In monolayer (1L) transition metal dichalcogenides (TMDs) the valence and conduction bands are spin-split because of the strong spin–orbit interaction. In tungsten-based TMDs the spin-ordering of the ...conduction band is such that the so-called dark excitons, consisting of electrons and holes with opposite spin orientation, have lower energy than A excitons. The transition from bright to dark excitons involves the scattering of electrons from the upper to the lower conduction band at the K point of the Brillouin zone, with detrimental effects for the optoelectronic response of 1L-TMDs, since this reduces their light emission efficiency. Here, we exploit the valley selective optical selection rules and use two-color helicity-resolved pump–probe spectroscopy to directly measure the intravalley spin–flip relaxation dynamics in 1L-WS2. This occurs on a sub-ps time scale, and it is significantly dependent on temperature, indicative of phonon-assisted relaxation. Time-dependent ab initio calculations show that intravalley spin–flip scattering occurs on significantly longer time scales only at the K point, while the occupation of states away from the minimum of the conduction band significantly reduces the scattering time. Our results shed light on the scattering processes determining the light emission efficiency in optoelectronic and photonic devices based on 1L-TMDs.
Neurofilament light chain (NfL) has emerged as a biomarker of neuroaxonal damage in several neurologic conditions. With increasing availability of fourth-generation immunoassays detecting NfL in ...blood, aspects of pre-analytical stability of this biomarker remain unanswered. This study investigated NfL concentrations in serum and plasma samples of 32 patients with neurological diagnoses using state of the art Simoa technology. We tested the effect of delayed freezing of up to 7 days and statistically determined stability and validity of measured concentrations. We found concentrations of NfL in serum and plasma to remain stable at room temperature when processing of samples is delayed up to 7 days (serum: mean absolute difference 0.9 pg/mL, intraindividual variation 1.2%; plasma: mean absolute difference 0.5 pg/mL, intraindividual variation 1.3%). Consistency of these results was nearly perfect for serum and excellent for plasma (intraclass correlation coefficients 0.99 and 0.94, respectively). In conclusion, the soluble serum and plasma NfL concentration remains stable when unprocessed blood samples are stored up to 7 days at room temperature. This information is essential for ensuring reliable study protocols, for example, when shipment of fresh samples is needed.
Monolayer transition metal dichalcogenides bear great potential for photodetection and light harvesting due to high absorption coefficients. However, these applications require dissociation of ...strongly bound photogenerated excitons. The dissociation can be achieved by vertically stacking different monolayers to realize band alignment that favors interlayer charge transfer. In such heterostructures, the reported recombination times vary strongly, and the charge separation and recombination mechanisms remain elusive. We use two color pump–probe microscopy to demonstrate that the charge separation in a MoSe2/WSe2 heterostructure is ultrafast (∼200 fs) and virtually temperature independent, whereas the recombination accelerates strongly with temperature. Ab initio quantum dynamics simulations rationalize the experiments, indicating that the charge separation is temperature-independent because it is barrierless, involves dense acceptor states, and is promoted by higher-frequency out-of-plane vibrations. The strong temperature dependence of the recombination, on the other hand, arises from a transient indirect-to-direct bandgap modulation by low-frequency shear and layer breathing motions.
Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is ...slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome.
Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary.
The median sNfL concentration in our GBS sample on admission was 85.5 pg/ml versus 9.1 pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (r
= 0.69, p < 0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5 pg/ml had a 93% chance of being discharged with an unimpaired walking ability.
sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome.
X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to ...life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
After spinal cord injury (SCI), secondary damage caused by oxidative stress, inflammation, and ischemia leads to neurological deterioration. In recent years, therapeutic approaches to trauma have ...focused on modulating this secondary cascade. There is increasing evidence that the success of cell-based SCI therapy is due mainly to secreted factors rather than to cell implantation per se. This study investigated peripheral blood mononuclear cells as a source of factors for secretome- (MNC-secretome-) based therapy. Specifically, we investigated whether MNC-secretome had therapeutic effects in a rat SCI contusion model and its possible underlying mechanisms. Rats treated with MNC-secretome showed substantially improved functional recovery, attenuated cavity formation, and reduced acute axonal injury compared to control animals. Histological evaluation revealed higher vascular density in the spinal cords of treated animals. Immunohistochemistry showed that MNC-secretome treatment increased the recruitment of CD68+ cells with concomitant reduction of oxidative stress as reflected by lower expression of inducible nitric oxide synthase. Notably, MNC-secretome showed angiogenic properties ex vivo in aortic rings and spinal cord tissue, and experiments showed that the angiogenic potential of MNC-secretome may be regulated by CXCL-1 upregulation in vivo. Moreover, systemic application of MNC-secretome activated the ERK1/2 pathway in the spinal cord. Taken together, these results indicate that factors in MNC-secretome can mitigate the pathophysiological processes of secondary damage after SCI and improve functional outcomes in rats.
•Secretome produced by apoptotic human peripheral blood mononuclear cells•Treatment with MNC-secretome improves hind limb motor function.•The production process of this secretome meets Good Manufacturing Guidelines.•Modulation and attenuation of secondary damage following SCI•Ex-vivo experiments demonstrate angiogenesis in aortic ring and spinal cord assays.
Multiple sclerosis (MS) pathophysiology comprises both inflammatory and neurodegenerative characteristics. Cerebrospinal fluid (CSF) analysis allows for assessment of inflammation while neurofilament ...light chain can indicate neuroaxonal damage. Retinal thinning is a robust prognostic biomarker for neurodegeneration in MS. To date, an association between CSF parameters upon MS diagnosis and retinal thinning has not been investigated.
We aimed to determine whether CSF parameters are associated with the evolution of retinal layer thinning in people with MS (pwMS).
For this longitudinal observational study, we investigated pwMS from the Vienna MS database (VMSD), who had undergone (1) a diagnostic lumbar puncture (LP) between 2015 and 2020, and (2) simultaneous optical coherence tomography (OCT) and/or (3) a follow-up OCT scan. Linear stepwise regression models were calculated with OCT parameters (peripapillary retinal nerve fiber layer pRNFL thickness at LP and at follow-up, annualized loss of pRNFL thickness aLpRNFL) as a dependent variable, and CSF parameters (white blood cell WBC count, total protein
TP, CSF/serum albumin ratio Q
, intrathecal synthesis of immunoglobulins, neurofilament light chain NfL in both CSF and serum
NfL/sNfL) as independent variables adjusted for age, sex, and disease duration.
We analyzed 61 pwMS (median age 30.0 years interquartile range 25.5-35.0, 57.4% female, median disease duration 1.0 month IQR 0-2.0 before LP, median follow-up 1.9 years IQR 1.1-3.5).
NfL and sNfL measurements were available in 26 and 31 pwMS, respectively. pRNFL thickness at LP was inversely associated with the CSF WBC count (β = -0.36; 95% CI -0.51, -0.08;
= 0.008). We did not find any association between other CSF parameters, including
NfL, sNfL, and aLpRNFL.
Increased WBC count as an indicator of acute inflammation and blood-brain-barrier breakdown seems to be associated with the amount of retinal thickness already lost at the time of LP. However, neither routine CSF parameters nor a singular NfL measurement allows the prediction of future retinal thinning.
Recent studies proposed cellular immunoprofiling as a surrogate for predicting treatment response and/or stratifying the occurrence of adverse events (AEs) in persons with multiple sclerosis (pwMS). ...However, applicability in real-world circumstances is not sufficiently addressed.
We aimed to explore whether standard routine clinical leukocyte phenotyping before treatment initiation could help stratify patients according to treatment response or AEs in a real-world MS cohort.
In this retrospective study, 150 pwMS were included, who had been newly initiated on a disease-modifying drug (DMD) and had been assessed for standard immunophenotyping before DMD initiation (baseline) and at least once during the following year. Multivariate models were used to assess an association of immune subsets and the association between immune cell profiles regarding treatment response and AEs.
We found that the composition of T cell subsets was associated with relapse activity, as an increased proportion of CD8
lymphocytes at baseline indicated a higher likelihood of subsequent relapse (about 9% per 1% increase in CD8+ proportion of all CD3+ cells). This was particularly driven by patients receiving anti-CD20 therapy, where also EDSS worsening was associated with a higher number of CD8+ cells at baseline (3% increase per 10 cells). In the overall cohort, an increase in the proportion of NK cells was associated with a higher risk of EDSS worsening (5% per 1% increase). Occurrence of AEs was associated with a higher percentage of T cells and a lower number of percentual NKT cells at baseline.
Immune cell profiles are associated with treatment response and the occurrence of AEs in pwMS. Hence, immunophenotyping may serve as a valuable biomarker to enable individually tailored treatment strategies in pwMS.
Vascular changes and alterations of oxygen metabolism are suggested to be implicated in multiple sclerosis (MS) pathogenesis and progression. Recently developed in vivo retinal fundus imaging ...technologies provide now an opportunity to non-invasively assess metabolic changes in the neural retina. This study was performed to assess retinal oxygen metabolism, peripapillary capillary density (CD), large vessel density (LVD), retinal nerve fiber layer thickness (RNFLT) and ganglion cell inner plexiform layer thickness (GCIPLT) in patients with diagnosed relapsing multiple sclerosis (RMS) and history of unilateral optic neuritis (ON). 16 RMS patients and 18 healthy controls (HC) were included in this study. Retinal oxygen extraction was modeled using O
2
saturations and Doppler optical coherence tomography (DOCT) derived retinal blood flow (RBF) data. CD and LVD were assessed using optical coherence tomography (OCT) angiography. RNFLT and GCIPLT were measured using structural OCT. Measurements were performed in eyes with (MS+ON) and without (MS-ON) history for ON in RMS patients and in one eye in HC. Total oxygen extraction was lowest in MS+ON (1.8 ± 0.2 μl O
2
/min), higher in MS-ON (2.1 ± 0.5 μl O
2
/min,
p
= 0.019 vs. MS+ON) and highest in HC eyes (2.3 ± 0.6 μl O
2
/min,
p
= 0.002 vs. MS, ANOVA
p
= 0.031). RBF was lower in MS+ON (33.2 ± 6.0 μl/min) compared to MS-ON (38.3 ± 4.6 μl/min,
p
= 0.005 vs. MS+ON) and HC eyes (37.2 ± 4.7 μl/min,
p
= 0.014 vs. MS+ON, ANOVA
p
= 0.010). CD, LVD, RNFLT and GCIPL were significantly lower in MS+ON eyes. The present data suggest that structural alterations in the retina of RMS patients are accompanied by changes in oxygen metabolism, which are more pronounced in MS+ON than in MS-ON eyes. Whether these alterations promote MS onset and progression or occur as consequence of disease warrants further investigation.
Clinical Trial Registration:
ClinicalTrials.gov
registry, NCT03401879.
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