Screening and Characterization of a New Iflavirus Virus in the Fruit Tree Pest Pyrops candelaria.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full length of PyCaV is 10,855 bp with the polyA tail, containing a single open-reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical iflavirus structure, including two rhv domains, an RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and an RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignments analysis suggested PyCaV is a new member in an unassigned genus of family Iflaviridae. Further in-depth analysis of the virus infection showed that PyCaV is distributed throughout the whole P. candelaria, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV was detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and location.

Benchmarking and Automating the Biotinylation Proteomics Workflow.

Protein biotinylation has been widely used in biotechnology with various labeling and enrichment strategies. However, different enrichment strategies have not been systematically evaluated due to the lack of a benchmarking model for fair comparison. Most biotinylation proteomics workflows suffer from lengthy experimental steps, non-specific bindings, limited throughput, and experimental variability. To address these challenges, we designed a two-proteome model, where biotinylated yeast proteins were spiked in unlabeled human proteins, allowing us to distinguish true enrichment from non-specific bindings. Using this benchmarking model, we compared common biotinylation proteomics methods and provided practical selection guidelines. We significantly optimized and shortened sample preparation from 3 days to 9 hours, enabling fully-automated 96-well plate sample processing. Next, we applied this optimized and automated workflow for proximity labeling to investigate the intricate interplay between mitochondria and lysosomes in living cells under both healthy state and mitochondrial damage. Our results suggested a time-dependent proteome remodeling and dynamic translocation within mitochondria and between mitochondria and lysosomes upon mitochondrial damage. This newly established benchmarking model and the fully-automated 9-hour workflow can be readily applied to the broad fields of protein biotinylation to study protein interaction and organelle dynamics.

Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus.

Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions1,2. Expansion of T follicular helper (TFH) and T peripheral helper (TPH) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE3,4. Human TFH and TPH cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs. 5,6), yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4+ T cell phenotypes in patients with SLE, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4+ T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ TPH/TFH cell differentiation and promote an IL-22+ phenotype. Type I interferon, a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ TPH/TFH cells on a polarization axis opposite from T helper 22 (TH22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states.

Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure.

The kidney and brain play critical roles in the regulation of blood pressure. Neuropeptide FF (NPFF), originally isolated from the bovine brain, has been suggested to contribute to the pathogenesis of hypertension. However, the roles of NPFF and its receptors, NPFF-R1 and NPFF-R2, in the regulation of blood pressure, via the kidney, are not known. In this study, we found that the transcripts and proteins of NPFF and its receptors, NPFF-R1 and NPFF-R2, were expressed in mouse and human renal proximal tubules (RPTs). In mouse RPT cells (RPTCs), NPFF, but not RF-amide-related peptide-2 (RFRP-2), decreased the forskolin-stimulated cAMP production in a concentration- and time-dependent manner. Furthermore, dopamine D1-like receptors colocalized and co-immunoprecipitated with NPFF-R1 and NPFF-R2 in human RPTCs. The increase in cAMP production in human RPTCs caused by fenoldopam, a D1-like receptor agonist, was attenuated by NPFF, indicating an antagonistic interaction between NPFF and D1-like receptors. The renal subcapsular infusion of NPFF in C57BL/6 mice decreased renal sodium excretion and increased blood pressure. The NPFF-mediated increase in blood pressure was prevented by RF-9, an antagonist of NPFF receptors. Taken together, our findings suggest that autocrine NPFF and its receptors in the kidney regulate blood pressure, but the mechanisms remain to be determined.

Association between obstructive sleep apnea and arrhythmia and heart rate variability among hypertensive patients.

BACKGROUND: The relationship between obstructive sleep apnea (OSA) and the occurrence of arrhythmias and heart rate variability (HRV) in hypertensive patients is not elucidated. Our study investigates the association between OSA, arrhythmias, and HRV in hypertensive patients. METHODS: We conducted a cross-sectional analysis involving hypertensive patients divided based on their apnea-hypopnea index (AHI) into two groups: the AHI ≤ 15 and the AHI > 15. All participants underwent polysomnography (PSG), 24-hour dynamic electrocardiography (DCG), cardiac Doppler ultrasound, and other relevant evaluations. RESULTS: The AHI > 15 group showed a significantly higher prevalence of frequent atrial premature beats and atrial tachycardia (P = 0.030 and P = 0.035, respectively) than the AHI ≤ 15 group. Time-domain analysis indicated that the standard deviation of normal-to-normal R-R intervals (SDNN) and the standard deviation of every 5-minute normal-to-normal R-R intervals (SDANN) were significantly higher in the AHI > 15 group (P = 0.020 and P = 0.033, respectively). Frequency domain analysis revealed that the low-frequency (LF), high-frequency (HF) components, and the LF/HF ratio were also significantly elevated in the AHI > 15 group (P < 0.001, P = 0.031, and P = 0.028, respectively). Furthermore, left atrial diameter (LAD) was significantly larger in the AHI > 15 group (P < 0.001). Both univariate and multivariable linear regression analyses confirmed a significant association between PSG-derived independent variables and the dependent HRV parameters SDNN, LF, and LF/HF ratio (F = 8.929, P < 0.001; F = 14.832, P < 0.001; F = 5.917, P = 0.016, respectively). CONCLUSIONS: Hypertensive patients with AHI > 15 are at an increased risk for atrial arrhythmias and left atrial dilation, with HRV significantly correlating with OSA severity.

Disease Progression and Multiparametric Imaging Characteristics of Spinocerebellar Ataxia Type 3 With Spastic Paraplegia.

Background and Objectives: Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3. Methods: We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model. Results: Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected p < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both p < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP. Discussion: SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.

A meta-analysis of the association between inflammatory cytokine polymorphism and neonatal sepsis.

OBJECTIVE: The purpose of this study is to investigate the relationship between single nucleotide polymorphisms of inflammatory cytokines and neonatal sepsis through meta-analysis. METHODS: We collected research literature on the correlation between inflammatory cytokine polymorphisms and neonatal sepsis published before August 2023 through computer searches of databases such as PubMed, Embase, etc. The Stata 14.0 software was utilized for Meta-analysis. To assess heterogeneity, the chi-squared Q-test and I2 statistics were used. The Egger and Begg tests were conducted to determine the possibility of publication bias. RESULTS: After reviewing 1129 articles, 29 relevant articles involving 3348 cases and 5183 controls were included in the study. The meta-analysis conducted on IL-1ßrs1143643 polymorphism revealed significant findings: the T allele genotype has a lower risk of neonatal sepsis(P = 0.000, OR = 0.224, 95% CI: 0.168-0.299), while the TC and TT genotypes showed an increased risk(TC: P = 0.000,OR = 4.251, 95% CI: 2.226-8.119; TT: P = 0.019,OR = 2.020, 95% CI: 1.122-3.639). Similarly, newborns with the IL-6-174 CC genotype had a significantly higher risk of sepsis(P = 0.000,OR = 1.591, 95% CI: 1.154-2.194), while those with the IL-8-rs4073 TT (P = 0.003,OR = 0.467, 95% CI: 0.280-0.777)and TT + AA(P = 0.003,OR = 0.497, 95% CI: 0.315-0.785) genotypes had a significantly lower risk of sepsis. For the IL-10-1082 gene, newborns with the AA genotype(P = 0.002,OR = 1.702, 95% CI: 1.218-2.377), as well as those with the AA + GA genotype(P = 0.016,OR = 1.731, 95% CI: 1.108-2.705), had a significantly higher risk of sepsis. Lastly, newborns carrying the TNF-α-308 A allele (P = 0.016,OR = 1.257, 95% CI: 1.044-1.513)or the AA genotype(P = 0.009,OR = 1.913, 95% CI: 1.179-3.10) have a significantly increased risk of sepsis. Notwithstanding, additional studies must be included for validation. Applying these cytokines in clinical practice and integrating them into auxiliary examinations facilitates the early detection of susceptible populations for neonatal sepsis, thereby providing a new diagnostic and therapeutic approach for neonatal sepsis.

Kv3.1 Interaction with UBR5 Is Required for Chronic Inflammatory Pain.

Chronic inflammatory pain caused by neuronal hyperactivity is a common and refractory disease. Kv3.1, a member of the Kv3 family of voltage-dependent K+ channels, is a major determinant of the ability of neurons to generate high-frequency action potentials. However, little is known about its role in chronic inflammatory pain. Here, we show that although Kv3.1 mRNA expression was unchanged, Kv3.1 protein expression was decreased in the dorsal spinal horn of mice after plantar injection of complete Freund's adjuvant (CFA), a mouse model of inflammatory pain. Upregulating Kv3.1 expression alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas downregulating Kv3.1 induced nociception-like behaviors. Additionally, we found that ubiquitin protein ligase E3 component n-recognin 5 (UBR5), a key factor in the initiation of chronic pain, binds directly to Kv3.1 to drive its ubiquitin degradation. Intrathecal injection of the peptide TP-CH-401, a Kv3.1 ubiquitination motif sequence, rescued the decrease in Kv3.1 expression and Kv currents through competitive binding to UBR5, and consequently attenuated mechanical and thermal hypersensitivity. These findings demonstrate a previously unrecognized pathway of Kv3.1 abrogation by UBR5 and indicate that Kv3.1 is critically involved in the regulation of nociceptive behavior. Kv3.1 is thus a promising new target for treating inflammatory pain.

Dynamic whole-transcriptome landscape of acute bilirubin encephalopathy in newborns.

Hyperbilirubinemia in newborns may progress to acute bilirubin encephalopathy (ABE), posing short- and long-term health risks. Despite extensive research identifying numerous mRNAs, lncRNAs, circRNAs, and miRNAs associated with brain injury, their roles in neonatal bilirubin-induced brain injury remain elusive. This study employed whole-transcriptome sequencing to ascertain the differentially expressed (DE) RNA profiles in a newborn ABE rat model, followed by bioinformatic analysis. A time-series competing endogenous RNA (ceRNA) regulatory network was established, and the expression trends of 9 arbitrarily chosen RNAs were verified through quantitative real-time polymerase chain reaction(qRT-PCR). In comparison with the control group, we identified 595, 888, and 1448 DE mRNAs; 22, 37, and 37 DE miRNAs; 1945, 1869, and 1997 DE lncRNAs; and 31, 28, and 36 DE circRNAs at 6 h, 12 h, and 24 h, respectively. Predominantly, these DERNAs contribute to biological functions and pathways associated with inflammation, immunity, metabolism, cell death, and neurodevelopmental regulation. Moreover, we constructed ceRNA networks of DE lncRNA/circRNA-DE miRNA-DE mRNA based on time series. The qRT-PCR expression trends for the selected 9 RNAs were generally similar to the RNA-seq outcomes. This investigation uniquely delineated the temporal expression patterns of mRNA and non-coding RNA in ABE, establishing ceRNA networks and identifying potential molecular mechanisms underlying bilirubin-induced hippocampal damage. Nonetheless, further studies are warranted to corroborate these findings in humans.

A sensitive Ag+-mediated magnetic relaxation and colorimetry dual-mode sensing platform.

To address the relatively low sensitivity of current redox reagent-mediated magnetic relaxation sensing methods, we present a novel Ag+-mediated magnetic sensing platform that enhances the sensitivity by three orders of magnitude. The new sensing platform is based on Ag+-catalyzed oxidation of Mn2+ to KMnO4, accompanied by a distinct color change, which facilitates colorimetric detection. In the case of insufficient Ag+ ions, MnO2 is an additional oxidation product and the KMnO4/MnO2 ratio is dependent on the concentration of Ag+. When combined with a specific quantity of reducing agent, both KMnO4 and MnO2 are reduced to Mn2+ with a large relaxivity, and the concentration of Mn2+ in the resultant solution inversely correlates with the amount of KMnO4 since KMnO4 consumes more reductant during reduction. Consequently, the transverse relaxation rate of the solution exhibits a negative correlation with the Ag+ concentration. Thus, by coupling this Ag+-mediated Mn2+ to KMnO4 transformation with reactions that modulate Ag+ concentration, a dual-mode sensing platform for magnetic relaxation and colorimetry can be realized. Herein, we take H2O2 as an example to verify the detection performance of this sensing platform since H2O2 can oxidize Ag0 in Ag@Fe3O4 nanoparticles to Ag+. Experimental findings demonstrate detection limits of 10 nM and 20 nM for the magnetic relaxation and colorimetry modes, respectively, affirming the excellent sensitivity and the potential practical application of this strategy.

Risk factors of neonatal stroke from different origins: a systematic review and meta-analysis.

Given the persistent ambiguity regarding the etiology of neonatal stroke across diverse origins, our objective was to conduct a comprehensive evaluation of both qualitative and quantitative risk factors. An exhaustive search of eight databases was executed to amass all pertinent observational studies concerning risk factors for neonatal stroke from various origins. Subsequent to independent screening, data extraction, and bias assessment by two researchers, a meta-analysis was conducted utilizing RevMan and Stata software. Nineteen studies, encompassing a total of 30 factors, were incorporated into this analysis. Beyond established risk factors, our investigation unveiled gestational diabetes (OR, 5.51; P < 0.00001), a history of infertility (OR, 2.44; P < 0.05), placenta previa (OR, 3.92; P = 0.02), postdates (OR, 2.07; P = 0.01), preterm labor (OR, 2.32; P < 0.00001), premature rupture of membranes (OR, 3.02; P = 0.007), a prolonged second stage of labor (OR, 3.94; P < 0.00001), and chorioamnionitis (OR, 4.35; P < 0.00001) as potential risk factors for neonatal cerebral arterial ischemic stroke. Additionally, postdates (OR, 4.31; P = 0.003), preterm labor (OR, 1.60; P < 0.00001), an abnormal CTG tracing (OR, 9.32; P < 0.0001), cesarean section (OR, 4.29; P = 0.0004), male gender (OR, 1.73; P = 0.02), and vaginal delivery (OR, 1.39; P < 0.00001) were associated with an elevated risk for neonatal hemorrhagic stroke. CONCLUSIONS: This study provides a succinct overview and comparative analysis of maternal, perinatal, and additional risk factors associated with neonatal cerebral artery ischemic stroke and neonatal hemorrhagic stroke, furnishing critical insights for healthcare practitioners involved in the diagnosis and prevention of neonatal stroke. This research also broadens the conceptual framework for future investigations. WHAT IS KNOWN: • Research indicates that prenatal, perinatal, and neonatal risk factors can elevate the risk of neonatal arterial ischemic stroke (NAIS). However, the risk factors for neonatal cerebral arterial ischemic stroke remain contentious, and those for neonatal hemorrhagic stroke (NHS) and neonatal cerebral venous sinus thrombosis (CVST) are still not well-defined. WHAT IS NEW: • This study is the inaugural comprehensive review and meta-analysis encompassing 19 studies that explore maternal, perinatal, and various risk factors linked to neonatal stroke of differing etiologies. Notably, our analysis elucidates eight risk factors associated with NAIS: gestational diabetes mellitus, a history of infertility, placenta previa, postdates, preterm birth, premature rupture of membranes, a prolonged second stage of labor, and chorioamnionitis. Furthermore, we identify six risk factors correlated with NHS: postdates, preterm birth, an abnormal CTG, the method of delivery, male gender, and vaginal delivery. Additionally, our systematic review delineates risk factors associated with CVST.

Visual-motor integration in children with unilateral cerebral palsy: application of the computer-aided measure of visual-motor integration.

BACKGROUND: Children with unilateral cerebral palsy (UCP) are encouraged to participate in the regular school curriculum. However, even when using the less-affected hand for handwriting, children with UCP still experience handwriting difficulties. Visual-motor integration (VMI) is a predictor of handwriting quality. Investigating VMI in children with UCP is important but still lacking. Conventional paper-based VMI assessments is subjective and use all-or-nothing scoring procedures, which may compromise the fidelity of VMI assessments. Moreover, identifying important shapes that are predictive of VMI performance might benefit clinical decision-making because different geometric shapes represent different developmental stepping stones of VMI. Therefore, a new computer-aided measure of VMI (the CAM-VMI) was developed to investigate VMI performance in children with UCP and to identify shapes important for predicting their VMI performance. METHODS: Twenty-eight children with UCP and 28 typically-developing (TD) children were recruited. All participants were instructed to complete the CAM-VMI and Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI). The test items of the CAM-VMI consisted of nine simple geometric shapes related to writing readiness. Two scores of the CAM-VMI, namely, Error and Effort, were obtained by image registration technique. The performances on the Beery-VMI and the CAM-VMI of children with UCP and TD children were compared by independent t-test. A series of stepwise regression analyses were used to identify shapes important for predicting VMI performance in children with UCP. RESULTS: Significant group differences were found in both the CAM-VMI and the Beery-VMI results. Furthermore, Error was identified as a significant aspect for predicting VMI performance in children with UCP. Specifically, the square item was the only significant predictor of VMI performance in children with UCP. CONCLUSIONS: This study was a large-scale study that provided direct evidence of impaired VMI in school-aged children with UCP. Even when using the less-affected hand, children with UCP could not copy the geometric shapes as well as TD children did. The copied products of children with UCP demonstrated poor constructional accuracy and inappropriate alignment. Furthermore, the predictive model suggested that the constructional accuracy of a copied square is an important predictor of VMI performance in children with UCP.

Elucidating the molecular basis of ATP-induced cell death in breast cancer: Construction of a robust prognostic model.

BACKGROUND: Breast cancer is a multifaceted and formidable disease with profound public health implications. Cell demise mechanisms play a pivotal role in breast cancer pathogenesis, with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence. AIM: To investigate the impact of ATP-induced cell death (AICD) on breast cancer, enhancing our understanding of its mechanism. METHODS: The foundational genes orchestrating AICD mechanisms were extracted from the literature, underpinning the establishment of a prognostic model. Simultaneously, a microRNA (miRNA) prognostic model was constructed that mirrored the gene-based prognostic model. Distinctions between high- and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized, with the aim of delineating common influence mechanisms, substantiated through enrichment analysis and immune infiltration assessment. RESULTS: The mRNA prognostic model in this study encompassed four specific mRNAs: P2X purinoceptor 4, pannexin 1, caspase 7, and cyclin 2. The miRNA prognostic model integrated four pivotal miRNAs: hsa-miR-615-3p, hsa-miR-519b-3p, hsa-miR-342-3p, and hsa-miR-324-3p. B cells, CD4+ T cells, CD8+ T cells, endothelial cells, and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways, while miRNA risk scores significantly enriched 29 signaling pathways, with 16 pathways being jointly enriched. CONCLUSION: Of paramount significance, distinct mRNA and miRNA signature models were devised tailored to AICD, both potentially autonomous prognostic factors. This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools, offering an unparalleled window for innovative interventions. Essentially, this paper reveals the hitherto enigmatic link between AICD and breast cancer, potentially leading to revolutionary progress in personalized oncology.

Multiomics Evaluation of Human iPSCs and iPSC-Derived Neurons.

Human induced pluripotent stem cells (iPSCs) can be differentiated into neurons, providing living human neurons to model brain diseases. However, it is unclear how different types of molecules work together to regulate stem cell and neuron biology in healthy and disease states. In this study, we conducted integrated proteomics, lipidomics, and metabolomics analyses with confident identification, accurate quantification, and reproducible measurements to compare the molecular profiles of human iPSCs and iPSC-derived neurons. Proteins, lipids, and metabolites related to mitosis, DNA replication, pluripotency, glycosphingolipids, and energy metabolism were highly enriched in iPSCs, whereas synaptic proteins, neurotransmitters, polyunsaturated fatty acids, cardiolipins, and axon guidance pathways were highly enriched in neurons. Mutations in the GRN gene lead to the deficiency of the progranulin (PGRN) protein, which has been associated with various neurodegenerative diseases. Using this multiomics platform, we evaluated the impact of PGRN deficiency on iPSCs and neurons at the whole-cell level. Proteomics, lipidomics, and metabolomics analyses implicated PGRN's roles in neuroinflammation, purine metabolism, and neurite outgrowth, revealing commonly altered pathways related to neuron projection, synaptic dysfunction, and brain metabolism. Multiomics data sets also pointed toward the same hypothesis that neurons seem to be more susceptible to PGRN loss compared to iPSCs, consistent with the neurological symptoms and cognitive impairment from patients carrying inherited GRN mutations.

The effects of obstructive sleep apnea on blood pressure variability and load in patients with hypertension.

BACKGROUND: Hypertension frequently coexists with obstructive sleep apnea (OSA), and their interplay substantially impacts the prognosis of affected individuals. Investigating the influence of OSA on blood pressure variability (BPV) and blood pressure load (BPL) in hypertensive patients has become a focal point of clinical research. METHODS: This cross-sectional study recruited hypertensive patients (n = 265) without discrimination and classified them into four groups based on their apnea-hypopnea index (AHI): control group (n = 40), AHI < 5; mild group (n = 74), 5 ≤ AHI ≤ 15; moderate group (n = 68), 15 < AHI ≤ 30; severe group (n = 83), AHI > 30. All participants underwent comprehensive assessments, including polysomnography (PSG) monitoring, 24-h ambulatory blood pressure (ABP) monitoring, cardiac Doppler ultrasound, and additional examinations when indicated. RESULTS: BPV and BPL exhibited significant elevations in the moderate and severe OSA groups compared to the control and mild OSA groups (P < 0.05). Moreover, interventricular septum thickness and left ventricular end-diastolic volume (LVEDV) demonstrated higher values in the moderate and severe OSA groups (P < 0.05). Multiple stepwise regression analysis identified noteworthy risk factors for elevated BPV in hypertensive patients with OSA, including AHI, maximum apnea time, total times of oxygen reduction, and mean time of apnea. CONCLUSION: Hypertensive patients with moderate to severe OSA exhibited substantially increased BPV and BPL. Moreover, BPV was correlated with AHI, maximum apnea time, total times of oxygen reduction, and mean time of apnea in hypertensive patients with OSA.

Contaminant Spot Check and Removal Assay (ContamSPOT) for Mass Spectrometry Analysis.

Mass spectrometry (MS) analysis is often challenged by contaminations from detergents, salts, and polymers that compromise data quality and can damage the chromatography and MS instruments. However, researchers often discover contamination issues only after they acquire the data. There is no existing contaminant assay that is sensitive enough to detect trace amounts of contaminants from a few microliters of samples prior to MS analysis. To address this crucial need in the field, we developed a sensitive, rapid, and cost-effective contaminant spot check and removal assay (ContamSPOT) to detect and quantify trace amounts of contaminants, such as detergents, salts, and other chemicals commonly used in the MS sample preparation workflow. Only 1 µL of the sample was used prior to MS injection to quantify contaminants by ContamSPOT colorimetric or fluorometric assay on a thin layer chromatography (TLC) plate. We also optimized contaminant removal methods to salvage samples with minimal loss when ContamSPOT showed a positive result. ContamSPOT was then successfully applied to evaluate commonly used bottom-up proteomic methods regarding the effectiveness of removing detergent, peptide recovery, reproducibility, and proteome coverage. We expect ContamSPOT to be widely adopted by MS laboratories as a last-step quality checkpoint prior to MS injection. We provided a practical decision tree and a step-by-step protocol with a troubleshooting guide to facilitate the use of ContamSPOT by other researchers. ContamSPOT can also provide a unique readout of sample cleanliness for developing new MS-based sample preparation methods in the future.

Implementing a continuous quality-improvement framework for tuberculosis infection prevention and control in healthcare facilities in China, 2017-2019.

BACKGROUND: Tuberculosis (TB) infection prevention and control (IPC) in healthcare facilities is key to reducing transmission risk. A framework for systematically improving TB IPC through training and mentorship was implemented in 9 healthcare facilities in China from 2017 to 2019. METHODS: Facilities conducted standardized TB IPC assessments at baseline and quarterly thereafter for 18 months. Facility-based performance was assessed using quantifiable indicators for IPC core components and administrative, environmental, and respiratory protection controls, and as a composite of all control types We calculated the percentage changes in scores over time and differences by IPC control type and facility characteristics. RESULTS: Scores for IPC core components increased by 72% during follow-up when averaged across facilities. The percentage changes for administrative, environmental, and respiratory protection controls were 39%, 46%, and 30%, respectively. Composite scores were 45% higher after the intervention. Overall, scores increased most during the first 6 months. There was no association between IPC implementation and provincial economic development or volume of TB services. CONCLUSIONS: TB IPC policies and practices showed most improvement early during implementation and did not differ consistently by facility characteristics. The training component of the project helped increase the capacity of healthcare professionals to manage TB transmission risks. Lessons learned here will inform national TB IPC guidance.

DNA N6-methyladenine methylase N6AMT1 controls neuropathic pain through epigenetically modifying Kcnj16 in dorsal horn neurons.

ABSTRACT: Nerve injury-induced aberrant changes in gene expression in spinal dorsal horn neurons are critical for the genesis of neuropathic pain. N6-methyladenine (m 6 A) modification of DNA represents an additional layer of gene regulation. Here, we report that peripheral nerve injury significantly decreased the level of m 6 A-specific DNA methyltransferase 1 ( N6amt1 ) in dorsal horn neurons. This decrease was attributed, at least partly, to a reduction in transcription factor Nr2f6 . Rescuing the decrease in N6amt1 reversed the loss of m 6 A at the promoter for inwardly rectifying potassium channel subfamily J member 16 ( Kcnj16 ), mitigating the nerve injury-induced upregulation of Kcnj16 expression in the dorsal horn and alleviating neuropathic pain hypersensitivities. Conversely, mimicking the downregulation of N6amt1 in naive mice erased DNA m 6 A at the Kcnj16 promoter, elevated Kcnj16 expression, and led to neuropathic pain-like behaviors. Therefore, decreased N6amt1 caused by NR2F6 is required for neuropathic pain, likely through its regulation of m 6 A-controlled KCNJ16 in dorsal horn neurons, suggesting that DNA m 6 A modification may be a potential new target for analgesic and treatment strategies.

Meeting Report on the 3rd Chinese American Society for Mass Spectrometry Conference-Advancing Biological and Pharmaceutical Mass Spectrometry.

Following the highly successful Chinese American Society for Mass Spectrometry (CASMS) conferences in the previous 2 years, the 3rd CASMS Conference was held virtually on August 28-31, 2023, using the Gather.Town platform to bring together scientists in the MS field. The conference offered a 4-day agenda with a scientific program consisting of two plenary lectures, and 14 parallel symposia in which a total of 70 speakers presented technological innovations and their applications in proteomics and biological MS and metabo-lipidomics and pharmaceutical MS. In addition, 16 invited speakers/panelists presented at two research-focused and three career development workshops. Moreover, 86 posters, 12 lightning talks, 3 sponsored workshops, and 11 exhibitions were presented, from which 9 poster awards and 2 lightning talk awards were selected. Furthermore, the conference featured four young investigator awardees to highlight early-career achievements in MS from our society. The conference provided a unique scientific platform for young scientists (i.e. graduate students, postdocs, and junior faculty/investigators) to present their research, meet with prominent scientists, learn about career development, and job opportunities (http://casms.org).