Nicotinamide mononucleotide maintains cytoskeletal stability and fortifies mitochondrial function to mitigate oocyte damage induced by Triocresyl phosphate.

Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.

Exploring the associations between competence in dementia care and work attitudes among formal caregivers in nursing homes.

AIMS: Based on the two-factor model of caregiving appraisals, this study aims to (1) investigate the relationships between competence in dementia care and job satisfaction (work attitudes in positive aspect) and turnover intention (work attitudes in negative aspect) among formal caregivers in nursing homes, and (2) examine the mediating roles of positive aspects of caregiving (caregiving appraisals in positive aspect) and caregiving burden (caregiving appraisals in negative aspect) in the above associations. DESIGN: A cross-sectional design was used. Structural equation modelling was employed to test the proposed model. STROBE checklist guides the reporting of this study. METHODS: Using the multistage cluster sampling method, 407 formal caregivers were selected from 43 nursing homes across 7 districts/counties in China. RESULTS: The proposed model shows a good model fit. Competence in dementia care shows significant positive associations with increased job satisfaction and decreased turnover intention among formal caregivers in nursing homes. Caregiving burden and positive aspects of caregiving mediate the relationships between competence in dementia care and both job satisfaction and turnover intention. Furthermore, the relationship between positive aspects of caregiving and job satisfaction is stronger than that with turnover intention, but the relationship between caregiving burden and turnover intention is not stronger than that with job satisfaction. CONCLUSIONS: The results demonstrate that the two-factor model of caregiving appraisals effectively elucidates the associations and underlying mechanisms between competence in dementia care and formal caregivers' work attitudes. Specifically, two crucial conclusions are drawn: (1) competence in dementia care is associated with higher levels of job satisfaction and lower levels of turnover intention among formal caregivers in nursing homes; (2) caregiving burden and positive aspects of caregiving serve as parallel mediators in these associations. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Policymakers and nursing homes managers should implement a series of measures aimed at formal caregivers in nursing home. Specifically, allocating more resources to enhance the competence in dementia care of formal caregivers is crucial, given its significant association with elevated job satisfaction and reduced turnover intention. Besides, positive and negative caregiving appraisals emerge as proximal factors influencing work attitudes of formal caregivers. Therefore, intervention projects focused on formal caregivers in nursing home should target enhancing positive experiences and alleviating caregiving burden. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

The relationship between bullying victimization and problematic behaviors: A focus on the intrapersonal emotional competence and interpersonal social competence.

BACKGROUND: Evidence consistently demonstrated that bullying victimization was associated with problematic behaviors among adolescents. However, scant attention has been given to simultaneous comparisons of the impacts of two distinct forms of victimization, traditional bullying victimization and cyberbullying victimization. In addition, the mechanisms underlying the relationship between bullying victimization and problem behavior remain inadequately explored. OBJECTIVE: This study aimed to examine the correlation between bullying victimization and problematic behaviors, as well as the mediating roles of intrapersonal emotional competence and interpersonal social competence. PARTICIPANTS AND SETTING: A sample of 26,450 adolescents with a mean age of 15.44 (SD = 0.56) across nine countries was derived from the Study on Social and Emotional Skills (SSES). METHODS: Data analysis was conducted using structural equation modeling, comprising three key components: the measurement model, the structural model, and the bootstrapping analysis for mediating effects. RESULTS: Both traditional bullying and cyberbullying victimization exhibited positive correlations with problematic behaviors, with cyberbullying victimization demonstrating a stronger effect. The mediating effects of intrapersonal emotional competence and interpersonal social competence were observed in the correlation between bullying victimization and problematic behaviors. CONCLUSIONS: This study not only contributed to our comprehension of the underlying mechanisms connecting bullying victimization and adolescent problematic behaviors, but also holds significance for policy development and practice.

Intergenerational Caregiving Patterns and Cognitive Health among the Sandwich Generation Within Four-Generation Families.

This study aims to investigate whether generational differences in intergenerational caregiving patterns (caring for parents only, caring for grandchildren only, and caring for parents and grandchildren simultaneously) are associated with cognitive health disparities among the sandwich generation within four-generation families, drawing upon the theories of intergenerational solidarity and intergenerational stake. Moreover, this study seeks to identify mediators that help explain these disparities. A nationally representative sample of 8,065 respondents was drawn from the 2011 and 2018 waves of the China Health and Retirement Longitudinal Study. The findings reveal that the sandwich generation caring for grandchildren only, as well as those caring for grandchildren and parents simultaneously, exhibit better cognitive health. However, caregiving for parents only is not significantly related to their cognitive health. This study identifies the inability to reduce depressive symptoms as a mediator explaining the insignificant association between caregiving for parents only and the cognitive health of the sandwich generation. The findings underscore the importance of offering support to the sandwich generation within four-generation families to enhance their cognitive health. Moreover, it is imperative to distinguish between different intergenerational caregiving patterns based on generational differences among the sandwich generation, with a specific emphasis on allocating public resources aimed at promoting cognitive health for those engaged in caring for parents.

The Long Arm of Childhood Bullying Victimization: Associations with Social Isolation, Gender Differences and Depression in Later Life.

The association between childhood bullying victimization and depression has been well-explored among young adults, but little is known about whether this relationship persists into later life stages, specifically during middle-aged and older phases. Moreover, the intricate mechanisms underpinning this association and the potential existence of gender differences within this context remain inadequately elucidated. To address this gap in knowledge, this study aims to investigate the association between childhood bullying victimization and depression in later life, with a focus on exploring the mediating role of social isolation and the moderating roles of gender. A nationally representative sample of 5,070 individuals (mean age = 61.02, SD = 9.48; male = 55%) was drawn from the China Health and Retirement Longitudinal Study. By employing the bootstrapping analysis method, the mediating role of social isolation was examined, and the moderating role of gender was tested through the generation of interaction items. The results reveal a significant association between childhood bullying victimization and severe depression in later life. Additionally, social isolation plays a mediating role in this association between childhood bullying victimization and social isolation, and the association between social isolation and depression, as well as the relationship between social isolation and depression, are both moderated by gender, presenting stronger effects for female groups than for male groups. However, no moderating role of gender is found in terms of the direct association between childhood bullying victimization and depression. These findings highlight the fact that childhood bullying is not only a problem in the immediate term but also a concern that affects individuals across entire life course. This study has implications for healthcare in proactively investigating, diagnosing, and treating depression by inquiring about childhood bullying victimization experiences. Furthermore, intervention policies that aim to reduce social isolation may be particularly beneficial in mitigating the negative associations, especially for female individuals.

High sensitivity and automatic chemiluminescence detection of glucose and lactate using a spin-disc paper-based device.

This paper reports a spin-disc paper-based device with 10 individual detection units containing electromagnetic modules controlling the sample incubation time before chemiluminescence (CL) signal detection. After the sample was added to the top paper chip and incubated with the enzyme, the electromagnet was turned off to allow contact between the top and bottom paper. The H2O2 generated by the sample flowed vertically to the bottom paper and initiated the oxidase of the luminol to generate the CL signal. After one detection the disc was automatically rotated to the next position to repeat the above detection. The advantage of using the device over the lateral flow and the in situ detection was firstly proved using the detection of H2O2 and the glucose/lactate sample with 5 minute incubation. The CL intensity was increased 300 times/1000 times as the glucose/lactate was incubated for 5 minutes compared to the non-incubated samples. Afterward, the device was employed to separately detect glucose and lactate diluted in PBS, artificial sweat, artificial saliva, and fresh cell culture media. Finally, the device was employed to detect the glucose and lactate in the media collected over the 24 hour culture of PC3 cells. The uptake and production rates of glucose and lactate were correspondingly determined as 0.328 ± 0.015 pmol h-1 per cell and 1.254 ± 0.053 pmol h-1 per cell, respectively. The reported device has wide application potential due to its capabilities in automatic detection of multiple samples with very high sensitivity and small sample volume (down to 0.5 µL).

Community support, social isolation and older adults' life satisfaction: evidence from a national survey in China.

OBJECTIVES: Despite the recognized importance of community social service and community built facility for enhancing older adults' life satisfaction, the mechanisms underlying their relationship have not been thoroughly examined. This study aims to complement the existing knowledge by investigating the mediating role of social disconnectedness and loneliness in the association between community support and life satisfaction among older adults. METHODS: Using data from the 2018 China Longitudinal Aging Social Survey, the study analyzes responses from 9,874 Chinese older adults (mean age = 71.30 years, SD = 7.30). We conducted descriptive statistics and Pearson's correlation to explore the variables. This study also used Mplus 8.0 to conduct a path analysis model that evaluated both the direct and indirect effects of community social service and built facility on life satisfaction. Social disconnectedness and loneliness were included as mediating variables in this model. RESULTS: The present study results show that both community social service and community built facility are positively associated with life satisfaction among older adults, and community social service is more imporatant for enhancing the life satisfaction. In addition, these associations are mediated by social disconnectedness and loneliness. CONCLUSION: Our research suggests that strengthening community social service programs and improving the built environment can reduce social disconnectedness and loneliness among older adults, ultimately enhancing their life satisfaction. Specifically, policymakers can invest in targeted interventions to enhance social connectedness and reduce loneliness, with the goal of improving the overall well-being of older adults.

Pyruvate dehydrogenase kinase 1 protects against neuronal injury and memory loss in mouse models of diabetes.

Hyperglycemia-induced aberrant glucose metabolism is a causative factor of neurodegeneration and cognitive impairment in diabetes mellitus (DM) patients. The pyruvate dehydrogenase kinase (PDK)-lactic acid axis is regarded as a critical link between metabolic reprogramming and the pathogenic process of neurological disorders. However, its role in diabetic neuropathy remains unclear. Here, we found that PDK1 and phosphorylation of pyruvate dehydrogenase (PDH) were obviously increased in high glucose (HG)-stimulated primary neurons and Neuro-2a cell line. Acetyl-coA, a central metabolic intermediate, might enhance PDK1 expression via histone H3K9 acetylation modification in HG condition. The epigenetic regulation of PDK1 expression provided an available negative feedback pattern in response to HG environment-triggered mitochondrial metabolic overload. However, neuronal PDK1 was decreased in the hippocampus of streptozotocin (STZ)-induced diabetic mice. Our data showed that the expression of PDK1 also depended on the hypoxia-inducible factor-1 (HIF-1) transcriptional activation under the HG condition. However, HIF-1 was significantly reduced in the hippocampus of diabetic mice, which might explain the opposite expression of PDK1 in vivo. Importantly, overexpression of PDK1 reduced HG-induced reactive oxygen species (ROS) generation and neuronal apoptosis. Enhancing PDK1 expression in the hippocampus ameliorated STZ-induced cognitive impairment and neuronal degeneration in mice. Together, our study demonstrated that both acetyl-coA-induced histone acetylation and HIF-1 are necessary to direct PDK1 expression, and enhancing PDK1 may have a protective effect on cognitive recovery in diabetic mice. Schematic representation of the protective effect of PDK1 on hyperglycemia-induced neuronal injury and memory loss. High glucose enhanced the expression of PDK1 in an acetyl-coA-dependent histone acetylation modification to avoid mitochondrial metabolic overload and ROS release. However, the decrease of HIF-1 may impair the upregulation of PDK1 under hyperglycemia condition. Overexpression of PDK1 prevented hyperglycemia-induced hippocampal neuronal injury and memory loss in diabetic mice.

CRISPR-based Genome Editing of a Diurnal Rodent, Nile Grass Rat ( Arvicanthis niloticus).

Diurnal and nocturnal mammals have evolved distinct pathways to optimize survival for their chronotype-specific lifestyles. Conventional rodent models, being nocturnal, may not sufficiently recapitulate the biology of diurnal humans in health and disease. Although diurnal rodents are potentially advantageous for translational research, until recently, they have not been genetically tractable. Here, we address this major limitation by demonstrating the first successful CRISPR genome editing of the Nile grass rat ( Arvicanthis niloticus ), a valuable diurnal rodent. We establish methods for superovulation; embryo development, manipulation, and culture; and pregnancy maintenance to guide future genome editing of this and other diurnal rodent species.

BHLHE40, a potential immune therapy target, regulated by FGD5-AS1/miR-15a-5p in pancreatic cancer.

Pancreatic cancer, as one of the neoplasms with the highest degree of malignancy, has become a main disease of concerns in recent years. BHLHE40, a critical transcription factor for remodeling of the tumor immune microenvironment, has been described to be substantially increased in a variety of tumor-associated immune cells. Nevertheless, the pro-cancer biological functions and underlying molecular mechanisms of BHLHE40 for pancreatic cancer and its unique microenvironment are unclear. Hereby, we investigated the pro-oncogenic role of BHLHE40 in the pancreatic cancer microenvironment by bioinformatics analysis and cell biology experiments and determined that the expression of BHLHE40 was obviously elevated in pancreatic cancer tissues than in adjacent normal tissues. In parallel, Kaplan-Meier survival analysis unveiled that lower expression of BHLHE40 was strongly associated with better prognosis of patients. Receiver operating characteristic (ROC) curve analysis confirmed the accuracy of the BHLHE40-related prediction model. Subsequent, spearman correlation analysis observed that higher expression of BHLHE40 might be involved in immunosuppression of pancreatic cancer. Silencing of BHLHE40 could inhibit proliferation, invasion, and apoptosis of pancreatic cancer in vitro and in vivo, implying that BHLHE40 is expected to be a potential therapeutic target for pancreatic cancer. In addition, we explored and validated the FGD5-AS1/miR-15a-5p axis as a potential upstream regulatory mode for high expression of BHLHE40 in pancreatic cancer. In summary, our data showed that ceRNA involved in the regulation of BHLHE40 contributes to the promotion of immunosuppressive response in pancreatic and is expected to be a diagnostic marker and potential immunotherapeutic target for pancreatic cancer.

Pollution-Free and Highly Sensitive Lactate Detection in Cell Culture Based on a Microfluidic Chip.

Cell metabolite detection is important for cell analysis. As a cellular metabolite, lactate and its detection play an important role in disease diagnosis, drug screening and clinical therapeutics. This paper reports a microfluidic chip integrated with a backflow prevention channel for cell culture and lactate detection. It can effectively realize the upstream and downstream separation of the culture chamber and the detection zone, and prevent the pollution of cells caused by the potential backflow of reagent and buffer solutions. Due to such a separation, it is possible to analyze the lactate concentration in the flow process without contamination of cells. With the information of residence time distribution of the microchannel networks and the detected time signal in the detection chamber, it is possible to calculate the lactate concentration as a function of time using the de-convolution method. We have further demonstrated the suitability of this detection method by measuring lactate production in human umbilical vein endothelial cells (HUVEC). The microfluidic chip presented here shows good stability in metabolite quick detection and can work continuously for more than a few days. It sheds new insights into pollution-free and high-sensitivity cell metabolism detection, showing broad application prospects in cell analysis, drug screening and disease diagnosis.

Chloramination of Nitromethane: Incomplete Chlorination and Unexpected Substitution Reaction.

Ozone is commonly used as a predisinfectant in potable water reuse treatment trains. Nitromethane was recently found as a ubiquitous ozone byproduct in wastewater, and the key intermediate toward chloropicrin during subsequent secondary disinfection of ozonated wastewater effluent with chlorine. However, many utilities have switched from free chlorine to chloramines as a secondary disinfectant. The reaction mechanism and kinetics of nitromethane transformation by chloramines, unlike those for free chlorine, are unknown. In this work, the kinetics, mechanism, and products of nitromethane chloramination were studied. The expected principal product was chloropicrin, because chloramines are commonly assumed to react similarly to, although more slowly than, free chlorine. Different molar yields of chloropicrin were observed under acidic, neutral, and basic conditions, and surprisingly, transformation products other than chloropicrin were found. Monochloronitromethane and dichloronitromethane were detected at basic pH, and the mass balance was initially poor at neutral pH. Much of the missing mass was later attributed to nitrate formation, from a newly identified pathway involving monochloramine reacting as a nucleophile rather than a halogenating agent, through a presumed SN2 mechanism. The study indicates that nitromethane chloramination, unlike chlorination, is likely to produce a range of products, whose speciation is a function of pH and reaction time.

Manipulating the Dynamic Adaptivity of a Fluid Interface to Maintain the Multipotency of Mesenchymal Stromal Cells.

The native extracellular matrix is highly dynamic with continuous mutual feedback between cells being responsible for many important cell function regulators. However, establishing bidirectional interaction between complex adaptive microenvironments and cells remains elusive. Herein an adaptive biomaterial based on lysozyme monolayers self-assembled at a perfluorocarbon FC40-water interface is reported. The dynamic adaptivity of interfacially assembled protein nanosheets is modulated independently of bulk mechanical properties by covalent crosslinking. This provides a scenario to establish bidirectional interactions of cells with liquid interfaces of varying dynamic adaptivity. This is found that growth and multipotency of human mesenchymal stromal cells (hMSCs) are enhanced at the highly adaptive fluid interface. The multipotency retention of hMSCs is mediated by low cell contractility and metabolomic activity involving the continuous mutual feedback between the cells and materials. Consequently, an understanding of the cells' response to dynamic adaptivity has substantial implications for regenerative medicine and tissue engineering.

Lysine and Arginine Reactivity and Transformation Products during Peptide Chlorination.

Chlorine reactions with peptide-bound amino acids form disinfection byproducts and contribute to pathogen inactivation by degrading protein structure and function. Peptide-bound lysine and arginine are two of the seven chlorine-reactive amino acids, but their reactions with chlorine are poorly characterized. Using N-acetylated lysine and arginine as models for peptide-bound amino acids and authentic small peptides, this study demonstrated conversion of the lysine side chain to mono- and dichloramines and the arginine side chain to mono-, di-, and trichloramines in ≤0.5 h. The lysine chloramines formed lysine nitrile and lysine aldehyde at ∼6% yield over ∼1 week. The arginine chloramines formed ornithine nitrile at ∼3% yield over ∼1 week but not the corresponding aldehyde. While researchers hypothesized that the protein aggregation observed during chlorination arises from covalent Schiff base cross-links between lysine aldehyde and lysine on different proteins, no evidence for Schiff base formation was observed. The rapid formation of chloramines and their slow decay indicate that they are more relevant than the aldehydes and nitriles to byproduct formation and pathogen inactivation over timescales relevant to drinking water distribution. Previous research has indicated that lysine chloramines are cytotoxic and genotoxic to human cells. The conversion of lysine and arginine cationic side chains to neutral chloramines should alter protein structure and function and enhance protein aggregation by hydrophobic interactions, contributing to pathogen inactivation.

The impact of widowhood on mental health of older adults.

Widowhood is identified as a risk factor for older adults' mental health, however, the underlying mechanisms and protective factors in this association has not been fully revealed. In order to add to the current knowledge, this study investigates the mediating roles of economic, social and psychological resources and the moderating role of community support in the relationship between widowhood and mental health. A sample of 7913 Chinese older people (Mean age = 71.14, SD = 7.19) is obtained from the 2018 wave of China Longitudinal Aging Social Survey. Results indicates that widowhood is negatively associated with older adults' mental health. Economic, social and psychological resources partially mediate the above association. Furthermore, the effect of widowhood is weaker for older people with more rather than less community support. This study not only illuminates the potential mechanisms of how widowhood influence mental health theoretically, but also provides valuable implications.

Construction of Dual-Shell Mo2C/C Microsphere towards Efficient Electromagnetic Wave Absorption.

Carbon-based carbides have attracted tremendous attention for electromagnetic energy attenuation due to their adjustable dielectric properties, oxidation resistance, and good chemical stability. Herein, we reasonably regulate the growth of dopamine hydrochloride on the surface of the Mo-glycerate (Mo-GL) microsphere and then transform the resultant Mo-polydopamine (Mo-PD) microsphere into a dual-shell Mo2C/C (DS-Mo2C/C) microsphere in a high-temperature pyrolysis process under an inert atmosphere. It is found that the pyrolysis temperature plays an important role in the graphitization degree of the carbon matrix and internal architecture. The fabrication of a dual-shell structure can be propitious to the optimization of impedance matching, and the introduction of Mo2C nanoparticles also prompts the accumulation of polarization loss. When the pyrolysis temperature reaches 800 °C, the optimized composite of DS-Mo2C/C-800 exhibits good EM absorption performance in the frequency range of 2.0-18.0 GHz. DS-Mo2C/C-800's qualified bandwidth can reach 4.4 GHz at a matching thickness of 1.5 mm, and the integrated qualified bandwidth (QBW) even exceeds 14.5 GHz with a thickness range of 1.5-5.0 mm. The positive effects of the dual-shell structure and Mo2C nanoparticles on EM energy attenuation may render the DS-Mo2C/C microsphere as a promising candidate for lightweight and broad bandwidth EM absorption materials in the future.

Mental States: A Key Point in Scam Compliance and Warning Compliance in Real Life.

The internet's convenience and anonymity have facilitated different types of covert fraud, resulting in economic, mental, and social harm to victims. Understanding why people are deceived and implementing appropriate interventions is critical for fraud reduction. Based on the Bayesian brain theory, individuals' mental states may be a key point in scam compliance and warning compliance. Fraud victims with different mental states may construct various hypotheses and explanations about the fraud they are exposed to, causing different cognition and behavior patterns. Therefore, we first conducted a semi-structured in-depth interview with online fraud victims to investigate the individual and social factors that affect victims' mental states. Grounded theory analysis showed five core factors influencing scam compliance: psychological traits, empirical factors, motivation, cognitive biases, and emotional imbalance. Based on our findings of psychological processes and deception's influential factors, we then designed warnings to inform victims of fraud, particularly for those involving novel types of scams. Tested on a real-life setting, our designed warnings effectively enhanced warning compliance, allowing more fraud victims to avoid financial losses.

Regulation of stem cell fate and function by using bioactive materials with nanoarchitectonics for regenerative medicine.

Nanoarchitectonics has emerged as a post-nanotechnology concept. As one of the applications of nanoarchitectonics, this review paper discusses the control of stem cell fate and function as an important issue. For hybrid nanoarchitectonics involving living cells, it is crucial to understand how biomaterials and their nanoarchitected structures regulate behaviours and fates of stem cells. In this review, biomaterials for the regulation of stem cell fate are firstly discussed. Besides multipotent differentiation, immunomodulation is an important biological function of mesenchymal stem cells (MSCs). MSCs can modulate immune cells to treat multiple immune- and inflammation-mediated diseases. The following sections summarize the recent advances of the regulation of the immunomodulatory functions of MSCs by biophysical signals. In the third part, we discussed how biomaterials direct the self-organization of pluripotent stem cells for organoid. Bioactive materials are constructed which mimic the biophysical cues of in vivo microenvironment such as elasticity, viscoelasticity, biodegradation, fluidity, topography, cell geometry, and etc. Stem cells interpret these biophysical cues by different cytoskeletal forces. The different cytoskeletal forces lead to substantial transcription and protein expression, which affect stem cell fate and function. Regulations of stem cells could not be utilized only for tissue repair and regenerative medicine but also potentially for production of advanced materials systems. Materials nanoarchitectonics with integration of stem cells and related biological substances would have high impacts in science and technology of advanced materials.

Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome-9.

BACKGROUND: Succinate-CoA ligase/synthetase (SCS) deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Variants in SUCLG1, the nuclear gene encoding the alpha subunit of the SCS enzyme playing a pivotal role in maintaining mtDNA integrity and stability, are associated with mitochondrial DNA depletion syndrome 9 (MTDPS9). METHODS: In this study, we reported an infant with clinical features of MTDPS9 from China. Whole exome sequencing (WES) was used to identify the genetic cause. Bioinformatic analysis and mtDNA level detection were performed to assess pathogenicity. RESULTS: The proband manifested with hypotonia, lactic acidosis, mild methylmalonic aciduria, hearing loss and psychomotor retardation. WES identified new compound heterozygous SUCLG1 variants of c.601A>G (p.R201G) in exon 6 and c.871G>C (p.A291P) in exon 8. Computational analysis predicted that these missense variants might alter structure stability and mitochondrial translocation of SUCLG1. qRT-PCR showed 68% depletion of mtDNA content in proband as compared to controls. CONCLUSION: Novel compound heterozygous variants c.601A>G (p.R201G) and c.871G>C (p.A291P) in SUCLG1 may cause MTDPS9 in this family. Our finding should be helpful for molecular diagnosis, genetic counseling and clinical management of SCS deficiency disorders.

Ultrasonic assisted preparation of ultrafine Pd supported on NiFe-layered double hydroxides for p-nitrophenol degradation.

NiFe-layered double hydroxide (NiFe-LDH)-loaded ultrafine Pd nanocatalysts (Pd/NiFe-LDHs) were prepared by a facile ultrasonic-assisted in situ reduction technology without any stabilizing agents or reducing agents. Pd/NiFe-LDHs were characterized by FT-IR, XRD, XPS, and TEM. PdNPs are uniformly dispersed on NiFe-LDHs with a particle size distribution of 0.77-2.06 nm and an average particle size of 1.43 nm. Hydroxyl groups in Fe-OH and Ni-OH were dissociated into hydrogen radicals (·H) excited by ultrasound, and ·H reduced Pd2+ to ultrafine PdNPs. Then, Pd was coordinated with O in Ni-O and Fe-O, which improved the stability of the catalysts. Pd/NiFe-LDHs completely degraded 4-NP in 5 min, and the TOF value was 597.66 h-1, which was 16.7 times that of commercial Pd/C. The 4-NP conversion rate remained at 98.75% over Pd/NiFe-LDHs after 10 consecutive catalytic cycles. In addition, the catalyst also has high catalytic activity for the reduction of Congo red, methylene blue, and methyl orange by NaBH4.