PD) rat models, 72 male Wistar rats were randomly divided into blank group, model group, Madopar group, and cinnamaldehyde high-, medium-, and low-dose groups. Except for the blank group, the other groups were intraperitoneally injected with reserpine of 0.1 mg·kg~(-1) once every other morning, and cinnamaldehyde and Madopar solutions were gavaged every afternoon. Open field test, rotarod test, and oral chewing movement evaluation were carried out in the experiment. The brain was taken and fixed. The positive expression of dopamine receptor D1(DRD1) was detected by TSA, and the changes in neurotransmitters such as dopamine(DA) and 3,4-dihydroxyphenylacetic acid(DOPAC) in the brain were detected by enzyme-linked immunosorbent assay(ELISA). The protein and mRNA expression levels of tyrosine hydroxylase(TH) and α-synuclein(α-Syn) in substantia nigra(SN) were detected by RT-PCR and Western blot. The results showed that after the injection of reserpine, the hair color of the model group became yellow and dirty; the arrest behavior was weakened, and the body weight was reduced. The spontaneous movement and exploration behavior were reduced, and the coordination exercise ability was decreased. The number of oral chewing was increased, but the cognitive ability was decreased, and the proportion of DRD1 positive expression area in SN was decreased. The expression of TH protein and mRNA was down-regulated, and that of α-Syn protein and mRNA was up-regulated. After cinnamaldehyde intervention, it had an obvious curative effect on PD model animals. The spontaneous movement behavior, the time of staying in the rod, the time of movement, the distance of movement, and the number of standing times increased, and the number of oral chewing decreased. The proportion of DRD1 positive expression area in SN increased, and the protein and mRNA expression levels of α-Syn were down-regulated. The protein and mRNA expression levels of TH were up-regulated. In addition, the levels of DA, DOPAC, and homovanillic acid(HVA) neurotransmitters in the brain were up-regulated. This study can provide a new experimental basis for clinical treatment and prevention of PD.

[Screening and promoting effect of grow-promoting fungi in rhizosphere of Angelica dahurica var. formosana].

Excessive application of chemical fertilizer has caused many problems in Angelica dahurica var. formosana planting, such as yield decline and quality degradation. In order to promote the green cultivation mode of A. dahurica var. formosana and explore rhizosphere fungus resources, the rhizosphere fungi with nitrogen fixation, phosphorus solubilization, potassium solubilization, iron-producing carrier, and IAA-producing properties were isolated and screened in the rhizosphere of A. dahurica var. formosana from the genuine and non-genuine areas, respectively. The strains were identified comprehensively in light of the morphological characteristics and ITS rDNA sequences, and the growth-promoting effect of the screened strains was verified by pot experiment. The results showed that 37 strains of growth-promoting fungi were isolated and screened from the rhizosphere of A. dahurica var. formosana, mostly belonging to Fusarium. The cultured rhizosphere growth-promoting fungi of A. dahurica var. formosana were more abundant and diverse in the genuine producing areas than in the non-genuine producing areas. Among all strains, Aspergillus niger ZJ-17 had the strongest growth promotion potential. Under the condition of no fertilization outdoors, ZJ-17 inoculation significantly promoted the growth, yield, and accumulation of effective components of A. dahurica var. formosana planted in the soil of genuine and non-genuine producing areas, with yield increases of 73.59% and 37.84%, respectively. To a certain extent, it alleviated the restriction without additional fertilization on the growth of A. dahurica var. formosana. Therefore, A. niger ZJ-17 has great application prospects in increasing yield and quality of A. dahurica var. formosana and reducing fertilizer application and can be actually applied in promoting the growth of A. dahurica var. formosana and producing biofertilizer.

Which Exercise Approaches Work for Relieving Cancer-Related Fatigue? A Network Meta-analysis.

OBJECTIVE: To determine the most effective exercise modalities for managing cancer-related fatigue during and after cancer treatment. DESIGN: Network meta-analysis (NMA) of randomized controlled trials. LITERATURE SEARCH: Seven electronic databases were systematically searched from inception to January 2022. STUDY SELECTION CRITERIA: Randomized controlled trials testing the effects of exercise on relieving cancer-related fatigue in adult patients with cancer. DATA SYNTHESIS: An NMA of 56 studies was conducted, and the PRISMA-NMA guidelines were followed when reporting results. To determine the most effective interventions, the surface under the cumulative ranking curve (SUCRA) value was calculated for each exercise modality. RESULTS: Combined aerobic and resistance exercise (standardized mean difference [SMD], 1.57; credible interval [CrI], 1.03-2.10), yoga (SMD, 1.02; CrI: 0.44, 1.60), and regular physical activity (SMD, 1.07; CrI: 0.21, 1.92) could significantly alleviate cancer-related fatigue compared to control groups (usual care, wait-list, and regular physical activity). Combined aerobic and resistance exercise (SUCRA, 97.2%) had the highest probability of efficacy, followed by yoga (SUCRA, 75.5%) and regular physical activity (SUCRA, 74.1%). During cancer treatment, combined aerobic and resistance exercise (SUCRA, 94.5%) ranked first in efficacy, followed by regular physical activity (SUCRA, 82.1%) and yoga (SUCRA, 73.8%). After cancer treatment, only combined aerobic and resistance exercise (SMD, 0.99; CrI: 0.13, 1.84) had a significant effect on cancer-related fatigue. CONCLUSION: Combined aerobic and resistance exercise, yoga, and regular physical activity were the most effective exercise modalities for alleviating cancer-related fatigue. Combined aerobic and resistance exercise is recommended during and after cancer treatment. J Orthop Sports Phys Ther 2023;53(6):1-10. Epub: 23 March 2023. doi:10.2519/jospt.2023.11251.

Effectiveness comparisons of various psychosocial therapies for cancer-related fatigue: A Bayesian network meta-analysis.

OBJECTIVES: The purpose of this network meta-analysis (NMA) is to compare the effect of several psychosocial therapies on CRF critically. METHODS: We applied systematic strategies based on eight databases, namely the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsycINFO, China Biology Medicine (CBM), Wan Fang database, VIP, and China National Knowledge Infrastructure (CNKI) database to preliminary literature retrieval to identify relevant randomized controlled trials (RCTs). Studies, including adult patients (≥18 years) diagnosed with cancer, were eligible regardless of cancer stage and current treatment. We carried out an expression analysis for comparing the efficacy of various psychosocial therapies using Bayesian NMA. A battery of analyses and assessments, such as conventional meta-analysis and risk of bias, were performed concurrently. RESULTS: We identified 41 RCTs including six different psychosocial interventions (4422 participants), namely cognitive-behavioral therapy (CBT), mindfulness-based stress reduction therapy (MBSR), psychoeducational therapy (PE), stress management therapy (SMT), meditation therapy (MT) and comprehensive therapy (CT). Our NMA results showed that three psychosocial intervention therapies were effective for CRF in cancer patients. The most effective psychosocial intervention was MBSR (SMD = -1.23, CrI: -1.88, -0.59, SUCRA = 83.33%), followed by PE (SMD = -0.86, CrI: -1.53, -0.18, SUCRA = 58.51%) and CBT (SMD = -0.84, CrI: -1.31, -0.37, SUCRA = 57.67%). CONCLUSIONS: Our study showed that MBSR was most likely to be the best psychosocial intervention to relieve CRF in cancer patients. Medical staff should pay attention to applying MBSR to cancer patients in future clinical care.

Age-dependent alteration in metabolism of vitamin B6 , neurotransmitters, and amino acids after 4'-O-methylpyridoxine administration in rats.

4'-O-methylpyridoxine (MPN), a recognized antivitamin B6 compound, is a potentially poisonous substance found in Ginkgo biloba L. In this work, the effects of MPN on the metabolism of vitamin B6 , neurotransmitters, and amino acids were compared in the plasma and brain of young and adult rats under various administration times. Results showed that the contents of MPN residues in the plasma and brain of young rats were 12.72 and 14.76 µM higher than adult rats, respectively. Moreover, the levels of 5-hydroxytryptamine and dopamine in the brain of young rats have decreased by 13.78% and 7.19%, respectively, compared with the control group, at 2 h after MPN administration. Furthermore, the principal component analysis revealed that MPN was an important contributor to the amino acid composition in the brain of young rats. These results suggest that age may lead to different toxic effects of MPN. PRACTICAL APPLICATION: 4'-O-methylpyridoxine is primarily responsible for poisoning due to overconsumption of Ginkgo biloba seeds. This study will provide an exploratory understanding of the age-dependent toxicity of 4'-O-methylpyridoxine.

Jasmonate- and abscisic acid-activated AaGSW1-AaTCP15/AaORA transcriptional cascade promotes artemisinin biosynthesis in Artemisia annua.

Artemisinin, a sesquiterpene lactone widely used in malaria treatment, was discovered in the medicinal plant Artemisia annua. The biosynthesis of artemisinin is efficiently regulated by jasmonate (JA) and abscisic acid (ABA) via regulatory factors. However, the mechanisms linking JA and ABA signalling with artemisinin biosynthesis through an associated regulatory network of downstream transcription factors (TFs) remain enigmatic. Here we report AaTCP15, a JA and ABA dual-responsive teosinte branched1/cycloidea/proliferating (TCP) TF, which is essential for JA and ABA-induced artemisinin biosynthesis by directly binding to and activating the promoters of DBR2 and ALDH1, two genes encoding enzymes for artemisinin biosynthesis. Furthermore, AaORA, another positive regulator of artemisinin biosynthesis responds to JA and ABA, interacts with and enhances the transactivation activity of AaTCP15 and simultaneously activates AaTCP15 transcripts. Hence, they form an AaORA-AaTCP15 module to synergistically activate DBR2, a crucial gene for artemisinin biosynthesis. More importantly, AaTCP15 expression is activated by the multiple reported JA and ABA-responsive TFs that promote artemisinin biosynthesis. Among them, AaGSW1 acts at the nexus of JA and ABA signalling to activate the artemisinin biosynthetic pathway and directly binds to and activates the AaTCP15 promoter apart from the AaORA promoter, which further facilitates formation of the AaGSW1-AaTCP15/AaORA regulatory module to integrate JA and ABA-mediated artemisinin biosynthesis. Our results establish a multilayer regulatory network of the AaGSW1-AaTCP15/AaORA module to regulate artemisinin biosynthesis through JA and ABA signalling, and provide an interesting avenue for future research exploring the special transcriptional regulation module of TCP genes associated with specialized metabolites in plants.

Wrist-ankle acupuncture has a positive effect on cancer pain: a meta-analysis.

BACKGROUND: Wrist-ankle acupuncture (WAA) as a kind of micro acupuncture therapy has been used to management cancer pain, however, the effects of WAA on cancer pain were controversial in the current studies. Therefore, the purpose of this meta-analysis was to critically evaluate the effect of wrist-ankle acupuncture (WAA) on cancer pain. METHODS: Seven digital databases were searched from the inception of databases to July 2020, including CNKI, Wanfang, VIP, CBM, Cochrane Library, PubMed and Embase. Randomized controlled trials conforming to the inclusion and exclusion criteria were screened and extracted; the risk of bias was evaluated using the Cochrane Collaboration criteria. The primary outcome indicators included pain relief rate and pain score, and the secondary outcome was adverse reaction incidence. All analyses were performed with Review Manager 5.3. RESULTS: A total of 13 studies with 1005 cancer patients (intervention group: 568, control group: 437) were included in this meta-analysis. The results demonstrated that the pain relief rate of experimental group (WAA / WAA + drug intervention) was better than that of control group (analgesic drug intervention), and the difference was statistically significant [RR = 1.31, 95%CI: 1.15 ~ 1.49, P < 0.01]. CONCLUSIONS: WAA has certain effect on cancer pain, and the effect of WAA combined with pharmacological intervention is better than that of drug therapy alone.

Music interventions can alleviate cancer-related fatigue: a metaanalysis.

PURPOSE: This study was designed to critically evaluate the effect of music interventions on cancer-related fatigue (CRF) in cancer patients. METHODS: Seven databases (Cochrane Library, PubMed, Embace, CBM, Wanfang, VIP, and CNKI) were systematically reviewed from inception to June 2020 for randomized controlled trials (RCTs). Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed form. All analyses were performed with Review Manager 5.3. RESULTS: A total of 8 qualified studies that included 467 patients (music interventions: 235, control: 232) were included. Cancer patients who completed adjuvant therapy in the music intervention group, especially those with malignant hematological diseases, reported reduced CRF levels compared with patients undergoing routine care. Regardless of the frequencies, music interventions can relieve fatigue in cancer patients. Providing prerecorded music and participating in live music both can mitigate CRF. CONCLUSIONS: Music interventions can be considered as an alternative therapy for relieving fatigue in cancer patients who are undergoing active treatment or have completed treatment.

Auricular acupressure for cancer-related fatigue during lung cancer chemotherapy: a randomised trial.

PURPOSE: To evaluate the effect of auricular acupressure (AA) on cancer-related fatigue (CRF), sleep disturbance and anxiety in lung cancer patients undergoing chemotherapy. MATERIALS AND METHODS: Patients were recruited from the respiratory department of a general hospital and were randomised into three groups. A 9-week course of AA using Semen Vaccariae (SV) (Group A)/AA using magnetic beads (Group B)/routine care (Group C) was implemented. CRF scores were used as the primary outcome while the sleep and anxiety scores were the secondary outcomes. Analysis of variance and least significant difference t-test were used to determine the intergroup differences and paired-sample t-test was used for the intragroup comparison. RESULTS: 100 lung cancer patients undergoing chemotherapy were included. Compared with Group C, AA could significantly alleviate CRF (F:24.63, p<0.01), especially for physical and affective fatigue and Group A was more effective for managing physical fatigue than Group B in per-protocol (PP) (-1.75 (-2.69 to -0.82), p<0.01)/Intention to Treat analysis (ITT) (-1.41 (-2.39 to -0.41), p=0.01) analysis. However, AA had no effect on cognitive fatigue. Compared with Group C, only Group A produced significant improvements in sleep quality in PP analysis (-1.17 (-2.23 to -0.10), p=0.03) while it yielded negative results in ITT analysis (-0.82 (-1.74 to 0.10), p=0.08). Compared with Group C, AA could significantly reduce anxiety in PP analysis (F:9.35, p<0.01) while there was no statistical difference between Group B and Group C (-0.95 (-2.81 to 0.90), p=0.31), Group A and Group B (-1.26 (-3.12 to 0.59), p=0.18) in ITT analysis. CONCLUSION: AA can alleviate CRF of lung cancer patients undergoing chemotherapy, especially for physical and affective fatigue. AA using SV is more effective for physical fatigue while AA using magnetic beads works better for anxiety. However, AA cannot improve the sleep quality. TRIAL REGISTRATION NUMBER: ISRCTNregistry (ISRCTN16408424).

Mindfulness-based stress reduction can alleviate cancer- related fatigue: A meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to critically evaluate the effects of mindfulness-based stress reduction (MBSR) on cancer-related fatigue (CRF). METHODS: A systematic search of eight databases (Web of Science, Pubmed, Cochrane Library, Spring link, CNKI, Wanfang, VIP, CBM) was performed, to find randomized controlled trials (RCTs) from inception to January 2019. Using Cochrane Collaboration criteria, two reviewers critically and independently assessed the risk of bias and extracted correlated data using the designed form. All analyses were performed with Review Manager 5.3. RESULTS: In all, fifteen RCTs were included in the systematic review, fourteen of which, consisting of 3008 patients (MBSR, 1502; control, 1506), were included in the meta-analysis. MBSR had a significant effect on fatigue in cancer patients, particularly among lung cancer patients. The meta-analysis also indicated that MBSR could significantly mitigate CRF compared with usual care or no intervention. 8 weeks of MBSR, supervised by experts, had a large effect on CRF. CONCLUSIONS: MBSR is effective for CRF management and can be recommended as a beneficial complementary therapy for CRF patients.

Yoga has a solid effect on cancer-related fatigue in patients with breast cancer: a meta-analysis.

PURPOSE: This study was designed to critically evaluate the effect of yoga on cancer-related fatigue in patients with breast cancer. METHODS: Eight databases (Cochrane Library, PubMed, Ovid-Medline, Web of Science, CBM, Wanfang, VIP, and CNKI) were systematically reviewed from inception to January 2019 for randomized controlled trials (RCTs). Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed form. All analyses were performed with Review Manager 5.3. RESULTS: A total of 17 qualified studies that included 2183 patients (yoga: 1112, control: 1071) were included in the meta-analysis. Yoga had a large effect on fatigue in post-treatment breast cancer patients and had a small effect on intra-treatment patients. The meta-analysis also indicated that supervised yoga class had a significant effect on CRF; the six-week program had a moderate beneficial effect while the 60/90 min/session supervised yoga class and the eight-week program demonstrated a large effect on fatigue in patients with breast cancer. Yoga could markedly mitigate the physical fatigue in breast cancer patients, had a medium impact on cognitive fatigue, and manifested a small effect on mental fatigue. Eight studies reported the adverse events, whereas ten studies did not. CONCLUSIONS: Yoga can be considered as an alternative therapy for relieving fatigue in breast cancer patients who have completed treatment or are undergoing anti-cancer treatment.

Up-regulation of lipid biosynthesis increases the oil content in leaves of Sorghum bicolor.

Synthesis and accumulation of the storage lipid triacylglycerol in vegetative plant tissues has emerged as a promising strategy to meet the world's future need for vegetable oil. Sorghum (Sorghum bicolor) is a particularly attractive target crop given its high biomass, drought resistance and C4 photosynthesis. While oilseed-like triacylglycerol levels have been engineered in the C3 model plant tobacco, progress in C4 monocot crops has been lagging behind. In this study, we report the accumulation of triacylglycerol in sorghum leaf tissues to levels between 3 and 8.4% on a dry weight basis depending on leaf and plant developmental stage. This was achieved by the combined overexpression of genes encoding the Zea mays WRI1 transcription factor, Umbelopsis ramanniana UrDGAT2a acyltransferase and Sesamum indicum Oleosin-L oil body protein. Increased oil content was visible as lipid droplets, primarily in the leaf mesophyll cells. A comparison between a constitutive and mesophyll-specific promoter driving WRI1 expression revealed distinct changes in the overall leaf lipidome as well as transitory starch and soluble sugar levels. Metabolome profiling uncovered changes in the abundance of various amino acids and dicarboxylic acids. The results presented here are a first step forward towards the development of sorghum as a dedicated biomass oil crop and provide a basis for further combinatorial metabolic engineering.

[Lignans from flower buds of Magnolia biondii].

The present study aims to investigate the lignans from the flower buds of Magnolia biondii. The isolation and purification of the compounds were performed by column chromatographies on Diaion HP-20, silica gel, and Sephadex LH-20, combined with semi-preparative HPLC. Their structures were elucidated on the basis of spectral data and physiochemical properties. Eighteen compounds were isolated and identified as magnolin (1), epimagnolin (2), eudesmin (3), kobusin (4), aschantin (5), lirioresinol B dimethyl ether (6), pinoresinol monomethy ether (7), (+)-de-O-methylmagnolin (8), isoeucommin A (9), syringaresinol 4-O-ß-D-glucopyranoside (10), phillygenin (11), lariciresinol-4'-O-ß-1-D-glucoside (12), conicaoside (13), (7'S, 8'R)-dihydrodehydrodiconiferylalcohol (14), 7R*, 8S*-dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside (15), 7S, 8R-erythro-7, 9, 9'-trihydroxy-3, 3'-dimethoxy-8-O-4'-neolignan 4-O-ß-D-glucopyranoside (16), 7S, 8R-erythro-4, 9, 9'-trihydroxy-3, 3'-dimethoxy-8-O-4'-neolignan-7-O-ß-D-glucopyranoside (17), and (+)-isolariciresinol (18). Compounds 7-18 are isolated from this plant for the first time.

Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis.

Interleukin-7 receptor (IL-7R) levels are tightly controlled during ontogeny: high on double-negative (DN) cells, absent on double-positive (DP) cells, and high once again on thymocytes undergoing positive selection. To determine if loss of IL-7-mediated survival signals in DP cells is necessary for normal antigen-specific selection, we created T-lineage-specific IL-7R alpha chain (IL-7Ralpha) transgenic (Tg) mice in which IL-7R is expressed throughout ontogeny. There was no effect of the IL-7Ralpha Tg on negative selection. Surprisingly, however, although the thymi of IL-7Ralpha Tg mice were comparable at birth, there was a decrease in thymocyte number as the mice aged. This was found to be due to competition between DN and IL-7R-expressing DP cells for endogenous IL-7, which resulted in decreased levels of Bcl-2 in DN cells, increased DN apoptosis, and decreased DN cell number. Therefore, the down-regulation of IL-7R on DP cells is an "altruistic" act required for maintaining an adequate supply of local IL-7 for DN cells.