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BACKGROUND: People who have come close to death may report an unusual experience known as a near-death experience (NDE). This study aims to investigate NDEs and their aftereffects in dialysis patients. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 710 dialysis patients at 7 centers in Taipei, Taiwan. PREDICTOR: Demographic characteristics, life-threatening experience, depression, and religiosity. OUTCOMES: NDE and self-perceived changes in attitudes or behaviors. MEASUREMENTS: Greyson's NDE scale, Royal Free Questionnaire, 10-Question Survey, Ring's Weighted Core Experience Index, and Beck Depression Inventory. RESULTS: 45 patients had 51 NDEs. Mean NDE score was 11.9 (95% confidence interval, 11.0 to 12.9). Out-of-body experience was found in 51.0% of NDEs. Purported precognitive visions, awareness of being dead, and 'tunnel experience' were uncommon (<10%). Compared with the no-NDE group, subjects in the NDE group were more likely to be women and younger at life-threatening events. Both frequency of participation in religious ceremonies and pious religious activity correlated significantly with NDE score in patients with NDEs (P < 0.01 and P = 0.01, respectively). The NDE group reported being kinder to others (P = 0.04) and more motivated (P = 0.02) after their life-threatening events than the no-NDE group. LIMITATIONS: Determining the incidence of NDEs is dependent on self-reporting. Many NDEs occurred before the patient began long-term dialysis therapy. Causality between NDE and aftereffects cannot be inferred. CONCLUSIONS: NDE is not uncommon in the dialysis population and is associated with positive aftereffects. Nephrology care providers should be aware of the occurrence and aftereffects of NDEs. The high occurrence of life-threatening events, availability of medical records, and accessibility and cooperativeness of patients make the dialysis population very suitable for NDE research.Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Context: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined.Objective: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia.Design, Setting, and Patients: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000.Main Outcome Measures: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses.Results: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001).Conclusion: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur. [ABSTRACT FROM AUTHOR]

Background: Progressive supranuclear palsy (PSP) is a tauopathy that involves subcortical regions but also extends to cortical areas. The clinical impact of different tau protein sites and their influence on glymphatic dysfunction have not been investigated., Patients and Methods: Participants (n = 55; 65.6 ± 7.1 years; 29 women) with PSP (n = 32) and age-matched normal controls (NCs; n = 23) underwent 18 F-Florzolotau tau PET, MRI, PSP Rating Scale (PSPRS), and Mini-Mental State Examination. Cerebellar gray matter (GM) and parametric estimation of reference signal intensity were used as references for tau burden measured by SUV ratios. Glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS)., Results: Parametric estimation of reference signal intensity is a better reference than cerebellar GM to distinguish tau burden between PSP and NCs. PSP patients showed higher cortical and subcortical tau SUV ratios than NCs ( P < 0.001 and <0.001). Cortical and subcortical tau deposition correlated with PSPRS, UPDRS, and Mini-Mental State Examination scores (all P 's < 0.05). Cortical tau deposition was further associated with the DTI-ALPS index and frontal-temporal-parietal GM atrophy. The DTI-ALPS indexes showed a significantly negative correlation with the PSPRS total scores ( P < 0.01). Finally, parietal and occipital lobe tau depositions showed mediating effects between the DTI-ALPS index and PSPRS score., Conclusions: Cortical tau deposition is associated with glymphatic dysfunction and plays a role in mediating glymphatic dysfunction and clinical severity. Our results provide a possible explanation for the worsening of clinical severity in patients with PSP., Competing Interests: Conflicts of interest sources of funding: T.C.Y. owns equity in APRINOIA Therapeutics. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The development of new synthetic methods for B-H bond activation has been an important research area in boron cluster chemistry, which may provide opportunities to broaden the application scope of boron clusters. Herein, we present a new reaction strategy for the direct site-selective B-H functionalization of nido -carboranes initiated by photoinduced cage activation via a noncovalent cage···π interaction. As a result, the nido -carborane cage radical is generated through a single electron transfer from the 3D nido -carborane cage to a 2D photocatalyst upon irradiation with green light. The resulting transient nido -carborane cage radical could be directly probed by an advanced time-resolved EPR technique. In air, the subsequent transformations of the active nido -carborane cage radical have led to efficient and selective B-N, B-S, and B-Se couplings in the presence of N-heterocycles, imines, thioethers, thioamides, and selenium ethers. This protocol also facilitates both the late-stage modification of drugs and the synthesis of nido -carborane-based drug candidates for boron neutron capture therapy (BNCT).

Background: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive., Purpose: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms., Methods: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms., Results: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice., Conclusion: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D., Competing Interests: Declaration of Competing Interest All authors have read and approve the content, and agree to submit for consideration for publication in the Journal of Phytomedicine. There is no conflict of interest of any authors in relation to the submission., (Copyright © 2023. Published by Elsevier GmbH.)

The extensive consumption of fossil fuels increases CO 2 concentration in the atmosphere, resulting in serious global warming problems. Meanwhile, the problem of water contamination by organic substances is another significant global challenge. We have successfully synthesized ZnGa 1.01 Te 2.13 /g-C 3 N 4 (ZGT/GCN) composites for the first time as effective photocatalysts for both pollutant degradation and CO 2 reduction. ZGT/GCN composites were synthesized by a simple hydrothermal method. The prepared photocatalysts were characterized by XRD, SEM, TEM-EDS, DRS, BET, PL, and XPS. The ZGT/GCN heterojunction exhibited considerably enhanced photocatalytic activity in the degradation of crystal violet (CV) as well as in the photoreduction of CO 2 when compared to pure ZGT and GCN semiconductors. The optimal rate constant for CV degradation was obtained with the ZGT-80%GCN composite (0.0442 h -1 ), which is higher than the constants obtained with individual ZGT and GCN by 7.75 and 1.63 times, respectively. Moreover, the CO 2 reduction yields into CH 4 by ZGT-80%GCN was 1.013 μmol/g in 72 h, which is 1.21 and 1.08 times larger than the yields obtained with ZGT and GCN. Scavenger and ESR tests were used to propose the photocatalytic mechanism of the ZGT/GCN composite as well as the active species in the CV degradation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Low-carbohydrate (LC) diets are popular among general and athletic populations attempting to lose body mass. This study investigated the effect of a 7-day LC or moderate-carbohydrate (MC) calorie-restricted diet followed by 18-h recovery on body composition and taekwondo-specific performance. In this randomised cross-over study, 12 male taekwondo athletes consumed an LC (10% of carbohydrate, 41% of protein, 49% of fat, and 15.8 ± 0.4 kcal/kg/day) or an isocaloric MC diet (60% of carbohydrate, 30% of protein, and 10% of fat) for 7 days. The participants then consumed a carbohydrate-rich recovery dinner (39.2 ± 3.1 kcal/kg) followed by breakfast (6.2 ± 0.4 kcal/kg) in both the trials. Three repeated sprint ability (RSA) tests were conducted after breakfast. The taekwondo-specific reaction battery was administered before the first RSA test and after each RSA test. The participants experienced similar magnitudes of significant loss of body mass in the LC (-2.4 ± 1.7%) and MC (-2.3 ± 1.7%) trials. Fat mass and fat percentage significantly decreased in the MC trial but remained unchanged in the LC trial after body mass loss. Fat free mass was maintained in both the trials. The average and peak power in the RSA tests and the premotor reaction time were similar between the trials. The participants experienced significantly higher fatigue in the LC trial. In conclusion, both the diets can help athletes rapidly lose body mass while maintaining performance as long as an adequate amount of carbohydrate is consumed during the recovery period.

Background: We previously reported that miR-195 exerts neuroprotection by inhibiting Sema3A and cerebral miR-195 levels decreased with age, both of which urged us to explore the role of miR-195 and miR-195-regulated Sema3 family members in age-associated dementia., Methods: miR-195a KO mice were used to assess the effect of miR-195 on aging and cognitive functions. Sema3D was predicted as a miR-195 target by TargetScan and then verified by luciferase reporter assay, while effects of Sema3D and miR-195 on neural senescence were assessed by beta-galactosidase and dendritic spine density. Cerebral Sema3D was over-expressed by lentivirus and suppressed by si-RNA, and effects of over-expression of Sema3D and knockdown of miR-195 on cognitive functions were assessed by Morris Water Maze, Y-maze, and open field test. The effect of Sema3D on lifespan was assessed in Drosophila. Sema3D inhibitor was developed using homology modeling and virtual screening. One-way and two-way repeated measures ANOVA were applied to assess longitudinal data on mouse cognitive tests., Results: Cognitive impairment and reduced density of dendritic spine were observed in miR-195a knockout mice. Sema3D was identified to be a direct target of miR-195 and a possible contributor to age-associated neurodegeneration as Sema3D levels showed age-dependent increase in rodent brains. Injection of Sema3D-expressing lentivirus caused significant memory deficits while silencing hippocampal Sema3D improved cognition. Repeated injections of Sema3D-expressing lentivirus to elevate cerebral Sema3D for 10 weeks revealed a time-dependent decline of working memory. More importantly, analysis of the data on the Gene Expression Omnibus database showed that Sema3D levels were significantly higher in dementia patients than normal controls (p < 0.001). Over-expression of homolog Sema3D gene in the nervous system of Drosophila reduced locomotor activity and lifespan by 25%. Mechanistically, Sema3D might reduce stemness and number of neural stem cells and potentially disrupt neuronal autophagy. Rapamycin restored density of dendritic spines in the hippocampus from mice injected with Sema3D lentivirus. Our novel small molecule increased viability of Sema3D-treated neurons and might improve autophagy efficiency, which suggested Sema3D could be a potential drug target. Video Abstract CONCLUSION: Our results highlight the importance of Sema3D in age-associated dementia. Sema3D could be a novel drug target for dementia treatment., (© 2023. The Author(s).)

Background: There are currently no specific tests for either idiopathic Parkinson's disease or Parkinson-plus syndromes. The study aimed to investigate the diagnostic performance of features extracted from the whole brain using diffusion tensor imaging concerning parkinsonian disorders., Methods: The retrospective data yielded 625 participants (average age: 61.4 ± 8.2, men/women: 313/312; healthy controls/idiopathic Parkinson's disease/multiple system atrophy/progressive supranuclear palsy: 219/286/51/69) between 2008 and 2017. Diffusion-weighted images were obtained using a 3T MR scanner. The 90th, 50th, and 10th percentiles of fractional anisotropy and mean/axial/radial diffusivity from each parcellated brain area were recorded. Statistical analysis was evaluated based on the features extracted from the whole brain, as determined using discriminant function analysis and support vector machine. 20% of the participants were used as an independent blind dataset with 5 times cross-verification. Diagnostic performance was evaluated by the sensitivity and the F1 score., Results: Diagnoses were accurate for distinguishing idiopathic Parkinson's disease from healthy control and Parkinson-plus syndromes (87.4 ± 2.1% and 82.5 ± 3.9%, respectively). Diagnostic F1 scores varied for Parkinson-plus syndromes with 67.2 ± 3.8% for multiple system atrophy and 71.6 ± 3.5% for progressive supranuclear palsy. For early and late detection of idiopathic Parkinson's disease, the diagnostic performance was 79.2 ± 7.4% and 84.4 ± 6.9%, respectively. The diagnostic performance was 68.8 ± 11.0% and 52.5 ± 8.9% in early and late detection to distinguish different Parkinson-plus syndromes., Conclusions: Features extracted from diffusion tensor imaging of the whole brain can provide objective evidence for the diagnosis of healthy control, idiopathic Parkinson's disease, and Parkinson-plus syndromes with fair to very good diagnostic performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

The efficient and selective functionalization of icosahedral carboranes (C 2 B 10 H 12 ) at the boron vertexes is a long-standing challenge owing to the presence of 10 inert B-H bonds in a similar chemical environment. Herein, we report a new reaction paradigm for direct B-H functionalization of icosahedral carboranes via B-H homolysis enabled by a nitrogen-centered radical-mediated hydrogen atom transfer (HAT) strategy. Both the HAT process of the carborane B-H bond and the resulting boron-centered carboranyl radical intermediate have been confirmed experimentally. The reaction occurs at the most electron-rich boron vertex with the lowest B-H bond dissociation energy (BDE). Using this strategy, diverse carborane derivatization, including thiolation, selenation, alkynylation, alkenylation, cyanation, and halogenation, have been achieved in satisfactory yields under a photoinitiated condition in a metal-free and redox-neutral fashion. Moreover, the synthetic utility of the current protocol was also demonstrated by both the scale-up reaction and the construction of carborane-based functional molecules. Therefore, this methodology opens a radical pathway to carborane functionalization, which is distinct from the B-H heterolytic mechanism in the traditional strategies.

Previous studies on biocatalytic transformations of pinenes by cytochrome P450 (CYP) enzymes reveal the formation of different oxygenated products from a single substrate due to the multistate reactivity of CYP and the many reactive sites in the pinene scaffold. Up until now, the detailed mechanism of these biocatalytic transformations of pinenes have not been reported. Hereby, we report a systematic theoretical study of the plausible hydrogen abstraction and hydroxylation reactions of α- and β-pinenes by CYP using the density functional theory (DFT) method. All DFT calculations in this study were based on B3LYP/LAN computational methodology using the Gaussian09 software. We used the B3LYP functional with corrections for dispersive forces, BSSE, and anharmonicity to study the mechanism and thermodynamic properties of these reactions using a bare model (without CYP) and a pinene-CYP model. According to the potential energy surface and Boltzmann distribution for radical conformers, the major reaction products of CYP-catalyzed hydrogen abstraction from β-pinene are the doublet trans (53.4%) and doublet cis (46.1%) radical conformer at delta site. The formation of doublet cis/trans hydroxylated products released a total Gibbs free energy of about 48 kcal/mol. As for alpha pinene, the most stable radicals were trans-doublet (86.4%) and cis-doublet (13.6%) at epsilon sites, and their hydroxylation products released a total of ~50 kcal/mol Gibbs free energy. Our results highlight the likely C-H abstraction and oxygen rebounding sites accounting for the multi-state of CYP (doublet, quartet, and sextet spin states) and the formation of different conformers due to the presence of cis/trans allylic hydrogen in α-pinene and β-pinene molecules.

Aromatic polycyclic systems have been extensively utilized as structural subunits for the preparation of various functional molecules. Currently, aromatics-based polycyclic systems are predominantly generated from the extension of two-dimensional (2D) aromatic rings. In contrast, polycyclic compounds based on the extension of three-dimensional (3D) aromatics such as boron clusters are less studied. Here, we report three types of boron cluster-cored tricyclic molecular systems, which are constructed from a 2D aromatic ring, a 3D aromatic nido -carborane, and an alkyne. These new tricyclic compounds can be facilely accessed by Pd-catalyzed B-H activation and the subsequent cascade heteroannulation of carborane and pyridine with an alkyne in an isolated yield of up to 85% under mild conditions without any additives. Computational results indicate that the newly generated ring from the fusion of the 3D carborane, the 2D pyridyl ring, and an alkyne is non-aromatic. However, such fusion not only leads to a 1 H chemical shift considerably downfield shifted owing to the strong diatropic ring current of the embedded carborane but also devotes to new/improved physicochemical properties including increased thermal stability, the emergence of a new absorption band, and a largely red-shifted emission band and enhanced emission efficiency. Besides, a number of bright, color-tunable solid emitters spanning over all visible light are obtained with absolute luminescence efficiency of up to 61%, in contrast to aggregation-caused emission quenching of, e.g., Rhodamine B containing a 2D-aromatics-fused structure. This work demonstrates that the new hybrid conjugated tricyclic systems might be promising structural scaffolds for the construction of functional molecules.

This study investigated oleate inhibition concentration on mesophilic and thermophilic sludge by utilizing acetate and H 2 /CO 2 (80:20, v / v ) as substrate, respectively. In addition, another batch experiment was carried out to explore the influence of oleate loads (mM-oleate/g-VS) on methane production. Generally, the mesophilic anaerobic system was more stable than the thermophilic system, which embodied higher microbial abundance, higher methane yield, and higher oleate tolerance. Furthermore, this study provides a possible methanogenic pathway impacted by oleate under mesophilic and thermophilic conditions according to functional microbial composition. Lastly, this paper provides noticeable and avoidable oleate concentrations and loads under different experimental conditions as a guide for future anaerobic bioreactors of lipidic waste biodegradation.

To safely walk in a community environment requires dual cognitive-walking ambulation ability for people with Parkinson's disease (PD). A past study showed inconsistent results on cognitive-walking performance for PD patients, possibly due to the various cognitive tasks used and task priority assignment. This study designed cognitive-walking tests that used executive-related cognitive tasks to evaluate patients with early-stage Parkinson's disease who did not have obvious cognitive deficits. The effect of assigning task prioritization was also evaluated. Sixteen individuals with PD (PD group) and 16 individuals without PD (control group) underwent single cognitive tests, single walking tests, dual walking tests, and prioritizing task tests. Three types of cognitive, spatial memory, Stroops, and calculation tasks were employed. The cognitive performance was evaluated by response time, accuracy, and speed-accuracy trade off composite score. The walking performance was evaluated by the temporal spatial gait characteristics and variation in gait. The results showed that the walking performance of the PD group was significantly worse than the control group in both single and dual walking conditions. The group difference in cognitive performance was shown in composite score under the dual calculation walking task but not under the single task. While assigning priority to walking, no group difference in walking was observed but the response accuracy rate of PD groups declined. This study concluded that the dual task walking test could sharpen the cognitive deficits for early-stage PD patients. The task priority assignment might not be recommended while testing gait deficits since it decreased the ability to discriminate group differences.

A near-real-time (NRT) aerosol forecast and diagnostic approach is developed based on the system of Infusing satellite Data into Environmental Applications for East Asia, herein denoted as IDEA-EA. The design incorporates a 0.5-degree Global Forecast System (GFS) and Visible Infrared Imaging Radiometer Suite (VIIRS) aerosol and cloud retrievals for meteorological and remote sensing inputs. The primary output of IDEA-EA includes aerosol forward and backward air mass trajectory forecasts, migration visualization, and data synthesis purposed for NRT aerosol detection, monitoring, and source tracing in East Asia. Two aerosol episodes of Southeast Asia (SEA) biomass burning and Chinese haze infusion with Gobi dust are illustrated by IDEA-EA to demonstrate its forecast and source tracing capabilities. In the case of SEA biomass burning (late March 2021), forward trajectories of IDEA-EA forecasted air masses with high aerosol optical depth (AOD) from SEA affecting Taiwan. The IDEA-EA forecasts were verified by increased AOD and surface PM 2.5 observations at a mountain site. In the case of the Chinese haze (October 30, 2019), backward trajectories from the northern tip of Taiwan traced air masses back to the east coast of mainland China and possibly further to the Gobi Desert. Compared with conventional numerical model simulations, the combination of the state-of-the-art aerosol remote sensing and trajectory modeling in IDEA-EA provides a cost-effective alternative for air quality management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Neuroinflammation plays a critical role in the neurological recovery of spinal cord injury (SCI). Adenosine can modulate neuroinflammation, whose uptake is mediated by nucleoside transporters. This study aimed to investigate the roles of equilibrative nucleoside transporter 1 (Ent1) in the inflammatory responses and functional recovery of SCI. Spinal cord contusion at the T10 dorsal portion was induced in mice to cause partial paralysis of the hindlimbs. Genetic deletion and pharmacological inhibition of Ent1 were used to evaluate the role of Ent1 in SCI. The outcomes were evaluated in terms of the Basso Mouse Scale (BMS), gait analysis, astrogliosis, microgliosis, and cytokine levels on day 14 post-injury. As a result, Ent1 deletion reduced neuroinflammation and improved the BMS score (4.88 ± 0.35 in Ent1 -/- vs. 3.78 ± 1.09 in Ent1 +/+ ) and stride length (3.74 ± 0.48 cm in Ent1 -/- vs. 2.82 ± 0.78 cm in Ent1 +/+ ) of mice with SCI. Along with the reduced lesion size, more preserved neurons were identified in the perilesional area of mice with Ent1 deletion (102 ± 23 in Ent1 -/- vs. 73 ± 10 in Ent1 +/+ ). The results of pharmacological inhibition were consistent with the findings of genetic deletion. Moreover, Ent1 inhibition decreased the protein level of complement 3 (an A1 marker), but increased the levels of S100 calcium-binding protein a10 (an A2 marker) and transforming growth factor-β, without changing the levels of inducible nitric oxide synthase (a M1 marker) and arginase 1 (a M2 marker) at the injured site. These findings indicate the important role of Ent1 in the pathogenesis and treatment of SCI., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this paper, silver niobate (AgNbO 3 ) material was synthesized by a solid-state reaction. AgNbO 3 was characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), UV-visible diffuse reflectance spectroscopy (DRS), and Brunauer-Emmett-Teller (BET) measurement. The photocatalytic activity of AgNbO 3 was investigated in degradation of sulfamethoxazole (SMX) under visible light, which is a widely used antibiotic with significant threats towards health and aquatic organisms. Persulfate (PS) oxidant was found to improve the efficiency of the proposed photocatalytic removal of SMX by AgNbO 3 . The different operational parameters in the AgNbO 3 /PS/Vis system were investigated. The best photocatalytic performance was achieved with 0.5 g L -1 AgNbO 3 , 1.0 mM PS, and pH = 5.0 as the optimal conditions, achieving 98% of SMX degradation after 8 h of visible-light irradiation. Scavenger and electron spin resonance (ESR) experiments were carried out to identify the major reactive species in the SMX degradation and to propose the photocatalytic mechanism by the AgNbO 3 /PS/Vis system. The photodecomposition was found to be majorly caused by holes and ˙O 2 - species, with ˙OH and SO 4 ˙ - radicals contributing to improve the photocatalytic process. The AgNbO 3 catalyst was stable and reusable with efficient photocatalytic activity in three successive recycling experiments and its XRD patterns remained virtually unchanged. The reported process of PS activation by the AgNbO 3 photocatalyst is promising for visible-light application in remediation of antibiotic-contaminated water., Competing Interests: There is no conflict to declare., (This journal is © The Royal Society of Chemistry.)

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower-limb spasticity. Cerebellar ataxia commonly co-occurs with complicated HSPs. HSP with concurrent cerebellar ataxia has significant clinical and genetic overlaps with hereditary cerebellar ataxia (HCA) and other inherited neurological diseases, adding to the challenge of planning genetic testing for the disease. In this study, we characterized clinical features of a cohort of 24 patients (male/female: 15/9) from 22 families who presented spastic paraparesis combined with cerebellar involvement, with a median disease onset age 20.5 (range 5-53) years. Aside from the core phenotype, 18 (75%) patients had additional neuropsychiatric and systemic manifestations. A stepwise genetic testing strategy stratified by mode of inheritance, distinct neuroimaging features (e.g., thin corpus callosum), population-specific prevalence and whole-exome sequencing was utilized to investigate the genetic etiology. Causative mutations in up to 10 genes traditionally related to HSP, HCA and other neurogenetic diseases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, neurodegeneration with brain iron accumulation, and progressive encephalopathy with brain atrophy and thin corpus callosum) were detected in 16 (73%) of the 22 pedigrees. Our study revealed the genetic complexity of HSP combined with cerebellar involvement. In contrast to the marked genetic diversity, the functions of the causative genes are restricted to a limited number of physiological themes. The functional overlap might reflect common underlying pathogenic mechanisms, to which the corticospinal tract and cerebellar neuron circuits may be especially vulnerable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lan, Lu, Wu, Chen, Sung, Tu and Chang.)

Diabetic foot ulcers (DFUs) are one of the most costly and troublesome complications of diabetes mellitus. The wound chronicity of DFUs remains the main challenge in the current and future treatment of this condition. Persistent inflammation results in chronic wounds characterized by dysregulation of immune cells, such as M1 macrophages, and impairs the polarization of M2 macrophages and the subsequent healing process of DFUs. The interactive regulation of M1 and M2 macrophages during DFU healing is critical and seems manageable. This review details how cytokines and signalling pathways are co-ordinately regulated to control the functions of M1 and M2 macrophages in normal wound repair. DFUs are defective in the M1-to-M2 transition, which halts the whole wound-healing machinery. Many pre-clinical and clinical innovative approaches, including the application of topical insulin, CCL chemokines, micro RNAs, stem cells, stem-cell-derived exosomes, skin substitutes, antioxidants, and the most recent Phase III-approved ON101 topical cream, have been shown to modulate the activity of M1 and M2 macrophages in DFUs. ON101, the newest clinically approved product in this setting, is designed specifically to down-regulate M1 macrophages and further modulate the wound microenvironment to favour M2 emergence and expansion. Finally, the recent evolution of macrophage modulation therapies and techniques will improve the effectiveness of the treatment of diverse DFUs.

Background: The therapeutic effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) is related to the modulation of pathological neural activities, particularly the synchronization in the β band (13-35 Hz). However, whether the local β activity in the STN region can directly predict the stimulation outcome remains unclear., Objective: We tested the hypothesis that low- β (13-20 Hz) and/or high- β (20-35 Hz) band activities recorded from the STN region can predict DBS efficacy., Methods: Local field potentials (LFPs) were recorded in 26 patients undergoing deep brain stimulation surgery in the subthalamic nucleus area. Recordings were made after the implantation of the DBS electrode prior to its connection to a stimulator. The maximum normalized powers in the theta (4-7 Hz), alpha (7-13 Hz), low- β (13-20 Hz), high- β (20-35 Hz), and low-γ (40-55 Hz) subbands in the postoperatively recorded LFP were correlated with the stimulation-induced improvement in contralateral tremor or bradykinesia-rigidity. The distance between the contact selected for stimulation and the contact with the maximum subband power was correlated with the stimulation efficacy. Following the identification of the potential predictors by the significant correlations, a multiple regression analysis was performed to evaluate their effect on the outcome., Results: The maximum high- β power was positively correlated with bradykinesia-rigidity improvement ( r s = 0.549, p < 0.0001). The distance to the contact with maximum high- β power was negatively correlated with bradykinesia-rigidity improvement ( r s = -0.452, p < 0.001). No significant correlation was observed with low- β power. The maximum high- β power and the distance to the contact with maximum high- β power were both significant predictors for bradykinesia-rigidity improvement in the multiple regression analysis, explaining 37.4% of the variance altogether. Tremor improvement was not significantly correlated with any frequency., Conclusion: High- β oscillations, but not low- β oscillations, recorded from the STN region with the DBS lead can inform stimulation-induced improvement in contralateral bradykinesia-rigidity in patients with PD. High- β oscillations can help refine electrode targeting and inform contact selection for DBS therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Chen, Tu, Liu, Chen, Wu, Yeap, Yeh, Lu and Chen.)

The mitochondrial protein sirtuin 3 (SIRT3) can counteract cell damage caused by oxidative stress and inflammation, and contribute to cell survival primarily by improving mitochondrial function. However, the effects of SIRT3 in dopaminergic neuronal cells (DACs) remain unclear. In our previous studies, microglia activation-associated cytotoxicity was observed to promote the apoptosis of DACs, along with the decrease of SIRT3 expression. The aim of the present study was to explore the potential neuroprotective effect of SIRT3 expression against dopaminergic neuron injury caused by microglia activation, and clarify its possible mechanisms. SIRT3 overexpression in DACs reduced the production of intracellular reactive oxygen species (ROS), cell apoptosis rate, mitochondrial membrane potential (ΔΨm) depolarization, opening of mitochondrial permeability transition pore (mPTP) and cyclophilin D (CypD) protein level, and promoted cell cycle progression. However, SIRT3 siRNA-mediated knockdown further aggravated microglia activation-mediated cytotoxicity, including ROS accumulation, increased cell apoptosis and mPTP opening, elevated the CypD level, enhanced mitochondrial ΔΨm depolarization, concomitant to cell cycle arrest at G 0 /G 1 phase. The mechanisms of SIRT3 mitigated microglia activation-induced DAC dysfunction, which included decreased mPTP opening and Bax/Bcl-2 ratio, inhibition of mitochondrial cytochrome c release to the cytoplasm, reduced caspase-3/9 activity, increased LC3II/LC3I and beclin-1 protein expression levels, and decreased nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1β and IL-18 protein expression. In conclusion, these results indicated that SIRT3 expression attenuated cell damage caused by microglia activation through the mitochondrial apoptosis pathway in DACs. The mitophagy-NLRP3 inflammasome pathway may also be associated with this neuroprotection. These findings may provide new intervention targets for the survival of dopaminergic neurons and the prevention and treatment of Parkinson's disease., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Jiang et al.)

Background: Succinate-CoA ligase/synthetase (SCS) deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Variants in SUCLG1, the nuclear gene encoding the alpha subunit of the SCS enzyme playing a pivotal role in maintaining mtDNA integrity and stability, are associated with mitochondrial DNA depletion syndrome 9 (MTDPS9)., Methods: In this study, we reported an infant with clinical features of MTDPS9 from China. Whole exome sequencing (WES) was used to identify the genetic cause. Bioinformatic analysis and mtDNA level detection were performed to assess pathogenicity., Results: The proband manifested with hypotonia, lactic acidosis, mild methylmalonic aciduria, hearing loss and psychomotor retardation. WES identified new compound heterozygous SUCLG1 variants of c.601A>G (p.R201G) in exon 6 and c.871G>C (p.A291P) in exon 8. Computational analysis predicted that these missense variants might alter structure stability and mitochondrial translocation of SUCLG1. qRT-PCR showed 68% depletion of mtDNA content in proband as compared to controls., Conclusion: Novel compound heterozygous variants c.601A>G (p.R201G) and c.871G>C (p.A291P) in SUCLG1 may cause MTDPS9 in this family. Our finding should be helpful for molecular diagnosis, genetic counseling and clinical management of SCS deficiency disorders., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Diabetic wounds exhibit chronic inflammation and delayed tissue proliferation or remodeling, mainly owing to prolonged proinflammatory (M1) macrophage activity and defects in transition to prohealing/proremodeling (M2a/M2c; CD206 + and/or CD163 + ) macrophages. We found that topical treatment with ON101, a plant-based potential therapeutic for diabetic foot ulcers, increased M2c-like (CD163 + and CD206 + ) cells and suppressed M1-like cells, altering the inflammatory gene profile in a diabetic mouse model compared with that in the controls. An in vitro macrophage-polarizing model revealed that ON101 directly suppressed CD80 + and CD86 + M1-macrophage polarization and M1-associated proinflammatory cytokines at both protein and transcriptional levels. Notably, conditioned medium collected from ON101-treated M1 macrophages reversed the M1-conditioned medium‒mediated suppression of CD206 + macrophages. Furthermore, conditioned medium from ON101-treated adipocyte progenitor cells significantly promoted CD206 + and CD163 + macrophages but strongly inhibited M1-like cells. ON101 treatment also stimulated the expression of GCSF and CXCL3 genes in human adipocyte progenitor cells. Interestingly, treatment with recombinant GCSF protein enhanced both CD206 + and CD163 + M2 markers, whereas CXCL3 treatment only stimulated CD163 + M2 macrophages. Depletion of cutaneous M2 macrophages inhibited ON101-induced diabetic wound healing. Thus, ON101 directly suppressed M1 macrophages and facilitated the GCSF- and CXCL3-mediated transition from M1 to M2 macrophages, lowering inflammation and leading to faster diabetic wound healing., (© 2022 The Authors.)

Parkinson's disease (PD) and carbon monoxide (CO) poisoning demonstrate parkinsonian features related to presynaptic dopaminergic deficits. However, their clinical features and treatment responses are different, indicating other roles of neurotransmitters in symptomatic modulation. In this study, we used 18 F-FP-(+)-DTBZ PET to explore vesicular monoamine transporter type 2 (VMAT2) distributions in 31 patients with PD, 39 patients with CO poisoning and parkinsonian features (n = 39), and 24 age-matched controls. In addition to the disease-specific VMAT2 topographies in PD and CO poisoning, we also constructed feature-specific functional networks. The cardinal features included tremor, rigidity, akinesia, and rapid alternating movements (RAM), and the overall motor severity was scored using Unified Parkinson Disease Rating Scale (UPDRS) and modified Hoehn-Yahr (mH-Y) Scale scores. Our results suggested that a reduction in VMAT2 signals in the caudate, amygdala, and hippocampus were more specific to CO poisoning, while low uptake in the putamen and substantia nigra was more specific to PD. UPDRS and mH-Y scores were related to striatum signals in both groups and hippocampus and raphe in the CO poisoning group. With regards to the cardinal features, the putamen was related to akinesia in both groups. The substantia nigra was related to rigidity in PD, and the caudate and nucleus accumbens were related to akinesia, RAM and rigidity in CO poisoning. Our study enhances the current understanding of different patterns of monoaminergic terminal deficits in patients with CO poisoning and PD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for the motor impairments of patients with advanced Parkinson's disease. However, mood or behavioral changes, such as mania, hypomania, and impulsive disorders, can occur postoperatively. It has been suggested that these symptoms are associated with the stimulation of the limbic subregion of the STN. Electrophysiological studies demonstrate that the low-frequency activities in ventral STN are modulated during emotional processing. In this study, we report 22 patients with Parkinson's disease who underwent STN DBS for treatment of motor impairment and presented stimulation-induced mood elevation during initial postoperative programming. The contact at which a euphoric state was elicited by stimulation was termed as the hypomania-inducing contact (HIC) and was further correlated with intraoperative local field potential recorded during the descending of DBS electrodes. The power of four frequency bands, namely, θ (4-7 Hz), α (7-10 Hz), β (13-35 Hz), and γ (40-60 Hz), were determined by a non-linear variation of the spectrogram using the concentration of frequency of time (conceFT). The depth of maximum θ power is located approximately 2 mm below HIC on average and has significant correlation with the location of contacts ( r = 0.676, p < 0.001), even after partializing the effect of α and β, respectively ( r = 0.474, p = 0.022; r = 0.461, p = 0.027). The occurrence of HIC was not associated with patient-specific characteristics such as age, gender, disease duration, motor or non-motor symptoms before the operation, or improvement after stimulation. Taken together, these data suggest that the location of maximum θ power is associated with the stimulation-induced hypomania and the prediction of θ power is frequency specific. Our results provide further information to refine targeting intraoperatively and select stimulation contacts in programming., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Wu, Tu, Yeh, Liu, Yeap, Chao, Chen, Lu and Chen.)

Parkinson's disease (PD), the most common neurodegenerative motor disorder, is currently incurable. Although many studies have provided insights on the substantial influence of genetic factors on the occurrence and development of PD, the molecular mechanism underlying the disease is largely unclear. Previous studies have shown that point mutations in the phospholipase A2 group VI gene (PLA2G6) correlate with young-onset dystonia-parkinsonism type 14 (PARK14). However, limited information is available regarding the pathogenic role of this gene and the mechanism underlying its function. To study the role of PLA2G6 mutations, we first used zebrafish larvae to screen six PLA2G6 mutations and revealed that injection of D331Y, T572I, and R741Q mutation constructs induced phenotypes such as motility defects and reduction in dopaminergic neurons. The motility defects could be alleviated by treatment with L-3, 4-dihydroxyphenylalanine (L-dopa), indicating that these mutations are pathological for PARK14 symptoms. Furthermore, the injection of D331Y and T572I mutation constructs reduced phospholipase activity of PLA2G6 and its lipid metabolites, which confirmed that these two mutations are loss-of-function mutations. Metabolomic analysis revealed that D331Y or T572I mutation led to higher phospholipid and lower docosahexaenoic acid (DHA) levels, indicating that reduced DHA levels are pathological for defective motor functions. Further, a dietary DHA supplement relieved the motility defects in PLA2G6 D331Y/D331Y knock-in mice. This result revealed that the D331Y mutation caused defective PLA2G6 phospholipase activity and consequently reduced the DHA level, which is the pathogenic factor responsible for PARK14. The results of this study will facilitate the development of therapeutic strategies for PARK14., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy., Methods: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested., Results: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy., Conclusion: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy., (© 2021. The Author(s).)

Background: Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood.The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice., Methods: Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events., Results: Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD -1.31, 95% CI -1.57 to -1.04, P < .00001) for motor UPDRS score, (16 trials; SMD -1.26, 95% CI -1.49 to -1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD -1.02, 95% CI -1.27 to -0.77, P < .00001) for mental UPDRS score, (10 trials; SMD -1.54, 95% CI -1.93 to -1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD -1.56, 95% CI -1.90 to -1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001)., Conclusions: P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Our previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD patients had higher C allele frequency. CC and CT genotype significantly increased risk of PD compared with TT genotype. SNP rs17525453 within RAB35 gene promoter leads to formation of transcription factor TFII-I binding site. Results of EMSA and supershift assay indicated that TFII-I binds to rs17525453 sequence of RAB35 gene promoter. Luciferase reporter assays showed that rs17525453 variant of RAB35 gene promoter possesses an augmented transcriptional activity. Our results suggest that functional variant rs17525453 within RAB35 gene promoter is likely to enhance transcriptional activity and upregulate RAB35 protein, which could lead to increased risk of PD in Taiwanese population., (Copyright © 2021. Published by Elsevier Inc.)

The first systematic synthesis of bismuth oxychloride/bismuth oxybromide/graphitic carbon nitride (BiO x Cl y /BiO m Br n /g-C 3 N 4 ) nano-composites used a controlled hydrothermal method. The structure, morphology and characteristic of BiO x Cl y /BiO m Br n /g-C 3 N 4 photocatalyst were measured by XRD, UV-vis-DRS, FT-IR, FE-TEM, FE-SEM-EDS, PL, BET, HR-XPS and EPR. Under visible light irradiation, the photodegradation activity was evaluated for the decolorization of crystal violet (CV) and 2-hydroxybenzoic acid (2-HBA) in aqueous solution. The catalytic performance showed that, when using sample BB2C1-4-250-30 wt% g-C 3 N 4 composite as a photocatalyst, the best reaction-rate-constant (k) was 0.071 h -1 . It was 1.5 times higher than the k value of BB2C1-4-250 as a photocatalyst. From the scavenging effect of various scavengers, the results of EPR showed that reactive OH was the main scavenger, while O 2 - , h + and 1 O 2 were the second scavenger in CV degradation. In this study, a possible photodegradation mechanism was proposed and discussed. In this work, our method of BiO x Cl y /BiO m Br n /g-C 3 N 4 preparation could be used for future mass production and the BiO x Cl y /BiO m Br n /g-C 3 N 4 composite materials could be applied to the environmental pollution control in future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This work reports the preparation and detailed characterization of stannum indium sulfide (SnIn 4 S 8 ) semiconductor photocatalyst for degradation of ethiofencarb (toxic insecticide) under visible-light irradiation. The as-prepared SnIn 4 S 8 showed catalytic efficiency of 98% in 24 h under optimal operating conditions (pH = 3, catalyst dosage of 0.5 g L -1 ). The photodegradation reaction followed pseudo-first-order kinetics. The major intermediates have been identified using gas chromatography/mass spectrometry. • O 2 - and • OH radicals appeared to be the primary active species in the degradation process as revealed by scavenger and electronic spin resonance studies, while photogenerated holes had a secondary role in this process. A plausible mechanism involving two routes was proposed for ethiofencarb degradation by SnIn 4 S 8 after identifying the major intermediate species: oxidative cleavage of the CH 2 -S and the amide bonds of the carbamate moiety. Lastly, SnIn 4 S 8 was found to be efficient, stable, and reusable in treating real water samples in three successive photodegradation experiments. This study demonstrates the prospect of SnIn 4 S 8 photocatalysis in treatment of natural and contaminated water from extremely toxic organic carbamates as ethiofencarb.

Polymorphonuclear neutrophils (PMNs) are traditionally regarded as professional phagocytic and acute inflammatory cells that engulf the microbial pathogens. However, accumulating data have suggested that PMNs are multi-potential cells exhibiting many important biological functions in addition to phagocytosis. These newly found novel activities of PMN include production of different kinds of cytokines/chemokines/growth factors, release of neutrophil extracellular traps (NET)/ectosomes/exosomes and trogocytosis (membrane exchange) with neighboring cells for modulating innate, and adaptive immune responses. Besides, PMNs exhibit potential heterogeneity and plasticity in involving antibody-dependent cellular cytotoxicity (ADCC), cancer immunity, autoimmunity, inflammatory rheumatic diseases, and cardiovascular diseases. Interestingly, PMNs may also play a role in ameliorating inflammatory reaction and wound healing by a subset of PMN myeloid-derived suppressor cells (PMN-MDSC). Furthermore, PMNs can interact with other non-immune cells including platelets, epithelial and endothelial cells to link hemostasis, mucosal inflammation, and atherogenesis. The release of low-density granulocytes (LDG) from bone marrow initiates systemic autoimmune reaction in systemic lupus erythematosus (SLE). In clinical application, identification of certain PMN phenotypes may become prognostic factors for severe traumatic patients. In the present review, we will discuss these newly discovered biological and pathobiological functions of the PMNs.

Introduction: White matter degeneration may contribute to clinical symptoms of parkinsonism. Objective: We used fixel-based analysis (FBA) to compare the extent and patterns of white matter degeneration in different parkinsonian syndromes-including idiopathic Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Methods: This is a retrospective interpretation of prospectively acquired data of patients recruited in previous studies during 2008 and 2019. Diffusion-weighted images were acquired on a 3-Tesla scanner (diffusion weighting b = 1000 s/mm 2 -applied along either 64 or 30 non-collinear directions) from 53 patients with PD (men/women: 29/24; mean age: 65.06 ± 5.51 years), 47 with MSA (men/women: 20/27; mean age: 63.00 ± 7.19 years), and 50 with PSP men/women: 20/30; mean age: 65.96 ± 3.14 years). Non-parametric permutation tests were used to detect intergroup differences in fixel-related indices-including fiber density, fiber cross-section, and their combination. Results: Patterns of white matter degeneration were significantly different between PD and atypical parkinsonisms (MSA and PSP). Compared with patients with PD, those with MSA and PSP showed a more extensive white matter involvement-noticeably descending tracts from primary motor cortex to corona radiata and cerebral peduncle. Lesions of corpus callosum were specific to PSP and absent in both MSA and PD. Discussion: FBA identified specific patterns of white matter changes in MSA and PSP patients compared to PD. Our results proved the utility of FBA in evaluation of implied biological processes of white matter changes in parkinsonism. Our study set the stage for future applications of this technique in patients with parkinsonian syndromes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nguyen, Cheng, Chen, Lin, Tsai, Lu, Weng, Wu, Hoang and Wang.)

Objective: The study was undertaken to identify a monogenic cause of early onset, generalized dystonia., Methods: Methods consisted of genome-wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, and protein expression studies in skin fibroblasts from patients., Results: We identified a heterozygous variant, c.388G>A, p.Gly130Arg, in the eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) gene, segregating with early onset isolated generalized dystonia in 5 patients of a Taiwanese family. EIF2AK2 sequencing in 191 unrelated patients with unexplained dystonia yielded 2 unrelated Caucasian patients with an identical heterozygous c.388G>A, p.Gly130Arg variant, occurring de novo in one case, another patient carrying a different heterozygous variant, c.413G>C, p.Gly138Ala, and one last patient, born from consanguineous parents, carrying a third, homozygous variant c.95A>C, p.Asn32Thr. These 3 missense variants are absent from gnomAD, and are located in functional domains of the encoded protein. In 3 patients, additional neurological manifestations were present, including intellectual disability and spasticity. EIF2AK2 encodes a kinase (protein kinase R [PKR]) that phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α), which orchestrates the cellular stress response. Our expression studies showed abnormally enhanced activation of the cellular stress response, monitored by PKR-mediated phosphorylation of eIF2α, in fibroblasts from patients with EIF2AK2 variants. Intriguingly, PKR can also be regulated by PRKRA (protein interferon-inducible double-stranded RNA-dependent protein kinase activator A), the product of another gene causing monogenic dystonia., Interpretation: We identified EIF2AK2 variants implicated in early onset generalized dystonia, which can be dominantly or recessively inherited, or occur de novo. Our findings provide direct evidence for a key role of a dysfunctional eIF2α pathway in the pathogenesis of dystonia. ANN NEUROL 2021;89:485-497., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The convenient cross-coupling of sp 2 or sp 3 carbons with a specific boron vertex on carborane cage represents significant synthetic values and insurmountable challenges. In this work, we report an Rh-catalyzed reaction between o-carborane and N-acyl-glutarimides to construct various B cage -C bonds. Under the optimized condition, the removable imine directing group (DG) leads to B(3)- or B(3,6)-C couplings, while the pyridyl DG leads to B(3,5)-Ar coupling. In particular, an unexpected rearrangement of amide reagent is observed in pyridyl directed B(4)-C(sp 3 ) formation. This scalable protocol has many advantages, including easy access, the use of cheap and widely available coupling agents, no requirement of an external ligand, base or oxidant, high efficiency, and a broad substrate scope. Leveraging the Rh I dimer and twisted amides, this method enables straightforward access to diversely substituted and therapeutically important carborane derivatives at boron site, and provides a highly valuable vista for carborane-based drug screening., (© 2020 Wiley-VCH GmbH.)

Selenium is an essential trace mineral element for humans. Although previous in vitro and animal studies have reported the vital role of selenium in bone, the results of the relationship between the selenium status and bone health were inconsistent in epidemiological studies. The risk of selenium deficiency is negligible for U.S. general population, however, the relationship between selenium status and bone health has never been surveyed in a nationally representative sample. In this study, we analyzed the data of 2983 adults (aged ≥40 years) in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 to investigate the association among three markers of the selenium status (measured from whole blood, serum, and dietary intake), total spine and femur bone mineral density (BMD), and FRAX scores, and history of bone fractures. We found a one-unit increase in the ln-whole-blood selenium level was correlated with an increase in the total femur BMD of 0.064 g/cm 2 (S.E. = 0.025; P = 0.022) in all participants and 0.086 g/cm 2 (S.E. = 0.031; P = 0.013) in menopausal women. Additionally, a one-unit increase in the ln-selenium intake amount was associated with an increase in the total femur BMD of 0.014 g/cm 2 (S.E. = 0.007; P = 0.043) in all participants. We also found that the dietary and whole-blood selenium statuses were negatively associated with the FRAX score, while levels of all the three selenium biomarkers were negatively associated with a history of bone fractures. In conclusion, increased selenium status is correlated with an increased total femur BMD, decreased FRAX scores, and a reduced incidence of previous bone fractures in the U.S. representative survey of adults. Further study is warranted to clarify the causal inference., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease with heterogeneous clinical manifestations. A diverse innate and adaptive immune dysregulation is involved in the immunopathogenesis of SLE. The dysregulation of immune-related cells may derive from the intricate interactions among genetic, epigenetic, environmental, and immunological factors. Of these contributing factors, non-coding RNAs (ncRNAs), including microRNAs (miRNAs, miRs), and long non-coding RNAs (lncRNAs) play critical roles in the post-transcriptional mRNA expression of cytokines, chemokines, and growth factors, which are essential for immune modulation. In the present review, we emphasize the roles of ncRNA expression in the immune-related cells and cell-free plasma, urine, and tissues contributing to the immunopathogenesis and tissue damage in SLE. In addition, the circular RNAs (circRNA) and their post-translational regulation of protein synthesis in SLE are also briefly described. We wish these critical reviews would be useful in the search for biomarkers/biosignatures and novel therapeutic strategies for SLE patients in the future.