CpG island reconfiguration for the establishment and synchronization of polycomb functions upon exit from naive pluripotency.

Polycomb group (PcG) proteins are essential for post-implantation development by depositing repressive histone modifications at promoters, mainly CpG islands (CGIs), of developmental regulator genes. However, promoter PcG marks are erased after fertilization and de novo established in peri-implantation embryos, coinciding with the transition from naive to primed pluripotency. Nevertheless, the molecular basis for this establishment remains unknown. In this study, we show that the expression of the long KDM2B isoform (KDM2BLF), which contains the demethylase domain, is specifically induced at peri-implantation and that its H3K36me2 demethylase activity is required for PcG enrichment at CGIs. Moreover, KDM2BLF interacts with BRG1/BRM-associated factor (BAF) and stabilizes BAF occupancy at CGIs for subsequent gain of accessibility, which precedes PcG enrichment. Consistently, KDM2BLF inactivation results in significantly delayed post-implantation development. In summary, our data unveil dynamic chromatin configuration of CGIs during exit from naive pluripotency and provide a conceptual framework for the spatiotemporal establishment of PcG functions.

Deep centroid: a general deep cascade classifier for biomedical omics data classification.

MOTIVATION: Classification of samples using biomedical omics data is a widely used method in biomedical research. However, these datasets often possess challenging characteristics, including high dimensionality, limited sample sizes, and inherent biases across diverse sources. These factors limit the performance of traditional machine learning models, particularly when applied to independent datasets. RESULTS: To address these challenges, we propose a novel classifier, Deep Centroid, which combines the stability of the nearest centroid classifier and the strong fitting ability of the deep cascade strategy. Deep Centroid is an ensemble learning method with a multi-layer cascade structure, consisting of feature scanning and cascade learning stages that can dynamically adjust the training scale. We apply Deep Centroid to three precision medicine applications-cancer early diagnosis, cancer prognosis, and drug sensitivity prediction-using cell-free DNA fragmentations, gene expression profiles, and DNA methylation data. Experimental results demonstrate that Deep Centroid outperforms six traditional machine learning models in all three applications, showcasing its potential in biological omics data classification. Furthermore, functional annotations reveal that the features scanned by the model exhibit biological significance, indicating its interpretability from a biological perspective. Our findings underscore the promising application of Deep Centroid in the classification of biomedical omics data, particularly in the field of precision medicine. AVAILABILITY AND IMPLEMENTATION: Deep Centroid is available at both github (github.com/xiexiexiekuan/DeepCentroid) and Figshare (https://figshare.com/articles/software/Deep_Centroid_A_General_Deep_Cascade_Classifier_for_Biomedical_Omics_Data_Classification/24993516).

Safflower CtFLS1-Induced Drought Tolerance by Stimulating the Accumulation of Flavonols and Anthocyanins in Arabidopsis thaliana.

Flavonol synthase gene (FLS) is a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily and plays an important role in plant flavonoids biosynthetic pathways. Safflower (Carthamus tinctorius L.), a key source of traditional Chinese medicine, is widely cultivated in China. Although the flavonoid biosynthetic pathway has been studied in several model species, it still remains to be explored in safflower. In this study, we aimed to elucidate the role of CtFLS1 gene in flavonoid biosynthesis and drought stress responses. The bioinformatics analysis on the CtFLS1 gene showed that it contains two FLS-specific motifs (PxxxIRxxxEQP and SxxTxLVP), suggesting its independent evolution. Further, the expression level of CtFLS1 in safflower showed a positive correlation with the accumulation level of total flavonoid content in four different flowering stages. In addition, CtFLS1-overexpression (OE) Arabidopsis plants significantly induced the expression levels of key genes involved in flavonol pathway. On the contrary, the expression of anthocyanin pathway-related genes and MYB transcription factors showed down-regulation. Furthermore, CtFLS1-OE plants promoted seed germination, as well as resistance to osmotic pressure and drought, and reduced sensitivity to ABA compared to mutant and wild-type plants. Moreover, CtFLS1 and CtANS1 were both subcellularly located at the cell membrane and nucleus; the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assay showed that they interacted with each other at the cell membrane. Altogether, these findings suggest the positive role of CtFLS1 in alleviating drought stress by stimulating flavonols and anthocyanin accumulation in safflower.

The miR396a-SlGRF8 module regulates sugar accumulation in the roots via SlSTP10 during the interaction between root-knot nematodes and tomato plants.

Root-knot nematodes (RKNs; Meloidogyne spp.) are a serious threat to crop production. The competition between plants and pathogens for assimilates influences the outcome of their interactions. However, the mechanisms by which plants and nematodes compete with each other for assimilates have not been elucidated. In this study, we demonstrated that miR396a plays a negative role in defense against RKNs and a positive role in sugar accumulation in tomato roots. The overexpression of SlGRF8 (Solanum lycopersicum growth-regulating factor 8), the target of miR396a, decreased the sugar content of the roots and the susceptibility to RKNs, whereas the grf8-cr mutation had the opposite effects. Furthermore, we confirmed that SlGRF8 regulated the sugar content in roots by directly activating the transcription of SlSTP10 (Solanum lycopersicum sugar transporter protein 10) in response to RKN stress. Moreover, SlSTP10 was expressed primarily in the tissues surrounding giant cells, and the SlSTP10 knockout increased both the sugar content in the roots and the plant's susceptibility to RKNs. Overall, this study provides important insight into the molecular mechanism through which the miR396a-SlGRF8-SlSTP10 module regulates sugar allocation in roots under RKN stress.

A Cinnamate 4-HYDROXYLASE1 from Safflower Promotes Flavonoids Accumulation and Stimulates Antioxidant Defense System in Arabidopsis.

C4H (cinnamate 4-hydroxylase) is a pivotal gene in the phenylpropanoid pathway, which is involved in the regulation of flavonoids and lignin biosynthesis of plants. However, the molecular mechanism of C4H-induced antioxidant activity in safflower still remains to be elucidated. In this study, a CtC4H1 gene was identified from safflower with combined analysis of transcriptome and functional characterization, regulating flavonoid biosynthesis and antioxidant defense system under drought stress in Arabidopsis. The expression level of CtC4H1 was shown to be differentially regulated in response to abiotic stresses; however, a significant increase was observed under drought exposure. The interaction between CtC4H1 and CtPAL1 was detected using a yeast two-hybrid assay and then verified using a bimolecular fluorescence complementation (BiFC) analysis. Phenotypic and statistical analysis of CtC4H1 overexpressed Arabidopsis demonstrated slightly wider leaves, long and early stem development as well as an increased level of total metabolite and anthocyanin contents. These findings imply that CtC4H1 may regulate plant development and defense systems in transgenic plants via specialized metabolism. Furthermore, transgenic Arabidopsis lines overexpressing CtC4H1 exhibited increased antioxidant activity as confirmed using a visible phenotype and different physiological indicators. In addition, the low accumulation of reactive oxygen species (ROS) in transgenic Arabidopsis exposed to drought conditions has confirmed the reduction of oxidative damage by stimulating the antioxidant defensive system, resulting in osmotic balance. Together, these findings have provided crucial insights into the functional role of CtC4H1 in regulating flavonoid biosynthesis and antioxidant defense system in safflower.

mTORC2 regulates hierarchical micro/nano topography-induced osteogenic differentiation via promoting cell adhesion and cytoskeletal polymerization.

Surface topography acts as an irreplaceable role in the long-term success of intraosseous implants. In this study, we prepared the hierarchical micro/nano topography using selective laser melting combined with alkali heat treatment (SLM-AHT) and explored the underlying mechanism of SLM-AHT surface-elicited osteogenesis. Our results show that cells cultured on SLM-AHT surface possess the largest number of mature FAs and exhibit a cytoskeleton reorganization compared with control groups. SLM-AHT surface could also significantly upregulate the expression of the cell adhesion-related molecule p-FAK, the osteogenic differentiation-related molecules RUNX2 and OCN as well as the mTORC2 signalling pathway key molecule Rictor. Notably, after the knocked-down of Rictor, there were no longer significant differences in the gene expression levels of the cell adhesion-related molecules and osteogenic differentiation-related molecules among the three titanium surfaces, and the cells on SLM-AHT surface failed to trigger cytoskeleton reorganization. In conclusion, the results suggest that mTORC2 can regulate the hierarchical micro/nano topography-mediated osteogenesis via cell adhesion and cytoskeletal reorganization.

Functional brain network mechanism of executive control dysfunction in temporal lobe epilepsy.

BACKGROUND: Executive control dysfunction is observed in a sizable number of patients with temporal lobe epilepsy (TLE). Neural oscillations in the theta band are increasingly recognized as having a crucial role in executive control network. The purpose of this study was to investigate the alterations in the theta band in executive control network and explore the functional brain network mechanisms of executive control dysfunction in TLE patients. METHODS: A total of 20 TLE patients and 20 matched healthy controls (HCs) were recruited in the present study. All participants were trained to perform the executive control task by attention network test while the scalp electroencephalogram (EEG) data were recorded. The resting state signals were collected from the EEG in the subjects with quiet and closed eyes conditions. Functional connectivity among EEGs in the executive control network and resting state network were respectively calculated. RESULTS: We found the significant executive control impairment in the TLE group. Compared to the HCs, the TLE group showed significantly weaker functional connectivity among EEGs in the executive control network. Moreover, in the TLE group, we found that the functional connectivity was significantly positively correlated with accuracy and negatively correlated with EC_effect. In addition, the functional connectivity of the executive control network was significantly higher than that of the resting state network in the HCs. In the TLE group, however, there was no significant change in functional connectivity strengths between the executive control network and resting state network. CONCLUSION: Our results indicate that the decreased functional connectivity in theta band may provide a potential mechanism for executive control deficits in TLE patients.

Systematically Evaluating Cell-Free DNA Fragmentation Patterns for Cancer Diagnosis and Enhanced Cancer Detection via Integrating Multiple Fragmentation Patterns.

Cell-free DNA (cfDNA) fragmentation patterns have immense potential for early cancer detection. However, the definition of fragmentation varies, ranging from the entire genome to specific genomic regions. These patterns have not been systematically compared, impeding broader research and practical implementation. Here, 1382 plasma cfDNA sequencing samples from 8 cancer types are collected. Considering that cfDNA within open chromatin regions is more susceptible to fragmentation, 10 fragmentation patterns within open chromatin regions as features and employed machine learning techniques to evaluate their performance are examined. All fragmentation patterns demonstrated discernible classification capabilities, with the end motif showing the highest diagnostic value for cross-validation. Combining cross and independent validation results revealed that fragmentation patterns that incorporated both fragment length and coverage information exhibited robust predictive capacities. Despite their diagnostic potential, the predictive power of these fragmentation patterns is unstable. To address this limitation, an ensemble classifier via integrating all fragmentation patterns is developed, which demonstrated notable improvements in cancer detection and tissue-of-origin determination. Further functional bioinformatics investigations on significant feature intervals in the model revealed its impressive ability to identify critical regulatory regions involved in cancer pathogenesis.

Immobilization of cross-linked enzymes aggregates on hierarchical covalent organic frameworks: Highly stable chemoenzymatic nanoreactor for asymmetric synthesis of optically active halohydrins.

Organometallic catalyst is extensively applied for the non-enzymatic regeneration of nicotinamide adenine dinucleotide (phosphate) cofactors, but suffering from the mutual inactivation with the enzymes in one pot. The spatially separated immobilization of organometallic catalyst and enzymes on suitable carriers not only can reduce their mutual inhabitation but also can enhance their reusability. Here in this work, we present a hierarchical porous COFs (HP-TpBpy) that incorporated with [(Cp*RhCl2]2 to generate the metalized COF, Rh-HP-TpBpy. The obtained Rh-HP-TpBpy exhibited superior performance in nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) regeneration using formate as the hydride donor, significantly outperforming the natural formate dehydrogenases in cofactor preference toward NADP+. Subsequently, the Lactobacillus fermentum short-chain dehydrogenase/reductase 1 (LfSDR1) was then cross-linked into enzyme aggregates (CLEA) and immobilized on hierarchical Rh-HP-TpBpy, achieving the integrated chemoenzymatic catalyst, LfSDR1@Rh-HP-TpBpy, which can catalyze the chemoenzymatic reduction of halogenated aryl ketones and give the corresponding optically active halohydrins with high conversion and enantiomeric excess (ee) value up to 99 %. The LfSDR1@Rh-HP-TpBpy also exhibits largely enhanced stability compared with the free LfSDR1 and the CLEAs-LfSDR1, enabling its excellent reusability.

Water-Immersion Stability of Self-Compacting Potassium Magnesium Phosphate Cement Paste.

For the repair of narrow cracks in concrete, the potassium magnesium phosphate cement (MKPC)-based material paste should have high fluidity and self-compacting ability, making it convenient for pouring and compacting. A self-compacting MKPC paste that meets the index requirements recommended by the European Federation of National Associations Representing for Concrete (EFNAFC) was prepared by increasing the water-cement ratio and adding water glass and fly ash (FA). Specimens of self-compacting MKPC paste were subjected to long-term water corrosion tests, which found that those high-fluidity MKPC paste specimens (reference sample M0) that were produced with only an increased water-cement ratio lost 15-30% of their strength. The residual ratio of folding to compression was 84.6%, and the volume expansion rate was 7.78 × 10-4 after immersion in water for 560 days. The strength residual rate of MKPC slurry (M1) modified by sodium silicate and fly ash is over 90% after 560 days of immersion in water, and the residual rate of flexural-compressive ratio is 101.3%, which meets the requirements of hydraulic cement-based materials. The volume expansion rate of M1 is 5.19 × 10-4, which is 67% of the reference sample M0 with the same water immersion age.

Ultralow background one-pot detection of Lead(II) using a non-enzymatic double-cycle system mediated by a hairpin-involved DNAzyme.

A double-cycle system has been developed for specifically detecting trace amounts of Pb2+ by significantly decreasing the background signal. The detection involves two types of RNA cleavage reactions: one using a Pb2+-specific GR5 DNAzyme (PbDz) and the other utilizing a newly constructed 10-23 DNAzyme with two hairpins embedded in its catalytic center (hpDz). The ring-structured hpDz (c-hpDz) exhibits significantly lower activity compared to the circular 10-23 DNAzyme without hairpin structures, which plays a crucial role in reducing the background signal. When Pb2+ is present, PbDz cleaves c-hpDz to its active form, which then disconnects the molecular beacon to emit the fluorescent signal. The method allows for rapid and sensitive Pb2+ detection within 40 min for 10 fM of Pb2+ and even as short as 10 min for 100 nM of Pb2+. Additionally, visual detection is possible through the non-crosslinking assembly of Au nanoparticles. The entire process can be performed in one pot and even one step, making it highly versatile and suitable for a wide range of applications, including food safety testing and environmental monitoring.

Influence of Synthetic Limestone Sand on the Frost Resistance of Magnesium Potassium Phosphate Cement Mortar.

Synthetic limestone sand has advantages, such as stable quality and adjustable particle size distribution, and has gradually substituted high-quality natural sand as a fine aggregate in concrete production. The project team has prepared Magnesium Potassium Phosphate Cement (MKPC) mortar by replacing part of the river sand with machine-made limestone sand in equal amounts, which proves that its physical and mechanical properties are obviously better than mortar prepared by whole river sand. However, the research on the impact of machine-made limestone sand on the durability of MKPC mortar has not been carried out. As the repairing material of concrete structures, the frost resistance of MKPC mortar must be evaluated. In this study, the effect of synthetic limestone sand on the frost resistance of Magnesium Potassium Phosphate Cement (MKPC) mortar was investigated by characterizing the strength, mass loss rate, and water absorption of specimens subjected to freeze-thaw cycling. MKPC mortars prepared using solely river sand (M0) or limestone sand (M1) were completely degraded after 225 freezing-thawing cycles in water, whereas the flexural and compressive strengths of MKPC mortar (M2) prepared using both river and synthetic limestone sands was 29.3 and 22.0% of the initial strengths, respectively. The water freeze-thaw resistance of M2 specimens were significantly higher than that of M0 and M1 specimens, and the sulfate freeze-thaw resistance of M1 and M2 were significantly higher than that of M0. The mass loss of MKPC mortar is not more than 0.4% when it is frozen and thawed 225 times in water and 5% Na2SO4 solution, which is far lower than the damage standard of 5%. Based on the favorable composition of the two aggregates, the initial open porosity of M2 was relatively low, owing to the lower water-cement ratio of the mortar at the same flow rate.

Epidemiological trends of severely immunosuppressed people living with HIV at time of starting antiretroviral treatment in China during 2005-2018.

OBJECTIVES: High HIV-related mortality is mainly associated with severe immunosuppression (CD4 count < 50 cells/µL) in people living with HIV (PLWH). This study intended to explore the trends in epidemic and early mortality among PLWH with severe immunosuppression for further targeted intervention. METHODS: We extracted the data of treatment-naïve PLWH with severe immunosuppression from China's National Free Antiretroviral Treatment (ART) Program database. Early mortality (within 6 or 12 months after initiating ART) and spatial, temporal, and population distribution were analyzed during 2005-2018. RESULTS: Of 748,066 treatment-naïve PLWH, 105,785 (14.1%) were severely immunosuppressed PLWH aged more than 15-year-old. The proportion of severely immunosuppressed PLWH peaked at 31.4% and then decreased with time, leveling off at approximately 11-12% from 2015 onward. Early mortality rates of these PLWH declined significantly (from 17.0% to 8.1% after 6 months of initiating ART; 20.4% to 10.6% after 12 months; both p values < 0.01) from 2005-2007 to 2016-2018. In the South-central and Southwest, the number of these PLWH was larger than that in the other regions during 2005-2018, and it increased to 4780 (37.1%) and 3370 (26.2%) in 2018. The proportion of PLWH aged 30-44 years among all treatment-naïve severely immunosuppressed PLWH in each region was higher than that of other age groups during 2005-2018. After the proportion decreased during 2005-2007, the proportion of PLWH aged 45-59 years in Southwest and South-central were increased steadily from 11% (69/626) and 16.7% (358/2140) in 2007 to 33.8% (1138/3370) and 34.0% (1626/4780) in 2018, respectively; the proportion of PLWH aged ≥60 years showed an increasing trend during 2005-2018; while changes in the proportion of those age groups were less pronounced in North and Northeast. The proportion of PLWH infected by heterosexual contact was high at 83% (2798/3370) in Southwest, and 75.1% (3588/4780) in South-central in 2018; conversely, proportion of PLWH infected by homosexual contacts was largest in North (57.8% [500/865]) and Northeast (59.9% [561/936]). CONCLUSIONS: The persistent burden of treatment-naïve PLWH with severe immunosuppression remains challenging. Our results provide evidence for policy-makers to allocate resources and establish targeting strategies to identify early infection of PLWH.

Inducible CRISPRa screen identifies putative enhancers.

Enhancers are critical cis-regulatory elements that regulate spatiotemporal gene expression and control cell fates. However, the identification of enhancers in native cellular contexts still remains a challenge. Here, we develop an inducible CRISPR activation (CRISPRa) system by transgenic expression of doxycycline (Dox)-inducible dCas9-VPR in mouse embryonic stem cells (iVPR ESC). With this line, a simple introduction of specific guide RNAs targeting promoters or enhancers allows us to realize the effect of CRISPRa in an inducible, reversible, and Dox concentration-dependent manner. Taking advantage of this system, we induce tiled CRISPRa across genomic regions (105 kilobases) surrounding T (Brachyury), one of the key mesodermal development regulator genes. Moreover, we identify several CRISPRa-responsive elements with chromatin features of putative enhancers, including a region the homologous sequence in which humans harbors a body height risk variant. Genetic deletion of this region in ESC does affect subsequent T gene activation and osteogenic differentiation. Therefore, our inducible CRISPRa ESC line provides a convenient platform for high-throughput screens of putative enhancers.

Identification of Diagnostic Markers Correlated With HIV+ Immune Non-response Based on Bioinformatics Analysis.

Background: HIV-infected immunological non-responders (INRs) are characterized by their inability to reconstitute CD4+ T cell pools after antiretroviral therapy. The risk of non-AIDS-related diseases in INRs is increased, and the outcome and prognosis of INRs are inferior to that of immunological responders (IRs). However, few markers can be used to define INRs precisely. In this study, we aim to identify further potential diagnostic markers associated with INRs through bioinformatic analyses of public datasets. Methods: This study retrieved the microarray data sets of GSE106792 and GSE77939 from the Gene Expression Omnibus (GEO) database. After merging two microarray data and adjusting the batch effect, differentially expressed genes (DEGs) were identified. Gene Ontology (GO) resource and Kyoto Encyclopedia of Genes and Genomes (KEGG) resource were conducted to analyze the biological process and functional enrichment. We performed receiver operating characteristic (ROC) curves to filtrate potential diagnostic markers for INRs. Gene Set Enrichment Analysis (GSEA) was conducted to perform the pathway enrichment analysis of individual genes. Single sample GSEA (ssGSEA) was performed to assess scores of immune cells within INRs and IRs. The correlations between the diagnostic markers and differential immune cells were examined by conducting Spearman's rank correlation analysis. Subsequently, miRNA-mRNA-TF interaction networks in accordance with the potential diagnostic markers were built with Cytoscape. We finally verified the mRNA expression of the diagnostic markers in clinical samples of INRs and IRs by performing RT-qPCR. Results: We identified 52 DEGs in the samples of peripheral blood mononuclear cells (PBMC) between INRs and IRs. A few inflammatory and immune-related pathways, including chronic inflammatory response, T cell receptor signaling pathway, were enriched. FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1 were considered as potential diagnostic markers. ssGSEA results showed that the IRs had significantly higher enrichment scores of seven immune cells compared with IRs. The miRNA-mRNA-TF network was constructed with 97 miRNAs, 6 diagnostic markers, and 26 TFs, which implied a possible regulatory relationship. Conclusion: The six potential crucial genes, FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1, may be associated with clinical diagnosis in INRs. Our study provided new insights into diagnostic and therapeutic targets.

High population-attributable fractions of traditional risk factors for non-AIDS-defining diseases among people living with HIV in China: a cohort study.

Morbidity and mortality of non-AIDS-defining diseases (NADs) have become the increasing burden of people living with HIV (PLWH) with long-term antiretroviral therapy (ART). We aimed to quantify the contribution of modifiable risk factors to NADs. We included PLWHs starting ART at the Third People's Hospital of Shenzhen (China) from Jan 1, 2010 to Dec 31, 2017. We defined NAD outcomes of interest as cardiovascular disease (CVD), end-stage liver disease (ESLD), advanced renal disease (ARD), and non-AIDS-defining cancers (NADCs). We estimated incidence of outcomes and population-attributable fractions (PAFs) of modifiable traditional and HIV-related risk factors for each outcome. Overall, 8,301 participants (median age at study entry, 31 years) contributed 33,146 person-years of follow-up (PYFU). Incidence of CVD (362/100,000 PYFU) was the highest among outcomes, followed by that of ARD (270/100,000 PYFU), ESLD (213/100,000 PYFU), and NADC (152/100,000 PYFU). Totally, 34.14% of CVD was attributable to smoking, 7.98% to hypertension, and 6.44% to diabetes. For ESLD, 24.57% and 25.04% of it could be avoided if chronic hepatitis B and C virus infection, respectively, did not present. The leading PAFs for ARD were declined estimated glomerular filtration rate (eGFR) (39.68%) and low CD4 count (39.61%), followed by diabetes (10.19%). PAFs of hypertension, diabetes, and smoking for CVD, and declined eGFR and diabetes for ARD increased with age. The contribution of traditional risk factors for these NADs far outweighed the HIV-related risk factors. Individual-level interventions and population-level policy-making is needed to focus on these factors to prevent NADs in long-term management of HIV infection.

Human umbilical cord mesenchymal stem cell transfusion in immune non-responders with AIDS: a multicenter randomized controlled trial.

We examined the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) infusion for immune non-responder (INR) patients with chronic HIV-1 infection, who represent an unmet medical need even in the era of efficient antiretroviral therapy (ART). Seventy-two INR patients with HIV were enrolled in this phase II randomized, double-blinded, multicenter, placebo-controlled, dose-determination trial (NCT01213186) from May 2013 to March 2016. They were assigned to receive high-dose (1.5 × 106/kg body weight) or low-dose (0.5 × 106/kg body weight) hUC-MSC, or placebo. Their clinical and immunological parameters were monitored during the 96-week follow-up study. We found that hUC-MSC treatment was safe and well-tolerated. Compared with baseline, there was a statistical increase in CD4+ T counts in the high-dose (P < 0.001) and low-dose (P < 0.001) groups after 48-week treatment, but no change was observed in the control group. Kaplan-Meier analysis revealed a higher cumulative probability of achieving an immunological response in the low-dose group compared with the control group (95.8% vs. 70.8%, P = 0.004). However, no significant changes in CD4/CD8+ T counts and CD4/CD8 ratios were observed among the three groups. In summary, hUC-MSC treatment is safe. However, the therapeutic efficacy of hUC-MSC treatment to improve the immune reconstitution in INR patients still needs to be further investigated in a large cohort study.

[Acute infection of Toxoplasma gondii affects the level of oxygen free radicals in serum and testes of mice].

OBJECTIVE: To observe the impact of Toxoplasma gondii infection on the level of oxygen free radicals and antioxidant enzyme in serum and testes of mice. METHODS: 40 BALB/c male mice were randomly divided into four groups. Five mice from each group were injected intraperitoneally with 2.5 x 10(3) tachyzoites of T. gondii, the others received PBS. Mice were sacrificed on the 1st, 3rd, 5th, and 7th day after inoculation. Samples of serum and testes were collected to determine the content of oxygen free radicals and superoxide dismutase (SOD). RESULTS: The concentration of the oxygen free radicals (NO, *OH, O2-) in serum and testes of the mice increased along with the days of infection. The concentration of SOD reached a peak on the 3rd day after the injection and then decreased. Both of oxygen free radicals and SOD showed a statistical difference with the control (P < 0.01). CONCLUSION: Acute infection of T. gondii leads to n increase of oxygen free radicals and SOD in the serum and testes of mice.

Risk factors and prevalence of diabetic retinopathy: A protocol for meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) is one of the serious complications of diabetes mellitus. Without further treatment, it can evolve into the stage of proliferation, which will lead to the formation of new blood vessels, vitreous hemorrhage, or anterior retinal hemorrhage, which will lead to severe vision loss and increase the risk of blindness. METHODS: The research literature on the risk factors of diabetic retinopathy published as of July 1, 2020 was searched through MEDLINE, Embase, ovid, Web of Science, Wanfang, CNKI, and other databases, The search strategy has been first developed in MEDLINE using MeSH subject headings combined with free-text terms and Stata12.0 software was used for meta-analysis. RESULTS: This study is ongoing and the results will be submitted to a peer-reviewed journal for publication. ETHICS AND DISSEMINATION: Ethical approval is not applicable, since this is an overview based on published articles. PROTOCOL REGISTRATION NUMBER: The registration number is INPLASY202070107, the DOI number is 10.37766/inplasy2020.7.0107.

Theta oscillation and functional connectivity alterations related to executive control in temporal lobe epilepsy with comorbid depression.

OBJECTIVE: Depression is widely acknowledged as the most common comorbidity of temporal lobe epilepsy (TLE), and executive control (EC) may be particularly impaired in patients with TLE with comorbid depression. The purpose of this study was to investigate brain network alterations in patients with TLE with or without depression using scalp electroencephalography (EEG), and to explore the potential mechanisms of TLE with comorbid depression. METHODS: Forty patients with TLE and 20 healthy controls (HC) were recruited for administered the BDI-II and HAMD-17 surveys. The patients with TLE were divided into those with depression (PDS, n = 20) and those without depression (nPDS, n = 20) according to the surveys. Neural oscillations and functional connectivity during performance of EC tasks were calculated during EEG. RESULTS: Theta oscillation and functional connectivity were significantly weakened in the PDS group compared to the nPDS and HC groups. Furthermore, the PDS group showed more serious EC dysfunction than nPDS group. CONCLUSIONS: Our results indicated that weakened theta oscillation and functional connectivity in the frontal lobe may be a mechanism of EC dysfunction in TLE with comorbid depression. SIGNIFICANCE: The present results suggest that the alterations in frontal lobe connections may help predict the depression in patients with TLE.