Developmental potential of non- and mono-pronuclear zygotes and associated clinical outcomes in IVF cycles.

Purpose: This study aims to evaluate the developmental potential of 0PN, 1PN, and 2PN zygotes in IVF cycles and compare their clinical outcomes. Methods: We conducted a retrospective cohort study involving IVF patients. Blastocyst formation rates were assessed with 0PN, 1PN, and 2PN zygotes. Subsequently, we collected clinical outcome data following the transfer of these zygotes. Results: The overall blastulation rate was similar between 0PN (29.6%) and 2PN (32.1%) zygotes, but 1PN zygotes exhibited a significantly lower blastulation rate (17.0%) compared to both 0PN and 2PN zygotes. Similarly, the overall rate of good-quality blastulation was comparable between 0PN (15.3%) and 2PN (17.5%) zygotes, while 1PN zygotes showed a significantly lower rate (7.0%) compared to both 0PN and 2PN. Clinical pregnancy, ectopic pregnancy, implantation, and live birth rates were similar among single blastocyst frozen embryo transfers (FET) of 0PN, 1PN, and 2PN. Additionally, no significant differences were observed between single- and double-blastocyst FET of 0PN and 2PN. Conclusions: Our findings suggest that 0PN and 2PN zygotes have comparable developmental potential, while 1PN embryos exhibit lower developmental potential. Blastocyst FET outcomes appear similar among 0PN, 1PN, and 2PN zygotes.

Long-term organic amendments increase the vulnerability of microbial respiration to environmental changes: Evidence from field and laboratory studies.

Organic amendments can improve soil fertility and microbial diversity, making agroecosystems more resilient to stress. However, it is uncertain whether organic amendments will enhance the functional capacity of soil microbial communities, thereby mitigating fluctuations in microbial respiration caused by environmental changes. Here, we examined the impacts of long-term organic amendments on the dynamics of microbial catabolic capacity (characterized by enzyme activities and carbon source utilization) and microbial respiration, as well as their interrelationships during a period with fluctuating temperature and rainfall in the field. We then subjected the field soil samples to laboratory heating disturbances to further evaluate the importance of microbial catabolic capacity in explaining patterns of microbial respiration. In both field and laboratory experiments, organic amendments tended to increase the stability of microbial catabolic capacity, but significantly increased the vulnerability of microbial respiration to environmental changes. However, the direction and driving factors of microbial respiration affected by environmental changes differed between the field and laboratory experiments. Environmental changes in the field suppressed the promotional effects of organic amendments on microbial respiration mainly through reducing microbial catabolic capacity, while laboratory heating further enhanced microbial respiration mainly due to increased soil resource availability. Together, these findings suggest that increased microbial respiration variations under organic amendments may potentially increase the uncertainty in predicting soil carbon emissions in the scenario of ongoing climate/anthropogenic changes, and highlight the necessity of linking laboratory studies on environmental changes to field conditions.

Is elevated baseline SHBG associated with increased ovulation?

Sexual hormone binding globulin (SHBG) is associated with the endocrine and reproductive systems. We aimed to investigate the role of SHBG in the reproductive process. Therefore, we conducted a secondary analysis of the PCOSAct (Polycystic Ovary Syndrome and Acupuncture Clinical Trial) study, which involved 21 sites in China and a total of 1000 women with PCOS. Out of these, 954 women with SHBG were included in the analysis. Through multivariate analysis of ovulation predictors, we found that age, BMI, estradiol, testosterone, and SHBG all showed a positive predictive value for ovulation (p = 0.0211, 0.0011, 0.0211, 0.0029, 0.0434, respectively). However, the LH to FSH ratio had a negative predictive value (p = 0.0539). Higher quartiles of SHBG were associated with a higher rate of ovulation, and per quartile increased was statistically significant (HR = 1.138, 95%CI [1.054,1.229]). The association remained significant even after adjusting for testosterone (HR = 1.263, 95%CI [1.059, 1.507]). On the other hand, quartiles of testosterone and estradiol did not exhibit any significant tendency toward ovulation. SHBG demonstrated predictive ability for ovulation, conception, pregnancy, and live birth (p < 0.05), and this correlation remained significant after adjusting intervention. Kaplan-Meier curves illustrated that increased levels of SHBG were a factor in high rates of ovulation, conception, and pregnancy. In comparison to other sexual hormones, a higher baseline level of SHBG was related to increased ovulation.

Spatiotemporal distribution of migraine in China: analyses based on baidu index.

BACKGROUND: In recent years, innovative approaches utilizing Internet data have emerged in the field of syndromic surveillance. These novel methods aim to aid in the early prediction of epidemics across various scenarios and diseases. It has been observed that these systems demonstrate remarkable accuracy in monitoring outbreaks even before they become apparent in the general population. Therefore, they serve as valuable complementary tools to augment existing methodologies. In this study, we aimed to investigate the spatiotemporal distribution of migraine in China by leveraging Baidu Index (BI) data. METHODS: Migraine-related BI data from January 2014 to December 2022 were leveraged, covering 301 city-level areas from 31 provincial-level regions by using the keyword "migraine ()". Prevalence data from the Global Burden of Disease study (GBD) were attracted to ensure the reliability of utilizing migraine-related BI data for research. Comprehensive analytical methods were then followed to investigate migraine's spatiotemporal distribution. The Seasonal-Trend decomposition procedure based on Loess (STL) was used to identify the temporal distribution. Spatial distribution was explored using the Getis-Ord Gi* statistic, standard deviation ellipse analysis, Moran's Index, and Ordinary Kriging. The top eight migraine-related search terms were analyzed through the Demand Graph feature in the Baidu Index platform to understand the public's concerns related to migraine. RESULTS: A strong association was observed between migraine-related BI and the prevalence data of migraine from GBD with a Spearman correlation coefficient of 0.983 (P = 4.96 × 10- 5). The overall trend of migraine-related BI showed a gradual upward trend over the years with a sharp increase from 2017 to 2019. Seasonality was observed and the peak period occurred in spring nationwide. The middle-lower reaches of the Yangtze River were found to be hotspots, while the eastern coastal areas had the highest concentration of migraine-related BI, with a gradual decrease towards the west. The most common search term related to migraine was "How to treat migraine quickly and effectively ()". CONCLUSIONS: This study reveals important findings on migraine distribution in China, underscoring the urgent need for effective prevention and management strategies.

CircRNAs: A Promising Star for Treatment and Prognosis in Oral Squamous Cell Carcinoma.

CircRNAs are a class of endogenous long non-coding RNAs with a single-stranded circular structure. Most circRNAs are relatively stable, highly conserved, and specifically expressed in tissue during the cell and developmental stages. Many circRNAs have been discovered in OSCC. OSCC is one of the most severe and frequent forms of head and neck cancer today, with a poor prognosis and low overall survival rate. Due to its prevalence, OSCC is a global health concern, characterized by genetic and epigenomic changes. However, the mechanism remains vague. With the advancement of biotechnology, a large number of circRNAs have been discovered in mammalian cells. CircRNAs are dysregulated in OSCC tissues and thus associated with the clinicopathological characteristics and prognosis of OSCC patients. Research studies have demonstrated that circRNAs can serve as biomarkers for OSCC diagnosis and treatment. Here, we summarized the properties, functions, and biogenesis of circRNAs, focusing on the progress of current research on circRNAs in OSCC.

Discovery of Tetronate-Containing Kongjuemycins from a Coral-Associated Actinomycete and Elucidation of Their Biosynthetic Origin.

Tetronate antibiotics make up a growing family of natural products with a wide variety of biological activities. Herein, we report four new tetronates kongjuemycins (KJMs, 5-8) from a coral-associated actinomycete Pseudonocardia kongjuensis SCSIO 11457, and the identification and characterization of the KJM biosynthetic gene cluster (kjm) by heterologous expression, comparative genomic analysis, isotope labeling, and gene knockout studies. The biosynthesis of KJMs is demonstrated to harness diverse precursors from primary metabolism for building secondary metabolites.

Biosynthesis and Engineered Overproduction of Everninomicins with Promising Activity against Multidrug-Resistant Bacteria.

Ribosome-targeting oligosaccharides, everninomicins (EVNs), are promising drug leads with a unique mode of action distinct from that of currently used antibiotics in human therapy. However, the low yields in natural microbial producers hamper an efficient preparation of EVNs for detailed structure-activity relationship analysis. Herein, we enhance the production of EVNs by duplicating the biosynthetic gene cluster (BGC) in Micromonospora sp. SCSIO 07395 and thus obtain multiple EVNs that are sufficient for bioactivity evaluation. EVNs (1-5) are shown to significantly inhibit the growth of multidrug-resistant Gram-positive staphylococcal, enterococcal, and streptococcal strains and Gram-negative pathogens Acinetobacter baumannii and Vibrio cholerae, with micromolar to nanomolar potency, which are comparable or superior to vancomycin, linezolid, and daptomycin. Furthermore, the BGC duplication strategy is proven effective in stepwisely improving titers of the bioactive EVN M (5) from the trace amount to 98.6 mg L-1. Our findings demonstrate the utility of a bioengineering approach for enhanced production and chemical diversification of the medicinally promising EVNs.

Biosynthetic Diversification of Fidaxomicin Aglycones by Heterologous Expression and Promoter Refactoring.

Fidaxomicin (Dificid) is a commercial macrolide antibiotic for treating Clostridium difficile infection. Total synthesis of fidaxomicin and its aglycone had been achieved through different synthetic schemes. In this study, an alternative biological route to afford the unique 18-membered macrolactone aglycone of fidaxomicin was developed. The promoter refactored fidaxomicin biosynthetic gene cluster from Dactylosporangium aurantiacum was expressed in the commonly used host Streptomyces albus J1074, thereby delivering five structurally diverse fidaxomicin aglycones with the corresponding titers ranging from 4.9 to 15.0 mg L-1. In general, these results validated a biological strategy to construct and diversify fidaxomicin aglycones on the basis of promoter refactoring and heterologous expression.

Identification and prevalence investigation of cyathocotylid trematode (Trematoda: Digenea: Cyathocotylidae) in Carassius auratus in Wuhu, China.

The family Cyathocotylidae trematode is a world-widely distributed parasite whose adults are mainly found in fish, reptiles, birds, and mammals in both freshwater and marine environments. However, little is known of the prevalence of these trematode in China. For the first time, we found Cyathocotylidae trematode in the Wuhu area. Therefore, we investigated the prevalence of metacercariae in Carassius auratus from Zhang Lake, Kui Lake, Qingyi River, and Yangtze River (Wuhu Section) in Wuhu area. A total of 392 one-year-old C. auratus were tested in January, April, July, and October 2019, respectively. After the fish were euthanized, the back, chest, and tail muscles were used for preliminary screening for the presence of metacercariae by direct compression method. Metacercariae were isolated by the artificial digestion method and then morphologically and molecularly identified by cox1 (642 bp) and ITS2 (418 bp) sequences amplification by PCR. Based on morphological features and sequence analysis, they were identified as cyathocotylid metacercariae. The four water sources have different degrees of prevalence throughout the year, the prevalence ranges from 28.45% (29/102) in Yangtze River to 50.55% (46/91) in Zhang Lake, with an average prevalence of 40.56% (159/392). There were also differences in the prevalence in different months: The highest occurred in July, which was 81.63% (80/98), while the lowest occurred in January, which was 8.89% (8/90). This study can provide basic data for the prevention and control of cyathocotylid trematode in this area.

The efficacy and mechanism of acupuncture in the treatment of male infertility: A literature review.

Fertility, a social, cultural, and medical issue, has aroused public attention because of its potential to predict future health. In recent years, the incidence of male infertility has increased significantly, and various risk factors, such as congenital factors, acquired factors, and idiopathic factors, have led to this situation. Male infertility causes substantial psychological and social distress in patients. With the implementation of the two-child policy, male infertility has brought enormous psychological and social pressure and huge economic burden to patients and the healthcare system. This has attracted the attention of not only men of childbearing age but also many male experts. The conventional therapeutic approaches for treating male infertility, including drugs, varicocele surgery, intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection, can restore fertility to a certain extent, but their efficacy is far from satisfactory, not to mention some adverse events. Therefore, acupuncture has been chosen by many men to treat their infertility and produced significant effects. In the present paper, the efficacy and mechanism of acupuncture in the treatment of male infertility were analyzed from different perspectives such as regulating hormone secretion, reducing inflammation, and improving semen parameters. The existing literature shows that acupuncture can effectively treat male infertility.

Oncogenic Role of HMGB1 as An Alarming in Robust Prediction of Immunotherapy Response in Colorectal Cancer.

OBJECTIVE: To assess the correlation between HMGB1 expression and the patient prognosis in a multicancer context. METHODS: The potential oncogenic role of HMGB1 was explored in forty tumors through the TCGA, GEO, and Oncomine datasets. We analyzed the clinical prognostic value and antitumor immunotherapy of HMGB1 in a multicancer context using GEO (GSE111636). RESULTS: High expression of HMGB1 is present in multicancer cases, and its low expression is closely associated with the prognostic survival of patients, in terms of both overall and disease-free survival in ACC and LUAD. Further investigation revealed that the high expression of gastric and lung cancer is closely associated with low risk and better prognosis of patients based on COX and Kaplan-Meier analysis of OS, FP and PPS. HMGB1 expression was found to be significantly correlated with cancer-associated fibroblast and CD8+ T cell infiltration in the TME. The analysis of GO functional annotation/KEGG pathways indicates that HMGB1 may regulate tumor immunity-related pathways, such as the tumor immunotherapy response in colorectal cancer. The function of four genes as hubs are confirmed by in vitro HMGB1 knockdown which led to inhibition of cell proliferation and metastasis in SW620 and SW480 cells. CONCLUSION: HMGB1 is a potential novel biomarker for improving clinical prognosis and antitumor immunotherapy efficacy. CDK1, HMGB2, SSRP1, and H2AFV may serve as key nodes for HMGB1 in colorectal cancer.

Secondary Intention Healing of Nasal Ala and Tip Defects: A Simple and Valuable Treatment Option.

Purpose: To investigate the cosmetic outcomes of secondary intention healing of small (<1.5cm) nasal ala and tip defects. Patients and Methods: From August 2017 to October 2020, 42 patients with nasal reconstructions using secondary intention healing were included. Defects after excision ranged from 0.5cm×0.7cm to 1.2cm×1.5cm in size. Foam dressing covering the wounds was changed every 3 to 5 days. Wound esthetic outcomes were graded as excellent, good, acceptable, and poor based on definitions described in the literature. Results: All 42 wounds healed in 3 to 4 weeks, with uniform color, no obvious adverse reactions and high patient satisfaction. Esthetic evaluation: 16 excellent cases (38.1%), 19 good cases (45.2%), 7 acceptable cases (16.7%) and 0 poor cases. Conclusion: Secondary intention healing of small nasal tip and ala defects in Chinese yielded satisfactory esthetic outcomes and should be an integral part of the surgeon's reconstructive algorithm.

The Effect of Age on IVF-ET Outcome in Infertile Patients with PCOS Based on Tiangui Theory in Chinese Medicine.

Objective: Our aim was to investigate the effect of age on the outcome of IVF-ET and ICSI in infertile PCOS patients under the guidance of Tiangui theory in traditional Chinese medicine. Method: This was a retrospective analysis of 532 infertile women with PCOS and 1,392 women with infertility due to tubal factors as the controls. All of the participants were divided into different age groups-aged 20-28 years, 29-35 years, and ≥36 years-according to the stages of female reproductive development in Tiangui theory as described in the Canon of Internal Medicine-Treatise of Ancient Natural Truth. We explored the effect of age on controlled ovarian hyperstimulation (including the initial dosage and duration of Gn and the estradiol level on the day of human chorionic gonadotropin administration); the numbers of retrieved oocytes, 2PN zygotes, and embryos; and the rates of fertilization, clinical pregnancy, abortion, live birth, and OHSS incidence. Results: Compared to controls, the maximum follicular diameter and the numbers of follicles with d ≥ 20 mm, retrieved oocytes, and 2PN zygotes were greater in the PCOS group with age >28 years (p < 0.05). The abortion rate of PCOS patients with age ≤28 years was higher than that of the controls. All PCOS groups and the control group showed reduced numbers of retrieved oocytes and live births with age. The difference in age was not significant in the PCOS groups but was significant in the control group (p < 0.05), and the trend in the PCOS groups was more gradual. Conclusion: The fertility of all subjects decreased with age, but PCOS patients decreased more slowly than in controls at the same age, which verified the applicability of the guiding principles of Tiangui theory in the clinic.

PUMILIO-mediated translational control of somatic cell cycle program promotes folliculogenesis and contributes to ovarian cancer progression.

Translational control is a fundamental mechanism regulating animal germ cell development. Gonadal somatic cells provide support and microenvironment for germ cell development to ensure fertility, yet the roles of translational control in gonadal somatic compartment remain largely undefined. We found that mouse homolog of conserved fly germline stem cell factor Pumilio, PUM1, is absent in oocytes of all growing follicles after the primordial follicle stage, instead, it is highly expressed in somatic compartments of ovaries. Global loss of Pum1, not oocyte-specific loss of Pum1, led to a significant reduction in follicular number and size as well as fertility. Whole-genome identification of PUM1 targets in ovarian somatic cells revealed an enrichment of cell proliferation pathway, including 48 key regulators of cell phase transition. Consistently granulosa cells proliferation is reduced and the protein expression of the PUM-bound Cell Cycle Regulators (PCCR) were altered accordingly in mutant ovaries, and specifically in granulosa cells. Increase in negative regulator expression and decrease in positive regulators in the mutant ovaries support a coordinated translational control of somatic cell cycle program via PUM proteins. Furthermore, postnatal knockdown, but not postnatal oocyte-specific loss, of Pum1 in Pum2 knockout mice reduced follicular growth and led to similar expression alteration of PCCR genes, supporting a critical role of PUM-mediated translational control in ovarian somatic cells for mammalian female fertility. Finally, expression of human PUM protein and its regulated cell cycle targets exhibited significant correlation with ovarian cancer and prognosis for cancer survival. Hence, PUMILIO-mediated cell cycle regulation represents an important mechanism in mammalian female reproduction and human cancer biology.

Genetic Risk for Overall Cancer and the Benefit of Adherence to a Healthy Lifestyle.

Cancer site-specific polygenic risk scores (PRS) effectively identify individuals at high risk of individual cancers, but the effectiveness of PRS on overall cancer risk assessment and the extent to which a high genetic risk of overall cancer can be offset by a healthy lifestyle remain unclear. Here, we constructed an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific PRSs. Lifestyle was determined according to smoking, alcohol consumption, physical activity, body mass index, and diet. Cox regression by sex was used to analyze associations of genetic and lifestyle factors with cancer incidence using UK Biobank data (N = 442,501). Compared with participants at low genetic risk (bottom quintile of CPRS), those at intermediate (quintiles 2 to 4) or high (top quintile) genetic risk had HRs of 1.27 (95% confidence interval, 1.21-1.34) or 1.91 (1.81-2.02) for overall cancer, respectively, for men, and 1.21 (1.16-1.27) or 1.62 (1.54-1.71), respectively, for women. A joint effect of genetic and lifestyle factors on overall cancer risk was observed, with HRs reaching 2.99 (2.45-3.64) for men and 2.38 (2.05-2.76) for women with high genetic risk and unfavorable lifestyle compared with those with low genetic risk and favorable lifestyle. Among participants at high genetic risk, the standardized 5-year cancer incidence was significantly reduced from 7.23% to 5.51% for men and from 5.77% to 3.69% for women having a favorable lifestyle. In summary, individuals at high genetic risk of overall cancer can be identified by CPRS, and risk can be attenuated by adopting a healthy lifestyle. SIGNIFICANCE: A new indicator of cancer polygenic risk score measures genetic risk for overall cancer, which could identify individuals with high cancer risk to facilitate decision-making about lifestyle modifications for personalized prevention.

Repurposing the 3-Isocyanobutanoic Acid Adenylation Enzyme SfaB for Versatile Amidation and Thioesterification.

Genome mining of microbial natural products enables chemists not only to discover the bioactive molecules with novel skeletons, but also to identify the enzymes that catalyze diverse chemical reactions. Exploring the substrate promiscuity and catalytic mechanism of those biosynthetic enzymes facilitates the development of potential biocatalysts. SfaB is an acyl adenylate-forming enzyme that adenylates a unique building block, 3-isocyanobutanoic acid, in the biosynthetic pathway of the diisonitrile natural product SF2768 produced by Streptomyces thioluteus, and this AMP-ligase was demonstrated to accept a broad range of short-chain fatty acids (SCFAs). Herein, we repurpose SfaB to catalyze amidation or thioesterification between those SCFAs and various amine or thiol nucleophiles, thereby providing an alternative enzymatic approach to prepare the corresponding amides and thioesters in vitro.

Diisonitrile-Mediated Reactive Oxygen Species Accumulation Leads to Bacterial Growth Inhibition.

The diisonitrile copper chelator SF2768 biosynthesized by Streptomyces thioluteus functions as a chalkophore that transports extracellular copper into producer cells in a complexed form. It was demonstrated that the treatment of eight bacteria, including Bacillus subtilis and Acinetobacter baumannii, with SF2768 led to a moderate growth inhibition which is associated with an increased level of reactive oxygen species (ROS). In addition, SF2768 and its diisonitrile analogues proved to be effective tyrosinase inhibitors. Three new analogues, SF2768 I, K, and L, were identified by detailed spectroscopic analysis.

MicroRNA-23a contributes to hippocampal neuronal injuries and spatial memory impairment in an experimental model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common form of epilepsy characterized by spontaneous recurrent seizures. It has been widely accepted that individuals with TLE tend to have neuronal injuries and memory impairment. However, little is known about the underlying molecular mechanisms. MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of target genes at the posttranscriptional level. An increasing body of evidence suggests that miRNAs play pivotal roles in the pathogenesis of epilepsy. Here, we sought to determine the role of miR-23a, one of the most common miRNAs involved in various cancer types, in hippocampal neuronal injuries and spatial memory impairment in an experimental model of TLE. We found that miR-23a is upregulated in the hippocampus after status epilepticus (SE) in kanic acid (KA)-induced TLE mice. Furthermore, the upregulation of miR-23a is accompanied by hippocampal oxidative damage, neuronal injuries and spatial memory impairment in TLE mice. Inhibition of miR-23a expression by miR-23a antagomirs reduced hippocampal oxidative stress, neuronal injuries and improved spatial memory, while an increase in miR-23a expression by miR-23a agomir exacerbated hippocampal oxidative stress, neuronal injuries and spatial memory impairment in TLE mice. Our findings suggest that miR-23a contributes to hippocampal oxidative damage and neuronal injuries, which may consequently contribute to spatial memory impairment in TLE mice. Thus, targeting miR-23a in the epileptic brain may provide a novel strategy for protecting against hippocampal neuronal injuries and improving spatial memory in TLE patients.

DAZL is a master translational regulator of murine spermatogenesis.

Expression of DAZ-like (DAZL) is a hallmark of vertebrate germ cells, and is essential for embryonic germ cell development and differentiation, yet the gametogenic function of DAZL has not been fully characterized and most of its in vivo direct targets remain unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells, meiotic arrest and spermatid arrest. Using the genome-wide high-throughput sequencing of RNAs isolated by cross-linking immunoprecipitation and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at the 3'-untranslated region and interacted with translation proteins including poly(A) binding protein. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts, were significantly decreased, resulting in a drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.

Mammalian Pum1 and Pum2 Control Body Size via Translational Regulation of the Cell Cycle Inhibitor Cdkn1b.

Body and organ size regulation in mammals involves multiple signaling pathways and remains largely enigmatic. Here, we report that Pum1 and Pum2, which encode highly conserved PUF RNA-binding proteins, regulate mouse body and organ size by post-transcriptional repression of the cell cycle inhibitor Cdkn1b. Binding of PUM1 or PUM2 to Pumilio binding elements (PBEs) in the 3' UTR of Cdkn1b inhibits translation, promoting G1-S transition and cell proliferation. Mice with null mutations in Pum1 and Pum2 exhibit gene dosage-dependent reductions in body and organ size, and deficiency for Cdkn1b partially rescues postnatal growth defects in Pum1-/- mice. We propose that coordinated tissue-specific expression of Pum1 and Pum2, which involves auto-regulatory and reciprocal post-transcriptional repression, contributes to the precise regulation of body and organ size. Hence PUM-mediated post-transcriptional control of cell cycle regulators represents an additional layer of control in the genetic regulation of organ and body size.