Molecular characterization of a new botybirnavirus that infects Alternaria sp. from tobacco.

The genus Alternaria comprises many important fungal pathogens that infect a wide variety of organisms. In this report, we present the discovery of a new double-stranded RNA (dsRNA) mycovirus called Alternaria botybirnavirus 2 (ABRV2) from a phytopathogenic strain, XC21-21C, of Alternaria sp. isolated from diseased tobacco leaves in China. The ABRV2 genome consists of two dsRNA components, namely dsRNA1 and dsRNA2, with lengths of 6,162 and 5,865 base pairs (bp), respectively. Each of these genomic dsRNAs is monocistronic, encoding hypothetical proteins of 201.6 kDa (P1) and 2193.3 kDa (P2). ABRV2 P1 and P2 share 50.54% and 63.13% amino acid sequence identity with the corresponding proteins encoded by dsRNA1 of Alternaria botybirnavirus 1 (ABRV1). Analysis of its genome organization and phylogenetic analysis revealed that ABRV2 is a new member of the genus Botybirnavirus.

ANCW: Affective norms for 4030 Chinese words.

Affective information contained in words is gaining increased attention among neurolinguists and psycholinguists around the world. This study established the Affective Norms for Chinese Words (ANCW) with valence, arousal, dominance, and concreteness ratings for 4030 words that were Chinese adaptations of the CET-4 (The National College English Test Band 4) official syllabus. Despite the existing Chinese affective norms such as the Chinese Affective Words System (CAWS), the ANCW provides much more and richer Chinese vocabulary. By using 7-point (ranging from 1 to 7) Likert scales in a paper-and-pencil procedure, we obtained ratings for all variables from 3717 Chinese undergraduates. The ANCW norms possessed good response reliability and were compatible with prior normative studies in Chinese. The pairwise correlation analysis revealed quadratic relations between valence and arousal, arousal and dominance, as well as valence and concreteness. Additionally, valence and dominance, as well as arousal and concreteness, presented a linear correlation, and concreteness and dominance were correlated. The ANCW provides reliable and standardized stimulus materials for further research involving emotional language processing.

LRTM1 promotes the differentiation of myoblast cells by negatively regulating the FGFR1 signaling pathway.

The proliferation and differentiation of myoblast cells are regulated by the fibroblast growth factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling pathway, negatively modulates the activation of ERK and promotes the differentiation of myoblast cells. LRTM1 is dynamically expressed during myoblast differentiation and skeletal muscle regeneration after injury. In mouse myoblast C2C12 cells, knockout (KO) of Lrtm1 significantly prevents the differentiation of myoblast cells; this effect is associated with the reduction of MyoD transcriptional activity and the overactivation of ERK kinase. Notably, further studies demonstrated that LRTM1 associates with p52Shc and inhibits the recruitment of p52Shc to FGFR1. Taken together, our findings identify a novel negative regulator of FGFR1, which plays an important role in regulating the differentiation of myoblast cells.

[Research progress on anti-alcoholic gastric injury active components and mechanisms of Chinese herbal medicine].

Alcohol is considered to be one of the main causes for gastric injury, and alcoholic gastric injury has been becoming one of the global health problems, which seriously affects the quality of human life. Many studies suggest that the active components extracted from Chinese herbal medicine can effectively reduce the degree of alcohol-induced gastric injury. The active components and its mechanism of anti-alcoholic gastric injury of Chinese herbal medicine reported in recent five years were preliminarily summarized according to the classification of terpenoids, flavonoids, polyphenols, polysaccharides, volatile oils, phenylpropanoids and alkaloids in this paper. The terpenoids could improve oxidative stress and inflammatory response by regulating relevant signaling pathways. The flavonoids are mainly related to antioxidant and anti-inflammatory properties. The polyphenols mainly regulate the level of relevant factors involved in inflammatory pathway, oxidative stress and apoptosis pathway. The polysaccharides could enhance the ability of gastric mucosal defense factor by inhibiting oxidative stress injury and inflammatory response. Phenylpropanoids could enhance the gastric mucosal defense factor. The volatile oils mainly inhibit H~+/K~+-ATPase activity or inflammatory reaction. Alkaloids are closely related to the inhibition of inflammatory response and the improvement of antioxidant system. This paper aims to provide reference for further research and development of Chinese herbal medicine against alcoholic gastric injury.

[Identification and target prediction of conserved microRNAs in Ammopiptanthus mongolicus].

Ammopiptanthus mongolicus, a woody plant growing in the desert, plays a vital role in vegetation maintaining and restoration in the arid region in northwest China. The plant exhibits an extremely high tolerance to abiotic stress such as drought and freezing stresses, and it has been used as an ideal model for abiotic stress tolerance research in trees. MicroRNA (miRNA) is a class of approximately 21nt endogenous non-protein-coding small RNA, which plays an important role in plant growth, development and responses to environmental stresses. By now, a large number of miRNAs have been reported in many plant species, but no studies describing A.mongolicus miRNA were published. In the present study, the types, expression levels, and putative target genes of conserved miRNAs in seedlings of A. mongolicus were analyzed using small RNA deep sequencing technology and bioinformatics methods. Nineteen conserved miRNAs, which belong to 10 miRNA families, were identified, with abundance ranging from 55 to 1920269 reads. Target prediction analysis determined the target genes of 14 conserved miRNAs. The functional classification analysis indicated that the conserved miRNAs participate in the development and environmental response by regulating the biological processes including the transcription regulation, hormone signal transduction, metabolisms and stress resistance.

Sanhua Tang protects against ischemic stroke by preventing blood-brain barrier injury: a network pharmacology and experiments.

OBJECTIVE: To assess the effect and mechanism of Sanhua Tang (, SHT) in treating ischemic stroke (IS) through the "Kaitong Xuanfu" theory by using network pharmacology and animal experiments. METHODS: The active ingredients and targets of SHT and IS were screened by public databases such as Traditional Chinese Medicine systems pharmacology, GeneCards, and online mendelian inheritance in man. Visual network topographies were constructed using R, Cytoscape 3.6.0, AutoDockTools, a user-sponsored molecular visualization system on an open-source foundation, and other software to analyze the correlation between targets and active ingredients. The middle cerebral artery occlusion (MCAO) model was established by operation. Animals were divided into the Sham group, MCAO group (M group), aloe-emodin (AE) group (MCAO rats treated with aloe-emodin), SHT at low dosage (SL group) (MCAO rats treated with SL), SHT at medium dosage (SM group), and SHT at high dosage (SH group). 2,3,5-triphenyl tetrazolium chloride staining was used to detect the volume of cerebral infarction; Nissl staining was used to observe the morphology of neuronal cells; transmission electron microscopy was used to observe the integrity of the blood-brain barrier (BBB); enzyme-linked immunosorbent assay was used to detect the content of interleukin-6 (IL-6), IL-10, tumor necrosis factor α (TNF-α) in serum. Western blot was used to detect the expression of vascular endothelial growth factor A (VEGFA) protein in the cerebral ischemic penumbra. RESULTS: Using network pharmacology and molecular docking validation, four active ingredients (lignan, naringenin, aloe-rhodopsin, and ß-sitosterol), seven target proteins (protein kinase b 1, IL-6, TNF, VEGFA, TP53, jun proto-oncogene, and cysteinyl aspartate specific proteinase 3), and inflammatory signaling pathways were identified. Animal experiments showed that the SH and AE groups had fewer neurological deficits, reduced brain infarct volumes, decreased serum inflammatory factor levels, increased expression of VEGFA protein, and less structural damage to neurons and BBB. CONCLUSION: The present study found that the therapeutic mechanism of SHT against IS may be related to the inhibition of BBB inflammatory damage, which is also the mechanism of "Kaitong Xuanfu." The high-dose group of SHT was relatively effective in regulating inflammatory factors, improving BBB permeability, and protecting neuronal cells from damage.

Safety and efficacy of cerebral embolic protection in transcatheter aortic valve implantation: an updated meta-analysis.

Background: The use of cerebral embolic protection devices during transcatheter aortic valve implantation (TAVI) reveals conflicting data. Aims: This updated meta-analysis aims to evaluate the efficacy and safety of the SENTINEL Cerebral Protection System. Methods: A literature search for relevant studies up to September 2022 was performed. Study outcomes were divided based on time period - overall (up to 30 days) and short (≤7 days). The outcomes studied include stroke (disabling, non-disabling), mortality, neuroimaging findings, transient ischaemic attack, acute kidney injury and major vascular and bleeding complications. Results: A total of 15 studies involving 294,134 patients were included. Regarding overall outcomes, significant reductions were noted for mortality (odds ratio [OR] 0.60, 95% confidence interval [CI]: 0.41-0.88; p=0.008), all stroke (OR 0.64, 95% CI: 0.46-0.88; p=0.006) and disabling stroke (OR 0.42, 95% CI: 0.23-0.74; p=0.003) using the SENTINEL device. No significant differences were noted for other outcomes. There was significant heterogeneity across the studies for mortality (p=0.013) and all stroke (p=0.003). Including only randomised data (n=4), there was only significant reduction in the incidence of disabling stroke (OR 0.39, 95% CI: 0.17-0.89; p=0.026) in the SENTINEL group. In studies reporting ≤7-day outcomes (n=8), use of the SENTINEL device demonstrated significantly lower rates of all stroke (p<0.001), disabling stroke (p<0.001) and major bleeding complications (p=0.02). No differences in neuroimaging outcomes were noted. Conclusions: In this updated meta-analysis, use of the SENTINEL Cerebral Protection System was associated with lower rates of mortality, all stroke and disabling stroke, although significant heterogeneity was noted for mortality and all stroke. Including exclusively randomised data, there was only significant reduction in the incidence of disabling stroke. No significant adverse outcomes with device use were noted.

Case report and literature review: Fabry disease misdiagnosing as polymyalgia rheumatica.

RATIONALE: The clinical manifestations of Fabry disease affect the nerves, kidneys, heart, skin, gastrointestinal tract and eyes. Our aim is to familiarize people with the FD diagnostic process by reporting this case. PATIENT CONCERNS: A 79-year-old-male patient presented with muscle pain and weakness in the extremities, also with an increasing erythrocyte sedimentation rate and C-reactive protein. Further examinations revealed that multiple organ involvement, such as rash, myocardial hypertrophy, peripheral neuropathy. DIAGNOSES: Cardiac MR demonstrated hypertrophic cardiomyopathy, myocardial fibrosis and low myocardial T1 value. The patient was eventually diagnosed with Fabry disease through proteomics and genetic testing. INTERVENTIONS: The treatment is enzyme replacement therapy (ERT). But this patient could not afford ERT and was given only general symptomatic treatment, pregabalin, and a gradual reduction in glucocorticoid. OUTCOMES: The patient's symptoms of joint pain and muscle weakness reduced significantly, and ESR and CRP had decreased to normal. LESSONS: FD is a rare disease and difficult to diagnose, but rare does not mean invisible. FD may present with signs and symptoms of rheumatic diseases. Rheumatologists should be aware and concerned about this disease.

Identification of novel bioactive proteins and their produced oligopeptides from Torreya grandis nuts using proteomic based prediction.

Torreya grandis nut is a chief functional food in China consumed for centuries. Besides its rich protein composition, increasing studies are now focusing on T. grandis functional proteins that have not yet identified. In this study, liquid chromatography coupled with mass spectrometry detection of smaller and major proteins, revealed that the major peptide was 36935.00 Da. Proteome sequencing annotated 142 proteins in total. Bioactive proteins such as defensin 4 was annotated and its anti-microbial function was verified. Finally, functional oligopeptides were predicted by searching sequences of digested peptides in databases. Ten group of oligopeptides were suggested to exhibit antioxidant, Angiotensin-converting enzyme inhibition, anti-inflammatory. The predicted antioxidant activity was experimentally validated. It is interesting that a peptide GYCVSDNN digested from defensin 4 showed antioxidant activity. This study reports novel functional peptides from T. grandis nuts that have not been isolated and/or included as functional ingredients in nutraceuticals and in food industry.

An Updated Meta-Analysis on the Clinical Outcomes of Percutaneous Left Atrial Appendage Closure Versus Direct Oral Anticoagulation in Patients With Atrial Fibrillation.

The availability of direct oral anticoagulants (DOACs) with known lower bleeding risk compared with warfarin have raised questions about the role of left atrial appendage closure (LAAC). We aimed to perform a meta-analysis to compare the clinical outcomes for LAAC versus DOACs. All studies directly comparing LAAC with DOACs up to January 2023 were included. The outcomes studied included the combined major adverse cardiovascular (CV) events outcomes, ischemic stroke and thromboembolic events, major bleeding, CV mortality, and all-cause mortality. Hazard ratios (HRs) and their 95% confidence interval were extracted or estimated from the data and pooled together with a random-effects model. A total of 7 studies (1 randomized controlled trial, 6 propensity-matched observational studies) were finally included, with a pooled population of 4,383 patients who underwent LAAC and 4,554 patients on DOACs. There were no significant differences between patients who underwent LAAC and patients on DOACs in terms of baseline age (75.0 vs 74.7, p = 0.27), CHA2DS2-VASc score (5.1 vs 5.1, p = 0.33), or HAS-BLED score (3.3 vs 3.3, p = 0.36). After a mean weighted follow-up of 22.0 months, LAAC was associated with significantly lower rates of combined major adverse CV event outcomes (HR 0.73 [0.56 to 0.95], p = 0.02), all-cause mortality (HR 0.68 [0.54 to 0.86], p = 0.02), and CV mortality (HR 0.55 [0.41 to 0.72], p<0.01). There were no significant differences in the rates of ischemic stroke or systemic embolism (HR 1.12 [0.92 to 1.35], p = 0.25), major bleeding (HR 0.94 [0.67 to 1.32], p = 0.71), or hemorrhagic stroke (HR 1.07 [0.74 to 1.54], p = 0.74) between LAAC and DOAC. In conclusion, percutaneous LAAC was found to be as efficacious as DOACs for stroke prevention, with lower all-cause and CV mortality. The rates of major bleeding and hemorrhagic stroke were similar. LAAC has a potential role to play in stroke prevention in patients with atrial fibrillation in the era of DOACs, but further randomized data are needed.

Chronic kidney disease and the risk of stent thrombosis after percutaneous coronary intervention with drug-eluting stents.

BACKGROUND: Chronic kidney disease (CKD) has been demonstrated to be associated with adverse clinical outcomes for patients with coronary artery disease (CAD). However, data on relation of CKD and stent thrombosis (ST) after drug-eluting stent (DES) implantation are limited. OBJECTIVES: This study was designed to examine whether CKD is associated with higher incidence of ST after elective coronary DES implantation compared with patients with normal renal function. METHODS: We consecutively enrolled 2,862 patients undergoing elective percutaneous coronary intervention (PCI) with DES. Demographic and clinical data were collected preoperatively. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min, calculated using the modified MDRD equation. The primary outcome was 1-year definite or probable ST. RESULTS: Four hundred and forty-five participants (15.5%) had CKD before procedure. The incidence of 1-year definite or probable ST was significantly higher in CKD patients compared with patients with normal renal function (1.8% vs. 0.6%, P = 0.014). After adjustment for multiple clinical and biochemical covariates, CKD was an independent predictor of 1-year definite or probable ST (hazard rate [HR] 0.396, 95% CI 0.165-0.951, P = 0.038). CONCLUSION: CKD is significantly associated with increased incidence of 1-year definite or probable ST in patients undergoing PCI with DES.

IGF2 expression in blood is not associated with its imprinting status in healthy pregnant Chinese women.

Loss of Imprinting (LOI) of IGF2 and over-expressed IGF2 are associated with tumorigenesis. Our previous epidemiological study found a relatively high frequency of IGF2 LOI in healthy mid-gestation pregnant women. The aim of this study is to determine whether the expression of IGF2 is associated with its imprinting status in healthy Chinese pregnant women. The IGF2 imprinting status of 300 pregnant women was analyzed. 20 cases of IGF2 LOI and 20 cases of IGF2 retention of imprinting (ROI) were selected randomly for IGF2 expression analysis. The expression pattern of IGF2 between the group with IGF2 ROI and group with IGF2 LOI in healthy Chinese pregnant women was evaluated by real time PCR and western blot. The result showed no significant differences between IGF2 ROI and LOI groups in mRNA and protein levels. These results imply that IGF2 imprinting status has no obvious impact on its expression. There may be some unknown important factors other than imprinting status driving IGF2 expression.

Glomerular Expression of S100A8 in Lupus Nephritis: An Integrated Bioinformatics Analysis.

Introduction: Lupus nephritis (LN) is a major risk factor of morbidity and mortality. Glomerular injury is associated with different pathogeneses and clinical presentations in LN patients. However, the molecular mechanisms involved are not well understood. This study aimed to explore the molecular characteristics and mechanisms of this disease using bioinformatics analysis. Methods: To characterize glomeruli in LN, microarray datasets GSE113342 and GSE32591 were downloaded from the Gene Expression Omnibus database and analyzed to determine the differentially expressed genes (DEGs) between LN glomeruli and normal glomeruli. Functional enrichment analyses and protein-protein interaction network analyses were then performed. Module analysis was performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape software. Immunofluorescence staining was performed to identify the glomerular expression of S100A8 in various International Society of Nephrology/Renal Pathology Society (ISN/RPS) class LN patients. The image of each glomerulus was acquired using a digital imaging system, and the green fluorescence intensity was quantified using Image-Pro Plus software. Results: A total of 13 DEGs, consisting of 12 downregulated genes and one upregulated gene (S100A8), were identified in the microarray datasets. The functions and pathways associated with the DEGs mainly include inflammatory response, innate immune response, neutrophil chemotaxis, leukocyte migration, cell adhesion, cell-cell signaling, and infection. We also found that monocytes and activated natural killer cells were upregulated in both GSE113342 and GSE32591. Glomerular S100A8 staining was significantly enhanced compared to that in the controls, especially in class IV. Conclusions: The DEGs identified in the present study help us understand the underlying molecular mechanisms of LN. Our results show that glomerular S100A8 expression varies in different pathological types; however, further research is required to confirm the role of S100A8 in LN.

Multiview Feature Fusion Representation for Interictal Epileptiform Spikes Detection.

Interictal epileptiform spikes (IES) of scalp electroencephalogram (EEG) signals have a strong relation with the epileptogenic region. Since IES are highly unlikely to be detected in scalp EEG signals, the primary diagnosis depends heavily on the visual evaluation of IES. However, visual inspection of EEG signals, the standard IES detection procedure is time-consuming, highly subjective, and error-prone. Furthermore, the highly complex, nonlinear, and nonstationary characteristics of EEG signals lead to the incomplete representation of EEG signals in existing computer-aided methods and consequently unsatisfactory detection performance. Therefore, a novel multiview feature fusion representation (MVFFR) method was developed and combined with a robustness classifier to detect EEG signals with/without IES. MVFFR comprises two steps: First, temporal, frequency, temporal-frequency, spatial, and nonlinear domain features are transformed by the IES to express the latent information effectively. Second, the unsupervised infinite feature-selection method determines the most distinct feature fusion representations. Experimental results using a balanced dataset of six patients showed that MVFFR achieved the optimal detection performance (accuracy: 89.27%, sensitivity: 89.01%, specificity: 89.54%, and precision: 89.82%) compared with other feature ranking methods, and the MVFFR-related method were complementary and indispensable. Additionally, in an independent test, MVFFR maintained excellent generalization capacity with a false detection rate per minute of 0.15 on the unbalanced dataset of one patient.

Application of deep eutectic solvents in protein extraction and purification.

Deep eutectic solvents (DESs) are a mixture of hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) molecules that can consist, respectively, of natural plant metabolites such as sugars, carboxylic acids, amino acids, and ionic molecules, which are for the vast majority ammonium salts. Media such as DESs are modular tools of sustainability that can be pointed toward the extraction of bioactive molecules due to their excellent physicochemical properties, their relatively low price, and accessibility. The present review focuses on the application of DESs for protein extraction and purification. The in-depth effects and principles that apply to DES-mediated extraction using various renewable biomasses will be discussed as well. One of the most important observations being made is that DESs have a clear ability to maintain the biological and/or functional activity of the extracted proteins, as well as increase their stability compared to traditional solvents. They demonstrate true potential for a reproducible but more importantly, scalable protein extraction and purification compared to traditional methods while enabling waste valorization in some particular cases.

Antiphospholipid antibodies and osteonecrosis in systemic lupus erythematosus: a meta-analysis.

Objectives: The present meta-analysis aimed to assess the relationship between antiphospholipid antibodies (aPLs) or antiphospholipid antibody syndrome (APS) and the incidence of osteonecrosis (ON) in systemic lupus erythematosus (SLE) patients.Methods: MEDLINE/Pubmed, EMBASE, Web of science, the Chinese Biomedical Literature Database (CBM), the Wan-Fang Database, and the China National Knowledge Infrastructure (CNKI) were searched from their inception up until 26 December 2020. Studies in English were included. Case-control studies and cohort studies were included. Studies pertaining to the link between aPLs or APS and ON patients were slated for inclusion in the current analysis.Results: Twenty-two studies involving a total of 3054 SLE patients were included. The positivities of anticardiolipin antibody (ACL), IgG ACL, IgM ACL, LA and APS in SLE is not associated with ON. One study showed that IgG or IgM ß2GP1 had no association with ON. No publication bias was detected. The quality of this evidence was low because of the high risk of bias across studies, and therefore robust inferences cannot be made.Conclusion: SLE patients demonstrated a weak association between aPLs and ON. The nature of the association between aPLs and ON in SLE needs to be investigated in-depth in future research.

The Short-term Effects of Temperature on Infectious Diarrhea among Children under 5 Years Old in Jiangsu, China: A Time-series Study (2015-2019).

The association between meteorological factors and infectious diarrhea has been widely studied in many countries. However, investigation among children under 5 years old in Jiangsu, China remains quite limited. Data including infectious diarrhea cases among children under five years old and daily meteorological indexes in Jiangsu, China from 2015 to 2019 were collected. The lag-effects up to 21 days of daily maximum temperature (Tmax) on infectious diarrhea were explored using a quasi-Poisson regression with a distributed lag non-linear model (DLNM) approach. The cases number of infectious diarrhea was significantly associated with seasonal variation of meteorological factors, and the burden of disease mainly occurred among children aged 0-2 years old. Moreover, when the reference value was set at 16.7°C, Tmax had a significant lag-effect on cases of infectious diarrhea among children under 5 years old in Jiangsu Province, which was increased remarkably in cold weather with the highest risk at 8°C. The results of DLNM analysis implicated that the lag-effect of Tmax varied among the 13 cities in Jiangsu and had significant differences in 8 cities. The highest risk of Tmax was presented at 5 lag days in Huaian with a maximum RR of 1.18 (95% CI: 1.09, 1.29). Suzhou which had the highest number of diarrhea cases (15830 cases), had a maximum RR of 1.04 (95% CI:1.03, 1.05) on lag 15 days. Tmax is a considerable indicator to predict the epidemic of infectious diarrhea among 13 cities in Jiangsu, which reminds us that in cold seasons, more preventive strategies and measures should be done to prevent infectious diarrhea.

Orientation-independent reaction activity monitoring with single particle and data analytics.

Single-particle analysis is the most powerful method to obtain accurate local information for understanding and monitoring chemical reactions. However, investigations about obtaining comprehensive information at the single-particle level to overcome individual errors and sampling randomness have not been reported to date. Plasmonic nanorods, which have excellent anisotropic optical and chemical properties, make us in situ acquisition of conformation and dynamics of the biological information. On the basis of their anisotropic optical properties of the plasmonic nanorods such as Au nanorods (AuNRs) and data analytics, herein we developed a high-throughput resonance scattering imaging method of AuNRs under dark-field microscopy (DFM) to monitor orientation-independent reaction activity of AuNRs. Data analytics are introduced to determine a large number of AuNRs orientation obtained from a series of polarized DFM images, allowing us to real-time monitor reaction activity of AuNRs at all orientations, and also makes it possible to study the global and local reaction processes of AuNRs at single-particle level. Our method is expected to provide a new strategy for analytical study and single-particle sensing in chemistry.

NIR-triggered drug delivery system for chemo-photothermal therapy of posterior capsule opacification.

Posterior capsule opacification (PCO) is the most common complication after cataract surgery and is likely to cause the second loss of vision. Pharmacological PCO prophylaxis has been proved to be effective, yet no clinical option is available due to the lack of a suitable mode of administration. In this work, we propose a unique concept of NIR dual-triggered drug release from black phosphorus (BP)-based implantable intraocular lens (IOL) for controlled drug release and chemo-photothermal combination therapy of PCO. Here, IOL is used as a "reservoir" of doxorubicin-loaded black phosphorus (BP-DOX), and BP is used as NIR activation agent for controlled drug release and photothermal therapy. This BP-DOX integrated IOL, namely BP-DOX@IOL, shows the characteristics of good transmittance, good mechanical property, NIR dual-triggered drug release behaviors, and excellent photothermal efficacy. In vivo studies reveal that there is no PCO occurrence in rabbits' model by using BP-DOX@IOL combined NIR irradiation, which exhibits distinct superiority on inhibiting PCO than the control group (100% PCO occurrence) 28 days post-surgery. This novel IOL drug delivery system would be a promising strategy for the future clinical application for PCO prophylaxis and treatment.

HCN Channel Activity Balances Quiescence and Proliferation in Neural Stem Cells and Is a Selective Target for Neuroprotection During Cancer Treatment.

Children suffering from neurologic cancers undergoing chemotherapy and radiotherapy are at high risk of reduced neurocognitive abilities likely via damage to proliferating neural stem cells (NSC). Therefore, strategies to protect NSCs are needed. We argue that induced cell-cycle arrest/quiescence in NSCs during cancer treatment can represent such a strategy. Here, we show that hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are dynamically expressed over the cell cycle in NSCs, depolarize the membrane potential, underlie spontaneous calcium oscillations and are required to maintain NSCs in the actively proliferating pool. Hyperpolarizing pharmacologic inhibition of HCN channels during exposure to ionizing radiation protects NSCs cells in neurogenic brain regions of young mice. In contrast, brain tumor-initiating cells, which also express HCN channels, remain proliferative during HCN inhibition. IMPLICATIONS: Our finding that NSCs can be selectively rescued while cancer cells remain sensitive to the treatment, provide a foundation for reduction of cognitive impairment in children with neurologic cancers.