Splicing factor YBX1 regulates bone marrow stromal cell fate during aging.

Senescence and altered differentiation potential of bone marrow stromal cells (BMSCs) lead to age-related bone loss. As an important posttranscriptional regulatory pathway, alternative splicing (AS) regulates the diversity of gene expression and has been linked to induction of cellular senescence. However, the role of splicing factors in BMSCs during aging remains poorly defined. Herein, we found that the expression of the splicing factor Y-box binding protein 1 (YBX1) in BMSCs decreased with aging in mice and humans. YBX1 deficiency resulted in mis-splicing in genes linked to BMSC osteogenic differentiation and senescence, such as Fn1, Nrp2, Sirt2, Sp7, and Spp1, thus contributing to BMSC senescence and differentiation shift during aging. Deletion of Ybx1 in BMSCs accelerated bone loss in mice, while its overexpression stimulated bone formation. Finally, we identified a small compound, sciadopitysin, which attenuated the degradation of YBX1 and bone loss in old mice. Our study demonstrated that YBX1 governs cell fate of BMSCs via fine control of RNA splicing and provides a potential therapeutic target for age-related osteoporosis.

Cytochrome b5 diversity in green lineages preceded the evolution of syringyl lignin biosynthesis.

Lignin production marked a milestone in vascular plant evolution, and the emergence of syringyl (S) lignin is lineage specific. S-lignin biosynthesis in angiosperms, mediated by ferulate 5-hydroxylase (F5H, CYP84A1), has been considered a recent evolutionary event. F5H uniquely requires the cytochrome b5 protein CB5D as an obligatory redox partner for catalysis. However, it remains unclear how CB5D functionality originated and whether it coevolved with F5H. We reveal here the ancient evolution of CB5D-type function supporting F5H-catalyzed S-lignin biosynthesis. CB5D emerged in charophyte algae, the closest relatives of land plants, and is conserved and proliferated in embryophytes, especially in angiosperms, suggesting functional diversification of the CB5 family before terrestrialization. A sequence motif containing acidic amino residues in Helix 5 of the CB5 heme-binding domain contributes to the retention of CB5D function in land plants but not in algae. Notably, CB5s in the S-lignin-producing lycophyte Selaginella lack these residues, resulting in no CB5D-type function. An independently evolved S-lignin biosynthetic F5H (CYP788A1) in Selaginella relies on NADPH-dependent cytochrome P450 reductase as sole redox partner, distinct from angiosperms. These results suggest that angiosperm F5Hs coopted the ancient CB5D, forming a modern cytochrome P450 monooxygenase system for aromatic ring meta-hydroxylation, enabling the reemergence of S-lignin biosynthesis in angiosperms.

Gene set correlation enrichment analysis for interpreting and annotating gene expression profiles.

Pathway analysis, including nontopology-based (non-TB) and topology-based (TB) methods, is widely used to interpret the biological phenomena underlying differences in expression data between two phenotypes. By considering dependencies and interactions between genes, TB methods usually perform better than non-TB methods in identifying pathways that include closely relevant or directly causative genes for a given phenotype. However, most TB methods may be limited by incomplete pathway data used as the reference network or by difficulties in selecting appropriate reference networks for different research topics. Here, we propose a gene set correlation enrichment analysis method, Gscore, based on an expression dataset-derived coexpression network to examine whether a differentially expressed gene (DEG) list (or each of its DEGs) is associated with a known gene set. Gscore is better able to identify target pathways in 89 human disease expression datasets than eight other state-of-the-art methods and offers insight into how disease-wide and pathway-wide associations reflect clinical outcomes. When applied to RNA-seq data from COVID-19-related cells and patient samples, Gscore provided a means for studying how DEGs are implicated in COVID-19-related pathways. In summary, Gscore offers a powerful analytical approach for annotating individual DEGs, DEG lists, and genome-wide expression profiles based on existing biological knowledge.

Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low-Density Lipoprotein Cholesterol.

OBJECTIVES: To investigate whether post-stroke statin therapy reduces subsequent major vascular events in statin-naïve patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non-atherosclerotic stroke) at stroke onset. METHODS: Patients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL-C below the target were assessed. The effect of post-stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting. RESULTS: The baseline LDL-C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low-to-moderate intensity, 23.5%; high intensity, 44.1%). Post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up (weighted hazard ratio 0.55, 95% confidence interval 0.42-0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL-C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL-C <70 mg/dL, post-stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29-0.70). The intensity of the most beneficial statin varied by subtype of stroke. INTERPRETATION: Statin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL-C below the target without pre-stroke lipid-lowering therapy. ANN NEUROL 2024;95:876-885.

Efficacy of Endovascular Thrombectomy in Acute Basilar Artery Occlusion with Low PC-ASPECTS: A Nationwide Prospective Registry-Based Study.

OBJECTIVE: We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS). METHODS: We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods. RESULTS: Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2. INTERPRETATION: Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799.

Memristive Switching Mechanism in Colloidal InP/ZnSe/ZnS Quantum Dot-Based Synaptic Devices for Neuromorphic Computing.

Quantum dots (QDs) have garnered a significant amount of attention as promising memristive materials owing to their size-dependent tunable bandgap, structural stability, and high level of applicability for neuromorphic computing. Despite these advantageous properties, the development of QD-based memristors has been hindered by challenges in understanding and adjusting the resistive switching (RS) behavior of QDs. Herein, we propose three types of InP/ZnSe/ZnS QD-based memristors to elucidate the RS mechanism, employing a thin poly(methyl methacrylate) layer. This approach not only allows us to identify which carriers (electron or hole) are trapped within the QD layer but also successfully demonstrates QD-based synaptic devices. Furthermore, to utilize the QD memristor as a synapse, long-term potentiation/depression (LTP/LTD) characteristics are measured, resulting in a low nonlinearity of LTP/LTD at 0.1/1. On the basis of the LTP/LTD characteristics, single-layer perceptron simulations were performed using the Extended Modified National Institute of Standards and Technology, verifying a maximum recognition rate of 91.46%.

Bergamot essential oil improves CUMS-induced depression-like behaviour in rats by protecting the plasticity of hippocampal neurons.

Bergamot essential oil (BEO) is an extract of the bergamot fruit with significant neuroprotective effect. This study was to investigate the effects and the underlying mechanism of BEO in mitigating depression. GC-MS were used to identify its constituents. Antidepressive properties of BEO were evaluated by sucrose preference test (SPT), force swimming test (FST) and open field test (OFT). Nissl staining was used to determine the number of Nissl bodies in hippocampus (HIPP) of rats. Changes in HIPP dendritic length and dendritic spine density were detected by Golgi-Cox staining. Immunohistochemistry and Western blot were used to detect the postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the HIPP of rats. The enzyme-linked immunosorbent assay was used to determine the 5-hydroxytryptamine (5-HT), insulin-like growth factor 1 (IGF-1) and interleukin-1ß (IL-1ß) in the HIPP, serum and cerebrospinal fluid (CSF) of rats. Inhaled BEO significantly improved depressive behaviour in chronic unpredictable mild stress (CUMS) rats. BEO increased Nissl bodies, dendritic length and spine density, PSD-95 and SYP protein in the HIPP. Additionally, BEO upregulated serum 5-HT, serum and CSF IGF-1, while downregulating serum IL-1ß. Collectively, inhaled BEO mitigates depression by protecting the plasticity of hippocampal neurons, hence, providing novel insights into treatment of depression.

Time Window for Induced Hypertension in Acute Small Vessel Occlusive Stroke With Early Neurological Deterioration.

BACKGROUND: Therapeutic-induced hypertension treatment (iHTN) is helpful for alleviating early neurological deterioration (END) in acute small vessel occlusive stroke. We examined the time parameters related to iHTN effectiveness in these patients. METHODS: We retrospectively reviewed patients with acute small vessel occlusive stroke who underwent iHTN for END, defined as an increase of ≥2 points in total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 point in motor items of NIHSS. The primary outcome was an early neurological improvement (ENI; a decrease of ≥2 points in total NIHSS score or ≥1 point in motor items of NIHSS), and the secondary outcome was any neurological improvement (a decrease of ≥1 point in the total NIHSS score). We conducted a multivariable logistic regression analysis, adjusting for demographics, risk factors, baseline clinical status, and intervention-related variables. We also generated a restricted cubic spline curve for the END-to-iHTN time cutoff. RESULTS: Among the 1062 patients with small vessel occlusive stroke screened between 2017 and 2021, 136 patients who received iHTN within 24 hours from END were included. The mean age was 65.1 (±12.0) years, and 61.0% were male. Sixty-five (47.8%) patients showed ENI and 77 (56.6%) patients showed any neurological improvement. END-to-iHTN time was significantly shorter in patients with ENI (150 [49-322] versus 290 [97-545] minutes; P=0.018) or any neurological improvement (150 [50-315] versus 300 [130-573] minutes; P=0.002). A 10-minute increase in the time between END and iHTN decreased the odds of achieving ENI (odds ratio, 0.984 [95% CI, 0.970-0.997]; P=0.019) or any neurological improvement (odds ratio, 0.978 [95% CI, 0.964-0.992]; P=0.002). The restricted cubic spline curve showed that the odds ratio of ENI reached its minimum at ≈3 hours. CONCLUSIONS: Among patients with small vessel occlusive stroke with END, a shorter interval between END and the initiation of iHTN was associated with increased odds of achieving neurological improvement. The efficacy of iHTN may be limited to induction within the first 3 hours of END.

Simultaneous suppression of lignin, tricin and wall-bound phenolic biosynthesis via the expression of monolignol 4-O-methyltransferases in rice.

Grass lignocelluloses feature complex compositions and structures. In addition to the presence of conventional lignin units from monolignols, acylated monolignols and flavonoid tricin also incorporate into lignin polymer; moreover, hydroxycinnamates, particularly ferulate, cross-link arabinoxylan chains with each other and/or with lignin polymers. These structural complexities make grass lignocellulosics difficult to optimize for effective agro-industrial applications. In the present study, we assess the applications of two engineered monolignol 4-O-methyltransferases (MOMTs) in modifying rice lignocellulosic properties. Two MOMTs confer regiospecific para-methylation of monolignols but with different catalytic preferences. The expression of MOMTs in rice resulted in differential but drastic suppression of lignin deposition, showing more than 50% decrease in guaiacyl lignin and up to an 90% reduction in syringyl lignin in transgenic lines. Moreover, the levels of arabinoxylan-bound ferulate were reduced by up to 50%, and the levels of tricin in lignin fraction were also substantially reduced. Concomitantly, up to 11 µmol/g of the methanol-extractable 4-O-methylated ferulic acid and 5-7 µmol/g 4-O-methylated sinapic acid were accumulated in MOMT transgenic lines. Both MOMTs in vitro displayed discernible substrate promiscuity towards a range of phenolics in addition to the dominant substrate monolignols, which partially explains their broad effects on grass phenolic biosynthesis. The cell wall structural and compositional changes resulted in up to 30% increase in saccharification yield of the de-starched rice straw biomass after diluted acid-pretreatment. These results demonstrate an effective strategy to tailor complex grass cell walls to generate improved cellulosic feedstocks for the fermentable sugar-based production of biofuel and bio-chemicals.

Optical design and fabrication of a multi-channel imaging spectrometer for combustion flame monitoring.

We design and construct a broadband integrated multi-channel imaging spectrometer (MCIS) from visible light to near-infrared. This system can directly obtain spectral images that conform to the consistent visual habits of the human eyes through a single exposure of the detector. The genetic algorithm is used to calculate system parameters to minimize pixel waste between spectral channels, achieving nearly 100% utilization of detector pixels. The field stop suppresses stray light in the system. This device is used for imaging an optical-resolution target, an object, and a furnace to verify the basic principles of the system. The results indicate that the system can effectively utilize detectors to monitor high-temperature objects in the visible to near-infrared wavelength range.

Autophagy in dry AMD: A promising therapeutic strategy for retinal pigment epithelial cell damage.

Dry age-related macular degeneration (AMD) is a prevalent clinical condition that leads to permanent damage to central vision and poses a significant threat to patients' visual health. Although the pathogenesis of dry AMD remains unclear, there is consensus on the role of retinal pigment epithelium (RPE) damage. Oxidative stress and chronic inflammation are major contributors to RPE cell damage, and the NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) inflammasome mediates the inflammatory response leading to apoptosis in RPE cells. Furthermore, lipofuscin accumulation results in oxidative stress, NLRP3 activation, and the development of vitelliform lesions, a hallmark of dry AMD, all of which may contribute to RPE dysfunction. The process of autophagy, involving the encapsulation, recognition, and transport of accumulated proteins and dead cells to the lysosome for degradation, is recognized as a significant pathway for cellular self-protection and homeostasis maintenance. Recently, RPE cell autophagy has been discovered to be closely linked to the development of macular degeneration, positioning autophagy as a cutting-edge research area in the realm of dry AMD. In this review, we present an overview of how lipofuscin, oxidative stress, and the NLRP3 inflammasome damage the RPE through their respective causal mechanisms. We summarized the connection between autophagy, oxidative stress, and NLRP3 inflammatory cytokines. Our findings suggest that targeting autophagy improves RPE function and sustains visual health, offering new perspectives for understanding the pathogenesis and clinical management of dry AMD.

Effects of fluorescent protein tdTomato on mouse retina.

Fluorescent proteins (FPs) have been widely used to investigate cellular and molecular interactions and trace biological events in many applications. Some of the FPs have been demonstrated to cause undesirable cellular damage by light-induced ROS production in vivo or in vitro. However, it remains unknown if one of the most popular FPs, tdTomato, has similar effects in neuronal cells. In this study, we discovered that tdTomato expression led to unexpected retinal dysfunction and ultrastructural defects in the transgenic mouse retina. The retinal dysfunction mainly manifested in the reduced photopic electroretinogram (ERG) responses and decreased contrast sensitivity in visual acuity, caused by mitochondrial damages characterized with cellular redistribution, morphological modifications and molecular profiling alterations. Taken together, our findings for the first time demonstrated the retinal dysfunction and ultrastructural defects in the retinas of tdTomato-transgenic mice, calling for a more careful design and interpretation of experiments involved in FPs.

Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

Association between Rapid Ventricular Response and Stroke Outcomes in Atrial Fibrillation-Related Cardiac Embolic Stroke.

INTRODUCTION: Patients with atrial fibrillation-related stroke (AF-stroke) are prone to developing rapid ventricular response (RVR). We investigated whether RVR is associated with initial stroke severity, early neurological deterioration (END) and poor outcome at 3 months. METHODS: We reviewed patients who had AF-stroke between January 2017 and March 2022. RVR was defined as having heart rate >100 beats per minute on initial electrocardiogram. Neurological deficit was evaluated with National Institutes of Health Stroke Scale (NIHSS) score at admission. END was defined as increase of ≥2 in total NIHSS score or ≥1 in motor NIHSS score within first 72 h. Functional outcome was score on modified Rankin Scale at 3 months. Mediation analysis was performed to examine potential causal chain in which initial stroke severity may mediate relationship between RVR and functional outcome. RESULTS: We studied 568 AF-stroke patients, among whom 86 (15.1%) had RVR. Patients with RVR had higher initial NIHSS score (p < 0.001) and poor outcome at 3 months (p = 0.004) than those without RVR. The presence of RVR [adjusted odds ratio (aOR) = 2.13; p = 0.013] was associated with initial stroke severity, but not with END and functional outcome. Otherwise, initial stroke severity [aOR = 1.27; p = <0.001] was significantly associated with functional outcome. Initial stroke severity as a mediator explained 58% of relationship between RVR and poor outcome at 3 months. CONCLUSION: In patients with AF-stroke, RVR was independently associated with initial stroke severity but not with END and functional outcome. Initial stroke severity mediated considerable proportion of association between RVR and functional outcome.

ASH2L upregulation contributes to diabetic endothelial dysfunction in mice through STEAP4-mediated copper uptake.

Endothelial dysfunction is a common complication of diabetes mellitus (DM) and contributes to the high incidence and mortality of cardiovascular and cerebrovascular diseases. Aberrant epigenetic regulation under diabetic conditions, including histone modifications, DNA methylation, and non-coding RNAs (ncRNAs) play key roles in the initiation and progression of diabetic vascular complications. ASH2L, a H3K4me3 regulator, triggers genetic transcription, which is critical for physiological and pathogenic processes. In this study we investigated the role of ASH2L in mediating diabetic endothelial dysfunction. We showed that ASH2L expression was significantly elevated in vascular tissues from diabetic db/db mice and in rat aortic endothelial cells (RAECs) treated with high glucose medium (11 and 22 mM). Knockdown of ASH2L in RAECs markedly inhibited the deteriorating effects of high glucose, characterized by reduced oxidative stress and inflammatory responses. Deletion of endothelial ASH2L in db/db mice by injection of an adeno-associated virus (AAV)-endothelial specific system carrying shRNA against Ash2l (AAV-shAsh2l) restored the impaired endothelium-dependent relaxations, and ameliorated DM-induced vascular dysfunction. We revealed that ASH2L expression activated reductase STEAP4 transcription in vitro and in vivo, which consequently elevated Cu(I) transportation into ECs by the copper transporter CTR1. Excess copper produced by STEAP4-mediated copper uptake triggered oxidative stress and inflammatory responses, resulting in endothelial dysfunction. Our results demonstrate that hyperglycemia triggered ASH2L-STEAP4 axis contributes to diabetic endothelial dysfunction by modulating copper uptake into ECs and highlight the therapeutic potential of blocking the endothelial ASH2L in the pathogenesis of diabetic vascular complications.

Association between renal insufficiency and lesion characteristics of posterior reversible encephalopathy syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized by cerebral blood flow dysregulation and the blood-brain barrier (BBB) disruption. While renal insufficiency has been considered a factor in BBB fragility, the relationship between renal insufficiency and the PRES lesions volume remains unclear. METHODS: This observational study was performed retrospectively. PRES patients were categorized into two groups with renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 on the day of symptom occurrence. Lesion volume was measured using fluid-attenuated inversion recovery (FLAIR) imaging, and the brain was divided into nine regions. The volume of the parietal-occipital-temporal lobe was considered typical, while the other six regions were labeled as atypical. RESULTS: The study included 200 patients, of whom 94 (47%) had renal insufficiency. Patients with renal insufficiency had a larger lesion volume (144.7 ± 125.2 cc) compared to those without renal insufficiency (110.5 ± 93.2 cc; p = 0.032); particularly in the atypical lesions volume (49.2 ± 65.0 vs. 29.2 ± 44.3 cc; p = 0.013). However, there was no difference in the reversibility of the lesions (35.2 ± 67.5 vs. 18.8 ± 33.4 cc; p = 0.129). Multiple regression analysis revealed that decreases in eGFR (ß = -0.34, 95% CI -0.62-0.05, p = 0.020) were positively associated with total lesion volume. CONCLUSION: Our findings suggest that PRES patients with renal insufficiency experience more severe lesion volumes, likely due to the atypical brain regions involvement. The lesions involving atypical regions may have a similar pathophysiology to typical lesions, as the PRES lesions reversibility was found to be similar between individuals with and without renal insufficiency.

Effect of decentration and tilt on the in vitro optical quality of monofocal and trifocal intraocular lenses.

PURPOSE: To evaluate and compare the effect of decentration and tilt on the optical quality of monofocal and trifocal intraocular lenses (IOL). METHODS: Optical quality of a monofocal IOL (AcrySof IQ SN60WF; Alcon Laboratories, Inc., USA) and a trifocal IOL (AcrySof IQ PanOptix; Alcon Laboratories, Inc., USA) was assessed using an in vitro optical bench (OptiSpheric IOL R&D; Trioptics GmbH, Germany). At apertures of 3.0 mm and 4.5 mm, modulation transfer function (MTF) at spatial frequency of 50 lp/mm, MTF curve and the United States Air Force (USAF) resolution test chart of the two IOLs were measured and compared at their focus with different degrees of decentration and tilt. Optical quality at infinity, 60 cm and 40 cm and the through-focus MTF curves were compared when the two IOLs were centered at apertures of 3.0 mm and 4.5 mm. Spectral transmittance of the two IOLs was measured by the UV-visible spectrophotometer (UV 3300 PC; MAPADA, China). RESULTS: The SN60WF and the PanOptix filtered blue light from 400 to 500 nm. Both IOLs at the far focus and the PanOptix at the intermediate focus showed a decrease in optical quality with increasing decentration and tilt. The PanOptix demonstrated enhanced optical quality compared to the previous gradient at the near focus at a decentration range of 0.3-0.7 mm with a 3.0 mm aperture, and 0.5 mm with a 4.5 mm aperture, whereas other conditions exhibited diminished optical quality with increasing decentration and tilt at the focus of both IOLs. When the two IOLs were centered, the SN60WF had better optical quality at infinity, while the PanOptix had better optical quality at 60 cm and 40 cm defocus. The optical quality of the SN60WF exceeded that of the PanOptix at far focus, with a 3 mm aperture decentration up to 0.7 mm and a 4.5 mm aperture decentration up to 0.3 mm; this observation held true for all tilts, irrespective of aperture size. As both decentration and tilt increased, the optical quality of the SN60WF deteriorated more rapidly than that of the PanOptix at the far focal point. CONCLUSIONS: The SN60WF showed a decrease in optical quality with increasing decentration and tilt. Optical quality of the PanOptix at the near focus increased in some decentration conditions and decreased in some conditions, while it showed a decrease at the other focuses with increasing decentration. While tilt only had a negative effect on optical quality. When both IOLs were centered, the PanOptix provided a wider range of vision, while the SN60WF provided better far distance vision. At the far focus, the SN60WF has better resistance to tilt than the PanOptix, but the optical quality degrades more quickly when decentered and tilted.

Electroacupuncture attenuates neuropathic pain via suppressing BIP-IRE-1α-mediated endoplasmic reticulum stress in the anterior cingulate cortex.

Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.

IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease.

Tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) also has an immunological function to suppress T cell activation in inflammatory circumstances, including graft-versus-host disease (GVHD), a fatal complication after allogeneic bone marrow transplantation (allo-BMT). Although the mononuclear cell expression of IDO1 has been associated with improved outcomes in GVHD, the underlying mechanisms remain unclear. Herein, we used IDO-deficient (Ido1-/-) BMT to understand why myeloid IDO limits the severity of GVHD. Hosts with Ido1-/- BM exhibited increased lethality, with enhanced proinflammatory and reduced regulatory T cell responses compared with wild type (WT) allo-BMT controls. Despite the comparable expression of the myeloid-derived suppressor cell (MDSC) mediators, arginase-1, inducible nitric oxide synthase, and interleukin 10, Ido1-/- Gr-1+CD11b+ cells from allo-BMT or in vitro BM culture showed compromised immune-suppressive functions and were skewed toward the Ly6ClowLy6Ghi subset, compared with the WT counterparts. Importantly, Ido1-/-Gr-1+CD11b+ cells exhibited elevated levels of reactive oxygen species (ROS) and neutrophil numbers. These characteristics were rescued by human IDO1 with intact heme-binding and catalytic activities and were recapitulated by the treatment of WT cells with the IDO1 inhibitor L1-methyl tryptophan. ROS scavenging by N-acetylcysteine reverted the Ido1-/-Gr-1+CD11b+ composition and function to an MDSC state, as well as improved the survival of GVHD hosts with Ido1-/- BM. In summary, myeloid-derived IDO1 enhances GVHD survival by regulating ROS levels and limiting the ability of Gr-1+CD11b+ MDSCs to differentiate into proinflammatory neutrophils. Our findings provide a mechanistic insight into the immune-regulatory roles of the metabolic enzyme IDO1.

Boosted Sacrificial-Agent-Free Selective Photoreduction of CO2 to CH3OH by Rhenium Atomically Dispersed on Indium Oxide.

Solar-energy-driven photoreduction of CO2 is promising in alleviating environment burden, but suffers from low efficiency and over-reliance on sacrificial agents. Herein, rhenium (Re) is atomically dispersed in In2O3 to fabricate a 2Re-In2O3 photocatalyst. In sacrificial-agent-free photoreduction of CO2 with H2O, 2Re-In2O3 shows a long-term stable efficiency which is enhanced by 3.5 times than that of pure In2O3 and is also higher than those on Au-In2O3, Ag-In2O3, Cu-In2O3, Ir-In2O3, Ru-In2O3, Rh-In2O3 and Pt-In2O3 photocatalysts. Moreover, carbon-based product of the photoreduction overturns from CO on pure In2O3 to CH3OH on 2Re-In2O3. Re promotes charge separation, H2O dissociation and CO2 activation, thus enhancing photoreduction efficiency of CO2 on 2Re-In2O3. During the photoreduction, CO is a key intermediate. CO prefers to desorption rather than hydrogenation on pure In2O3, as CO binds to pure In2O3 very weakly. Re strengthens the interaction of CO with 2Re-In2O3 by 5.0 times, thus limiting CO desorption but enhancing CO hydrogenation to CH3OH. This could be the origin for photoreduction product overturn from CO on pure In2O3 to CH3OH on 2Re-In2O3. The present work opens a new way to boost sacrificial-agent-free photoreduction of CO2.