The association between methylmalonic acid, a biomarker of mitochondrial dysfunction, and cause-specific mortality in Alzheimer's disease and Parkinson's disease.

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the leading causes of death among the elderly. Recent research has demonstrated that mitochondrial dysfunction, which is hallmark of neurodegenerative diseases, is a contributor to the development of these diseases. Methods and materials: Methylmalonic acid (MMA), AD, PD, inflammatory markers and covariates were extracted from the National Health and Nutrition Examination Survey (NHANES). The classification of the inflammatory markers was done through quartile conversion. A restricted cubic spike function was performed to study their dose-response relationship. MMA subgroups from published studies were used to explore the correlation between different subgroups and cause-specific mortality. Multivariable weighted Cox regression was carried out to investigate MMA and cause-specific mortality in patients with AD and PD. Weighted survival analysis was used to study the survival differences among MMA subgroups. Results: A non-linear correlation was observed between MMA and AD-specific death and PD-specific mortality. The presence of MMA Q4 was linked to increased death rates among AD patients (HR = 6.39, 95%CI: 1.19-35.24, P = 0.03) after controlling for potential confounders in a multivariable weighted Cox regression model. In PD patients, the MMA Q4 (Q4: HR: 5.51, 95 % CI: 1.26-24, P = 0.02) was also related to increased mortality. The results of survival analysis indicated that the poorer prognoses were observed in AD and PD patients with MMA Q4. Conclusion: The higher level of mitochondria-derived circulating MMA was associated with a higher mortality rate in AD and PD patients. MMA has the potential to be a valuable indicator for evaluating AD and PD patients' prognosis in the clinic.

PfAgo-Based Zika Virus Detection.

As a mosquito-borne flavivirus, Zika virus (ZIKV) has been identified as a global health threat. The virus has been linked to severe congenital disabilities, including microcephaly and other congenital malformations, resulting in fatal intrauterine death. Therefore, developing sensitive and specific methods for the early detection and accurate diagnosis of the ZIKV is essential for controlling its spread and mitigating its impact on public health. Herein, we set up a novel nucleic acid detection system based on Pyrococcus furiosus Argonaute (PfAgo)-mediated nucleic acid detection, targeting the non-structural protein 5 (NS5) region of the ZIKV genome (abbreviated ZIKV-PAND). Without preamplification with the polymerase chain reaction (PCR), the minimum detection concentration (MDC) of ZIKV-PAND was about 10 nM. When introducing an amplification step, the MDC can be dramatically decreased to the aM level (8.3 aM), which is comparable to qRT-PCR assay (1.6 aM). In addition, the diagnostic findings from the analysis of simulated clinical samples or Zika virus samples using ZIKV-PAND show a complete agreement of 100% with qRT-PCR assays. This correlation can aid in the implementation of molecular testing for clinical diagnoses and the investigation of ZIKV infection on an epidemiological scale.

[Construction and characterization of an infectious clone for human bocaparvovirus HBoV1].

Human bocaparvovirus 1 (HBoV1) is one of the two parvoviruses that infect humans and cause diseases. Infection with HBoV1 in infants and young children aged 2-5 years can lead to mild or severe acute respiratory diseases, with the most severe cases posing a life-threatening risk. Similar to other parvoviruses, the HBoV1 DNA genome consists of two terminal reverse repeats (ITRs) at its ends, which are necessary for viral genome replication. However, up to now, it has remained a technical challenge to clone the entire ITRs through PCR amplification. In this study, we successfully constructed a full-length infectious clone of HBoV1, termed as pSKHBoV1, by synthesizing and cloning the terminal ITRs in a stepwise manner. After transfecting HEK293 cells with the infectious clone pSKHBoV1, we were able to reconstitute the viral replication cycle. This included the expression of key non-structural proteins, post-transcriptional modification and processing of viral RNA, viral genome replication, and potentially the production of progeny virions containing the defined DNA genome. The successful construction of the infectious clone pSKHBoV1 lays the foundation for future studies on HBoV1 replication and propagation, virus-host interaction, and the development of viral vaccines.

Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy.

Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher's test, p = 2.02 × 10-6, adjusted α = 4.52 × 10-6). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy.

[Clinical efficacy of shallow-needle therapy combined with estazolam on insomnia of liver stagnation transforming into fire pattern: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of shallow-needle therapy combined with estazolam on insomnia differentiated as liver stagnation transforming into fire and its effect on adrenocorticotropic hormone (ACTH) and cortisol (CORT), so as to explore the mechanism of this combined treatment. METHODS: A total of 119 patients with insomnia of liver stagnation transforming into fire pattern were randomly divided into shallow-needle therapy group (n=40), medication group (n=39), and shallow-needle therapy combined with medication group (combined therapy group,n=40). In the shallow-needle therapy group, the patients were treated with finger pressure and operation with shallow stimulating at Zhenjing (Dong's extra point, sedative point) and Taichong (LR3). In the medication group, the patients were administered with estazolam (1 mg) orally. In the combined therapy group, both shallow-needle therapy and medication were administered. The treatment was given once daily in each group, 10 days as one session of treatment and 2 sessions were required. Before and after the treatment, Pittsburgh sleep quality index scale (PSQI) and Self-rating anxiety scale (SAS) were used to assess sleep and anxiety status. ELISA was used to detect the contents of ACTH and CORT in plasma. The clinical efficacy was evaluated in each group. RESULTS: In within-group comparison, PSQI scores, SAS scores and the concentrations of ACTH and CORT in plasma were all decreased (P<0.05) after treatment for the patients of three groups. After treatment, the total PSQI score, the score for sleep latency, sleep duration and daytime dysfunction, as well as SAS score in the combined therapy group were all lower than those of the shallow-needle therapy group (P<0.05); the total PSQI score, the score for sleep duration and sleep efficiency, as well as SAS score were lower when compared with the medication group (P<0.05). The total effective rates were 87.50% (35/40), 82.05% (32/39) and 95.00% (38/40) in the shallow-needle therapy group, the medication group and the combined therapy group, respectively. The total effective rate in the combined therapy group was higher than those of the shallow-needle therapy group and the medication group separately (P<0.05). CONCLUSION: Shallow-needle therapy combined with estazolam is effective on insomnia of liver stagnation transforming into fire pattern, and its underlying effect mechanism is related to the reduction of plasma ACTH and CORT levels.

Hierarchical Ni(OH)2/Cu(OH)2 interwoven nanosheets in situ grown on Ni-Cu-P alloy plated cotton fabric for flexible high-performance energy storage.

Flexible energy storage electrodes with high conductivity and capacity are crucial for wearable electronic clothes. Herein, a flexible hierarchical Ni(OH)2/Cu(OH)2 interwoven nanosheets in situ coated on Ni-Cu-P alloy plated cotton fabric textile (NCO/CF), which displays perfect conductive and electrochemical performance, is prepared by electroless deposition and electrochemical oxidation method. While the Ni-Cu-P alloy layer coated on the fabric effectively contributes to excellent mechanical performance and electro-conductivity of the as-prepared NCO/CF electrode, the hierarchical Ni(OH)2/Cu(OH)2 interwoven nanosheets in the oxidation layer effectively lead to a high energy storage performance with a specific areal capacity of 4.7 C cm-2 at a current density of 2 mA cm-2. When the power density of the two-electrode system based on NCO/CF and the carbon cloth (CC) is 2.4 mW cm-2, the energy density is 1.38 mW h cm-2. Furthermore, the flexible solid-state energy storage f-NCO/CF//CC is assembled in a self-powered system and supplies continuous power for electronic devices, demonstrating that NCO/CF is promising to be applied in various energy storage devices to power portable and wearable devices in the future.

Long non-coding RNA zinc finger antisense 1 functions as an oncogene in acute promyelocytic leukemia cells.

Despite progress in the diagnosis and treatment of acute promyelocytic leukemia (APL), its prognosis remains poor. Multiple studies have shown that long non-coding RNAs (lncRNAs) are involved in carcinogenesis and metastasis. The present study assessed the function of the lncRNA zinc finger antisense 1 (ZFAS1) in APL. In a cohort of 33 patients, ZFAS1 was significantly overexpressed compared with the level in healthy controls. To investigate the specific mechanisms of this upregulation, in vitro studies showed that silencing of ZFAS1 by small interfering RNA significantly inhibited cell proliferation in APL cells. Moreover, downregulation of ZFAS1 increased cellular apoptosis, decreased expression of B-cell lymphoma-2 and of induced myeloid leukemia cell differentiation protein Mcl-1, increased the expression of apoptosis regulator BAX and promoted the release of cytochrome c and Diablo homolog mitochondrial into the cytoplasm. In conclusion, these data indicate that ZFAS1 may serve as an oncogene in APL and may thus be a useful target for future clinical management.

Mass, number and surface area concentrations of alpha-quartz exposures of refractory material manufacturing workers.

This study set out to assess the respirable mass, surface area, and number concentrations of the alpha-quartz content particles (C(r-m), C(r-s) and C(r-n)) to which workers were exposed in six different exposure groups, the raw material handling (n=10), crushing (n=12), mixing (n=12), forming (n=10), furnace (n=10), and packaging (n=10), in a refractory material manufacturing plant. For C(r-m), the exposure values in sequence were found as: mixing (68.1 microg/m3)>packaging (55.9 microg/m3)>raw material handling (53.3 microg/m3)>furnace (31.0 microg/m3)>crushing (29.8 microg/m3)>forming (22.4 microg/m3). We also found that ~21.2-68.2% of the above Cr-m exceeded the current TLV-TWA for the alpha-quartz content (50 microg/m3) suggesting a need for initiating control strategies immediately. We further conducted particle size-segregating samplings in four workplaces: crushing (n=3), mixing (n=3), forming (n=3), and furnace (n=3). We found that all resultant particle size distributions shared a quite similar geometric standard deviation (sigma(g); =2.24-2.92), but the process area, associated with higher mechanical energy (i.e., crushing process), contained finer alpha-quartz content particles (mass median aerodynamic diameter; MMAD=3.22 microm) than those areas associated with lower mechanical energy (i.e., mixing, forming, and furnace; MMAD=6.17, 5.95, and 8.92 microm, respectively). These results gave a ratio of C(r-m) in the above four exposure groups (i.e., crushing: mixing: forming: furnace=1.00: 2.30: 0.753: 1.04) which was quite different from those of C(r-s) (1.00: 1.74: 0.654: 0.530) and C(r-n) (1.00: 1.27: 0.572: 0.202). Our results clearly indicate the importance of measuring particle size distributions for assessing workers' free silica exposures.