Regenerative treatment of ophthalmic diseases with stem cells: Principles, progress, and challenges.

Background: Degenerate eye disorders, such as glaucoma, cataracts and age-related macular degeneration (AMD), are prevalent causes of blindness and visual impairment worldwide. Other eye disorders, including limbal stem cell deficiency (LSCD), dry eye diseases (DED), and retinitis pigmentosa (RP), result in symptoms such as ocular discomfort and impaired visual function, significantly impacting quality of life. Traditional therapies are limited, primarily focus on delaying disease progression, while emerging stem cell therapy directly targets ocular tissues, aiming to restore ocular function by reconstructing ocular tissue. Main text: The utilization of stem cells for the treatment of diverse degenerative ocular diseases is becoming increasingly significant, owing to the regenerative and malleable properties of stem cells and their functional cells. Currently, stem cell therapy for ophthalmopathy involves various cell types, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and retinal progenitor cells (RPCs). In the current article, we will review the current progress regarding the utilization of stem cells for the regeneration of ocular tissue covering key eye tissues from the cornea to the retina. These therapies aim to address the loss of functional cells, restore damaged ocular tissue and or in a paracrine-mediated manner. We also provide an overview of the ocular disorders that stem cell therapy is targeting, as well as the difficulties and opportunities in this field. Conclusions: Stem cells can not only promote tissue regeneration but also release exosomes to mitigate inflammation and provide neuroprotection, making stem cell therapy emerge as a promising approach for treating a wide range of eye disorders through multiple mechanisms.

Fate of Cd during mineral transformation by sulfate-reducing bacteria in clay-size fractions from soils with high geochemical background.

Sulfate-reducing bacteria (SRB) can immobilize heavy metals in soils through biomineralization, and the parent rock and minerals in the soil are critical to the immobilization efficiency of SRB. To date, there is little knowledge about the fate of Cd associated with the parent rocks and minerals of soil during Cd immobilized by SRB. In this study, we created a model system using clay-size fraction of soil and SRB to explore the role of SRB in immobilizing Cd in soils from stratigraphic successions with high geochemical background. In the system, clay-size fractions (particle size < 2 µm) with concentration of Cd (0.24-2.84 mg/kg) were extracted from soils for bacteria inoculation. After SRB reaction for 10 days, the Cd fraction tended to transform into iron-manganese bound. Further, two clay-size fractions, i.e., the non-crystalline iron oxide (Fe-OX) and the crystalline iron oxide (Fe-CBD), were separated by extraction. The reaction of SRB with them verified the transformation of primary iron-bearing minerals into secondary iron-bearing minerals, which contributed to Cd redistribution. This study shows that SRB could exploit the composition and structure of minerals to induce mineral recrystallization, thereby aggravating Cd redistribution and immobilization in clay-size fractions from stratigraphic successions with high geochemical background.

Distribution of potentially toxic elements in soils and sediments in Pearl River Delta, China: Natural versus anthropogenic source discrimination.

Although anthropogenic contamination has been regarded as the most important source of potentially toxic elements (PTEs) in soils of large river delta plains, the extent to which human activities affect PTEs in soils is worth exploring. This study used high density geochemical data to distinguish source patterns of PTEs in soils of the Pearl River Delta Economic Zone, a large industrialized and urbanized area in China. Enrichment factor, discriminant analysis, principal components analysis, cumulative distribution function, and positive matrix factorization were used to identify sources of PTEs in soils. The results indicated that parent material was the most significant factor affecting geochemical characteristics of PTEs in soils. Median concentrations of Cd, Cr, Cu, Hg, Pb, and Zn were 0.400, 88.5, 40.5, 0.143, 43.0, and 116.0 mg/kg for stream sediments, 0.333, 75.7, 39.0, 0.121, 42.6, and 98.5 mg/kg for deep soils, and 0.365, 74.0, 45.1, 0.143, 44.6, and 119.5 mg/kg for surface soils, respectively, all of which exceed relevant reference standards. Compared with stream sediments and deep soils, surface soils exhibit substantial concentrations of PTEs. Chemical weathering and erosion of parent materials distributed in the Pearl River Delta were the main sources of PTEs in soils. Diffuse contamination and many small local contamination sources distributed throughout the study area were the most significant anthropogenic sources of PTEs in surface soils. Intensive human activities failed to change the soil geochemical characteristics derived from the parent material at the regional scale. However, it could induce non-point source pollution and local severe PTEs pollution in surface soils.

Application of expanding bilateral sphenoid sinus plasty in the treatment of sphenoid sinus diseases.

Expanding bilateral sphenoid sinus plasty is an essential technique for the treatment of sphenoid sinus diseases, such as refractory sphenoid sinusitis, sphenoid sinus cyst, fungal sphenoid sinusitis, sphenoid sinus carcinoma and sphenoid sinus chordoma. The present study evaluated the potential application of expanding bilateral sphenoid sinus plasty in the treatment of sphenoid sinus diseases. A retrospective medical record review of 42 patients treated with the expanding bilateral sphenoid sinus plasty from December 2012 to December 2018 was performed in a tertiary-care university hospital. A follow-up of the surgical effects and complications was performed. Of the 42 patients, the symptoms were relieved after operation in all except preoperative hyposmia in 2 and impaired vision in one with no obvious improvement. No complications such as nasal bleeding, olfactory hypofunction and perforation of nasal septum occurred. Follow-up data revealed good mucosal epithelization in all patients within a mean time of 8.6 weeks. Endoscopic sinus reexamination demonstrated that the sphenoid sinus orifice was well opened, and no cases of sphenoid sinus orifice closure were observed. Expanding bilateral sphenoid sinus plasty, with advantages of clearly exposed surgical field, full opening of the sinus cavity, high surgical safety, short epithelialization time and intuitionistic postoperative follow-up, demonstrated great promise for greater use in the treatment of sphenoid sinus diseases in the future.

USP7 represses lineage differentiation genes in mouse embryonic stem cells by both catalytic and noncatalytic activities.

USP7, a ubiquitin-specific peptidase (USP), plays an important role in many cellular processes through its catalytic deubiquitination of various substrates. However, its nuclear function that shapes the transcriptional network in mouse embryonic stem cells (mESCs) remains poorly understood. We report that USP7 maintains mESC identity through both catalytic activity-dependent and -independent repression of lineage differentiation genes. Usp7 depletion attenuates SOX2 levels and derepresses lineage differentiation genes thereby compromising mESC pluripotency. Mechanistically, USP7 deubiquitinates and stabilizes SOX2 to repress mesoendodermal (ME) lineage genes. Moreover, USP7 assembles into RYBP-variant Polycomb repressive complex 1 and contributes to Polycomb chromatin-mediated repression of ME lineage genes in a catalytic activity-dependent manner. USP7 deficiency in its deubiquitination function is able to maintain RYBP binding to chromatin for repressing primitive endoderm-associated genes. Our study demonstrates that USP7 harbors both catalytic and noncatalytic activities to repress different lineage differentiation genes, thereby revealing a previously unrecognized role in controlling gene expression for maintaining mESC identity.

Environmental implication of geochemical record in the Arctic Ny-Ålesund glacial sediment, Svalbard (Norway).

Glacial sediments as an important end member of the global dust system, could indicate changes in global climate, aerosols sources, ocean elements, and productivity. With global warming, ice caps shrinking and glaciers retreat at high latitudes have attracted concern. To understand the response of glacier to environment and climate in modern high latitude ice-marginal environments, this paper investigated glacial sediments in the Ny-Ålesund region of the Arctic and clarified the response of polar environmental to global changes through geochemical characteristics of glacial sediments. The results showed that: 1) main factors affecting the elements distribution of the Ny-Ålesund glacial sediments were thought as soil formation, bedrock and weathering, and biological activity; 2) variations of SiO2/Al2O3 and SiO2/Al2O3 + Fe2O3, indicating low weathering of the soil. The ratio of Na2O/K2O indicating a weak chemical weathering, was negatively correlated to the CIA. With the average CIA of Ny-Ålesund glacial sediments for main minerals of quartz, feldspar, and muscovite as well as dolomite and calcite 50.13, which implied glacial sediments at the early stage of chemical weathering and depletion of Ca and Na; 3) the separating effect of stones and soils by stone circle formation due to thermal conductivity and frost heave makes sediments in stone circle have lower chemical weathering with only two main minerals, albite and quartz; 4) changes of carbonate content in sediments with glacier front retreating in different period implied that weathering rate of calcite averagely reached an estimate of 0.0792%wt/year in glacier A. The succession of vegetation made biological weathering become an important driving force for carbonate leaching from glacial sediments. These results and data provide scientifically significant archive for future global change studies.

Zn isotope signatures in soil FeMn nodules with karst high geochemical background.

Zn isotope has the potential to be used as an environmental tracer, due to its role in fingerprinting specific sources and processes. However, few studies have focused on Zn isotope system in terrestrial ferromanganese (FeMn) nodules, which is important on understanding the behaviors of Zn in soils. In this study, we analyse the isotopic composition in soil FeMn nodules and surrounding materials from a typical karst region in Guangxi Province, southwestern China and use advanced synchrotron-based methods to characterize Zn speciation. The Zn isotope compositions of the FeMn nodules range from 0.09 to 0.66 ‰, with an average value of 0.24 ‰. Pb isotope fingerprinting reveals that the major material sources contributing to the FeMn nodules are the surrounding soil (δ66Zn: ~0.36 ‰) and partly weathered carbonate bedrock (δ66Zn: ~0.58 ‰), which contain heavier Zn isotopes than the nodules. Synchrotron-based X-ray fluorescence (µ-SXRF) shows that Zn is well correlated with both Fe and Mn. X-ray absorption near edge spectroscopy (XANES) measurements reveal that Zn is associated with both goethite and birnessite phases, with goethite-sorbed Zn accounting for ~76 % of the total Zn and birnessite-sorbed Zn accounting for ~24 %. By combining these new results, the isotopically light Zn in the FeMn nodules compared to their sources can be explained by equilibrium sorption of Zn on goethite and birnessite, during which light Zn is preferentially sorbed. Our study provides important new data on Zn isotope compositions in terrestrial soil FeMn nodules and constrains associated mechanisms, and have implications for using Zn isotopes as environmental tracers.

The regulatory mechanism of HSP70 in endoplasmic reticulum stress in pepsin-treated laryngeal epithelium cells and laryngeal cancer cells.

BACKGROUNDS: Excessive pepsin can damage both normal laryngeal epithelial cells and laryngeal cancer (LC) cells. Heat shock protein 70 (HSP70) is closely related to pepsin. In this paper, we will explore the different significance of the regulatory role of HSP70 in endoplasmic reticulum stress (ERS) level in pepsin-treated laryngeal epithelial cells and LC cells. METHODS: In cell experiments, laryngeal epithelial cells and LC cells were selected and induced by different concentrations of pepsin. Cell activity was detected by CCK8, cell apoptosis was detected by flow cytometry, and autophagy was detected by autophagy detection kit. The expression of ER)-related proteins was detected by immunofluorescence (IF) and Western blot. Cell transfection was used to inhibit HSP70 expression in both cells, and ERS, apoptosis, and autophagy were measured using related techniques. In animal experiments, a mouse model bearing LC was established. TUNEL assay detected apoptosis, autophagy kit detected autophagy, and ER-related protein expression was detected by Western blot. RESULTS: HSP70 was increased in pepsin-stimulated laryngeal epithelial cells and LC cells, thereby inhibiting ER and ER-induced apoptosis and autophagy. Inhibition of HSP70 reduced the expression of glucose regulated protein 78 (GRP78) in pepsin-stimulated laryngeal epithelial cells and LC cells, and only inhibited downstream apoptosis-related pathways in laryngeal epithelial cells rather than in LC cells. Inhibition of HSP70 and ER could significantly promote apoptosis and inhibit tumor growth in the absence of pepsin stimulation in vivo. CONCLUSION: ER level regulated by HSP70 had different significance in laryngeal epithelial cells and LC cells treated with pepsin.

Association between trace metals exposure and hearing loss.

Background: Trace metals have side-effect on human health. The association between trace metals exposure and hearing loss remains unclear. Methods: A total of 8,128 participants were exacted for analysis of association between trace metals and hearing loss from the database of the National Health and Nutrition Examination Survey (NHANES) (2013-2018). Multivariable logistic regression and restricted cubic spline models were used to examine the association between trace metals and hearing loss. Results: Participants with hearing loss had a higher level of lead, cadmium, molybdenum, tin, thallium, and tungsten (all p < 0.05). After adjusting for confounders, compared with the reference of the lowest quartile, the ORs with 95%CIs for hearing loss across quartiles were 1.14 (0.86, 1.51), 1.49 (1.12, 1.98), 1.32 (0.97, 1.80) for cobalt, and 1.35 (0.98, 1.87), 1.58 (1.15, 2.16), 1.75 (1.28, 2.40) for tin. Individuals with the level of cobalt at third quartile had 49% higher risks of hearing loss than those at lowest quartile. And participants with highest quartile of tin had 1.75-folds risks of hearing loss than those with lowest quartile of tin. There were increasing trends in risks of hearing loss with a raised level of thallium (p for trend <0.05). Restricted cubic spline regression analysis indicated that there was a nonlinear association between hearing loss and the levels of tin (p for nonlinearity = 0.021). Subgroup analysis showed that individuals of female, without hypertension and diabetes, and with a higher level of low-density lipoprotein cholesterol had modified effects on the associations between hearing loss and exposure to tin. Conclusions: Our study indicated that exposure to cobalt and tin were significantly associated with hearing loss.

A process-based model for describing redox kinetics of Cr(VI) in natural sediments containing variable reactive Fe(II) species.

Sediment-associated Fe(II) is a critical reductant for immobilizing groundwater contaminants, such as Cr(VI). The reduction reactivity of sediment-associated Fe(II) is dependent on its binding environment and influenced by the biogeochemical transformation of other elements (i.e., C, N and Mn), challenging the description and prediction of the reactivity of Fe(II) in natural sediments. Here, anaerobic batch experiments were conducted to study the variation in sediment-associated Fe(II) reactivity toward Cr(VI) in natural sediments collected from an intensive agricultural area located in Guangxi, China, where nitrate is a common surface water and groundwater contaminant. Then, a process-based model was developed to describe the coupled biogeochemical processes of C, N, Mn, Fe, and Cr. In the process-based model, Cr(VI) reduction by sediment-associated Fe(II) was described using a previously developed multirate model, which categorized the reactive Fe(II) into three fractions based on their extractabilities in sodium acetate and HCl solutions. The experimental results showed that Fe(II) generation was inhibited by NO3- and/or NO2-. After NO3- and NO2- were exhausted, the Fe(II) content and its reduction rate toward Cr(VI) increased rapidly. As the Fe(II) content increased, the three reactive Fe(II) fractions exhibited approximately linear correlations with aqueous Fe(II) concentrations ( [Formula: see text] ), which was probably driven by sorptive equilibrium and redox equilibrium between aqueous and solid phases. The model results indicated that the reaction rate constants of the three Fe(II) fractions (kn) significantly increased with incubation time, and log(kn) correlated well with [Formula: see text] [ [Formula: see text] , [Formula: see text] and [Formula: see text] ]. The numerical model developed in this study provides an applicable method to describe and predict Cr(VI) removal from groundwater under dynamic redox conditions.

Nickel bioaccessibility in soils with high geochemical background and anthropogenic contamination.

Abnormally high concentrations of metals including nickel (Ni) in soils result from high geochemical background (HB) or anthropogenic contamination (AC). Metal bioaccessibility in AC-soils has been extensively explored, but studies in HB-soils are limited. This study examined the Ni bioaccessibility in basalt and black shale derived HB-soils, with AC-soils and soils without contamination (CT) being used for comparison. Although HB- and AC-soils had similar Ni levels (123 ± 43.0 vs 155 ± 84.7 mg kg-1), their Ni bioaccessibility based on the gastric phase of the Solubility Bioaccessibility Research Consortium (SBRC) in vitro assay was different. Nickel bioaccessibility in HB-soils was 6.42 ± 3.78%, 2-times lower than the CT-soils (12.0 ± 9.71%) and 6-times lower than that in AC-soils (42.6 ± 16.3%). Based on the sequential extraction, a much higher residual Ni fractionation in HB-soils than that in CT- and AC-soils was observed (81.9 ± 9.52% vs 68.6 ± 9.46% and 38.7 ± 16.0%). Further, correlation analysis indicate that the available Ni (exchangeable + carbonate-bound + Fe/Mn hydroxide-bound) was highly correlated with Ni bioaccessibility, which was also related to the organic carbon content in soils. The difference in co-localization between Ni and other elements (Fe, Mn and Ca) from high-resolution NanoSIMS analysis provided additional explanation for Ni bioaccessibility. In short, based on the large difference in Ni bioaccessibility in geochemical background and anthropogenic contaminated soils, it is important to base contamination sources for proper risk assessment of Ni-contaminated soils.

Molecular scale assessment of defluoridation of coal-mining wastewater by calcined Mg/Al layered double hydroxide using 19F solid-state NMR, XPS, and HRTEM.

Calcination is an effective way to improve the F- adsorption capacity of layered double hydroxide (LDH) materials, however, a molecular scale understanding of the enhanced defluoridation capability of calcined LDHs (CLDH) is lacking. This study investigated the mechanisms of F- adsorption by CLDH using 19F solid-state NMR, X-ray photoelectron spectroscopy (XPS), and high-resolution TEM. Under calcination process, LDH underwent three periods: surface dehydration below 200 °C, structural dehydroxylation at 200-400 °C, and release of interlayer carbonate groups above 400 °C. Additionally, XPS and XRD characterization showed that CLDH could not recover to the original structural symmetry even after rehydration and reconstitution. The F- affinity was greatly enhanced for the calcined LDH, especially at high pH. At pH 10, the adsorption capacity could reach 22.0 mg F-/g for CLDH (500 °C calcined), about 6 times larger than that of LDH. The XRD analyses revealed that the F-adsorbed CLDH had a poorer crystalline degree as the calcination temperature increased, consistent with the TEM observation of abundant defects and Mg/Al oxides on the CLDH sheets. 19F solid-state NMR spectra of the CLDH after F- adsorption showed that the formation of surface Al-F is the predominant F- adsorption mode at pH 7, whereas the Mg-F local coordination mode is the pronounced F- adsorption mechanism under alkaline conditions (pH 10). The present study provided a comprehensive understanding of CLDH in F- adsorption and suggested that calcination is a promising treatment for promoting the efficacy of polluted anion scavenging.

Epigenetic network of EZH2/SFRP1/Wnt in the epithelial-mesenchymal transition of laryngeal carcinoma cells.

Enhancer of Zeste Homologue 2 (EZH2) as a histone methyltransferase epigenetically regulates laryngeal carcinoma (LGC) progression. The present study sought to explore the role and mechanism of EZH2 in the epithelial-mesenchymal transition (EMT) of LGC cells. Expressions of EZH2, secreted frizzled-related protein 1 (SFRP1), and trimethylation of lysine 27 on histone H3 (H3K27me3) in LGC tissues or cells were detected via reverse transcription quantitative polymerase chain reaction (qRT-PCR) and western blotting. Upon transfection of si-EZH2, si-SFRP1, oe-SFRP1, or H3K27me3 upregulation, cell viability was assessed via cell counting kit-8, protein levels of E-cadherin, N-cadherin, ß-catenin, c-Myc, and Cyclin D1 were determined via western blotting, and Vimentin expression was determined via immunofluorescence. The enrichment level of H3K27me3 in the SFRP1 promoter was measured via chromatin immunoprecipitation-PCR. EZH2 was highly expressed in LGC tissues and cells. Silencing EZH2 repelled the EMT of LGC cells. Mechanically, EZH2 upregulated H3K27me3 in the SFRP1 promotor to inhibit SFRP1 expression, and SFRP1 overexpression inactivated the Wnt pathway. H3K27me3 upregulation or SFRP1 downregulation reversed the inhibition of silencing EZH2 in the EMT of LGC cells. Overall, EZH2 upregulated H3K27me3 in the SFRP1 promoter to inhibit SFRP1 expression and activate the Wnt pathway, thereby facilitating the EMT of LGC cells.

Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells.

Chemo and siRNA synergic treatments for tumors is a promising new therapeutic trend. Selenocystine, a selenium analog of cysteine, has been considered a potential antitumor agent due to its redox perturbing role. In this study, we developed a nanocarrier for siRNA based on a selenocystine analog engineered polyetherimide and achieved traceable siRNA delivery and the synergic killing of tumor cells. Notably, we applied the label-free Schiff base fluorescence mechanism, which enabled us to trace the siRNA delivery and to monitor the selenocystine analogs' local performance. A novel selenocystine-derived fluorescent Schiff base linker was used to crosslink the polyetherimide, thereby generating a traceable siRNA delivery vehicle with green fluorescence. Moreover, we found that this compound induced tumor cells to undergo senescence. Together with the delivery of a siRNA targeting the anti-apoptotic BCL-xl/w genes in senescent cells, it achieved a synergistic inhibition function by inducing both senescence and apoptosis of tumor cells. Therefore, this study provides insights into the development of label-free probes, prodrugs, and materials towards the synergic strategies for cancer therapy.

Transferability of heavy metal(loid)s from karstic soils with high geochemical background to peanut seeds.

Globally distributed karstic soils are characterized by the high accumulation of heavy metal(loid)s, such as Cd. Biogeochemistries and transferability of metal(loid)s in such soils are notably different from that in soils of anthropogenic pollution as evidenced by increasing studies about rice and maize. To solve the question about metal(loid) background and transferability in the system of karstic soils and crops with underground fruits, we designedly collected 246 paired soil-peanut seed samples in a world-famous karstic region in Southwestern China covering an area of 98,700 km2. The concentrations of eight regulatory metal(loid)s (Cd, As, Cr, Cu, Hg, Ni, Pb, and Zn) in soil samples exceeded current standards to different degrees, demonstrating a typical high background. However, the transferability of metal(loid)s from soils to peanut seeds is quite low, resulting in a low exceedance rate of metal(loid)s (Cd, 12.2% and Pb, 1.2%) in seeds ("seed metal(loid)s"), in accordance with the results that metal(loid)s in soils mostly distributed in the inert/residual fractions. Based on the distinct response characteristics of peanut seed metal(loid)s to soil status from rice/maize grain metals, a model was further developed for effectively predicting the concentration of Cd in peanut seeds. Collectively, this study provides a basis for the assessment of soil environmental quality and safety zoning of upland field in karst areas.

Tracing and quantifying the sources of heavy metals in the upper and middle reaches of the Pearl River Basin: New insights from Sr-Nd-Pb multi-isotopic systems.

A method based on Sr, Nd and Pb multi-isotopic systems indicates that the different rock types (carbonate rock, basalt and black rock series) and sulfide deposits exposed in the Pearl River Basin show markedly different Sr, Nd and Pb isotopic characteristics. By establishing the mass balance equations of heavy metal content and isotope ratios, we use the inverse method to obtain the contribution that natural weathering of carbonate rocks, basalts and black rock series as well as the mining of sulfide deposits have on heavy metal content in riverbed sediments in the Pearl River Basin. Even though carbonate rocks constitute more than 60% of the exposed area in the upper reaches of the Pearl River Basin, this lithology only contributes 9% of the heavy metal content in sediments due to the relatively low content of heavy metals found in this rock type. Basalt weathering on average contributes 64% of the Cr content and 42% of the Ni content found in the sediments, while 53% of the Cd content is derived from the weathering of the black rock series. The negative impact mining has on this environment cannot be ignored as it is the most important source of As (71%) and Pb (60%) in all samples. This is especially the case in the Diaojiang River Basin, where sulfide mining activities still contribute more than 90% of the content of Zn, Pb, Cd and As within the sediments even though many mining sites have been closed since 2000.

Neuronal intranuclear inclusion disease tremor-dominant subtype: A mimicker of essential tremor.

BACKGROUND AND PURPOSE: The GGC repeat expansion in the NOTCH2NLC gene has been identified as the genetic cause of neuronal intranuclear inclusion disease (NIID). Recently, this repeat expansion was also reported to be associated with essential tremor (ET). However, some patients with this repeat expansion, initially diagnosed with ET, were eventually diagnosed with NIID. Therefore, controversy remains regarding the clinical diagnosis of these expansion-positive patients presenting with tremor-dominant symptoms. This study aimed to clarify the clinical phenotype in tremor-dominant patients who have the GGC repeat expansion in the NOTCH2NLC gene. METHODS: We screened for pathogenic GGC repeat expansions in 602 patients initially diagnosed with ET and systematically re-evaluated the clinical features of the expansion-positive probands and their family members. RESULTS: Pathogenic GGC repeat expansion in the NOTCH2NLC gene was detected in 10 probands (1.66%). Seven of these probands were re-evaluated and found to have systemic areflexia, cognitive impairment, and abnormal nerve conduction, which prompted a change of diagnosis from ET to NIID. Three of the probands had typical hyperintensity in the corticomedullary junction on diffusion-weighted imaging. Intranuclear inclusions were detected in all four probands who underwent skin biopsy. CONCLUSIONS: The NIID tremor-dominant subtype can be easily misdiagnosed as ET. We should take NIID into account for differential diagnosis of ET. Systemic areflexia could be an important clinical clue suggesting that cranial magnetic resonance imaging examination, or even further genetic testing and skin biopsy examination, should be used to confirm the diagnosis of NIID.

Carbonate bedrock control of soil Cd background in Southwestern China: Its extent and influencing factors based on spatial analysis.

Previous studies have found that Cadmium (Cd) may be condensed during the processes of the weathering and soil formation over carbonate bedrock, which is a typical phenomenon in the southwest region of China. However, the extent of the high value background and the geographical factors influencing its spatial distribution are still unknown. This study collected data from the Multi-Purpose Regional Geochemical Survey (MPRGS) and the Regional Geochemistry-National Reconnaissance Program (RGNR) to investigate the extent and its controlling factors based on spatial analysis. It was found that the RGNR is an ideal data source for regional Cd background studies. Spatially, the high Cd area (Cd > 1.5 m/kg with reference of the GB15618-2018 soil environmental quality in China, 68.9 × 103 km2) coincide well with the carbonate distribution. In the total area (68.9 × 103 km2) with high Cd concentration, 89.8% is related to carbonates. The composition of parent rock, climate conditions, and landuse are controlling factors of the enrichment. The high Cd background effect of limestone is higher than that of dolomite and their effects decease with increasing detritus component they contain. Warm and humid climate in forest land helps to enrich Cd during weathering. Soil Cd concentration related to carbonate background can be predicted by major element concentrations, which is useful for differentiating Cd background from human pollution in the future soil pollution monitoring. Modelling by artificial neural network (ANN) is recommended rather than tradition multiple linear methods (LM) as the latter may have the effect of collinearity.

Enhanced Fluoride Uptake by Layered Double Hydroxides under Alkaline Conditions: Solid-State NMR Evidence of the Role of Surface >MgOH Sites.

Layered double hydroxides (LDHs) are potential low-cost filter materials for use in fluoride removal from drinking water, but molecular-scale defluoridation mechanisms are lacking. In this research, we employed 19F solid-state NMR spectroscopy to identify fluoride sorption products on 2:1 MgAl LDH and to reveal the relationship between fluoride sorption and the LDH structure. A set of six 19F NMR peaks centered at -140, -148, -156, -163, -176, and -183 ppm was resolved. Combining quantum chemical calculations based on density function theory (DFT) and 19F{27Al} transfer of populations in double resonance (TRAPDOR) analysis, we could assign the peaks at -140, -148, -156, and -163 ppm to Al-F (F coordinated to surface Al) and those at -176 and -183 ppm to Mg-F (F coordinated to surface Mg only). Interestingly, the spectroscopic data reveal that the formation of Al-F is the predominant mode of F- sorption at low pH, whereas the formation of Mg-F is predominant at high pH (or a higher Mg/Al ratio). This finding supports the fact that the F- uptake of 2:1 MgAl LDH was nearly six times that of activated alumina at pH 9. Overall, we explicitly revealed the different roles of the surface >MgOH and >AlOH sites of LDHs in defluoridation, which explained why the use of classic activated alumina for defluoridation is limited at high pH. The findings from this research may also provide new insights into material screening for potential filters for F- removal under alkaline conditions.

Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells.

Congenital cataracts are the leading cause of childhood blindness. To date, surgical removal of cataracts is the only established treatment, but surgery is associated with multiple complications, which often lead to visual impairment. Therefore, mechanistic studies and drug-candidate screening have been intrigued by the aims of developing novel therapeutic strategies. However, these studies have been hampered by a lack of an appropriate human-disease model of congenital cataracts. Herein, we report the establishment of a human congenital cataract in vitro model through differentiation of patient-specific induced pluripotent stem cells (iPSCs) into regenerated lenses. The regenerated lenses derived from patient-specific iPSCs with known causative mutations of congenital cataracts (CRYBB2 [p. P24T] and CRYGD [p. Q155X]) showed obvious opacification that closely resembled that seen in patients' cataracts in terms of opacification severity and disease course accordingly, as compared with lentoid bodies (LBs) derived from healthy individuals. Increased protein aggregation and decreased protein solubility corresponding to the patients' cataract severity were observed in the patient-specific LBs and were attenuated by lanosterol treatment. Taken together, the in vitro model described herein, which recapitulates patient-specific clinical manifestations of congenital cataracts and protein aggregation in patient-specific LBs, provides a robust system for research on the pathological mechanisms of cataracts and screening of drug candidates for cataract treatment.