DNA polymerase delta governs parental histone transfer to DNA replication lagging strand.

Chromatin replication is intricately intertwined with the recycling of parental histones to the newly duplicated DNA strands for faithful genetic and epigenetic inheritance. The transfer of parental histones occurs through two distinct pathways: leading strand deposition, mediated by the DNA polymerase ε subunits Dpb3/Dpb4, and lagging strand deposition, facilitated by the MCM helicase subunit Mcm2. However, the mechanism of the facilitation of Mcm2 transferring parental histones to the lagging strand while moving along the leading strand remains unclear. Here, we show that the deletion of Pol32, a nonessential subunit of major lagging-strand DNA polymerase δ, results in a predominant transfer of parental histone H3-H4 to the leading strand during replication. Biochemical analyses further demonstrate that Pol32 can bind histone H3-H4 both in vivo and in vitro. The interaction of Pol32 with parental histone H3-H4 is disrupted through the mutation of the histone H3-H4 binding domain within Mcm2. Our findings identify the DNA polymerase δ subunit Pol32 as a critical histone chaperone downstream of Mcm2, mediating the transfer of parental histones to the lagging strand during DNA replication.

A nanobody inhibiting porcine reproductive and respiratory syndrome virus replication via blocking self-interaction of viral nucleocapsid protein.

Porcine reproductive and respiratory syndrome (PRRS) is a serious global pig industry disease. Understanding the mechanism of viral replication and developing efficient antiviral strategies are necessary for combating with PRRS virus (PRRSV) infection. Recently, nanobody is considered to be a promising antiviral drug, especially for respiratory viruses. The present study evaluated two nanobodies against PRRSV nucleocapsid (N) protein (PRRSV-N-Nb1 and -Nb2) for their anti-PRRSV activity in vitro and in vivo. The results showed that intracellularly expressed PRRSV-N-Nb1 significantly inhibited PRRSV-2 replication in MARC-145 cells (approximately 100%). Then, the PRRSV-N-Nb1 fused with porcine IgG Fc (Nb1-pFc) as a delivering tag was produced and used to determine its effect on PRRSV-2 replication in porcine alveolar macrophages (PAMs) and pigs. The inhibition rate of Nb1-pFc against PRRSV-2 in PAMs could reach >90%, and it can also inhibit viral replication in vivo. Epitope mapping showed that the motif Serine 105 (S105) in PRRSV-2 N protein was the key amino acid binding to PRRSV-N-Nb1, which is also pivotal for the self-interaction of N protein via binding to Arginine 97. Moreover, viral particles were not successfully rescued when the S105 motif was mutated to Alanine (S105A). Attachment, entry, genome replication, release, docking model analysis, and blocking enzyme-linked immunosorbent assay (ELISA) indicated that the binding of PRRSV-N-Nb1 to N protein could block its self-binding, which prevents the viral replication of PRRSV. PRRSV-N-Nb1 may be a promising drug to counter PRRSV-2 infection. We also provided some new insights into the molecular basis of PRRSV N protein self-binding and assembly of viral particles.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) causes serious economic losses to the swine industry worldwide, and there are no highly effective strategies for prevention. Nanobodies are considered a promising novel approach for treating diseases because of their ease of production and low costing. Here, we showed that PRRSV-N-Nb1 against PRRSV-N protein significantly inhibited PRRSV-2 replication in vitro and in vivo. Furthermore, we demonstrated that the motif Serine 105 (S105) in PRRSV-N protein was the key amino acid to interact with PRRSV-N-Nb1 and bond to its motif R97, which is important for the self-binding of N protein. The PRRSV-N-Nb1 could block the self-interaction of N protein following viral assembly. These findings not only provide insights into the molecular basis of PRRSV N protein self-binding as a key factor for viral replication for the first time but also highlight a novel target for the development of anti-PRRSV replication drugs.

Measures of resting-state brain network segregation and integration vary in relation to data quantity: implications for within and between subject comparisons of functional brain network organization.

Measures of functional brain network segregation and integration vary with an individual's age, cognitive ability, and health status. Based on these relationships, these measures are frequently examined to study and quantify large-scale patterns of network organization in both basic and applied research settings. However, there is limited information on the stability and reliability of the network measures as applied to functional time-series; these measurement properties are critical to understand if the measures are to be used for individualized characterization of brain networks. We examine measurement reliability using several human datasets (Midnight Scan Club and Human Connectome Project [both Young Adult and Aging]). These datasets include participants with multiple scanning sessions, and collectively include individuals spanning a broad age range of the adult lifespan. The measurement and reliability of measures of resting-state network segregation and integration vary in relation to data quantity for a given participant's scan session; notably, both properties asymptote when estimated using adequate amounts of clean data. We demonstrate how this source of variability can systematically bias interpretation of differences and changes in brain network organization if appropriate safeguards are not included. These observations have important implications for cross-sectional, longitudinal, and interventional comparisons of functional brain network organization.

Dissociable Effects of Alzheimer's Disease-Related Cognitive Dysfunction and Aging on Functional Brain Network Segregation.

Alzheimer's disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared with individuals without dementia. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping alterations on the functional connectome of the brain is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization toward AD characterization. Relationships between AD dementia severity and participant's age on resting-state brain system segregation were examined in 326 cognitively healthy and 275 cognitively impaired human individuals recruited through the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 601; age range, 55-96 years; 320 females). Greater dementia severity and increasing age were independently associated with lower brain system segregation. Further, dementia versus age relationships with brain network organization varied according to the processing roles of brain systems and types of network interactions. Aging was associated with alterations to association systems, primarily among within-system relationships. Conversely, dementia severity was associated with alterations that included both association systems and sensory-motor systems and was most prominent among cross-system interactions. Dementia-related network alterations were evident regardless of the presence of cortical amyloid burden, revealing that the measures of functional network organization are unique from this marker of AD-related pathology. Collectively, these observations demonstrate the specific and widespread alterations in the topological organization of large-scale brain networks that accompany AD and highlight functionally dissociable brain network vulnerabilities associated with AD-related cognitive dysfunction versus aging.SIGNIFICANCE STATEMENT Alzheimer's disease (AD)-associated cognitive dysfunction is hypothesized to be a consequence of brain network damage. It is unclear exactly how brain network alterations vary with dementia severity and whether they are distinct from alterations associated with aging. We evaluated functional brain network organization measured at rest among individuals who varied in age and dementia status. AD and aging exerted dissociable impacts on the brain's functional connectome. AD-associated brain network alterations were widespread and involved systems that subserve not only higher-order cognitive operations, but also sensory and motor operations. Notably, AD-related network alterations were independent of amyloid pathology. The research furthers our understanding of AD-related brain dysfunction and motivates refining existing frameworks of dementia characterization with measures of functional network organization.

High-Throughput Proteomics Enabled by a Fully Automated Dual-Trap and Dual-Column LC-MS.

This Technical Note describes a dual-column liquid chromatography system coupled to mass spectrometry (LC-MS) for high-throughput bottom-up proteomic analysis. This system made full use of two 2-position 10-port valves and a binary pump with an integrated loading pump of a commercial LC instrument to provide successive operation of two parallel subsystems. Each subsystem consisted of a set of trap columns and an analytical column. A T-junction union was used to split the mobile phase from the loading pump into two parts. This allowed one set of columns to be washed and equilibrated, followed by the injection of the next sample, while the previous sample was eluting and being analyzed on the other set of columns, thereby greatly increasing the analysis throughput. This approach showed high reproducibility for the analysis of HeLa tryptic digests with average relative standard deviation (RSD) values of 1.75%, 6.90%, and 5.19% for the identification number of proteins, peptides, and peptide-spectrum matches (PSMs), respectively, across 10 consecutive runs. The capacity for peptide and protein identification, as well as proteome depth, of the dual-column LC system was comparable to a conventional single-column system. Due to its simple equipment requirements and set up process, this method should be highly accessible for other laboratories.

Enhanced Label-Free Photoelectrochemical Strategy for Pollutant Detection: Using Surface Oxygen Vacancies-Enriched BiVO4 Photoanode.

Label-free photoelectrochemical sensors have the advantages of high sensitivity and a simple electrode structure. However, its performance is greatly limited due to the photoactive materials' weak photoactivity and poor stability. Herein, a robust homogeneous photoelectrochemical (PEC) aptasensor has been constructed for atrazine (ATZ) based on photoetching (PE) surface oxygen vacancies (Ov)-enriched Bismuth vanadate (BiVO4) (PE-BVO). The surface of the Ov improves the carrier separation ability of BiVO4, thus providing a superior signal substrate for the sensor. A thiol molecular layer self-assembled on PE-BVO acts as a blocker, while 2D graphene acts as a signal-on probe after release from the aptamer-graphene complex. The fabricated sensor has a wide linear detection range of 0.5 pM to 10.0 nM and a low detection limit of 0.34 pM (S/N = 3) for ATZ. In addition, it can efficiently work in a wide pH range (3-13) and high ionic strength (∼6 M Na+), which provides promising opportunities for detecting environmental pollutants under complex conditions.

Sexual Behavior and Perceived Risk for Oropharyngeal Cancer Among Men Who Have Sex With Men: A Psychometric Scale Validation.

BACKGROUND: Men who have sex with men (MSM) are at increased risk for human papillomavirus-associated oropharyngeal cancer (HPV-OPC). The objective of this analysis was to create a psychometrically validated scale to measure perception of risk for HPV-OPC. METHODS: We conducted an exploratory and a confirmatory factor analysis to determine and confirm the latent factor structure. We used a path diagram to evaluate the relationship between the validated scale and perceived risk for HPV-OPC. The model was determined to be a good fit if it met all criteria: root mean square error of approximation ≤0.06, standardized root mean residual ≤0.08, Comparative Fit Index ≥0.90, and Tucker-Lewis Index ≥0.90. We report standardized estimates and 95% confidence intervals. RESULTS: This cross-sectional study recruited 1315 MSM. A majority (73.33%) of MSM had performed fellatio on ≥20 partners, 36.98% had rimmed ≥20 partners, and 5.31% had performed cunnilingus on ≥10 partners in their lifetime.Six sexual history survey items loaded onto 2 latent factors: sexual risk behaviors: class 1 and sexual risk behaviors: class 2. The final model statistics indicated good fit: root mean square error of approximation = 0.064, standardized root mean residual = 0.059, Comparative Fit Index = 0.996, and Tucker-Lewis Index = 0.993. Sexual risk behaviors: class 1 was associated with greater perceived risk for HPV-OPC (0.217; 95% confidence interval, 0.138-0.295). Age, HIV status, HPV vaccination status, and sexual risk behaviors: class 2 were not associated with perceived risk for HPV-OPC. CONCLUSION: Men who have sex with men assessed risk for HPV-OPC based on their lifetime number of cisgender male sexual partners, rimming partners, and fellatio partners but not other sexual behaviors. Men who have sex with men may be responsive to future HPV-OPC educational interventions and opportunities for screening.

A capillary-based centrifugal indicator equipped with in situ pathogenic bacteria culture for fast antimicrobial susceptibility testing.

Antimicrobial resistance has become a major global health threat due to the misuse and overuse of antibiotics. Rapid, affordable, and high-efficiency antimicrobial susceptibility testing (AST) is among the effective means to solve this problem. Herein, we developed a capillary-based centrifugal indicator (CBCI) equipped with an in situ culture of pathogenic bacteria for fast AST. The bacterial incubation and growth were performed by macro-incubation, which seamlessly integrated the capillary indicator. Through simple centrifugation, all the bacterial cells were confined at the nanoliter-level capillary column. The packed capillary column height could linearly reflect the bacterial count, and the minimum inhibitory concentration (MIC) was determined based on the difference in the column height between the drug-added groups and the control group. The AST results could easily be determined by the naked eye or smartphone imaging. Thus, the CBCI realized the combination of macro-bacterial incubation and early micro assessment, which accelerated the phenotypic AST without complex microscopic counting or fluorescent labelling. The whole operation process was simple and easy to use. AST results could be determined for E. coli ATCC strains within 3.5 h, and the output results for clinical samples were consistent with the hospital reports. We expect this AST platform to become a useful tool in limiting antimicrobial resistance, especially in remote/resource-limited areas or in underdeveloped countries.

Golgi-localized APYRASE 1 is critical for Arabidopsis growth by affecting cell wall integrity under boron deficiency.

Many nucleoside triphosphate-diphosphohydrolases (NTPDases/APYRASEs, APYs) play a key role in modulating extracellular nucleotide levels. However, the Golgi-localized APYs, which help control glycosylation, have rarely been studied. Here, we identified AtAPY1, a gene encoding an NTPDase in the Golgi apparatus, which is required for cell wall integrity and plant growth under boron (B) limited availability. Loss of function in AtAPY1 hindered cell elongation and division in root tips while increasing the number of cortical cell layers, leading to swelling of the root tip and abundant root hairs under low B stress. Further, expression pattern analysis revealed that B deficiency significantly induced AtAPY1, especially in the root meristem and stele. Fluorescent-labeled AtAPY1-GFP localized to the Golgi stack. Biochemical analysis showed that AtAPY1 exhibited a preference of UDP and GDP hydrolysis activities. Consequently, the loss of function in AtAPY1 might disturb the homoeostasis of NMP-driven NDP-sugar transport, which was closely related to the synthesis of cell wall polysaccharides. Further, cell wall-composition analysis showed that pectin content increased and borate-dimerized RG-II decreased in apy1 mutants, along with a decrease in cellulose content. Eventually, altered polysaccharide characteristics presumably cause growth defects in apy1 mutants under B deficiency. Altogether, these data strongly support a novel role for AtAPY1 in mediating responses to low B availability by regulating cell wall integrity.

Microalgal astaxanthin ameliorates cypermethrin-induced necroptosis and inflammation via targeting mitochondrial Ca2+ homeostasis and the ROS-NF-κB-RIPK3/MLKL axis in carp hepatocytes (Cyprinus carpio).

Cypermethrin is a toxic pesticide that has infiltrated water bodies due to its widespread use. This contamination has led to detrimental effects on the immune organs of aquatic species, including fish. The natural fat-soluble orange-red carotenoid, astaxanthin (MAT), derived from microalgae, possesses anti-inflammatory, antioxidant, and immunomodulatory properties. To elucidate the mechanism of CY induced damage to carp liver cells and assess the potential protective effects of MAT, we established a carp hepatocyte model exposed to CY and/or MAT. Hepatocytes from carp (Cyprinus carpio) were treated with either 8 µM CY or 60 µM MAT for 24 h. Upon exposure CY, a significant increase in reactive oxygen species (ROS) was observed alongside a diminution in the activities of key antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), suggesting an impairment of cellular antioxidant capacity. Subsequently, acridine orange/ethidium bromide (AO/EB) staining and flow cytometry analysis revealed that hepatocytes exposed to CY exhibited a higher incidence of necroptosis, associated with an elevated mitochondrial Ca2+ concentration, which contributed to cellular dysfunction. Furthermore, exposure to CY also activated the ROS-NF-κB-RIPK3/MLKL signaling pathway, increasing the levels of necroptosis-related regulatory factors (RIP1, RIP3, and MLKL) in hepatocytes and the expression of inflammatory genes (IL-6, IFN-γ, IL-4, IL-1ß, and TNF-α), which led to immune dysfunction in hepatocytes. The immunotoxic effects induced by CY were mitigated by MAT treatment, suggesting its potential in alleviating the aforementioned changes caused by CY. Overall, the data suggested that MAT therapy could enhance hepatocyte defenses against CY-induced necroptosis and inflammatory responses by regulating mitochondrial Ca2+ homeostasis and inhibiting the ROS-NF-κB-RIPK3/MLKL signaling cascade. This study elucidated the potential benefits of employing MAT to protect farmed fish from agrobiological hazards during CY exposure, underscoring the practical applications of MAT in aquaculture.

Association of the combination of obstructive sleep apnea risk and sleep duration with ideal cardiovascular health metrics in patients undergoing hemodialysis.

BACKGROUND: The purpose of this study was to explore the separate and combined associations of obstructive sleep apnea (OSA) risk and sleep duration with ideal cardiovascular health metrics in hemodialysis (HD) patients. METHODS: 470 HD participants (average: 59.48 ± 12.89 y, 281 men) were included in this study. Sleep duration was measured as self-reported average sleep time during the previous month. The OSA risk was assessed using the STOP-BANG questionnaire. Participants were divided into three groups based on the number of ideal cardiovascular health (CVH) metrics: 0-2,3-4, and 5-7. Ordinal logistic regression was conducted to model the associations of CVH metrics with sleep duration, OSA risk, and their combined effects by adjusting for specific covariates. RESULTS: After adjusting for covariates, short sleep duration (< 7 h) (OR = 0.53; 95% CI [ 0.30, 0.92]) and OSA risk (OR = 0.58; 95% CI [0.32, 0.83]) were negatively associated with better CVH (ideal vs. intermediate; intermediate vs. poor), respectively. For HD patients with both short sleep duration and OSA risk, the odds of ideal CVH metrics were reduced by 72% (odds ratio 0.28 [95% CI 0.13, 0.60]). CONCLUSIONS: Short sleep duration and OSA risk are separately and jointly associated with poor CVH in hemodialysis patients. Suitable interventions for sleep may minimize the risk of developing cardiovascular disease.

Astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasis.

Cadmium (Cd) is a dangerous heavy metal with high toxicity that is known to impair development. Astilbin (ASB) is a protective flavonoid compound. We aimed to explore whether ASB can antagonize the myocardial developmental toxicity of Cd exposure. Cd (2 µg) and/or ASB (0.002 µg) were injected into embryonized eggs that were 1 day old. Histological examinations revealed Cd-induced ventricular dilation, reduced wall thickness, and disrupted myocardial fiber connections, while co-administration of ASB mitigated these effects. Electron microscopy confirmed ASB's ability to counteract Cd-induced myocardial cell myofibril damage. Real-time quantitative PCR (QRT-PCR) and western blot (WB) molecular investigations revealed that Cd increased endoplasmic reticulum stress in myocardial tissue and primary cardiomyocytes, as shown by raised expression of stress-related genes (GRP78, XBP1, GRP94, ATF4, ATF6, IRE1, and CHOP). Moreover, Cd disrupted calcium homeostasis, affecting important genes linked to Ca2+ channels and causing an excess of Ca2+ in the cytoplasm. In addition, we detected genes related to development and differentiation-related genes in myocardial tissue and primary cardiomyocytes. The results showed that the downregulation of transcription factors in the IrxA cluster, Mefs, and Tbxs families after Cd exposure indicated that cardiac transcription was hindered and cardiac markers (TnnT2, TnnC1, Gata4, Gata6, and Nkx2-5) were abnormally expressed. ASB successfully mitigated these disturbances. During the cell cycle, primary cardiomyocytes undergo growth arrest in flow cytometry. These results suggest that the maturation and differentiation of cardiomyocytes are inhibited after Cd exposure, and ASB has an antagonistic effect on Cd. The present study indicated that Cd could trigger developmental cardiotoxicity in chicken embryos and primary cardiomyocytes by endoplasmic reticulum stress and Ca2+ overload, respectively, while ASB has an antagonistic effect.

Chlorantraniliprole induces mitophagy, ferroptosis, and cytokine homeostasis imbalance in grass carp (Ctenopharyngodon idella) hepatocytes via the mtROS-mitochondrial fission/fusion axis.

Chlorantraniliprole (CAP) is a bis-amide pesticide used for pest control mainly in agricultural production activities and rice-fish co-culture systems. CAP residues cause liver damage in non-target organism freshwater fish. However, it is unclear whether CAP-exposure-induced liver injury in fish is associated with mitochondrial dysfunction-mediated mitophagy, ferroptosis, and cytokines. Therefore, we established grass carp hepatocyte models exposed to different concentrations of CAP (20, 40, and 80 µM) in vitro. MitoSOX probe, JC-1 staining, immunofluorescence double staining, Fe2+ staining, lipid peroxidation staining, qRT-PCR, and Western blot were used to verify the physiological regulatory mechanism of CAP induced liver injury. In the present study, the CAP-treated groups exhibited down-regulation of antioxidant-related enzyme activities and accumulation of peroxides. CAP treatment induced an increase in mitochondrial reactive oxygen species (mtROS) levels and altered expression of mitochondrial fission/fusion (Drp1, Fis1, Mfn1, Mfn2, and Opa1) genes in grass carp hepatocytes. In addition, mitophagy (Parkin, Pink1, p62, LC3II/I, and Beclin-1), ferroptosis (GPX4, COX2, ACSL4, FTH, and NCOA4), and cytokine (IFN-γ, IL-18, IL-17, IL-6, IL-10, IL-1ß, IL-2, and TNF-α)-related gene expression was significantly altered. Collectively, these findings suggest that CAP exposure drives mitophagy activation, ferroptosis occurrence, and cytokine homeostasis imbalance in grass carp hepatocytes by triggering mitochondrial dysfunction mediated by the mtROS-mitochondrial fission/fusion axis. This study partly explained the physiological regulation mechanism of grass carp hepatocyte injury induced by insecticide CAP from the physiological and biochemical point of view and provided a basis for evaluating the safety of CAP environmental residues to non-target organisms.

Synthesis, and Insecticidal Activities of Propargyloxy-Diphenyl Oxide-Sulfonamide Derivatives.

Agricultural pests are the primary contributing factor to crop yield reduction, particularly in underdeveloped regions. Despite the significant efficacy of pesticides in pest control, their extensive use has led to the drug-fast of insecticide resistance. Developing of new environmentally friendly plant-based pesticides is an urgent necessity. In this study, a series of diaryl ether compounds containing propargyloxy and sulfonamide groups were designed. The synthesis of these 36 compounds primarily relied on nuclear magnetic resonance for structure determination, while single-crystal X-ray diffraction was employed for certain compounds. Meanwhile, the insecticidal activities against Mythimna separata were also assessed. Some of the compounds exhibited significantly enhanced activity, the LC50 value of the highest activity compound TD8 (0.231 mg/mL) demonstrating respective increases by 100-fold compared to the plant pesticide celangulin V (23.9 mg/mL), and a 5-fold increase with the positive control L-1 (1.261 mg/mL). The interaction between the target compound and the target, as well as the consistency of the target, were verified through symptomological analysis and molecular docking. The structure-activity relationships were also conducted. This study offered a novel trajectory for the advancement and formulation of future pesticides.

Forensic parameters and population analysis of 21 autosomal STR loci in the Wuhu Han population from Anhui Province, East China.

BACKGROUND: At present, there are no available genetic data on the AGCU EX22 Kit from the Wuhu Han population. AIM: This study investigates the applicability of the AGCU EX22 kit, designed for the Chinese population for forensic analysis and population genetics of the Wuhu Han population. SUBJECTS AND METHODS: Bloodstains from 1565 unrelated healthy individuals in Wuhu city, Anhui Province, were collected for analysis. The AGCU EX22 kit was used for amplification, and capillary electrophoresis was used to separate the amplification products. Allele frequencies and forensic parameters were determined. The Wuhu Han population was compared to 10 reference populations through genetic distance, a phylogenetic neighbor-joining tree and principal component analysis. RESULTS: In total, 281 alleles and 1187 genotypes were observed. No significant deviations from Hardy-Weinberg equilibrium at any locus were found after Bonferroni's correction. The 21 autosomal short tandem repeat (STR) genetic markers exhibited high informativeness and polymorphism. The cumulative power of discrimination and power of exclusion were 0.999999999999999999999999913380 and 0.999999996752339, respectively. Population comparisons revealed a genetic affinity between Wuhu Han and southern Han populations, except for the Guangdong Han population, which aligned with the traditional geographical division in China. CONCLUSION: The AGCU EX22 Kit, containing 21 STR loci, is suitable for forensic application and population genetics studies in the Wuhu Han population.

Effects of 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid on Enhancing Grip Strength and Inhibiting Protein Catabolism Induced by Exhaustive Exercise.

3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA), also known as dihydroferulic acid, is a hydroxycinnamic acid derivative that can be derived from the microbial transformation of dietary polyphenols or naturally obtained from fermented foods. Although numerous studies have documented its antioxidant and anti-obesity effects, the effect of HMPA on muscle function remains unknown. This study investigated the effects of HMPA on muscle strength and exercise endurance capacity. Mice were orally administered low and high doses of HMPA for 14 days and subjected to grip force and treadmill exhaustion tests to evaluate muscle function. Our results showed that HMPA-administered groups significantly enhanced absolute grip strength (p = 0.0256) and relative grip strength (p = 0.0209), and low-dose HMPA decreased the plasma level of blood urea nitrogen after exercise (p = 0.0183), but HMPA did not affect endurance performance. Low-dose HMPA administration increased Myf5 expression in sedentary mice (p = 0.0106), suggesting that low-dose HMPA may promote muscle development. Additionally, HMPA improved hepatic glucose and lipid metabolism, and inhibited muscular lipid metabolism and protein catabolism, as indicated by changes in mRNA expression levels of related genes. These findings suggest that HMPA may be a promising dietary supplement for muscle health and performance.

Effect of substrate material and abutment geometry on the accuracy of intraoral scanning: An in vitro study.

STATEMENT OF PROBLEM: Digital scanning is gradually replacing conventional impression making, but consensus on how tooth preparation influences the accuracy of intraoral scanning is lacking. PURPOSE: The purpose of this in vitro study was to evaluate the effect of substrate material and abutment geometry on the accuracy of digital casts obtained by intraoral scanning. MATERIAL AND METHODS: The height and total occlusal convergence (TOC) angle were measured in 5 different groups that contained 5 specimens of different materials: natural tooth, cobalt chromium alloy, titanium, zirconium dioxide ceramic, and resin. The specimens were scanned with an industrial scanner to obtain reference data. Each specimen was placed in a maxillary standard dentition model that was assembled in a head simulator. Each dentition model was scanned 10 times with an intraoral scanner (IOS) under operatory lighting conditions to acquire intraoral scanning files for each specimen. All data were imported into a metrology software program and processed. A total of 10 trueness deviations, the mean superimposition results between IOS scanning data and reference data, and precision deviations, the mean superimposition results between IOS scanning data in pairs, were recorded. Two-way analysis of variance (ANOVA) and Tukey multiple comparison test were used to analyze the accuracy of intraoral scanning in relation to the height or TOC angle of the abutment (α=.05). The total means of each substrate material were compared with the Kruskal-Wallis test and Dunn test for multiple comparisons. RESULTS: The accuracy of scanning images was related to material and abutment geometry (P<.05). Bias was larger as abutment height increased with most substrates. Larger TOC angles increased the accuracy of the digital scans. The trueness deviation of translucent materials and the precision deviation of reflective materials were generally larger. CONCLUSIONS: Substrate material and abutment geometry influence the accuracy of intraoral scanning. The accuracy of IOS generally tended to improve with decreasing height and increasing TOC angle and was affected by different substrates.

The RING zinc finger protein LbRZF1 promotes salt gland development and salt tolerance in Limonium bicolor.

The recretohalophyte Limonium bicolor thrives in high-salinity environments because salt glands on the above-ground parts of the plant help to expel excess salt. Here, we characterize a nucleus-localized C3HC4 (RING-HC)-type zinc finger protein of L. bicolor named  RING  ZINC  FINGER PROTEIN  1 (LbRZF1). LbRZF1 was expressed in salt glands and in response to NaCl treatment. LbRZF1 showed no E3 ubiquitin ligase activity. The phenotypes of overexpression and knockout lines for LbRZF1 indicated that LbRZF1 positively regulated salt gland development and salt tolerance in L. bicolor. lbrzf1 mutants had fewer salt glands and secreted less salt than did the wild-type, whereas LbRZF1-overexpressing lines had opposite phenotypes, in keeping with the overall salt tolerance of these plants. A yeast two-hybrid screen revealed that LbRZF1 interacted with LbCATALASE2 (LbCAT2) and the transcription factor LbMYB113, leading to their stabilization. Silencing of LbCAT2 or LbMYB113 decreased salt gland density and salt tolerance. The heterologous expression of LbRZF1 in Arabidopsis thaliana conferred salt tolerance to this non-halophyte. We also identified the transcription factor LbMYB48 as an upstream regulator of LbRZF1 transcription. The study of LbRZF1 in the regulation network of salt gland development also provides a good foundation for transforming crops and improving their salt resistance.

Evaluation of the Binding Preference of Microtubes for Nanoproteomics Sample Preparation.

Nonspecific binding between the protein and the container is an often-neglected cause of sample loss in large-scale proteomics sample preparation. In nanoproteomics, due to the small sample size, this absorption loss is no longer negligible, and researchers often adopt low binding plasticware to minimize the sample loss. However, there has been little discussion in the scientific literature on the differences in microtube performance on reducing protein/peptide binding. Therefore, the exact impact of sample loss during the sample preparation is not well understood. Here, we investigated the protein/peptide loss during the nanoproteomics experiment process. Our results showed that there are significant differences in nonspecific binding among the tested microtubes, with a protein recovery rate ranging from less than 10% to over 90% for different microtubes. Interestingly, we found that the storage temperature could also be one of the key factors that contribute to protein recovery from the plastic container. In addition, we investigated the binding preferences of different microtubes by the physical characteristics of the identified proteins and peptides, such as isoelectric point, hydrophobicity, length, and charge. Our findings help to better understand protein/peptide loss in proteomics sample preparation and provide further guidance for researchers in choosing proper containers for their precious sample.

The intricate relationship between autoimmunity disease and neutrophils death patterns: a love-hate story.

Autoimmune diseases are pathological conditions that result from the misidentification of self-antigens in immune system, leading to host tissue damage and destruction. These diseases can affect different organs and systems, including the blood, joints, skin, and muscles. Despite the significant progress made in comprehending the underlying pathogenesis, the complete mechanism of autoimmune disease is still not entirely understood. In autoimmune diseases, the innate immunocytes are not functioning properly: they are either abnormally activated or physically disabled. As a vital member of innate immunocyte, neutrophils and their modes of death are influenced by the microenvironment of different autoimmune diseases due to their short lifespan and diverse death modes. Related to neutrophil death pathways, apoptosis is the most frequent cell death form of neutrophil non-lytic morphology, delayed or aberrant apoptosis may contribute to the development anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). In addition, NETosis, necroptosis and pyroptosis which are parts of lytic morphology exacerbate disease progression through various mechanisms in autoimmune diseases. This review aims to summarize recent advancements in understanding neutrophil death modes in various autoimmune diseases and provide insights into the development of novel therapeutic approaches for autoimmune diseases.