Redox-Stable and Multicolor Electrochromic Polyamides with Four Triarylamine Cores in the Repeating Unit.

Two new triarylamine-based diamine monomers, namely, N,N'-bis(4-methoxyphenyl)-N,N'-bis(4-(4-aminophenyl-4'-methoxyphenylamino)phenyl)-p-phenylenediamine (3) and N,N'-bis(4-methoxyphenyl)-N,N'-bis(4-((4-aminophenyl-1-naphthyl)amino)phenyl)-p-phenylenediamine (7), were successfully synthesized and led to two series of electroactive polyamides by polycondensation reactions with common aromatic dicarboxylic acids. The polymers demonstrated multicolored electrochromism, high optical contrast, and remarkable enhancements in redox and electrochromic stability. Compared to other triarylamine-based polymers, the studied polyamides exhibited enhanced electrochromic stability (only 3~6% decay of its coloration efficiency at 445 nm after 14,000 switching cycles) at the first oxidation stage. The polyamides also showed strong absorption in the near-infrared region upon oxidation. Polymers with multicolored electrochromism and high redox stability can be developed by incorporation of four triarylamine cores in each repeat unit and electron-donating methoxy groups on the active sites of the triphenylamine units.

Manipulating the Rate and Overpotential for Electrochemical Water Oxidation: Mechanistic Insights for Cobalt Catalysts Bearing Noninnocent Bis(benzimidazole)pyrazolide Ligands.

Electrochemical water oxidation is known as the anodic reaction of water splitting. Efficient design and earth-abundant electrocatalysts are crucial to this process. Herein, we report a family of catalysts (1-3) bearing bis(benzimidazole)pyrazolide ligands (H 2 L1-H 2 L3). H 2 L3 contains electron-donating substituents and noninnocent components, resulting in catalyst 3 exhibiting unique performance. Kinetic studies show first-order kinetic dependence on [3] and [H2O] under neutral and alkaline conditions. In contrast to previously reported catalyst 1, catalyst 3 exhibits an insignificant kinetic isotope effect of 1.25 and zero-order dependence on [NaOH]. Based on various spectroscopic methods and computational findings, the L3Co2 III(µ-OH) species is proposed to be the catalyst resting state and the nucleophilic attack of water on this species is identified as the turnover-limiting step of the catalytic reaction. Computational studies provided insights into how the interplay between the electronic effect and ligand noninnocence results in catalyst 3 acting via a different reaction mechanism. The variation in the turnover-limiting step and catalytic potentials of species 1-3 leads to their catalytic rates being independent of the overpotential, as evidenced by Eyring analysis. Overall, we demonstrate how ligand design may be utilized to retain good water oxidation activity at low overpotentials.

Chemokine-mediated cell migration into the central nervous system in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) has been associated with different forms of immune compromise. This study analyzes the chemokine signals and attracted immune cells in cerebrospinal fluid (CSF) during PML to define immune cell subpopulations relevant for the PML immune response. In addition to chemokines that indicate a general state of inflammation, like CCL5 and CXCL10, the CSF of PML patients specifically contains CCL2 and CCL4. Single-cell transcriptomics of CSF cells suggests an enrichment of distinct CD4+ and CD8+ T cells expressing chemokine receptors CCR2, CCR5, and CXCR3, in addition to ITGA4 and the genetic PML risk genes STXBP2 and LY9. This suggests that specific immune cell subpopulations migrate into the central nervous system to mitigate PML, and their absence might coincide with PML development. Monitoring them might hold clues for PML risk, and boosting their recruitment or function before therapeutic immune reconstitution might improve its risk-benefit ratio.

Cell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment.

5q-associated spinal muscular atrophy (SMA) is a motoneuron disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Adaptive immunity may contribute to SMA as described in other motoneuron diseases, yet mechanisms remain elusive. Nusinersen, an antisense treatment, enhances SMN2 expression, benefiting SMA patients. Here we have longitudinally investigated SMA and nusinersen effects on local immune responses in the cerebrospinal fluid (CSF) - a surrogate of central nervous system parenchyma. Single-cell transcriptomics (SMA: N = 9 versus Control: N = 9) reveal NK cell and CD8+ T cell expansions in untreated SMA CSF, exhibiting activation and degranulation markers. Spatial transcriptomics coupled with multiplex immunohistochemistry elucidate cytotoxicity near chromatolytic motoneurons (N = 4). Post-nusinersen treatment, CSF shows unaltered protein/transcriptional profiles. These findings underscore cytotoxicity's role in SMA pathogenesis and propose it as a therapeutic target. Our study illuminates cell-mediated cytotoxicity as shared features across motoneuron diseases, suggesting broader implications.

Direct sub-atmospheric pressure ionization mass spectrometry: Evaporation/sublimation-driven ionization is amazing, fundamentally, and practically.

This paper covers direct sub-atmospheric pressure ionization mass spectrometry (MS). The discovery, applications, and mechanistic aspects of novel ionization processes for use in MS that are not based on the high-energy input from voltage, laser, and/or high temperature but on sublimation/evaporation within a region linking a higher to lower pressure and modulated by heat and collisions, are discussed, including how this new reality has guided a series of discoveries, instrument developments, and commercialization. A research focus, inter alia, is on how best to understand, improve, and use these novel ionization processes, which convert volatile and nonvolatile compounds from solids (sublimation) or liquids (evaporation) into gas-phase ions for analysis by MS providing reproducible, accurate, sensitive, and prompt results. Our perception on how these unprecedented versus traditional ionization processes/methods relate to each other, how they can be made to coexist on the same mass spectrometer, and an outlook on new and expanded applications (e.g., clinical, portable, fast, safe, and autonomous) is presented, and is based on ST's Opening lecture presentation at the Nordic Mass spectrometry Conference, Geilo, Norway, January 2023. Focus will be on matrix-assisted ionization (MAI) and solvent-assisted ionization (SAI) MS covering the period from 2010 to 2023; a potential paradigm shift in the making.

Advancing carbohydrate quantification in MALDI mass spectrometry by the rapidly freeze-drying droplet (RFDD) method.

Quantitative carbohydrate analysis faces challenges in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), including insufficient sensitivity and inconsistent spatial distribution of ion intensity. This study introduces an innovative sample preparation approach, the Rapidly Freeze-Drying Droplet (RFDD) method, aimed at overcoming these challenges by enhancing the homogeneity of the sample morphology and signal intensity in MALDI. Compared to conventional preparation methods, the RFDD method reduces the laser energy threshold and demonstrates a remarkable increase in signal intensity for carbohydrates, facilitating the detection of high-molecular-weight polysaccharides (>10 kDa). The RFDD-prepared samples exhibit a uniformly distributed signal intensity that overcomes the 'sweet spot' issue in MALDI. The enhanced signal intensity and reproducibility lead to reliable quantitative analysis of carbohydrates, eliminating the need for expensive isotopic standards in each sample. A straightforward and accessible approach is presented for general laboratories, revolutionizing carbohydrate analysis in MALDI-MS.

Urinary catheter placement and adverse urinary outcomes with a focus on elevated risk in men with indwelling Foley catheters.

BACKGROUND: Prior studies indicated a link between urinary catheter use and urinary complications, highlighting the need for comprehensive, gender-specific investigations. This study explored the association through a national retrospective cohort, emphasizing gender disparities and long-term outcomes. METHODS: Our study utilized data from the entire population covered by Taiwan's National Health Insurance Research Database from 2000 to 2017. We included 148,304 patients who had undergone Foley catheter placement and their propensity-scores matched controls in the study. We evaluated urinary complications, which encompassed urinary tract cancer, urolithiasis, urethral stricture, obstructive uropathy, reflux uropathy, fistula, diverticulum, caruncle, false passage, prolapsed urethral mucosa, urinary tract rupture, and urinary tract infection. These were assessed using the Fine and Gray sub-distribution proportional hazards model to compare between the Foley and non-Foley groups. Sensitivity analyses were conducted with different matching ratios. RESULTS: In the study, the non-Foley group presented a marginally higher mean age (75.24 ± 10.47 years) than the Foley group (74.09 ± 10.47 years). The mean duration of Foley catheterization was 6.1 ± 4.19 years. Men with Foley catheterization exhibited the highest adjusted sub-distribution hazard ratios for urinary tract cancer (6.57, 95% CI: 5.85-7.37), followed by women with Foley catheterization (4.48, 95% CI: 3.98-5.05), and men without catheterization (1.58, 95% CI: 1.39-1.8) in comparison with women without the procedure. Furthermore, men with Foley catheterization were found to be at the greatest risk for complications such as urolithiasis, urethral stricture, obstructive and reflux uropathy, fistula, diverticulum, caruncle, false passage, prolapsed urethral mucosa, and urinary tract rupture. Conversely, women with urinary catheterization were most susceptible to urinary tract infections. CONCLUSIONS: The evidence confirms that urinary catheterization significantly increases urinary complications, particularly among men. Our study underscores the crucial need for healthcare providers to carefully evaluate the necessity of catheterization, aim to shorten its duration whenever feasible, and strictly adhere to established protocols to minimize complications.

Prothymosin α accelerates dengue virus-induced thrombocytopenia.

Thrombocytopenia is the hallmark finding in dengue virus (DENV) infection. Prothymosin α (ProT) has both intracellular and extracellular functions involved in cell cycle progression, cell differentiation, gene regulation, oxidative stress response, and immunomodulation. In this study, we found that ProT levels were elevated in dengue patient sera as well as DENV-infected megakaryoblasts and their culture supernatants. ProT transgenic mice had reduced platelet counts with prolonged bleeding times. Upon treatment with DENV plus anti-CD41 antibody, they exhibited severe skin hemorrhage. Furthermore, overexpression of ProT suppressed megakaryocyte differentiation. Infection with DENV inhibited miR-126 expression, upregulated DNA (cytosine-5)-methyltransferase 1 (DNMT1), downregulated GATA-1, and increased ProT expression. Upregulation of ProT led to Nrf2 activation and reduced reactive oxygen species production, thereby suppressing megakaryopoiesis. We report the pathophysiological role of ProT in DENV infection and propose an involvement of the miR-126-DNMT1-GATA-1-ProT-Nrf2 signaling axis in DENV-induced thrombocytopenia.

Single-cell profiling reveals preferential reduction of memory B cell subsets in cladribine patients that correlates with treatment response.

Background: Cladribine is a highly effective immunotherapy that is applied in two short-term courses over 2 years and reduces relapse rate and disease progression in patients with relapsing multiple sclerosis (MS). Despite the short treatment period, cladribine has a long-lasting effect on disease activity even after recovery of lymphocyte counts, suggesting a yet undefined long-term immune modulating effect. Objectives: Our aim was to provide a more profound understanding of the detailed effects of cladribine, also with regard to the patients' therapy response. Design: We performed an open-labeled, explorative, prospective, single-arm study, in which we examined the detailed lymphocyte subset development of MS patients who received cladribine treatment over 2 years. Methods: We performed in-depth profiling of the effects of cladribine on peripheral blood lymphocytes by flow cytometry, bulk RNA sequencing of sorted CD4+ T cells, CD8+ T cells, and CD19+ B cells as well as single-cell RNA sequencing of peripheral blood mononuclear cells in a total of 23 MS patients before and at different time points up to 24 months after cladribine treatment. Data were correlated with clinical and cranial magnetic resonance imaging (MRI) disease activity. Results: Flow cytometry revealed a predominant and sustained reduction of memory B cells compared to other B cell subsets after cladribine treatment, whereas T cell subsets were slightly reduced in a more uniform pattern. The overall transcriptional profile of total blood B cells exhibited reduced expression of proinflammatory and T cell activating genes, while single-cell transcriptomics revealed that gene expression within each B cell cluster did not change over time. Stable patients displayed stronger reductions of selected memory B cell clusters as compared to patients with clinical or cerebral MRI disease activity. Conclusion: We describe a pronounced and sustained effect of cladribine on the memory B cell compartment, and the resulting change in B cell subset composition causes a significant alteration of B cell transcriptional profiles resulting in reduced proinflammatory and T cell activating capacities. The extent of reduction in selected memory B cell clusters by cladribine may predict treatment response.

Association between pain and cognitive and daily functional impairment in older institutional residents: a cross-sectional study.

BACKGROUND: Pain is often neglected in disabled older population, especially in Taiwan where the population of institutional residents is rapidly growing. Our study aimed to investigate pain prevalence and associated factors among institutional residents to improve pain assessment and management. METHODS: This nationwide study recruited 5,746 institutional residents in Taiwan between July 2019 and February 2020. Patient self-report was considered the most valid and reliable indicator of pain. A 5-point verbal rating scale was used to measure pain intensity, with a score ranging from 2 to 5 indicating the presence of pain. Associated factors with pain, including comorbidities, functional dependence, and quality of life, were also assessed. RESULTS: The mean age of the residents was 77.1 ± 13.4 years, with 63.1% of them aged over 75 years. Overall, 40.3% of the residents reported pain, of whom 51.2% had moderate to severe pain. Pain was more common in residents with comorbidities and significantly impacted emotions and behavior problems, and the mean EQ5D score, which is a measure of health-related quality of life (p < .001). Interestingly, pain was only related to instrumental activities of daily living (IADL) and not activities of daily living (ADL). On the other hand, dementia was significantly negatively associated with pain (p < .001), with an estimated odds of 0.63 times (95% CI: 0.53-0.75) for the presence of pain when compared to residents who did not have dementia. CONCLUSIONS: Unmanaged pain is common among institutional residents and is associated with comorbidities, IADL, emotional/behavioral problems, and health-related quality of life. Older residents may have lower odds of reporting pain due to difficulty communicating their pain, even through the use of a simple 5-point verbal rating scale. Therefore, more attention and effort should be directed towards improving pain evaluation in this vulnerable population .

Synthetic lethality in human bladder cancer cells by curcumin via concurrent Aurora A inhibition and autophagy induction.

Combination therapies to induce mixed-type cell death and synthetic lethality have the potential to overcome drug resistance in cancer. In this study, we demonstrated that the curcumin-enhanced cytotoxicity of cisplatin/carboplatin in combination with gemcitabine was associated with Aurora A suppression-mediated G2/M arrest, and thus apoptosis, as well as MEK/ERK-mediated autophagy in human bladder cancer cells. Animal study data confirmed that curcumin combined with cisplatin/gemcitabine reduced tumorigenesis of xenograft in mice and this phenomenon was associated with elevated expressions of p-ERK and reduced p-Aurora A in tumors. Gene analyses using data repositories further revealed that reduced Aurora A expression alone did not significantly elevate the sensitivity of human bladder carcinoma cells to these anticancer drugs. Unlike other major cancer types, human bladder urothelial carcinoma tissue coexpressed higher AURKA and lower MAP1LC3B than normal tissue, and reduced Aurora A and induction of autophagy have been clinically associated with a better prognosis in patients with early but not advanced stage bladder cancer. Therefore, our results suggest that treatment strategies can utilize the synthetic lethal pair to concurrently suppress oncogenic Aurora A and induce autophagy by coadministrating curcumin with anticancer drugs for early-stage bladder cancer with high expression of Aurora A.

Orthogonal Glycosylation with Phosphate Acceptors for Expeditious Synthesis of Bacterial Inner Core Oligosaccharides.

We report a practical one-pot glycosylation strategy for synthesis of bacterial inner core oligosaccharides that composed of unavailable L-glycero-D-manno and D-glycero-D-manno-heptopyranose components. The glycosylation method features a new orthogonal glycosylation procedure; whereby a phosphate acceptor is coupled with a thioglycosyl donor producing a disaccharide phosphate, which can be engaged in another orthogonal glycosylation procedure to couple with a thioglycosyl acceptor. The phosphate acceptors used in above one-pot procedure are directly prepared from thioglycosyl acceptors via the in-situ phosphorylation. Such phosphate acceptor preparation protocol eliminates the traditional protection and deprotection procedures. Based on the new one-pot glycosylation strategy, two partial inner core structures of Yersinia pestis lipopolysaccharide and Haemophilus ducreyi lipooligosaccharide were acquired.

Identification of Sexually Dimorphic Genes in Pectoral Fin as Molecular Markers for Assessing the Sex of Japanese Silver Eels (Anguilla japonica).

The Japanese eel (Anguilla japonica) is an important species in East Asian aquaculture. However, the production of seedlings for this purpose still depends on natural resources, as the commercial production of glass eels is not yet possible. Confusion about the sex of silver eels is one of the factors affecting the success rate of artificial maturation. This study sought to devise a harmless method to precisely assess the sex of silver eels. Partial pectoral fins were collected from females and males and the total RNA was extracted for transcriptomic analysis to identify sexually dimorphic genes as molecular markers for sex typing. An online database was constructed to integrate the annotations of transcripts and perform comparative transcriptome analysis. This analysis identified a total of 29 candidate sexually dimorphic genes. Ten were selected for a real-time quantitative polymerase chain reaction (RT-qPCR) to validate the transcriptomic data and evaluate their feasibility as markers. The transcriptomic analysis and RT-qPCR data implicated three potential markers (LOC111853410, kera, and dcn) in sex typing. The expression of LOC111853410 was higher in females than in males. In contrast, the expression of kera and dcn was higher in males than in females. The ΔCT values of three markers were analyzed to determine their inferred thresholds, which can be used to determine the sex of Japanese eels. The results suggested that if a silver eel had a pectoral fin with the pectoral fin having the ΔCT of LOC111853410 < 11.3, the ΔCT of kera > 11.4, or the ΔCT of dcn > 6.5 can be assessed it could be assessed as female. Males could be assessed by the ΔCT of LOC111853410 > 11.3, the ΔCT of kera < 11.4, or the ΔCT of dcn < 6.5 in their pectoral fins. The molecular functions of these markers and the biological significance of their differential expression require further exploration.

Multimodal Analgesia with Local Wound Infiltration and Intravenous Parecoxib for Thyroidectomy.

Background and objective: Adequate postoperative pain control is an important component to enhance recovery. Multimodal analgesia with various pain control techniques has been widely used to alleviate postoperative pain. The use of either wound infiltration or a superficial cervical plexus block has been reported to be effective for pain management after thyroid surgery. The present study evaluated the effect of multimodal analgesia using lidocaine wound infiltration combined with intravenous parecoxib for patients monitored after thyroidectomy. Materials and Methods: A total of 101 patients with a multimodal analgesia protocol being monitored after thyroidectomy were enrolled. After the induction of anesthesia, multimodal analgesia was performed through wound infiltration of 1% lidocaine and epinephrine at a ratio of 1:200,000 (5 µg/mL) combined 40 mg intravenous parecoxib before skin excision. Patients were divided into two groups for this retrospective analysis based on the injection dose of lidocaine they received. Patients in Group I (the control, n = 52) received a 5 mL injection solution, while those in Group II (the study, n = 49) received a 10 mL dosage in a time-sequential manner, in accordance with a previous clinical trial. The primary outcome was measuring postoperative pain intensity at rest, as well as during motion and coughing, which was measured at the postoperative anesthetic care unit (PACU) and on the first day after the operation (POD 1) in the ward. Pain intensity was assessed using a numerical rating scale (NRS). The secondary outcomes were postoperative adverse events including anesthetic-related side effects, as well as airway and pulmonary complications. Results: Most of the patients reported no pain or mild pain during the observation period. The patients in Group II had a lower pain intensity during motion than Group I (NRS 1.47 ± 0.89 vs. 1.85 ± 0.96, p = 0.043) when measured at the postoperative anesthetic care unit. Pain intensity during coughing was also significantly lower in the study group than in the control group (NRS 1.61 ± 0.95 vs. 1.96 ± 0.79, p = 0.049) when measured at the postoperative anesthetic care unit. There were no severe adverse events in either of the groups. Only one patient (1.9%) in Group I experienced temporary vocal palsy. Conclusions: The use of lidocaine with an equal volume of intravenous parecoxib provided comparable analgesia with minimal adverse events when monitoring thyroidectomy.

Alemtuzumab treatment exemplifies discordant immune effects of blood and cerebrospinal fluid in multiple sclerosis.

BACKGROUND AND OBJECTIVES: Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than peripheral blood. While CSF leukocytes are known to be distinct from blood, the immediate effects of peripheral leukocyte depletion on CSF leukocytes have not been studied in humans. METHODS: We here analyzed CSF and blood from two relapsing-remitting multiple sclerosis (RRMS) patients early after peripheral leukocyte depletion with the anti-CD52 antibody alemtuzumab compared to untreated RRMS and control patients using single cell RNA-sequencing. RESULTS: As expected for alemtuzumab, most leukocyte lineages including T cells were synchronously depleted from CSF and blood, while - surprisingly - pDCs were maintained in CSF but depleted from blood by alemtuzumab. Transcriptionally, genes associated with migration were elevated only in the CSF after alemtuzumab. Predicted cellular interactions indicated a central role of pDCs and enhanced migration signaling in the CSF after alemtuzumab. DISCUSSION: The CSF and blood compartments are thus partially uncoupled, emphasizing that the CNS is only partially accessible even for treatments profoundly affecting the blood.

Hyperbaric Oxygen Therapy Alleviates Paclitaxel-Induced Peripheral Neuropathy Involving Suppressing TLR4-MyD88-NF-κB Signaling Pathway.

Paclitaxel (PAC) results in long-term chemotherapy-induced peripheral neuropathy (CIPN). The coexpression of transient receptor potential vanilloid 1 (TRPV1) and Toll-like receptor 4 (TLR4) in the nervous system plays an essential role in mediating CIPN. In this study, we used a TLR4 agonist (lipopolysaccharide, LPS) and a TLR4 antagonist (TAK-242) in the CIPN rat model to investigate the role of TLR4-MyD88 signaling in the antinociceptive effects of hyper-baric oxygen therapy (HBOT). All rats, except a control group, received PAC to induce CIPN. Aside from the PAC group, four residual groups were treated with either LPS or TAK-242, and two of them received an additional one-week HBOT (PAC/LPS/HBOT and PAC/TAK-242/HBOT group). Mechanical allodynia and thermal hyperalgesia were then assessed. The expressions of TRPV1, TLR4 and its downstream signaling molecule, MyD88, were investigated. The mechanical and thermal tests revealed that HBOT and TAK-242 alleviated behavioral signs of CIPN. Immunofluorescence in the spinal cord dorsal horn and dorsal root ganglion revealed that TLR4 overexpression in PAC- and PAC/LPS-treated rats was significantly downregulated after HBOT and TAK-242. Additionally, Western blots showed a significant reduction in TLR4, TRPV1, MyD88 and NF-κB. Therefore, we suggest that HBOT may alleviate CIPN by modulating the TLR4-MyD88-NF-κB pathway.

The Risk Factors for Radiolucent Nephrolithiasis among Workers in High-Temperature Workplaces in the Steel Industry.

Workers in high-temperature workplaces with inadequate water supply may exhibit symptoms of chronic dehydration and have increased risk of nephrolithiasis. The aim of this study was to investigate the risk of radiolucent stone formation among workers in a high-temperature workplace and the related risk factors associated with the condition. We collected data from 1681 workers in a steel factory in Southern Taiwan who underwent regular health examinations. Radiolucent stones were defined as positive findings on ultrasound with negative radiographic images. The prevalences of nephrolithiasis and radiolucent stones in this study were 12.0% and 5.1%, respectively. Heat exposure and age were two major risk factors influencing the probability of radiolucent stones. We combined the age and heat exposure into four groups (over and under 35 years of age with and without heat exposure) in a logistic regression. For workers younger than 35 years, the odds ratio of radiolucent stones was 2.695 (95% confidence interval: 1.201-6.049) in workers with heat exposure compared to workers without. Our investigation further demonstrated that heat exposure was a main risk factor for radiolucent stone formation. In conclusion, our identification of heat exposure as an independent factor for radiolucent stone development in steel workers highlights the need for attention to be paid to those working in similar environments.

Integrated single-cell transcriptomics of cerebrospinal fluid cells in treatment-naïve multiple sclerosis.

Multiple sclerosis (MS) is a chronic and often disabling autoimmune disease of the central nervous system (CNS). Cerebrospinal fluid (CSF) surrounds and protects the CNS. Analysis of CSF can aid the diagnosis of CNS diseases, help to identify the prognosis, and underlying mechanisms of diseases. Several recent studies have leveraged single-cell RNA-sequencing (scRNA-seq) to identify MS-associated changes in CSF cells that are considerably more altered than blood cells in MS. However, not all alterations were replicated across all studies. We therefore integrated multiple available scRNA-seq datasets of CSF cells from MS patients with early relapsing-remitting (RRMS) disease. We provide a searchable and interactive resource of this integrated analysis ( https://CSFinMS.bxgenomics.com ) facilitating diverse visualization and analysis methods without requiring computational skills. In the present joint analysis, we replicated the known expansion of B lineage and the recently described expansion of natural killer (NK) cells and some cytotoxic T cells and decrease of monocytes in the CSF in MS. The previous observation of the abundance of Th1-like Th17 effector memory cells in the CSF was not replicated. Expanded CSF B lineage cells resembled class-switched plasmablasts/-cells (e.g., SDC1/CD138, MZB1) as expected. Our integrative analysis thus validates increased cell type diversity and B cell maturation in the CSF in MS and improves accessibility of available data.

Spinal Irisin Gene Delivery Attenuates Burn Injury-Induced Muscle Atrophy by Promoting Axonal Myelination and Innervation of Neuromuscular Junctions.

Muscle loss and weakness after a burn injury are typically the consequences of neuronal dysregulation and metabolic change. Hypermetabolism has been noted to cause muscle atrophy. However, the mechanism underlying the development of burn-induced motor neuropathy and its contribution to muscle atrophy warrant elucidation. Current therapeutic interventions for burn-induced motor neuropathy demonstrate moderate efficacy and have side effects, which limit their usage. We previously used a third-degree burn injury rodent model and found that irisin-an exercise-induced myokine-exerts a protective effect against burn injury-induced sensory and motor neuropathy by attenuating neuronal damage in the spinal cord. In the current study, spinal irisin gene delivery was noted to attenuate burn injury-induced sciatic nerve demyelination and reduction of neuromuscular junction innervation. Spinal overexpression of irisin leads to myelination rehabilitation and muscular innervation through the modulation of brain-derived neurotrophic factor and glial-cell-line-derived neurotrophic factor expression along the sciatic nerve to the muscle tissues and thereby modulates the Akt/mTOR pathway and metabolic derangement and prevents muscle atrophy.

Nonalcoholic Fatty Liver Disease Is Related to Abnormal Corrected QT Interval and Left Ventricular Hypertrophy in Chinese Male Steelworkers.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased risks of corrected QT (QTc) prolongation and left ventricular hypertrophy (LVH), both of which are associated with the development of cardiovascular disease. Rotating night shift work and a higher risk of incident NAFLD have been reported in male steelworkers. This study aimed to investigate the association of the severity of NAFLD with a prolonged QTc interval and LVH in a large cohort of Chinese male steelworkers. METHODS: We examined baseline data of 2998 male steel workers aged 26 to 71 years at two plants. All workers at both plants received regular health assessments, including 12-lead ECG and echocardiography. Abdominal ultrasonography was performed to evaluate the severity of NAFLD. QTc prolongation was defined as follows: normal ≤ 430 ms, borderline 431-450 ms, and abnormal ≥ 451 ms. LVH was defined as a left ventricular mass index (LVMI) >131 g/m2. Associations of NAFLD with an abnormal QTc interval and LVH were examined using univariate and multivariate analyses. RESULTS: The QTc interval and the LVMI were significantly correlated with the NAFLD fibrosis score, and the severity of NAFLD was correlated with an abnormal QTc interval and LVH (p for trend < 0.05). Multivariate analysis showed that in comparison to the workers without NAFLD, the odds ratios of having an abnormal QTc interval and LVH were 2.54 (95% CI: 1.22-5.39, p = 0.013) times and 2.23 (95% CI: 1.02-5.01, p = 0.044) times higher in the workers with moderate/severe NAFLD. CONCLUSIONS: NAFLD may be closely associated with the risks of an abnormal QTc interval and LVH, suggesting that regular electrocardiogram and echocardiogram monitoring could be used to evaluate the risk of arrhythmia and LVH in male steelworkers with NAFLD.