Sertoli cells are the source of stem cell factor for spermatogenesis.

Several cell types have been proposed to create the required microenvironment for spermatogenesis. However, expression patterns of the key growth factors produced by these somatic cells have not been systematically studied and no such factor has been conditionally deleted from its primary source(s), raising the question of which cell type(s) are the physiological sources of these growth factors. Here, using single-cell RNA sequencing and a series of fluorescent reporter mice, we found that stem cell factor (Scf), one of the essential growth factors for spermatogenesis, was broadly expressed in testicular stromal cells, including Sertoli, endothelial, Leydig, smooth muscle and Tcf21-CreER+ stromal cells. Both undifferentiated and differentiating spermatogonia were associated with Scf-expressing Sertoli cells in the seminiferous tubule. Conditional deletion of Scf from Sertoli cells, but not any other Scf-expressing cells, blocked the differentiation of spermatogonia, leading to complete male infertility. Conditional overexpression of Scf in Sertoli cells, but not endothelial cells, significantly increased spermatogenesis. Our data reveal the importance of anatomical localization for Sertoli cells in regulating spermatogenesis and that SCF produced specifically by Sertoli cells is essential for spermatogenesis.

LKB1 suppresses KSHV reactivation and promotes primary effusion lymphoma progression.

Viruses normally reprogram the host cell metabolic pathways as well as metabolic sensors to facilitate their persistence. The serine-threonine liver kinase B1 (LKB1) is a master upstream kinase of 5'-AMP-activated protein kinase (AMPK) that senses the energy status and therefore regulates the intracellular metabolic homeostasis. Previous studies showed that AMPK restricts Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication in endothelial cells during primary infection and promotes primary effusion lymphoma (PEL) cell survival. However, the role of LKB1 in KSHV lytic reactivation and KSHV-associated malignancies is unclear. In this study, we found that LKB1 is phosphorylated or activated in KSHV-positive PEL cells. Mechanistically, KSHV-encoded vCyclin mediated LKB1 activation in PEL cells, as vCyclin knockout ablated, while vCyclin overexpression enhanced LKB1 activation. Furthermore, knockdown of LKB1 inactivated AMPK and induced KSHV reactivation, as indicated by the increased expression of viral lytic genes and the increased virions in supernatants. Accordingly, AMPK inhibition by functional knockdown or a pharmacologic inhibitor, Compound C, promoted KSHV reactivation in PEL cells. Furthermore, inhibition of either LKB1 or AMPKα1 efficiently induced cell death by apoptosis of PEL cells both in vitro and in vivo. Together, these results identify LKB1 as a vulnerable target for PEL, which could be potentially exploited for treating other virus-associated diseases.IMPORTANCEKaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus associated with several human cancers, such as primary effusion lymphoma (PEL). Here, we showed that serine-threonine liver kinase B1 (LKB1), upstream of 5' AMP-activated protein kinase (AMPK), is activated by KSHV-encoded vCyclin and maintains KSHV latency in PEL cells. Inhibition of either LKB1 or AMPK enhances KSHV lytic replication from latency, which at least partially accounts for PEL cell death by apoptosis. Compound C, a potent AMPK inhibitor, induced KSHV reactivation and efficiently inhibited PEL progression in vivo. Thus, our work revealed that LKB1 is a potential therapeutic target for KSHV-associated cancers.

Preoxidation and Prilling Combined with Doping Strategy to Build High-Performance Recycling Spent LiFePO4 Materials.

Direct regeneration has gained much attention in LiFePO4 battery recycling due to its simplicity, ecofriendliness, and cost savings. However, the excess carbon residues from binder decomposition, conductive carbon, and coated carbon in spent LiFePO4 impair electrochemical performance of direct regenerated LiFePO4. Herein, we report a preoxidation and prilling collaborative doping strategy to restore spent LiFePO4 by direct regeneration. The excess carbon is effectively removed by preoxidation. At the same time, prilling not only reduces the size of the primary particles and shortens the diffusion distance of Li+ but also improves the tap density of the regenerated materials. Besides, the Li+ transmission of the regenerated LiFePO4 is further improved by Ti4+ doping. Compared with commercial LiFePO4, it has excellent low-temperature performance. The collaborative strategy provides a new insight into regenerating high-performance spent LiFePO4.

High-Entropy Configuration Strategy to Build High Performance Na-Ion Layered Oxide Cathodes Derived from Simple Techniques.

Layered transition metal oxides are commonly used as the cathode materials in sodium-ion batteries due to their low cost and easy manufacturing. However, the application is hindered by poor rate performance and complex phase transitions. To address these challenges, a new seven-component high-entropy layered oxide cathode material, O3-NaNi0.25Fe0.15Mn0.3Ti0.1Sn0.05Co0.05Li0.1O2 (HEO) has been developed. The entropy stabilization effect plays a crucial role in improving the performance of electrochemical systems and the stability of structures. The HEO exhibits a specific discharge capacity of 154.1 mA h g-1 at 0.1 C and 94.5 mA h g-1 at 7 C. In-situ and ex-situ XRD results demonstrate that the HEO effectively retards complex phase transitions. This work provides a high-entropy design for the storage materials with a high energy density. Meanwhile, it eliminates industry doubts about the performance of sodium ion layered oxide cathode materials.

Prilling and Coating Strategy to Synthesize High-Performance Spherical NaNi0.4Fe0.2Mn0.4O2 Cathode Materials for Sodium Ion Batteries.

Low-cost sodium ion batteries are of great significance in large-scale energy storage applications. With its high energy density and simple synthesis process, layered transition-metal oxides have become one of the most likely sodium ion battery cathode materials to replace lithium ion batteries in the energy storage market. Here, we report a prilling and MoS2 coating strategy to prepare the spherical cathode material. The spherical micronano particles shorten the diffusion path of Na+, restrain the complexity phase transitions, and enhance the tap density of the materials. In addition, the MoS2 coating improves the electrical conductivity of the material and the structural stability of the cathode material in air. The initial specific discharge capacity is 148.4 mA h g-1 at 0.1 C, which can be maintained at 128.9 mA h g-1 after exposure to air for 10 days. This method dramatically improves the energy density and structural stability of the cathode material, which provides a new scheme for preparing high-performance sodium ion batteries.

Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approach.

Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways.

Synthesis and Kinetics of CO2-Responsive Gemini Surfactants.

Surfactants are hailed as "industrial monosodium glutamate", and are widely used as emulsifiers, demulsifiers, water treatment agents, etc., in the petroleum industry. However, due to the unidirectivity of conventional surfactants, the difficulty in demulsifying petroleum emulsions generated after emulsification with such surfactants increases sharply. Therefore, it is of great significance and application value to design and develop a novel switchable surfactant for oil exploitation. In this study, a CO2-switchable Gemini surfactant of N,N'-dimethyl-N,N'-didodecyl butylene diamine (DMDBA) was synthesized from 1, 4-dibromobutane, dodecylamine, formic acid, and formaldehyde. Then, the synthesized surfactant was structurally characterized by infrared (IR) spectroscopy, hydrogen nuclear magnetic resonance (1H NMR) spectroscopy, and electrospray ionization mass spectrometry (ESI-MS); the changes in conductivity and Zeta potential of DMDBA before and after CO2/N2 injection were also studied. The results show that DMDBA had a good CO2 response and cycle reversibility. The critical micelle concentration (CMC) of cationic surfactant obtained from DMDBA by injecting CO2 was 1.45 × 10-4 mol/L, the surface tension at CMC was 33.4 mN·m-1, and the contact angle with paraffin was less than 90°, indicating that it had a good surface activity and wettability. In addition, the kinetic law of the process of producing surfactant by injecting CO2 was studied, and it was found that the process was a second-order reaction. The influence of temperature and gas velocity on the reaction dynamics was explored. The calculated values from the equation were in good agreement with the measured values, with a correlation coefficient greater than 0.9950. The activation energy measured during the formation of surfactant was Ea = 91.16 kJ/mol.

Factors, Mechanisms, and Kinetics of Spontaneous Emulsification for Heavy Oil-in-Water Emulsions.

In challenging reservoirs where thermal recovery falls short, cold or chemical oil recovery methods are crucial. Spontaneous emulsification (SE), triggered by gentle disturbance, significantly enhances oil recovery. In elucidating SE mechanisms and kinetics, SE processes via direct contact between oil and aqueous phases without stirring were conducted. The effects of temperature, emulsifier concentration, pH, NaCl concentration, and the oil-to-water ratio on SE were investigated through droplet size analysis and turbidity measurements. Furthermore, the emulsification mechanism and derived emulsification kinetics based on turbidity data were obtained. The results underscore the feasibility of SE for oil-water systems, reducing viscous and capillary resistances without agitation. The emulsified oil mass increased with the temperature, pH, and aqueous-to-oil phase volume ratio while decreasing with the NaCl concentration. In this study, for GD-2 crude oil, the optimal emulsified oil amount occurred at a betaine surfactant (BetS-2) emulsifier concentration of 0.45%. Microscopic photo analysis indicated narrow particle size distributions and small droplets, which remained stable over time under various experimental conditions. A combined SE mechanism involving ultralow interfacial tension, interfacial turbulence due to Marangoni effects, and "diffusion and stranding" due to in situ emulsifier hydrophilicity, was speculated. Additionally, an analogous second-order kinetic equation for SE was proposed, indicating exceptional correlation with calculated and experimentally measured values. This study offers theoretical insight for enhancing oil recovery in chemical and cold production of heavy oil in oilfields.

Surface Modification of Calcined Kaolinite for Enhanced Solvent Dispersion and Mechanical Properties in Polybutylene Adipate/Terephthalate Composites.

In order to regulate the surface properties of calcined kaolinite for the purpose of achieving uniform distribution within various polar dispersion media, 3-aminopropyltriethoxysilane and phenyl glycidyl ether were employed to chemically modify calcined kaolinite. The grafting rate, surface properties, and dispersion properties of calcined kaolinite particles in different polar organic media were changed by varying the dosage of the modifiers. FT-IR analysis confirmed successful surface modification, while thermogravimetric analysis indicated a maximum graft coverage of 18.44 µmol/m2 for the modified particles. Contact angle measurements and particle size distribution analyses demonstrated the effective adjustment of surface characteristics by the modifiers. Specifically, at a mass ratio of 1.0 of modifier to kaolinite particles, the modified particles exhibited a contact angle of around 125°, achieving uniform dispersion in different polarity media. Particle size distribution ranged from 1600 nm to 2100 nm in cyclohexane and petroleum ether, and from 900 nm to 1200 nm in dioxane, ethyl acetate, and DMF, showcasing a significant improvement in dispersion performance compared to unmodified particles. Concurrently, to improve the mechanical properties of PBAT, modified particles were incorporated into the PBAT matrix, and the effect of modified particle addition on the tensile strength and fracture tensile rate of the composites was investigated. The optimal amount of modified particles is 6 wt.%~8 wt.%. This article aims at synthesizing modifier molecules containing different hydrophilic and hydrophobic groups to chemically graft onto the surface of calcined kaolinite. The hydrophilic and hydrophobic groups on the modified particles can adapt to dispersed systems of different polarities and achieve good distribution within them. The modified particles are added to PBAT to achieve good compatibility and enhance the mechanical properties of the composite material.

Controlling and Tuning the Dispersion Properties of Calcined Kaolinite Particles in Various Organic Solvents via the Modification Method Using Triethoxyvinylsilane and 3-Mercaptopropionic Acid.

The surface of calcined kaolinite particles underwent chemical modification using Vinyltriethoxysilane (VTMS) and 3-mercaptopropionic acid (3-MPA). The grafting ratio of VTMS on the calcined kaolinite surface was adjusted by varying its quantity. FT-IR analysis revealed the initial grafting of VTMS onto the kaolinite surface, resulting in the formation of a C=C reactive site on the surface. Subsequently, an olefin click reaction with 3-MPA occurred, leading to the effective grafting of 3-MPA onto the kaolinite surface and the formation of an efficient coating. Thermal analysis indicated that the optimal grafting level was achieved at a modifier content V:K ratio of 0.5. The estimated grafting ratio of the modifier on the kaolinite surface was approximately 40% when V:K was 0.5. Water contact angle and dispersion experiments demonstrated that the surface properties of kaolinite were effectively controlled by this modification approach. At V:K = 0.3, the modified kaolinite particles exhibited good dispersion in both polar and non-polar solvents. In polar solvents, the average particle size of modified kaolinite was below 1100 nm, while in non-polar solvents, it did not exceed 5000 nm. Considering all aspects, a V:K ratio of 0.3 is recommended. Further investigation into the impact of adding 3-MPA on the surface properties of modified kaolinite particles based on V:K = 0.3 revealed that the hydrophilicity of the modified particles could be enhanced. However, it is advised to keep the maximum M:V ratio (3-MPA to kaolinite) at 1.0.

Construction of Preoperative Assessment Program for Day Surgery in Geriatric Cataract Patients: An Evidence-Based Delphi Study.

PURPOSE: To construct a scientific cataract day surgery preoperative assessment program to provide a scientific assessment tool for health care providers. DESIGN: Literature review, two-round e-Delphi study, and quantitative studies. METHODS: With the recommended opinions of clinical practice guidelines for cataract surgery as the guiding framework, an item pool was formed on the basis of literature review and guideline content analysis, and the dimensions and items of evaluation program were determined by two rounds of correspondence consultation using Delphi expert method. Then, 315 patients from an ophthalmic hospital were selected for investigation to analyze its reliability and validity. FINDINGS: The positive coefficients for the 2 rounds of correspondence with experts were 100.00% and 95.83%, and the authority coefficients were 0.90 and 0.89. Kendall's coordination coefficient W values of 0.29 and 0.24 for the first and second rounds and the differences were statistically different (P < .05). The coefficient of variation was 0.14 and 0.10, respectively. The formal assessment items included 3 first-level indicators, 12 secondary-level indicators, and 48 tertiary indicators, with an overall Cronbach's coefficient of 0.66 and cumulative variance contributions of 69.19%, 65.84%, and 57.15% for the 3 first-level indicators. CONCLUSION: The high reliability of the preoperative cataract day surgery program compiled by applying evidence-based analysis and the Delphi method can provide scientific guidance to clinical nurses for preoperative assessment, which in turn ensures patient safety and improves the quality of patient access services.

Polystyrene nanoplastics aggravates lipopolysaccharide-induced apoptosis in mouse kidney cells by regulating IRE1/XBP1 endoplasmic reticulum stress pathway via oxidative stress.

Nanoplastics (NPs) pollution poses a huge threat to the ecosystem and has become one of the environmental pollutants that have attracted much attention. There is increasing evidence that both oxidative stress and endoplasmic reticulum stress (ERS) are associated with polystyrene nanoplastics (PS-NPs) exposure. Lipopolysaccharide (LPS) has been shown to induce apoptotic damage in various tissues, but whether PS-NPs can aggravate LPS-induced apoptosis in mouse kidneys through oxidative stress-regulated inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) ERS pathway remains unclear. In this study, based on the establishment of in vitro and in vivo PS-NPs and LPS exposure models alone and in combination in mice and HEK293 cells, the effects and mechanisms of PS-NPs on LPS-induced renal cell apoptosis were investigated. The results showed that PS-NPs could aggravate LPS-induced apoptosis. PS-NPs/LPS can induce ERS through oxidative stress, activate the IRE1/XBP1 pathway, and promote the expression of apoptosis markers (Caspase-3 and Caspase-12). Kidney oxidative stress, ERS, and apoptosis in PS-NPs + LPS combined exposure group were more severe than those in the single exposure group. Interestingly, 4-phenylbutyric acid-treated HEK293 cells inhibited the expression of the IRE1/XBP1 ERS pathway and apoptotic factors in the PS-NPs + LPS combined exposure group. N-acetyl-L-cysteine effectively blocked the activation of the IRE1/XBP1 ERS pathway, suggesting that PS-NPs-induced oxidative stress is an early event that triggers ERS. Collectively, these results confirmed that PS-NPs aggravated LPS-induced apoptosis through the oxidative stress-induced IRE1/XBP1 ERS pathway. Our study provides new insights into the health threats of PS-NPs exposed to mammals and humans.

The role of FUT8-catalyzed core fucosylation in Alzheimer's amyloid-ß oligomer-induced activation of human microglia.

Fucosylation, especially core fucosylation of N-glycans catalyzed by α1-6 fucosyltransferase (fucosyltransferase 8 or FUT8), plays an important role in regulating the peripheral immune system and inflammation. However, its role in microglial activation is poorly understood. Here we used human induced pluripotent stem cells-derived microglia (hiMG) as a model to study the role of FUT8-catalyzed core fucosylation in amyloid-ß oligomer (AßO)-induced microglial activation, in view of its significant relevance to the pathogenesis of Alzheimer's disease (AD). HiMG responded to AßO and lipopolysaccharides (LPS) with a pattern of pro-inflammatory activation as well as enhanced core fucosylation and FUT8 expression within 24 h. Furthermore, we found increased FUT8 expression in both human AD brains and microglia isolated from 5xFAD mice, a model of AD-like cerebral amyloidosis. Inhibition of fucosylation in AßO-stimulated hiMG reduced the induction of pro-inflammatory cytokines, suppressed the activation of p38MAPK, and rectified phagocytic deficits. Specific inhibition of FUT8 by siRNA-mediated knockdown also reduced AßO-induced pro-inflammatory cytokines. We further showed that p53 binds to the two consensus binding sites in the Fut8 promoter, and that p53 knockdown abolished FUT8 overexpression in AßO-activated hiMG. Taken together, our evidence supports that FUT8-catalyzed core fucosylation is a signaling pathway required for AßO-induced microglia activation and that FUT8 is a component of the p53 signaling cascade regulating microglial behavior. Because microglia are a key driver of AD pathogenesis, our results suggest that microglial FUT8 could be an anti-inflammatory therapeutic target for AD.

TERC haploid cell reprogramming: a novel therapeutic strategy for aplastic anemia.

The telomerase RNA component (TERC) gene plays an important role in telomerase-dependent extension and maintenance of the telomeres. In the event of TERC haploinsufficiency, telomere length is often affected; this, in turn, can result in the development of progeria-related diseases such as aplastic anemia (AA) and congenital keratosis. Cell reprogramming can reverse the differentiation process and can, therefore, transform cells into pluripotent stem cells with stronger differentiation and self-renewal abilities; further, cell reprograming can also extend the telomere length of these cells, which may be crucial in the diagnosis and treatment of telomere depletion diseases such as AA. In this study, we summarized the effects of TERC haploid cell reprogramming on telomere length and the correlation between this alteration and the pathogenesis of AA; by investigating the role of cell reprogramming in AA, we aimed to identify novel diagnostic indicators and therapeutic strategies for patients with AA.

ADEIP: an integrated platform of age-dependent expression and immune profiles across human tissues.

Gene expression and immune status in human tissues are changed with aging. There is a need to develop a comprehensive platform to explore the dynamics of age-related gene expression and immune profiles across tissues in genome-wide studies. Here, we collected RNA-Seq datasets from GTEx project, containing 16 704 samples from 30 major tissues in six age groups ranging from 20 to 79 years old. Dynamic gene expression along with aging were depicted and gene set enrichment analysis was performed among those age groups. Genes from 34 known immune function categories and immune cell compositions were investigated and compared among different age groups. Finally, we integrated all the results and developed a platform named ADEIP (http://gb.whu.edu.cn/ADEIP or http://geneyun.net/ADEIP), integrating the age-dependent gene expression and immune profiles across tissues. To demonstrate the usage of ADEIP, we applied two datasets: severe acute respiratory syndrome coronavirus 2 and human mesenchymal stem cells-assoicated genes. We also included the expression and immune dynamics of these genes in the platform. Collectively, ADEIP is a powerful platform for studying age-related immune regulation in organogenesis and other infectious or genetic diseases.

Precision Nutrition and Cardiovascular Disease Risk Reduction: the Promise of High-Density Lipoproteins.

PURPOSE OF REVIEW: Emerging evidence supports the promise of precision nutritional approaches for cardiovascular disease (CVD) prevention. Here, we discuss current findings from precision nutrition trials and studies reporting substantial inter-individual variability in responses to diets and dietary components relevant to CVD outcomes. We highlight examples where early precision nutrition research already points to actionable intervention targets tailored to an individual's biology and lifestyle. Finally, we make the case for high-density lipoproteins (HDL) as a compelling next generation target for precision nutrition aimed at CVD prevention. HDL possesses complex structural features including diverse protein components, lipids, size distribution, extensive glycosylation, and interacts with the gut microbiome, all of which influence HDL's anti-inflammatory, antioxidant, and cholesterol efflux properties. Elucidating the nuances of HDL structure and function at an individual level may unlock personalized dietary and lifestyle strategies to optimize HDL-mediated atheroprotection and reduce CVD risk. RECENT FINDINGS: Recent human studies have demonstrated that HDL particles are key players in the reduction of CVD risk. Our review highlights the role of HDL and the importance of personalized therapeutic approaches to improve their potential for reducing CVD risk. Factors such as diet, genetics, glycosylation, and gut microbiome interactions can modulate HDL structure and function at the individual level. We emphasize that fractionating HDL into size-based subclasses and measuring particle concentration are necessary to understand HDL biology and for developing the next generation of diagnostics and biomarkers. These discoveries underscore the need to move beyond a one-size-fits-all approach to HDL management. Precision nutrition strategies that account for personalized metabolic, genetic, and lifestyle data hold promise for optimizing HDL therapies and function to mitigate CVD risk more potently. While human studies show HDL play a key role in reducing CVD risk, recent findings indicate that factors such as diet, genetics, glycosylation, and gut microbes modulate HDL function at the individual level, underscoring the need for precision nutrition strategies that account for personalized variability to optimize HDL's potential for mitigating CVD risk.

Construction of a Preoxidation and Cation Doping Regeneration Strategy to Improve Rate Performance Recycling Spent LiFePO4 Materials.

Efficient recycling of spent lithium-ion batteries (LIBs) is significant for solving environmental problems and promoting resource conservation. Economical recycling of LiFePO4 (LFP) batteries is extremely challenging due to the inexpensive production of LFP. Herein, we report a preoxidation combine with cation doping regeneration strategy to regenerate spent LiFePO4 (SLFP) with severely deteriorated. The binder, conductive agent, and residual carbon in SLFP are effectively removed through preoxidation treatment, which lays the foundation for the uniform and stable regeneration of LFP. Mg2+ doping is adopted to promote the diffusion efficiency of lithium ions, reduces the charge-transfer impedance, and further improves the electrochemical performance of the regenerated LFP. The discharge capacity of SLFP with severe deterioration recovers successfully from 43.2 to 136.9 mA h g-1 at 0.5 C. Compared with traditional methods, this technology is simple, economical, and environment-friendly. It provided an efficient way for recycling SLFP materials.

Examining the Relationship Between Sleep Apnea Diagnosis and Suicide Risk in Veterans With Traumatic Brain Injury: A VA TBI Model Systems Study.

OBJECTIVE: Obstructive sleep apnea (OSA) is a common sleep disorder in people with traumatic brain injury (TBI). Although sleep disturbances have been associated with an increased risk of suicide compared with the general population, the relationship between OSA and suicide risk after TBI is not well documented. In this study, we hypothesized that OSA diagnosis would predict suicide risk in veterans with TBI. SETTING: Five Veterans Affairs (VA) Polytrauma Rehabilitation Centers. PARTICIPANTS: Participants were drawn from the VA TBI Model Systems study, with follow-up interviews at year 1 ( n = 392), year 2 ( n = 444), year 5 ( n = 498), or year 10 ( n = 252) post-TBI (7.8%-14.5% follow-up attrition). DESIGN: This was a retrospective analysis from observational data using logistic regression with repeated measurements. Suicide ideation and suicide attempts were examined as outcomes at each follow-up to evaluate the relationship between OSA and suicide risk after adjusting for other risk factors determined a priori via literature review. MAIN MEASURES: Suicidal ideation (Patient Health Questionnaire-9 item 9), suicide attempt during the past year (self-reported), and OSA diagnosis (self-reported). RESULTS: Contrary to study hypotheses, OSA diagnosis had no statistically significant association with suicide ideation or attempt after accounting for known predictors. However, greater depression symptoms, headache severity, and pre-TBI suicidal ideation and attempts predicted suicide risk at follow-up after accounting for other predictors. CONCLUSIONS: Results of this study did not support a relationship between OSA and suicide risk, possibly due to methodological limitations of OSA measurement. Future research on this topic should include objective measures of OSA severity and OSA treatment including adherence. Although suicide is a low base rate occurrence, the impact is disastrous and further research is needed to mitigate suicide risk.

Advancements in Research on Constructing Physiological and Pathological Liver Models and Their Applications Utilizing Bioprinting Technology.

In recent decades, significant progress has been made in liver tissue engineering through the use of 3D bioprinting technology. This technology offers the ability to create personalized biological structures with precise geometric design capabilities. The complex and multifaceted nature of liver diseases underscores the need for advanced technologies to accurately mimic the physiological and mechanical characteristics, as well as organ-level functions, of liver tissue in vitro. Bioprinting stands out as a superior option over traditional two-dimensional cell culture models and animal models due to its stronger biomimetic advantages. Through the use of bioprinting, it is possible to create liver tissue with a level of structural and functional complexity that more closely resembles the real organ, allowing for more accurate disease modeling and drug testing. As a result, it is a promising tool for restoring and replacing damaged tissue and organs in the field of liver tissue engineering and drug research. This article aims to present a comprehensive overview of the progress made in liver tissue engineering using bioprinting technology to provide valuable insights for researchers. The paper provides a detailed account of the history of liver tissue engineering, highlights the current 3D bioprinting methods and bioinks that are widely used, and accentuates the importance of existing in vitro liver tissue models based on 3D bioprinting and their biomedical applications. Additionally, the article explores the challenges faced by 3D bioprinting and predicts future trends in the field. The progress of 3D bioprinting technology is poised to bring new approaches to printing liver tissue in vitro, while offering powerful tools for drug development, testing, liver disease modeling, transplantation, and regeneration, which hold great academic and practical significance.

Innovative approach to identify multigenomic and environmental interactions associated with birth defects in family-based hybrid designs.

Genes, including those with transgenerational effects, work in concert with behavioral, environmental, and social factors via complex biological networks to determine human health. Understanding complex relationships between causal factors underlying human health is an essential step towards deciphering biological mechanisms. We propose a new analytical framework to investigate the interactions between maternal and offspring genetic variants or their surrogate single nucleotide polymorphisms (SNPs) and environmental factors using family-based hybrid study design. The proposed approach can analyze diverse genetic and environmental factors and accommodate samples from a variety of family units, including case/control-parental triads, and case/control-parental dyads, while minimizing potential bias introduced by population admixture. Comprehensive simulations demonstrated that our innovative approach outperformed the log-linear approach, the best available method for case-control family data. The proposed approach had greater statistical power and was capable to unbiasedly estimate the maternal and child genetic effects and the effects of environmental factors, while controlling the Type I error rate against population stratification. Using our newly developed approach, we analyzed the associations between maternal and fetal SNPs and obstructive and conotruncal heart defects, with adjustment for demographic and lifestyle factors and dietary supplements. Fourteen and 11 fetal SNPs were associated with obstructive and conotruncal heart defects, respectively. Twenty-seven and 17 maternal SNPs were associated with obstructive and conotruncal heart defects, respectively. In addition, maternal body mass index was a significant risk factor for obstructive defects. The proposed approach is a powerful tool for interrogating the etiological mechanism underlying complex traits.