Preclinical Studies of Gene Replacement Therapy for CDKL5 Deficiency Disorder.

Cyclin dependent kinase-like 5 (CDKL5) Deficiency Disorder (CDD) is a rare neurodevelopmental disorder caused by a mutation in the X-linked CDKL5 gene. CDKL5 is a serine/threonine kinase that is critical for axon outgrowth, dendritic morphogenesis, as well as synapse formation, maturation, and maintenance. This disorder is characterized by early-onset epilepsy, hypotonia, and failure to reach cognitive and motor developmental milestones. Because the disease is monogenic, delivery of the CDKL5 gene to the brain of patients should provide clinical benefit. To this end, we designed a gene therapy vector, adeno-associated virus (AAV)9.Syn.hCDKL5, in which human CDKL5 gene expression is driven by the synapsin promoter. In biodistribution studies conducted in mice, intracerebroventricular (ICV) injection resulted in broader, more optimal biodistribution than did intracisterna magna (ICM) delivery. AAV9.Syn.hCDKL5 treatment increased phosphorylation of EB2, a bona fide CDKL5 substrate, demonstrating biological activity in vivo. Our data provides proof-of-concept that ICV delivery of AAV9.Syn.hCDKL5 to neonatal male Cdkl5 knockout mice reduces pathology and reduces aberrant behavior. Functional improvements were seen at doses of 3e11 to 5e11 vector genomes (vg)/g brain, which resulted in transfection of ≥50% of the neurons. Functional improvements were not seen at lower doses suggesting a requirement for broad distribution for efficacy.

Comprehensive assessment of refined greenhouse gas emissions from China's livestock sector.

Livestock and poultry products are an essential human food source. However, the rapid development of the livestock sector (LS) has caused it to become a significant source of greenhouse gas (GHG) emissions. Consequently, investigating the spatio-temporal characteristics and evolution of GHG emissions is crucial to facilitate the green development of the LS and achieve "peak carbon and carbon neutrality". This study combined life cycle assessment (LCA) with the IPCC Tier II method to construct a novel GHG emissions inventory. The GHG emissions of 31 provinces in China from 2000 to 2021 were calculated, and their spatio-temporal characteristics were revealed. Then, the stochastic impacts by regression on population, affluence, and technology (STIRPAT) model was used to identify the main driving factors of GHG emissions in six regions of China and explore the emission reduction potential. The results showed that GHG emissions increased and then decreased from 2000 to 2021, following a gradual and steady trend. The peak of 628.55 Mt CO2-eq was reached in 2006. The main GHG-producing segments were enteric fermentation, slaughtering and processing, and manure management, accounting for 45.39 %, 26.34 %, and 23.08 % of total GHG emissions, respectively. Overall, the center of gravity of GHG emissions in China migrated northward, with spatial aggregation observed since 2016. The high emission intensity regions were mainly located west of the "Hu Huanyong line". Economic efficiency and emissions intensity were the main drivers of GHG emissions. Under the baseline scenario, GHG emissions are not projected to peak until 2050. Therefore, urgent action is needed to promote the low-carbon green development of the LS in China. The results can serve as scientific references for the macro-prevention and control of GHG emissions, aiding strategic decision-making. Additionally, they can provide new ideas for GHG accounting in China and other countries around the world.

The influence of the prolactin/vasoinhibin axis on post-stroke lesion volume, astrogliosis, and survival.

Ischemic stroke is a significant global health issue, ranking fifth among all causes of death and a leading cause of serious long-term disability. Ischemic stroke leads to severe outcomes, including permanent brain damage and neuronal dysfunction. Therefore, decreasing and preventing neuronal injuries caused by stroke has been the focus of therapeutic research. In recent years, many studies have shown that fluctuations in hormonal levels influence the prognosis of ischemic stroke. Thus, it is relevant to understand the role of hormones in the pathophysiological mechanisms of ischemic stroke for preventing and treating this health issue. Here, we investigate the contribution of the prolactin/vasoinhibin axis, an endocrine system regulating blood vessel growth, immune processes, and neuronal survival, to the pathophysiology of ischemic stroke. Male mice with brain overexpression of prolactin or vasoinhibin by adeno-associated virus (AAV) intracerebroventricular injection or lacking the prolactin receptor (Prlr-/-) were exposed to transient middle cerebral artery occlusion (tMCAO) for 45 min followed by 48 h of reperfusion. Overexpression of vasoinhibin or the absence of the prolactin receptor led to an increased lesion volume and decreased survival rates in mice following tMCAO, whereas overexpression of prolactin had no effect. In addition, astrocytic distribution in the penumbra was altered, glial fibrillary acidic protein and S100b mRNA expressions were reduced, and interleukin-6 mRNA expression increased in the ischemic hemisphere of mice overexpressing vasoinhibin. Of note, prolactin receptor-null mice (Prlr-/-) showed a marked increase in serum vasoinhibin levels. Furthermore, vasoinhibin decreased astrocyte numbers in mixed hippocampal neuron-glia cultures. These observations suggest that increased vasoinhibin levels may hinder astrocytes' protective reactivity. Overall, this study suggests the involvement of the prolactin/vasoinhibin axis in the pathophysiology of ischemic stroke-induced brain injury and provides insights into the impact of its dysregulation on astrocyte reactivity and lesion size. Understanding these mechanisms could help develop therapeutic interventions in ischemic stroke and other related neurological disorders.

Efficient Selective Adsorption of Rubidium and Cesium from Practical Brine Using a Metal-Organic Framework-Based Magnetic Adsorbent.

Rubidium (Rb) and cesium (Cs) have important applications in highly technical fields. Salt lakes contain huge reserves of Rb and Cs with industrial significance, which can be utilized after extraction. In this study, a composite magnetic adsorbent (Fe3O4@ZIF-8@AMP, AMP = ammonium phosphomolybdate) was prepared and its adsorption properties for Rb+ and Cs+ were studied in simulated and practical brine. The structure of the adsorbent was characterized by SEM, XRD, N2 adsorption-desorption, FT-IR, and vibrating sample magnetometer (VSM). The adsorbent had good adsorption affinity for Rb+ and Cs+. The Langmuir model and pseudo-second-order dynamics described the adsorbing isotherm and kinetic dates, respectively. The adsorption capacity and adsorption rate of Fe3O4@ZIF-8@AMP were increased by 1.86- and 2.5-fold compared with those of powdered crystal AMP, owing to the large specific surface area and high dispersibility of the adsorbent in the solution. The adsorbent was rapidly separated from the solution within 17 s using an applied magnetic field owing to the good magnetic properties. The composite adsorbent selectively adsorbed Rb+ and Cs+ from the practical brine even in the presence of a large number of coexisting ions. The promising adsorbent can be used to extract Rb+ and Cs+ from aqueous solutions.

Tumor lymphangiogenesis index reveals the immune landscape and immunotherapy response in lung adenocarcinoma.

Background: Lymphangiogenesis (LYM) has an important role in tumor progression and is strongly associated with tumor metastasis. However, the clinical application of LYM has not progressed as expected. The potential value of LYM needs to be further developed in lung adenocarcinoma (LUAD) patients. Methods: The Sequencing data and clinical characteristics of LUAD patients were downloaded from The Cancer Genome Atlas and GEO databases. Multiple machine learning algorithms were used to screen feature genes and develop the LYM index. Immune cell infiltration, immune checkpoint expression, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and drug sensitivity analysis were used to explore the correlation of LYM index with immune profile and anti-tumor therapy. Results: We screened four lymphangiogenic feature genes (PECAM1, TIMP1, CXCL5 and PDGFB) to construct LYM index based on multiple machine learning algorithms. We divided LUAD patients into the high LYM index group and the low LYM index group based on the median LYM index. LYM index is a risk factor for the prognosis of LUAD patients. In addition, there was a significant difference in immune profile between high LYM index and low LYM index groups. LUAD patients in the low LYM index group seemed to benefit more from immunotherapy based on the results of TIDE algorithm. Conclusion: Overall, we confirmed that the LYM index is a prognostic risk factor and a valuable predictor of immunotherapy response in LUAD patients, which provides new evidence for the potential application of LYM.

Basic magnesium sulfate@TiO2 composite for efficient adsorption and photocatalytic degradation of 4-dodecylmorpholine in brine.

More than 70% of the potash fertilizer globally is produced by the froth flotation process, in which 4-dodecylmorpholine (DMP) serves as a reverse flotation agent. As the potash fertilizer production rapidly rises, the increased DMP levels in discharged brine pose a threat to the production of high-value chemicals. In this paper, composite particles of basic magnesium sulfate@TiO2 (BMS@TiO2) were prepared using a simple and mild loading method. These particles were utilized for the adsorption and photocatalytic degradation of DMP in brine. Compared with normal powdered materials, the granular BMS@TiO2 in this study can be easily separated from liquid, and the degradation intermediates will not enter the brine without causing secondary pollution. BMS@TiO2 consists of 5·1·7 phase (5Mg(OH)2·MgSO4·7H2O) whisker clusters embedding 2.3% TiO2. The adsorption equilibrium of DMP on BMS@TiO2 particles was achieved through hydrogen bonding and pore interception with the adsorption capacity of approximately 5 mg g-1 after 6 h. The photodegradation efficiency of DMP adsorbed on BMS@TiO2 reached about 92% within 16 h, which is compared with that of pure TiO2 nanoparticles. Additionally, excellent stability and recyclability of BMS@TiO2 were also observed in five cycle tests of adsorption and photocatalytic degradation of DMP, and the possible photocatalytic degradation pathways and mechanism of DMP are proposed following molecular electrostatic potential analysis. This work provides a sustainable and environmentally friendly approach for eliminating organic micropollutants from water environments.

Systemic immune-inflammation index and in-stent restenosis in patients with acute coronary syndrome: a single-center retrospective study.

BACKGROUND: In-stent restenosis (ISR) has been shown to be correlated with inflammation. This study aimed to examine the relationship between systemic immune-inflammation index (SII, an innovative inflammatory biomarker) and ISR in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation. METHODS: Subjects who were diagnosed with ACS and underwent DES implantation were enrolled retrospectively. All individuals underwent follow-up coronary angiography at six to forty-eight months after percutaneous coronary intervention (PCI). SII was defined as [(platelet count × neutrophil count)/lymphocyte count], and Ln-transformed SII (LnSII) was carried out for our analysis. Multivariate logistic regression analysis was employed to assess the association between LnSII and DES-ISR. RESULTS: During a median follow-up period of 12 (11, 20) months, 523 ACS patients who underwent follow-up angiography were included. The incidence of DES-ISR was 11.28%, and patients in the higher LnSII tertile trended to show higher likelihoods of ISR (5.7% vs. 12.1% vs. 16.0%; P = 0.009). Moreover, each unit of increased LnSII was correlated with a 69% increased risk of DES-ISR (OR = 1.69, 95% CI 1.04-2.75). After final adjusting for confounders, a significant higher risk of DES-ISR (OR = 2.52, 95% CI 1.23-5.17) was found in participants in tertile 3 (≥ 6.7), compared with those in tertiles 1-2 (< 6.7). Subgroup analysis showed no significant dependence on age, gender, body mass index, current smoking, hypertension, and diabetes for this positive association (all P for interaction > 0.05). CONCLUSION: High levels of SII were independently associated with an increased risk of DES-ISR in ACS patients who underwent PCI. Further prospective cohort studies are still needed to validate our findings.

Different Degrees of Sulfated Laminaria Polysaccharides Recovered Damaged HK-2 Cells and Inhibited Adhesion of Nano-COM and Nano-COD Crystals.

Purpose: The crystal adhesion caused by the damage of renal tubular epithelial cells (HK-2) is the key to the formation of kidney stones. However, no effective preventive drug has been found. This study aims to explore the recovery effects of four Laminaria polysaccharides (SLPs) with different sulfate (-OSO3-) contents on damaged HK-2 cells and the difference in the adhesion of damaged cells to nanometer calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) before and after recovery. Methods: Sodium oxalate (2.6 mmol/L) was used to damage HK-2 cells to establish a damaged model. SLPs (LP0, SLP1, SLP2, and SLP3) with -OSO3- contents of 0.73%, 15.1%, 22.8%, and 31.3%, respectively, were used to restore the damaged cells, and the effects of SLPs on the adhesion of COM and COD, with a size of about 100 nm before and after recovery, were measured. Results: The following results were observed after SLPs recovered the damaged HK-2 cells: increased cell viability, restored cell morphology, decreased reactive oxygen levels, increased mitochondrial membrane potential, decreased phosphatidylserine eversion ratio, increased cell migration ability, reduced expression of annexin A1, transmembrane protein, and heat shock protein 90 on the cell surface, and reduced adhesion amount of cells to COM and COD. Under the same conditions, the adhesion ability of cells to COD crystals was weaker than that to COM crystals. Conclusions: As the sulfate content in SLPs increases, the ability of SLPs to recover damaged HK-2 cells and inhibit crystal adhesion increases. SLP3 with high -OSO3- content may be a potential drug to prevent kidney stones.

Intramyocardial Hemorrhage Leads to Higher MACE Rate by Increasing Myocardial Infarction Volume in Patients with STEMI.

Background and Aims: Whether IMH can directly cause persistent myocardial necrosis after reperfusion therapy in STEMI patients is still unclear. We conducted a prospective study to compare the cardiovascular parameters in patients with STEMI with and without IMH to explore the potential correlations between IMH and poor outcomes. Methods and Results: We prospectively enrolled 65 consecutive patients with newly diagnosed STEMI admitted to the CCU of the Second Xiangya Hospital of Central South University between April 2019 and November 2021, all of whom underwent primary PCI. Of these, 38 (58.5%) and 27 (41.5%) patients were in the IMH-absent and IMH-present groups, respectively. At a mean time of 5-7 days after reperfusion therapy, the volume of MI measured using LGE sequence was larger in STEMI patients with IMH than in patients without IMH (34.2 ± 12.7 cm3 vs 21.1 ± 13.1 cm3, P<0.001). HsTNT levels were significantly higher in the IMH-present group than in the IMH-absent [2500.0 (1681.5-4307.0) pg/mL vs 1710.0 (203.0-3363.5) pg/mL, P=0.021] group during hospitalization. The LVEF measured using CMR in the IMH-present group was lower than that in the IMH-absent group (30.7 ± 9.8% vs 42.3 ± 11.0%, P < 0.001). The rate of MACE at 12 months in IMH-present group was significantly higher than in the IMH-absent group (9/27 VS 2/38, P = 0.012). Conclusion: IMH can lead to further expansion of MI volumes in patients with STEMI, resulting in lower LVEF and higher MACE rate in the post-discharge follow-up.

Association between systemic immune-inflammation index and serum uric acid in U.S. adolescents: A population-based study.

BACKGROUND AND AIMS: Serum uric acid (SUA) has been reported to be associated with inflammation, and elevated SUA is increasingly prevalent in adolescents. The systemic immune-inflammation index (SII) is an innovative and integrated inflammatory indicator that has not yet been studied with SUA in adolescents. We therefore aimed to investigate the potential relationship between SII and SUA in U.S. adolescents. METHODS AND RESULTS: A total of 5,568 adolescents aged 12-19 years from NHANES 2009-2018 were analyzed. SII was calculated as platelet count × neutrophil count/lymphocyte count. Elevated SUA was defined as ≥ 5.5 mg/dL. SII was Ln-transformed for analysis for the skewed distribution. Multivariate linear and multiple logistic regression analyses were conducted to explore the association of SII with SUA and elevated SUA. A generalized additive model and a fitted smoothing curve were also performed. The prevalence of elevated SUA was 35.4 %. Multivariate linear regression analyses indicated that LnSII was positively associated with SUA level (ß = 0.15, 95 % CI: 0.09-0.20). Multiple logistic analyses indicated that LnSII was associated with a 38 % increased risk of elevated SUA (OR = 1.38, 95 % CI: 1.11-1.70). The smooth curve fitting showed that the associations of LnSII with SUA and elevated SUA were linear. Besides, subgroup analyses showed a stronger association between LnSII and SUA in adolescents aged ≥17 years (P for interaction <0.05). CONCLUSIONS: SII was positively associated with SUA level and elevated SUA in U.S. adolescents, particularly in populations aged ≥17 years.

Age-related macular degeneration and cardiovascular disease in US population: an observational study.

BACKGROUND: As far as we know, age-related macular degeneration (AMD) has become one of the predominant causes of visual impairments. Previous studies have revealed that AMD and many cardiovascular diseases (CVDs) share the same pathologic and genotypic factors, making the connection between AMD and CVD a hot topic. However, the conclusions of the available studies on the relationship between them are somewhat divergent. METHODS: We screened 5523 eligible participants from the National Health and Nutrition Examination Survey (NHANES) database from 2005 through 2008 for an observational clinical study design. Binary logistic regression modelling was used to estimate the relations between AMD and various CVDs with and without adjustment for demographics, health status, and behaviours related to health. RESULTS: Binary logistic regression analyses showed that AMD was able to increase the risk of CVDs in patients both unadjusted and after adjusting for confounding variables. CONCLUSIONS: Within this study, preventing the development of AMD might cut down the incidence of several CVDs, in particular, significantly lowering the stroke risk. These findings indicate that interventions to prevent AMD may also help to prevent CVDs. In general, late AMD has a more severe impact on the risk of CVDs compared with early AMD. These results could help clinical ophthalmology and cardiovascular medicine in their clinical education and interventions.

Relationship between Dietary Decanoic Acid and Coronary Artery Disease: A Population-Based Cross-Sectional Study.

BACKGROUND: Coronary artery disease (CAD) is a cardiovascular disease with significant personal health and socioeconomic consequences. The biological functions of decanoic acid and the pathogenesis of CAD overlap considerably; however, studies exploring their relationship are limited. METHODS: Data from 34,186 Americans from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018 were analyzed. The relationship between dietary decanoic acid (DDA) and CAD prevalence was explored using weighted multivariate logistic regression models, generalized summation models, and fitted smoothing curves. Stratified analyses and interaction tests were conducted to explore the potential modifiers between them. RESULTS: DDA was negatively associated with CAD prevalence, with each 1 g/d increase in the DDA being associated with a 21% reduction in CAD prevalence (odds ratio (OR) 0.79, 95% confidence interval (CI) 0.61-1.02). This relationship persisted after log10 and trinomial transformations, respectively. The OR after log10 transformation was 0.81 (95% CI 0.69-0.96), and the OR for tertile 3 compared with tertile 1 was 0.83 (95% CI 0.69-1.00). The subgroup analyses found this relationship to be significant among males and non-Hispanic white individuals, and there was a significant interaction (interaction p-values of 0.011 and 0.012, respectively). CONCLUSIONS: DDA was negatively associated with the prevalence of CAD, and both sex and race may modify this relationship.

Sox7-positive endothelial progenitors establish coronary arteries and govern ventricular compaction.

The cardiac endothelium influences ventricular chamber development by coordinating trabeculation and compaction. However, the endothelial-specific molecular mechanisms mediating this coordination are not fully understood. Here, we identify the Sox7 transcription factor as a critical cue instructing cardiac endothelium identity during ventricular chamber development. Endothelial-specific loss of Sox7 function in mice results in cardiac ventricular defects similar to non-compaction cardiomyopathy, with a change in the proportions of trabecular and compact cardiomyocytes in the mutant hearts. This phenotype is paralleled by abnormal coronary artery formation. Loss of Sox7 function disrupts the transcriptional regulation of the Notch pathway and connexins 37 and 40, which govern coronary arterial specification. Upon Sox7 endothelial-specific deletion, single-nuclei transcriptomics analysis identifies the depletion of a subset of Sox9/Gpc3-positive endocardial progenitor cells and an increase in erythro-myeloid cell lineages. Fate mapping analysis reveals that a subset of Sox7-null endothelial cells transdifferentiate into hematopoietic but not cardiomyocyte lineages. Our findings determine that Sox7 maintains cardiac endothelial cell identity, which is crucial to the cellular cross-talk that drives ventricular compaction and coronary artery development.

Association study of urinary iodine concentrations and coronary artery disease among adults in the USA: National Health and Nutrition Examination Survey 2003-2018.

Iodine is a vital trace element in the human body and is associated with several important coronary artery disease (CAD) risk factors. We aimed to explore the correlation between urinary iodine concentration (UIC) and CAD. Data from 15 793 US adults in the National Health and Nutrition Examination Survey (2003-2018) were analysed. We conducted multivariable logistic regression models and fitted smoothing curves to study the correlation between UIC and CAD. Furthermore, we performed subgroup analysis to investigate possible effect modifiers between them. We found a J-shaped association between UIC and CAD, with an inflection point at Lg UIC = 2·65 µg/l. This result indicated a neutral association (OR 0·89; 95 % CI 0·68, 1·16) between UIC and CAD as Lg UIC < 2·65 µg/l, but the per natural Lg [UIC] increment was OR 2·29; 95 % CI 1·53, 3·43 as Lg UIC ≥ 2·65 µg/l. An interaction between diabetes and UIC might exist. The increase in UIC results in an increase in CAD prevalence (OR 1·84, 95 % CI 1·32, 2·58) in diabetes but results in little to no difference in non-diabetes (OR 0·98, 95 % CI 0·77, 1·25). The J-shaped correlation between UIC and CAD and the interaction between diabetes and UIC should be confirmed in a prospective study with a series of UIC measurements. If excessive iodine precedes CAD, then this new finding could guide clinical practice and prevent iodine deficiency from being overcorrected.

Association of gamma-tocopherol serum concentrations and blood pressure among adults in the United States: a cross-sectional study.

Background: hypertension is one of the major preventable risk factors for numerous diseases. The role of vitamin E in blood pressure (BP) has been controversial. We aimed to investigate the relationship between gamma-tocopherol serum concentration (GTSC) and BP. Methods: Data from 15,687 US adults from the National Health and Nutrition Examination Survey (NHANES) were analyzed. The correlations of GTSC with systolic BP (SBP), diastolic BP (DBP), and prevalence of hypertension were investigated by multivariate logistic regression models, generalized summation models, and fitted smoothing curves. Subgroup analyses were performed to investigate possible effect modifiers between them. Results: With each natural log increase in GTSC, SBP, and DBP increased by 1.28 mmHg (ß 1.28, 95% CI 0.71-1.84) and 1.15 mmHg (ß 1.15, 95% CI 0.72-1.57), respectively, both P for trend < 0.001; the prevalence of hypertension increased by 12% (OR 1.12, 95% CI 1.03-1.22), P for trend 0.008. In subgroup analysis, in drinkers, with each natural log increase in GTSC, SBP, and DBP increased by 1.77 mmHg (ß 1.77,95% CI 1.13-2.41) and 1.37 mmHg (ß 1.37,95% CI 0.9-1.85), respectively, whereas they were not correlated in non-drinkers. Conclusion: GTSC was linearly and positively associated with SBP, DBP, and the prevalence of hypertension, and alcohol consumption may modify the relationship of GTSC with SBP and DBP.

FoxC1 activates limbal epithelial stem cells following corneal epithelial debridement.

Limbal epithelial stem cells are not only critical for corneal epithelial homeostasis but also have the capacity to change from a relatively quiescent mitotic phenotype to a rapidly proliferating cell in response to population depletion following corneal epithelial wounding. Pax6+/- mice display many abnormalities including corneal vascularization and these aberrations are consistent with a limbal stem cell deficiency (LSCD) phenotype. FoxC1 has an inhibitory effect on corneal avascularity and a positive role in stem cell maintenance in many tissues. However, the role of FoxC1 in limbal epithelial stem cells remains unknown. To unravel FoxC1's role(s) in limbal epithelial stem cell homeostasis, we utilized an adeno-associated virus (AAV) vector to topically deliver human FOXC1 proteins into Pax6 +/- mouse limbal epithelium. Under unperturbed conditions, overexpression of FOXC1 in the limbal epithelium had little significant change in differentiation (PAI-2, Krt12) and proliferation (BrdU, Ki67). Conversely, such overexpression resulted in a marked increase in the expression of putative limbal epithelial stem cell markers, N-cadherin and Lrig1. After corneal injuries in Pax6 +/- mice, FOXC1 overexpression enhanced the behavior of limbal epithelial stem cells from quiescence to a highly proliferative status. Overall, the treatment of AAV8-FOXC1 may be beneficial to the function of limbal epithelial stem cells in the context of a deficiency of Pax6 function.

Utilization of the retinal organoid model to evaluate the feasibility of genetic strategies to ameliorate retinal disease(s).

Organoid models have quickly become a popular research tool to evaluate novel therapeutics on 3-D recapitulated tissue. This has enabled researchers to use physiologically relevant human tissue in vitro to augment the standard use of immortalized cells and animal models. Organoids can also provide a model when an engineered animal cannot recreate a specific disease phenotype. In particular, the retinal research field has taken advantage of this burgeoning technology to provide insight into inherited retinal disease(s) mechanisms and therapeutic intervention to ameliorate their effects. In this review we will discuss the use of both wild-type and patient-specific retinal organoids to further gene therapy research that could potentially prevent retinal disease(s) progression. Furthermore, we will discuss the pitfalls of current retinal organoid technology and present potential solutions that could overcome these hurdles in the near future.

Development and Validation of a Novel Prognostic Tool to Predict Recurrence of Paroxysmal Atrial Fibrillation after the First-Time Catheter Ablation: A Retrospective Cohort Study.

There is no gold standard to tell frustrating outcomes after the catheter ablation of paroxysmal atrial fibrillation (PAF). The study aims to construct a prognostic tool. We retrospectively analyzed 315 patients with PAF who underwent first-time ablation at the Second Xiangya Hospital of Central South University. The endpoint was identified as any documented relapse of atrial tachyarrhythmia lasting longer than 30 s after the three-month blanking period. Univariate Cox regression analyzed eleven preablation parameters, followed by two supervised machine learning algorithms and stepwise regression to construct a nomogram internally validated. Five factors related to ablation failure were as follows: female sex, left atrial appendage emptying flow velocity ≤31 cm/s, estimated glomerular filtration rate <65.8 mL/(min·1.73 m2), P wave duration in lead aVF ≥ 120 ms, and that in lead V1 ≥ 100 ms, which constructed a nomogram. It was correlated with the CHA2DS2-VASc score but outperformed the latter evidently in discrimination and clinical utility, not to mention its robust performances in goodness-of-fit and calibration. In addition, the nomogram-based risk stratification could effectively separate ablation outcomes. Patients at risk of relapse after PAF ablation can be recognized at baseline using the proposed five-factor nomogram.

Magnetic Separation of Oxoacid of Boron from Salt-Lake Brine by Synergistically Enhanced Boron Adsorbents of Glucose-Functionalized SiO2 and Graphene.

The adsorption separation and extraction of low-concentration boron from salt-lake brine have great significance. Magnetic separation avoids the problem of adsorbent granulation and improves the usage efficiency. The silicon-based adsorbents have attracted interest due to their superior acid and alkali resistance, in which polyhydroxy graphene enhances the adsorption of boron ions. Herein different boron adsorbents, derived by magnetic separation, were developed and characterized by SEM, TEM, XPS, VSM, FT-IR, and XRD analysis. The adsorption-desorption performance of boron adsorbents with different compositions was evaluated. The isotherms and kinetics parameters of the boron extraction were evaluated based on adsorption-desorption tests. The graphene-based magnetic adsorbent (Go-Fe3O4@SiO2@mSiO2-Glu) registered a high boron adsorption capacity of 23.90 mg/g at pH = 9 in the boron solution and 24.84 mg/g for East Taigener salt-lake brine. The Na+, Mg2+, Ca2+, and Cl- ions have little interference with the boron adsorption. The adsorbents exhibit magnetic separation performance and good cycle life. The results showed that acid-alkali desorption solution has little effect on the adsorbents, and the composite of graphene enhances the adsorption of boron ions. The adsorbents developed in this study are promising to recover boron from low-concentration boron-containing salt-lake brines.

Case Report: Lung Adenocarcinoma Initially Presenting With Cutaneous and Subcutaneous Metastases.

Cutaneous and subcutaneous soft tissue metastases are rare in lung adenocarcinoma and suggest poor prognosis. We report a patient with lung adenocarcinoma who initially presented with cutaneous and subcutaneous metastases to the abdomen that were initially presumed to be herpes zoster and an occult subcutaneous soft tissue mass. Because the lesions progressed over 3 weeks despite routine herpes zoster treatment, magnetic resonance imaging was performed and showed a presumed sarcoma; however, 18F-fluourodeoxyglucose positron emission tomography/computed tomography demonstrated pulmonary lesions. Biopsy of the abdominal lesion confirmed poorly differentiated lung adenocarcinoma. Early diagnosis of soft tissue metastasis can be difficult. Clinicians should suspect internal organ malignancy when a progressive cutaneous or subcutaneous soft tissue lesion is encountered.