Communication between the stem cell niche and an adjacent differentiation niche through miRNA and EGFR signaling orchestrates exit from the stem cell state in the Drosophila ovary.

The signaling environment, or niche, often governs the initial difference in behavior of an adult stem cell and a derivative that initiates a path towards differentiation. The transition between an instructive stem cell niche and differentiation niche must generally have single-cell resolution, suggesting that multiple mechanisms might be necessary to sharpen the transition. Here, we examined the Drosophila ovary and found that Cap cells, which are key constituents of the germline stem cell (GSC) niche, express a conserved microRNA (miR-124). Surprisingly, loss of miR-124 activity in Cap cells leads to a defect in differentiation of GSC derivatives. We present evidence that the direct functional target of miR-124 in Cap cells is the epidermal growth factor receptor (EGFR) and that failure to limit EGFR expression leads to the ectopic expression of a key anti-differentiation BMP signal in neighboring somatic escort cells (ECs), which constitute a differentiation niche. We further found that Notch signaling connects EFGR activity in Cap cells to BMP expression in ECs. We deduce that the stem cell niche communicates with the differentiation niche through a mechanism that begins with the selective expression of a specific microRNA and culminates in the suppression of the major anti-differentiation signal in neighboring cells, with the functionally important overall role of sharpening the spatial distinction between self-renewal and differentiation environments.

Kidney Function Measures and Mortality: A Mendelian Randomization Study.

RATIONALE & OBJECTIVE: Individuals with a low estimated glomerular filtration rate (eGFR) are at a high risk of death. However, the causes underpinning this association are largely uncertain. This study aimed to assess the causal relationship of low eGFR with all-cause and cause-specific mortality. STUDY DESIGN: Retrospective cohort study incorporating Mendelian randomization (MR). SETTING & PARTICIPANTS: Individual-level data from 436,214 White participants (54.3% female; aged 56.8±8.0 years) included in the UK Biobank. EXPOSURES: eGFR estimated using cystatin C (eGFRcyst). OUTCOMES: The outcomes of interest included all-cause mortality, cardiovascular mortality, cancer mortality, infection mortality, and other-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards analysis for the conventional observational analyses; linear and nonlinear MR analyses implemented using genetic allele scores as instrumental variables representing kidney function to estimate the effect of kidney function on the survival outcomes. RESULTS: During a median follow-up of 12.1 years, there were 30,489 deaths, 6,098 of which were attributed to cardiovascular events, 15,538 to cancer, 1,516 to infection, and 7,227 to other events. In the conventional observational analysis, eGFRcyst exhibited a nonlinear association with all the outcomes. MR analysis suggested that a genetically predicted lower eGFRcyst was linearly associated with a higher rate of cardiovascular mortality (HR, 1.43; 95% CI, 1.18-1.75) across the entire measurement range (every 10-mL/min/1.73m2 decrement). Nonetheless, no causal associations between eGFRcyst and all-cause mortality (HR, 1.07; 95% CI, 0.98-1.17) or any types of noncardiovascular mortality were detected. LIMITATIONS: Potential misclassification of the actual cause of death, a nonrepresentative sample, and potential error in the interpretation of the magnitude of associations generated in MR analyses. CONCLUSIONS: These findings suggest a potential causal association between low eGFR and cardiovascular mortality in the general population, but no causal relationship with all-cause mortality or noncardiovascular mortality was observed. Further studies in other populations are warranted to confirm these findings. PLAIN-LANGUAGE SUMMARY: This study investigated the existence of a causal relationship between lower kidney function and death of different causes. Using data from 436,214 people in the United Kingdom, we applied conventional statistical analyses and those incorporating genetic data to implement Mendelian randomization, an approach that estimates causal associations. The observational analysis showed a nonlinear association between kidney function and various types of mortality outcomes. However, Mendelian randomization analysis suggested a linear increase in the risk of cardiovascular mortality with lower kidney function, but no causal link between the level of kidney function and all-cause or noncardiovascular mortality was identified. Managing kidney health may help reduce cardiovascular mortality, but caution is needed in interpreting the magnitudes of these results. Further validation in other populations and in those with advanced kidney failure is needed.

Unraveling the complex evolutionary history of lepidopteran chromosomes through ancestral chromosome reconstruction and novel chromosome nomenclature.

BACKGROUND: Lepidoptera is one of the most species-rich animal groups, with substantial karyotype variations among species due to chromosomal rearrangements. Knowledge of the evolutionary patterns of lepidopteran chromosomes still needs to be improved. RESULTS: Here, we used chromosome-level genome assemblies of 185 lepidopteran insects to reconstruct an ancestral reference genome and proposed a new chromosome nomenclature. Thus, we renamed over 5000 extant chromosomes with this system, revealing the historical events of chromosomal rearrangements and their features. Additionally, our findings indicate that, compared with autosomes, the Z chromosome in Lepidoptera underwent a fast loss of conserved genes, rapid acquisition of lineage-specific genes, and a low rate of gene duplication. Moreover, we presented evidence that all available 67 W chromosomes originated from a common ancestor chromosome, with four neo-W chromosomes identified, including one generated by fusion with an autosome and three derived through horizontal gene transfer. We also detected nearly 4000 inter-chromosomal gene movement events. Notably, Geminin is transferred from the autosome to the Z chromosome. When located on the autosome, Geminin shows female-biased expression, but on the Z chromosome, it exhibits male-biased expression. This contributes to the sexual dimorphism of body size in silkworms. CONCLUSIONS: Our study sheds light on the complex evolutionary history of lepidopteran chromosomes based on ancestral chromosome reconstruction and novel chromosome nomenclature.

Association Between Thromboelastography and Coronary Heart Disease.

BACKGROUND Thromboelastography (TEG) is a novel blood viscoelasticity detection method revealing blood coagulation status and has been reported to be helpful in predicting clinical outcomes in patients with cardiovascular diseases (CVD). In this study, we aimed to investigate the association between TEG and CVD. MATERIAL AND METHODS A single-center case-control study was performed. Individuals who took TEG tests at Tongji Hospital in Wuhan, China from 2015 to 2019 were included. The nearest-neighbor Mahalanobis matching with replacement, within propensity score calipers of 0.25 was used to control the covariate imbalance between CVD patients and controls. Logistic regression analyses were conducted to assess the relationship between TEG and CVD. Subgroup and sensitivity analyses were performed to evaluate the robustness of the association between TEG and CVD. RESULTS After matching, a total of 151 participants were included in this study, with 83 patients having CVD (49 patients having coronary heart disease [CHD] and 34 patients having an ischemic stroke). By comparison, CHD patients had a significantly higher maximum amplitude (MA) (P=0.02) than controls. After multivariable adjustment, MA (OR 1.11, 95% CI 1.01-1.24, P=0.04) was independently associated with CHD. The association between MA and CHD remained robust across subgroups and in sensitivity analyses. CONCLUSIONS The current study suggests that MA is significantly associated with CHD. Enhanced platelet reactivity as described by high MA might be associated with risk of CHD. The exact role of MA in the measurement of CHD risk needs to be further examined in large-scale prospective cohort studies.

A 3D bioprinted antibacterial hydrogel dressing of gelatin/sodium alginate loaded with ciprofloxacin hydrochloride.

Skin plays a crucial role in human physiological functions, however, it was vulnerable to bacterial infection which delayed wound healing. Nowadays, designing an individual wound dressing with good biocompatibility and sustaining anti-infection capability for healing of chronic wounds are still challenging. In this study, various concentrations of the ciprofloxacin (CIP) were mixed with gelatine (Gel)/sodium alginate (SA) solution to prepare Gel/SA/CIP (GAC) bioinks, following the fabrication of GAC scaffold by an extrusion 3D bioprinting technology. The results showed that the GAC bioinks had good printability and the printed GAC scaffolds double-crosslinked by EDC/NHS and CaCl2 had rich porous structure with appropriate pore size, which were conducive to drug release and cell growth. It demonstrated that the CIP could be rapidly released by 70% in 5 min, which endowed the GAC composite scaffolds with an excellent antibacterial ability. Especially, the antibacterial activities of GAC7.5 against Escherichia coli and Staphylococcus aureus within 24 h were even close to 100%, and the inhibition zones were still maintained 14.78 ± 0.40 mm and 14.78 ± 0.40 mm, respectively, after 24 h. Meanwhile, GAC7.5 also demonstrated impressive biocompatibility which can promote the growth and migration of L929 and accelerate wound healing. Overall, the GAC7.5 3D bioprinting scaffold could be used as a potential skin dressing for susceptible wounds with excellent antibacterial activity and good biocompatibility to meet urgent clinical needs.

A capsule-based scaffold incorporating decellularized extracellular matrix and curcumin for islet beta cell therapy in type 1 diabetes mellitus.

The transplantation of islet beta cells offers an alternative to heterotopic islet transplantation for treating type 1 diabetes mellitus (T1DM). However, the use of systemic immunosuppressive drugs in islet transplantation poses significant risks to the body. To address this issue, we constructed an encapsulated hybrid scaffold loaded with islet beta cells. This article focuses on the preparation of the encapsulated structure using 3D printing, which incorporates porcine pancreas decellularized extracellular matrix (dECM) to the core scaffold. The improved decellularization method successfully preserved a substantial proportion of protein (such as Collagen I and Laminins) architecture and glycosaminoglycans in the dECM hydrogel, while effectively removing most of the DNA. The inclusion of dECM enhanced the physical and chemical properties of the scaffold, resulting in a porosity of 83.62% ± 1.09% and a tensile stress of 1.85 ± 0.16 MPa. In teams of biological activity, dECM demonstrated enhanced proliferation, differentiation, and expression of transcription factors such as Ki67, PDX1, and NKX6.1, leading to improved insulin secretion function in MIN-6 pancreatic beta cells. In the glucose-stimulated insulin secretion experiment on day 21, the maximum insulin secretion from the encapsulated structure reached 1.96 ± 0.08 mIU ml-1, representing a 44% increase compared to the control group. Furthermore, conventional capsule scaffolds leaverage the compatibility of natural biomaterials with macrophages to mitigate immune rejection. Here, incorporating curcumin into the capsule scaffold significantly reduced the secretion of pro-inflammatory cytokine (IL-1ß, IL-6, TNF-α, IFN-γ) secretion by RAW264.7 macrophages and T cells in T1DM mice. This approach protected pancreatic islet cells against immune cell infiltration mediated by inflammatory factors and prevented insulitis. Overall, the encapsulated scaffold developed in this study shows promise as a natural platform for clinical treatment of T1DM.

Coordinated molecular and ecological adaptations underlie a highly successful parasitoid.

The success of an organism depends on the molecular and ecological adaptations that promote its beneficial fitness. Parasitoids are valuable biocontrol agents for successfully managing agricultural pests, and they have evolved diversified strategies to adapt to both the physiological condition of hosts and the competition of other parasitoids. Here, we deconstructed the parasitic strategies in a highly successful parasitoid, Trichopria drosophilae, which parasitizes a broad range of Drosophila hosts, including the globally invasive species D. suzukii. We found that T. drosophilae had developed specialized venom proteins that arrest host development to obtain more nutrients via secreting tissue inhibitors of metalloproteinases (TIMPs), as well as a unique type of cell-teratocytes-that digest host tissues for feeding by releasing trypsin proteins. In addition to the molecular adaptations that optimize nutritional uptake, this pupal parasitoid has evolved ecologically adaptive strategies including the conditional tolerance of intraspecific competition to enhance parasitic success in older hosts and the obligate avoidance of interspecific competition with larval parasitoids. Our study not only demystifies how parasitoids weaponize themselves to colonize formidable hosts but also provided empirical evidence of the intricate coordination between the molecular and ecological adaptations that drive evolutionary success.

Cohort profile for the Tongji Cardiovascular Health Study: a prospective multiomics cohort study.

PURPOSE: The Tongji Cardiovascular Health Study aimed to further explore the onset and progression mechanisms of cardiovascular disease (CVD) through a combination of traditional cohort studies and multiomics analysis, including genomics, metabolomics and metagenomics. STUDY DESIGN AND PARTICIPANTS: This study included participants aged 20-70 years old from the Geriatric Health Management Centre of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology. After enrollment, each participant underwent a comprehensive series of traditional and novel cardiovascular risk factor assessments at baseline, including questionnaires, physical examinations, laboratory tests, cardiovascular health assessments and biological sample collection for subsequent multiomics analysis (whole genome sequencing, metabolomics study from blood samples and metagenomics study from stool samples). A biennial follow-up will be performed for 10 years to collect the information above and the outcome data. FINDINGS TO DATE: A total of 2601 participants were recruited in this study (73.4% men), with a mean age of 51.5±11.5 years. The most common risk factor is overweight or obesity (54.8%), followed by hypertension (39.7%), hyperlipidaemia (32.4%), current smoking (23.9%) and diabetes (12.3%). Overall, 13.1% and 48.7% of men and women, respectively, did not have any of the CVD risk factors (hypertension, hyperlipidaemia, diabetes, cigarette smoking and overweight or obesity). Additionally, multiomics analyses of a subsample of the participants (n=938) are currently ongoing. FUTURE PLANS: With the progress of the cohort follow-up work, it is expected to provide unique multidimensional and longitudinal data on cardiovascular health in China.

Investigation on repairing diabetic foot ulcer based on 3D bio-printing Gel/dECM/Qcs composite scaffolds.

Diabetic foot ulcers are one of the most serious of the numerous complications of diabetes mellitus, causing great physical trauma and financial stress to patients, and accelerating wound healing in diabetic patients remains one of the major clinical challenges. Exosomes from adipose-derived stem cells can directly and indirectly promote wound healing. However, due to the low retention rate of exosomes in the wound, exosome treatment is difficult to achieve the expected effect. Therefore, it is of great significance to synthesize a composite scaffold that can stably load exosomes and has antibacterial properties. In this study, fresh pig skin was decellularized to obtain decellularized matrix (dECM). Secondly, quaternized chitosan (Qcs) was modified with quaternary ammonium salt to make it soluble in water after quaternization. Finally, Gel-dECM-Qcs (GDQ) bioink was prepared by adding acellular matrix and quaternized chitosan with temperature sensitive gelatin (Gel) as carrier. Tissue engineered composite scaffolds were then prepared by extrusion 3D printing technology. Subsequently, the physicochemical properties, biocompatibility and antimicrobial capacity of the composite scaffolds were determined, and the data showed that the composite scaffolds had good mechanical properties, biocompatibility and antimicrobial capacity, and the maximum stress of the composite scaffolds was 1.16 ± 0.05 MPa, the composite scaffolds were able to proliferate and adhered to the L929 cells, and the kill rates of composite scaffolds against E. coli and S. aureus after incubation for 24 h were 93.24 ± 1.22 % and 97.34 ± 0.23 %, respectively. Overall, the GDQ composite scaffolds have good mechanical properties adapted to skin bending, its good biocompatibility can promote the growth and migration of fibroblasts, reshape injured tissues, accelerate the wound healing, and excellent antimicrobial ability can inhibit the growth of E. coli and S. aureus, reducing the impact of bacterial infections on wounds. Moreover, the composite scaffolds have the potential to be used as exosom-loaded hydrogel dressings, which provides a basis for the subsequent research on the repair of diabetic foot ulcers.

The odorant receptor co-receptor gene contributes to mating and host-searching behaviors in parasitoid wasps.

BACKGROUND: Biological control of pest insects by parasitoid wasps is an effective and environmentally friendly strategy compared with the use of synthetic pesticides. Successful courtship and host-search behaviors of parasitoid wasps are important for biological control efficiency and are often mediated by chemical odorant cues. The odorant receptor co-receptor (Orco) gene has an essential role in the perception of odors in insects. However, the function of Orco in the mating and host-searching behaviors of parasitoid wasps remains underexplored. RESULTS: We identified the full-length Orco genes of four Drosophila parasitoid species in the genus Leptopilina, namely L. heterotoma, L. boulardi, L. syphax and L. drosophilae. Sequence alignment and membrane-topology analysis showed that Leptopilina Orcos had similar amino acid sequences and topology structures. Phylogenetic analysis revealed that Leptopilina Orcos were highly conserved. Furthermore, the results of quantitative real-time polymerase chain reactions showed that all four Orco genes had a typical antennae-biased tissue expression pattern. After knockdown of Orco in these different parasitoid species, we found that Orco-deficient male parasitoid wasps, but not females, lost their courtship ability. Moreover, Orco-deficient female parasitoid wasps presented impaired host-searching performance and decreased oviposition rates. CONCLUSION: Our study demonstrates that Orcos are essential in the mating and host-searching behaviors of parasitoid wasps. To our knowledge, this is the first time that the functions of Orco genes have been characterized in parasitoid wasps, which broadens our understanding of the chemoreception basis of parasitoid wasps and contributes to developing advanced pest management strategies. © 2022 Society of Chemical Industry.