Ionic Covalent Organic Framework-Based Membranes for Selective and Highly Permeable Molecular Sieving.

Two-dimensional covalent organic frameworks (COFs) with uniform pores and large surface areas are ideal candidates for constructing advanced molecular sieving membranes. However, a fabrication strategy to synthesize a free-standing COF membrane with a high permselectivity has not been fully explored yet. Herein, we prepared a free-standing TpPa-SO3H COF membrane with vertically aligned one-dimensional nanochannels. The introduction of the sulfonic acid groups on the COF membrane provides abundant negative charge sites in its pore wall, which achieve a high water flux and an excellent sieving performance toward water-soluble drugs and dyes with different charges and sizes. Furthermore, the COF membrane exhibited long-term stability, fouling resistance, and recyclability in rejection performance. We envisage that this work provides new insights into the effect of ionic ligands on the design of a broad range of COF membranes for advanced separation applications.

MACC: a visual interactive knowledgebase of metabolite-associated cell communications.

Metabolite-associated cell communications play critical roles in maintaining the normal biological function of human through coordinating cells, organs and physiological systems. Though substantial information of MACCs has been continuously reported, no relevant database has become available so far. To address this gap, we here developed the first knowledgebase (MACC), to comprehensively describe human metabolite-associated cell communications through curation of experimental literatures. MACC currently contains: (a) 4206 carefully curated metabolite-associated cell communications pairs involving 244 human endogenous metabolites and reported biological effects in vivo and in vitro; (b) 226 comprehensive cell subtypes and 296 disease states, such as cancers, autoimmune diseases, and pathogenic infections; (c) 4508 metabolite-related enzymes and transporters, involving 542 pathways; (d) an interactive tool with user-friendly interface to visualize networks of multiple metabolite-cell interactions. (e) overall expression landscape of metabolite-associated gene sets derived from over 1500 single-cell expression profiles to infer metabolites variations across different cells in the sample. Also, MACC enables cross-links to well-known databases, such as HMDB, DrugBank, TTD and PubMed etc. In complement to ligand-receptor databases, MACC may give new perspectives of alternative communication between cells via metabolite secretion and adsorption, together with the resulting biological functions. MACC is publicly accessible at: http://macc.badd-cao.net/.

Functional to structural plasticity in unilateral sudden sensorineural hearing loss: neuroimaging evidence.

A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.

Internet addiction-induced brain structure and function alterations: a systematic review and meta-analysis of voxel-based morphometry and resting-state functional connectivity studies.

Internet addiction (IA) is a growing social concern and has been intensively studied in recent years. Previous imaging studies have shown that IA may impair brain structure and function, but with no robust conclusions. We conducted a systematic review and meta-analysis of neuroimaging studies in IA. Two separate meta-analyses were conducted for voxel-based morphometry (VBM) studies and resting-state functional connectivity (rsFC) studies. All meta-analyses were performed using two analysis methods activation likelihood estimation (ALE) and seed-based d mapping with permutation of subject images (SDM-PSI). The ALE analysis of VBM studies revealed less gray matter volume (GMV) in the supplementary motor area (SMA) (1176 mm3), anterior cingulate cortex (ACC) (one cluster size is 744 mm3 and the other is 688 mm3), and orbitofrontal cortex (OFC) (624 mm3) in subjects with IA. The SDM-PSI analysis showed less GMV in the ACC (56 voxels). The ALE analysis of rsFC studies showed stronger rsFC from posterior cingulate cortex (PCC) (880 mm3) or insula (712 mm3) to the whole brain in subjects with IA; however, the SDM-PSI analysis revealed no obvious rsFC alteration. These changes may underlie the core symptoms of IA, which include emotional regulation disorder, distraction, and impaired executive control. Our results reflect the common features of neuroimaging studies related to IA in recent years and may potentially help inform the development of more effective diagnostic and treatment approaches.

Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis.

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

The brain structure and function abnormalities of migraineurs: A systematic review and neuroimaging meta-analysis.

Objectives: To quantitatively summarize the specific changes in brain structure and function in migraine patients. Methods: A literature screening of migraine was conducted from inception to Sept 1, 2022, in PubMed, Web of Science, Cochrane Library, and Medline databases using the keyword combination of "migraine and MRI." Activation likelihood estimation (ALE) was performed to assess the differentiation of functional connectivity (FC), regional homogeneity (ReHo), and gray matter volume (GMV) of migraine patients. Results: Eleven voxel-based morphometry (VBM) studies and 25 resting-state fMRI (rs-fMRI) studies (16 FC and 9 ReHo studies) were included in this study. ALE analysis revealed the ReHo increase in the brainstem and left thalamus, with no decreased area. Neither increased nor decreased regions were detected in FC and GMV of migraine patients. Conclusions: The left thalamus and brainstem were the significantly activated regions of migraine. It is a meaningful insights into the pathophysiology of migraine. The consistent alterated brain areas of morphometrical and functional in migraine patients were far from reached based on current studies.

Intersubject correlation analysis reveals the plasticity of cerebral functional connectivity in the long-term use of social media.

Owing to the limitations of cross-sectional studies, it is unclear whether social media induce brain changes, or if individuals with certain biological traits are more likely to use social media. Functional connectivity (FC) can reflect cerebral functional plasticity, and if social media can influence cerebral FC, then the FC of light social media users should be more similar to that of heavy users after they "heavily" used social media for a long period. We combined longitudinal study design and intersubject correlation (ISC) analysis to investigate this similarity. Thirty-five heavy and 21 light social media users underwent cognitive tests and functional MRIs. The 21 light social media users underwent another functional MRI scan after completing an additional four-week social media task. We conducted the ISC at the group, individual, and brain-region levels to investigate the similarity of FC and locate the brain regions most affected by social media. The FC of light social media users was more similar to that of heavy social media users after they completed the four-week social media task. Then, social media had an impact on half of the brain, involving almost all brain networks. Finally, cerebral FC that mostly affected by social media was associated with selective attention. We concluded that the impact of social media use on cerebral functional connectivity changes is revealed by ISC method and longitudinal design, which may provide guidance for clinical practice. The methods used in the current research could also be applied to similar domains.

Dynamic alterations of functional connectivity and amplitude of low-frequency fluctuations in patients with unilateral sudden sensorineural hearing loss.

Unilateral sudden sensorineural hearing loss (SSNHL) adversely affects the quality of life, leading to increased risk of depression and cognitive decline. Our previous studies have mainly focused on the static brain function abnormalities in SSNHL patients. However, the dynamic features of brain activity in SSNHL patients are not elucidated. To explore the dynamic brain functional alterations in SSNHL patients, age- and sex- matched SSNHL patients (n = 38) and healthy controls (HC, n = 44) were enrolled. The dynamic functional connectivity (dFC) and dynamic amplitude of low-frequency fluctuation (dALFF) methods were used to compare the temporal features and dynamic neural activity between the two groups. In dFC analyses, the multiple functional connectivities (FCs) were clustered into 2 different states; a greater proportion of FCs in SSNHL patients showed sparse state compared with HC. In dALFF analyses, SSNHL individuals exhibited decreased dALFF variability in bilateral inferior occipital gyrus, middle occipital gyrus, calcarine, right lingual gyrus, and right fusiform gyrus. dALFF variability showed a negative correlation with activated partial thromboplatin time. The dynamic characteristics of SSNHL patients were different from static functional connectivity and static amplitude of low-frequency fluctuation, especially within the visual cortices. These findings suggest that SSNHL patients experience cross-modal plasticity and visual compensation, which may be closely related to the pathophysiology of SSNHL.

Incidence of Cerebral Infarction in Northwest China From 2009 to 2018.

BACKGROUND: There is a lack of epidemiological analysis of patients with cerebral infarction in northwest China. In the present investigation, we conducted a retrospective analysis to collect information on epidemiological characteristics of patients with cerebral infarction in five provinces of northwest China and the Shanxi Province of patients who were hospitalized in the Tangdu Hospital. This project should provide a scientific basis for active prevention and treatment of cerebral infarction. MATERIAL AND METHODS: A retrospective analysis of patients with epidemic characteristics of cerebral infarction that were admitted to the Tangdu Hospital of northwest China from January 2009 to December 2018. RESULTS: A total of 18,302 patients (aged 1-97 years) with confirmed cerebral infarction, including 12,201 males and 6,101 females, were retrospectively enrolled in this study. The most common lesion site was the cerebellum (51.5%). The incidence of cerebral infarction was slightly higher in workers and laborers, favoring male patients and those aged 40-70 years. The difference between men and women gradually increased after the age of 30. CONCLUSIONS: In this study, 18,302 hospitalized patients with cerebral infarction from different occupations were included. Those engaged in physical labor were more likely to have a cerebral infarction. The incidence of cerebral infarction in males was higher than in females. Cerebellar and cerebral area infarctions were the most common.

Apelin ameliorated acute heart failure via inhibiting endoplasmic reticulum stress in rabbits.

This study aimed to investigate whether inhibition of endoplasmic reticulum stress (ERS) mediated the ameliorative effect of apelin on acute heart failure (AHF). Rabbit model of AHF was induced by sodium pentobarbital. Cardiac dysfunction and injury were detected in the rabbit models of AHF, including impaired hemodynamic parameters and increased levels of CK-MB and cTnI. Apelin treatment dramatically improved cardiac impairment caused by AHF. ERS, indexed by increased GRP78, CHOP, and cleaved-caspase12 protein levels, was simultaneously attenuated by apelin. Apelin also could ameliorate increased protein levels of cleaved-caspase3 and Bax, and improved decreased protein levels of Bcl-2. Two common ERS stimulators, tunicamycin (Tm) and dithiothreitol (DTT) blocked the ameliorative effect of apelin on AHF. Phosphorylated Akt levels increased after apelin treatment in the rabbit models of AHF. The Akt signaling inhibitors wortmannin and LY294002 could block the cardioprotective effect of apelin, which could be relieved by ERS inhibitor 4-phenyl butyric acid (4-PBA). The aforementioned beneficial effects of apelin could all be blocked by APJ receptor antagonist F13A. 4-PBA and SC79, an Akt activator, can restore the ameliorative effect of apelin on AHF blocked by F13A. Apelin treatment dramatically ameliorated cardiac impairment caused by AHF, which might be mediated by APJ/Akt/ERS signaling pathway. These results will shed new light on AHF therapy.

The Determinant of DNA Repair Pathway Choices in Ionising Radiation-Induced DNA Double-Strand Breaks.

Ionising radiation- (IR-) induced DNA double-strand breaks (DSBs) are considered to be the deleterious DNA lesions that pose a serious threat to genomic stability. The major DNA repair pathways, including classical nonhomologous end joining, homologous recombination, single-strand annealing, and alternative end joining, play critical roles in countering and eliciting IR-induced DSBs to ensure genome integrity. If the IR-induced DNA DSBs are not repaired correctly, the residual or incorrectly repaired DSBs can result in genomic instability that is associated with certain human diseases. Although many efforts have been made in investigating the major mechanisms of IR-induced DNA DSB repair, it is still unclear what determines the choices of IR-induced DNA DSB repair pathways. In this review, we discuss how the mechanisms of IR-induced DSB repair pathway choices can operate in irradiated cells. We first briefly describe the main mechanisms of the major DNA DSB repair pathways and the related key repair proteins. Based on our understanding of the characteristics of IR-induced DNA DSBs and the regulatory mechanisms of DSB repair pathways in irradiated cells and recent advances in this field, We then highlight the main factors and associated challenges to determine the IR-induced DSB repair pathway choices. We conclude that the type and distribution of IR-induced DSBs, chromatin state, DNA-end structure, and DNA-end resection are the main determinants of the choice of the IR-induced DNA DSB repair pathway.

Generalized Multi-Hit Model of Radiation-Induced Cell Survival with a Closed-Form Solution: An Alternative Method for Determining Isoeffect Doses in Practical Radiotherapy.

The standard linear-quadratic (LQ) model is currently the preferred model for describing the ionizing radiation-induced cell survival curves and tissue responses. And the LQ model is also widely used to calculate isoeffect doses for comparing different fractionated schemes in clinical radiotherapy. Despite its ubiquity, because the actual dose-response curve may appear linear at high doses in the semilogarithmic plot, the application of the LQ model is greatly challenged in the high-dose region, while the dose employed in stereotactic body radiotherapy (SBRT) is often in this area. Alternatively, the biophysical models of radiation-induced effects with a linear-quadratic-linear (LQL) characteristic can well fit the dose-survival curve of cells in vitro. However, most of these LQL models are phenomenological and have not fully considered the biophysical mechanism of radiation-induced damage and repair, and the fitting quality decreases in some high-dose ranges. In this work, to provide an alternative model to describe the cell survival curves in high-dose ranges and predict the biologically effective dose (BED) for SBRT, we propose a novel generalized multi-hit model with a closed-form solution by considering an upper bound on the number of lethal damages induced by radiation that can be repaired in a cell. This model has a clear biophysical basis and a simple expression, and also has the LQL characteristic under low- and high-dose approximate conditions. The experimental data fitting indicated that compared to the standard LQ model and our previously generalized target model, the current model can better fit the radiation-induced cell survival curves in the high-dose ranges (P < 0.05). The current model parameters and parameter ratios were determined from the fits in different kinds of cell lines irradiated with various dose rates and linear energy transfer (LET), which indicates that the model parameters significantly depend on the dose rate and LET. Based on the current model, we derived two equivalence formulae for the BED calculations in the low- and high-dose ranges, and then calculated the BED for the clinical data of SBRT from 17 selected studies. The correlation analysis showed that there were significant linear correlations between the BED at isocenter and planning target volume (PTV) edge calculated by this model and the LQ model (R > 0.86, P < 0.001). In conclusion, the generalized multi-hit model proposed in this work can be used as an alternative tool to handle in vitro radiation-induced cell survival curves in high-dose ranges, and calculate the in vivo BED for comparing the dose fractionation schemes in clinical radiotherapy.

Identification of potential radiation-responsive biomarkers based on human orthologous genes with possible roles in DNA repair pathways by comparison between Arabidopsis thaliana and homo sapiens.

Rapid and reliable ionization radiation (IR) exposure estimation has become increasingly important in environment due to the urgent requirement of medical evaluation and treatment in the event of nuclear accident emergency. Human DNA repair genes can be identified as important candidate biomarkers to assess IR exposure, while how to find the enough sensitive and specific biomarkers in the DNA repair networks is still challenged and not fully determined. The conserved features of DNA repair pathways may facilitate interdisciplinary studies that cross the traditional boundaries between animal and plant biology, with the aim of identifying undiscovered human DNA repair genes for potential radiation-responsive biomarkers. In this work, an in silico method of homologous comparison was performed to identify the human orthologues of A. thaliana DNA repair genes, and thereby to explore the sensitive and specific human radiation-responsive genes to evaluate the IR exposure levels. The results showed that a total of 16 putative candidate genes were involved in the human DNA repair pathways of homologous recombination (HR) and non-homologous end joining (NHEJ), and most of them were confirmed by previous experiments. Additionally, we analyzed the gene expression patterns of these 16 candidate genes in several human transcript microarray datasets with different IR treatments. The results indicated that most of the gene expression levels for these candidate genes were significantly changed under different radiation treatments. Based on these results, we integrated these putative human DNA repair genes into the DNA repair pathways to propose new insights of the HR and NHEJ pathways, which can also provide the potential targets for the development of radiation biomarkers. Notably, two putative DNA repair genes, named ERCC1 and ESCO2, were identified and were considered to be the sensitive and specific biomarkers in response to γ-ray exposures.

Fitting the Generalized Target Model to Cell Survival Data of Proton Radiation Reveals Dose-Dependent RBE and Inspires an Alternative Method to Estimate RBE in High-Dose Regions.

The imprecise estimation of the relative biological effectiveness (RBE) of proton radiation has been one of the main challenges for further calculating the biologically effective dose in proton therapy. Since dose levels can greatly influence the proton RBE, the relationship between the two should be clarified first. In addition, since the dose-response curves are usually too complex to readily assess RBE in high-dose regions, a reliable and simple method is needed to predict the RBE of proton radiation accurately in clinically relevant doses. The standard linear-quadratic (LQ) model is widely used to determine the RBE of particles for clinical applications. However, there has been some debate over its use when modeling the cell survival curves in high-dose regions, since those survival curves usually show linear behavior in the semilogarithmic plot. By considering both cellular repair effects and indirect effects of radiation, we have proposed a generalized target model with linear-quadratic linear (LQL) characteristics. For the more accurate evaluation of proton RBE in radiotherapy, here we used this generalized target model to fit the cell survival data in V79 and C3H 10T1/2 cells exposed to proton radiation with different LETs. The fitting results show that the generalized target model works as well as the LQ model in general. Based on the fitting parameters of the generalized target model, the RBE of six given doses DT (RBET) could be calculated in the corresponding cell lines with different LETs. The results show that the RBET gradually decreases with increased dose in both cell types. In addition, inspired by the calculation method of the maximum values of RBE (RBEM) in the low-dose region, a novel method was proposed for estimating the RBE in the high-dose region (RBEH) based on the slope ratio of the dose-response curves in this region. Linear regression analysis indicated a significant linear correlation between the proposed RBEH and the RBET in high-dose regions, which suggests that the current method can be used as an alternative tool, which is both simple and robust, to estimate RBE in high-dose regions.

In-silico Antigenicity Determination and Clustering of Dengue Virus Serotypes.

Emerging or re-emerging dengue virus (DENV) causes dengue fever epidemics globally. Current DENV serotypes are defined based on genetic clustering, while discrepancies are frequently observed between the genetic clustering and the antigenicity experiments. Rapid antigenicity determination of DENV mutants in high-throughput way is critical for vaccine selection and epidemic prevention during early outbreaks, where accurate prediction methods are seldom reported for DENV. Here, a highly accurate and efficient in-silico model was set up for DENV based on possible antigenicity-dominant positions (ADPs) of envelope (E) protein. Independent testing showed a high performance of our model with AUC-value of 0.937 and accuracy of 0.896 through quantitative Linear Regression (LR) model. More importantly, our model can successfully detect those cross-reactions between inter-serotype strains, while current genetic clustering failed. Prediction cluster of 1,143 historical strains showed new DENV clusters, and we proposed DENV2 should be further classified into two subgroups. Thus, the DENV serotyping may be re-considered antigenetically rather than genetically. As the first algorithm tailor-made for DENV antigenicity measurement based on mutated sequences, our model may provide fast-responding opportunity for the antigenicity surveillance on DENV variants and potential vaccine study.