Clinical benefits of novel non-nucleoside reverse transcriptase inhibitors: A prospective cohort study.

INTRODUCTION: The efficacy and safety of ainuovirine+lamivudine+tenofovir (ANV+3TC+TDF) and efavirenz+lamivudine+tenofovir (EFV+3TC+TDF) have been confirmed in previous clinical trials; however, there are no related studies on patient-reported outcomes. This study aimed to evaluate the effectiveness and safety of these 2 antiretroviral therapy regimens and to understand the patient's symptom experience and subjective experience of sleep quality through patient-reported outcomes. METHODS: This is a single-center prospective cohort study with 243 patients evaluated from October 1, 2021 to June 30, 2022. Virological effectiveness and patient-reported outcomes results were analyzed. The primary endpoint was the proportion of HIV viral load <50 copies/mL (virological suppression rate) at 48 weeks and the changes in the HIV symptom index and Pittsburgh sleep quality index. RESULTS: The virological suppression rates in the ANV+3TC+TDF and EFV+3TC+TDF groups were 83.6% (102/122) and 87.6% (106/121), respectively, at 48 weeks. In the ANV+3TC+TDF group, the scores of HIV symptom index and pittsburgh sleep quality index in the 48th week were lower than the baseline level (p < 0.05). Logistic regression results showed that the baseline regimen EFV+3TC+TDF was a risk factor for dizziness/lightheadedness (odds ratio = 3.153, 95% confidence interval: 1.473-6.748, p = 0.003), sadness/depression odds ratio = 2.404, 95% confidence interval:1.188-4.871, p = 0.015), and difficulty sleeping (odds ratio = 2.802, 95% confidence interval: 1.437-5.463, p = 0.002) at 48 weeks. CONCLUSIONS: Both regimens showed good virological effectiveness; however, compared with ANV+3TC+TDF, the EFV+3TC+TDF regimen reduced the prevalence of HIV-related symptoms.

Killing capacity analysis of tumor-infiltrating cytotoxic lymphocytes and impact on lymph node metastasis in differentiated papillary carcinoma of thyroid with the BRAF V600E mutation.

BACKGROUND: Cytotoxic lymphocytes (CLs) express potent toxins, including perforin (P) and granzyme-B (G), which brings about target cell death. The purpose of this study was to evaluate the killing capacity of tumor-infiltrating CLs by means of P and G analysis, and explore the association with lymph node metastasis in papillary carcinoma of thyroid (PTC) without Hashimoto's thyroiditis (HT). METHODS: Infiltration of lymphocytes in PTC was observed in frozen sections. Both fresh tumor tissues and paracancerous tissues with lymphocyte infiltration were collected and prepared into a single cell suspension. Flow cytometry was used to detect the percentages of CD3+P+, CD3+G+, CD8+P+, and CD8+G+ T lymphocytes (TLs) and CD16-CD56+P+ and CD16-CD56+G+ natural killer (NK) cells. Finally, we investigated differential expression of P and G in NK cells and cytotoxic T lymphocytes (CTLs) in paired tumor tissues (group T, n = 44) and paracancerous tissues (group N, n = 44) from patients with PTC with the BRAF V600E mutation. Furthermore, patients were divided into two groups according to whether cervical central lymph node metastasis (CCLNM) existed: group A (with lymph node metastases, n = 27) and group B (with nonlymph node metastases, n = 17). Patients were also divided into three groups according to the total number of positive CCLNM: group B, group C (with low-level lymph node metastases, less than 5, n = 17) and group D (with high-level lymph node metastases, no less than 5, n = 10). RESULTS: The percentage of CD3+P+ CTLs was significantly higher in group N than in group T (P < 0.05). The percentage of CD8+G+ CTLs was significantly higher in group T than in group N (P < 0.05). The percentages of CD3+G+, CD16-CD56+P+and CD16-CD56+G+ NK cells showed no significant difference in either group T or group N (P > 0.05). The percentages of CD3+P+ CTLs in group A and group C were significantly higher in the paracancerous tissue than in the tumor tissue (P < 0.05). The percentages of CD8+G+ CTLs in group A and group C were significantly higher in the tumor tissues than in the paracancerous tissues (P < 0.05). The percentage of CD16-CD56+G+ NK cells in group D was significantly higher in the tumor tissues than in the paracancerous tissues (P < 0.05). CONCLUSIONS: The killing capacity of infiltrating CLs in PTC differed between tumor tissues and paracancerous tissues. In cases with CCLNM, higher expression of CD16-CD56+G+ NK cells in tumor tissues may be associated with a high risk of lymph node metastasis.

Comparison of dolutegravir+Lamivudine and bictegravir/emtricitabine/tenofovir alafenamide in antiretroviral therapy-naïve patients infected with HIV: preliminary results from clinical practice.

BACKGROUND: The efficacy and safety of dolutegravir+lamivudine (DTG +3TC) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) have been demonstrated in clinical trials of treatment-naïve therapy. However, real-life data are lacking. We investigated and compared the virological outcomes and safety of DTG + 3TC with BIC/FTC/TAF in an adult cohort of people living with HIV (PLWH). RESEARCH DESIGN AND METHODS: We performed a retrospective cohort analysis of PLWH who were naïve to antiretroviral therapy and initiated the antiretroviral regimen of DTG + 3TC or BIC/FTC/TAF from January 2020 to March 2022. Treatment effectiveness, defined as the capability of treatment to achieve viral suppression (viral load < 50 copies/mL), was analyzed. Changes in immunology, metabolism, liver and renal function after 48 weeks of treatment were evaluated. RESULTS: At 48 weeks, both groups showed high viral suppression, with 82.4% (108/131) and 89% (129/145) of the patients in the BIC/FTC/TAF and DTG + 3TC groups, respectively, having viral suppression (OR = 0.58, 95% CI: 0.29-1.15, P = 0.3). No differences existed in immunology, metabolism, liver and renal function; however, BIC/FTC/TAF led to greater weight gain. CONCLUSIONS: Both optimization strategies showed high tolerability in antiretroviral therapy-naïve patients, with no differences in virological efficacy; however, BIC/FTC/TAF may be related to the risk of weight gain risk. Further research is required to evaluate this problem.

Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir Plus Lamivudine for Switch Therapy in Patients with HIV-1 Infection: A Real-World Cohort Study.

INTRODUCTION: Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir plus lamivudine (DTG + 3TC) are well tolerated and effective in clinical trials. This study aimed to evaluate the safety and efficacy of these two schemes in a real-world setting and to obtain the first dataset for switching to BIC/FTC/TAF and DTG + 3TC in a Chinese population. METHODS: This retrospective single-center cohort study in China included participants who switched to DTG + 3TC or BIC/FTC/TAF between January 2020 and February 2023. The main endpoint was the proportion of participants with HIV-1 RNA levels of ≥ 50 copies/mL. Safety, tolerance, and the incidence of low-level viremia (LLV) were evaluated. RESULTS: A total of 525 participants were included, 454 of whom were included in the PP analysis. At week 48, the proportions of participants with HIV-1 RNA ≥ 50 copies/mL were 4.4% (10/225) for DTG + 3TC and 6.1% (14/229) for BIC/FTC/TAF; virological efficacy did not differ significantly between the two groups. Consistent results were obtained in an intent-to-treat (ITT) analysis. The incidences of LLV were 3.6% (7/193) and 4.9% (10/206), respectively. During the study, none of the participants stopped taking drugs because of a lack of efficacy or adverse reactions. CONCLUSIONS: Both regimens are well tolerated and effective for switching HIV-1 infection therapy. However, the detection of genotypic drug resistance should be considered when baseline virological non-suppression is observed.

Genomic analysis of Colletotrichum camelliae responsible for tea brown blight disease.

BACKGROUND: Colletotrichum camelliae, one of the most important phytopathogenic fungi infecting tea plants (Camellia sinensis), causes brown blight disease resulting in significant economic losses in yield of some sensitive cultivated tea varieties. To better understand its phytopathogenic mechanism, the genetic information is worth being resolved. RESULTS: Here, a high-quality genomic sequence of C. camelliae (strain LT-3-1) was sequenced using PacBio RSII sequencing platform, one of the most advanced Three-generation sequencing platforms and assembled. The result showed that the fungal genomic sequence is 67.74 Mb in size (with the N50 contig 5.6 Mb in size) containing 14,849 putative genes, of which about 95.27% were annotated. The data revealed a large class of genomic clusters potentially related to fungal pathogenicity. Based on the Pathogen Host Interactions database, a total of 1698 genes (11.44% of the total ones) were annotated, containing 541 genes related to plant cell wall hydrolases which is remarkably higher than those of most species of Colletotrichum and others considered to be hemibiotrophic and necrotrophic fungi. It's likely that the increase in cell wall-degrading enzymes reflects a crucial adaptive characteristic for infecting tea plants. CONCLUSION: Considering that C. camelliae has a specific host range and unique morphological and biological traits that distinguish it from other species of the genus Colletotrichum, characterization of the fungal genome will improve our understanding of the fungus and its phytopathogenic mechanism as well.

Clinical efficacy, safety, and subjective experience based on ePRO in HIV-infected individuals administered Bictegravir/Emtricitabine/Tenofovir Alafenamide in southwest China.

BACKGROUND: Prospective studies examining long-term therapeutic outcomes of the Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) regimen in human immunodeficiency virus (HIV) infection remain limited. This study assessed the actual efficacy and safety of BIC/FTC/TAF in HIV-infected individuals in southwest China. METHODS: This was a single-center, prospective study enrolling ART-naïve (n = 32) and ART-experienced (n = 177) HIV-infected patients administered BIC/FTC/TAF treatment between March 2022 and August 2022. The data were collected until February 28, 2023. Virological reactions and adverse events to the treatment were recorded, and patient subjective feelings in the form of Electronic Patient Reporting Outcome (ePRO) were collected. The primary endpoint was the rate of patients with HIV viral load <50 copies/mL at Week 24. RESULTS: At Week 24, 87.5% and 95.5% of ART-naïve and ART-experienced HIV patients had a viral load <50 copies/mL, respectively. CD4 cell counts in ART-naïve and ART-experienced patients increased significantly by 163.5 cells/µL (p = .002) and 55.0 cells/µL (p = .022), respectively. By Week 24, no patients had discontinued the BIC/FTC/TAF treatment due to adverse events. Based on ePRO data, ART-naïve and ART-experienced patients at Week 24 had stable disease symptom burden, quality of life, and depression level after treatment with BIC/FTC/TAF. CONCLUSION: BIC/FTC/TAF reduces the viral load in ART-naïve patients with high viral load as well as ART-experienced patients with residual viremia. The patient's subjective experience was maintained stable after treatment with BIC/FTC/TAF. This study also revealed a very low incidence for BIC/FTC/TAF drug-related side effects.

A special satellite-like RNA of a novel hypovirus from Pestalotiopsis fici broadens the definition of fungal satellite.

Satellites associated with plant or animal viruses have been largely detected and characterized, while those from mycoviruses together with their roles remain far less determined. Three dsRNA segments (dsRNA 1 to 3 termed according to their decreasing sizes) were identified in a strain of phytopathogenic fungus Pestalotiopsis fici AH1-1 isolated from a tea leaf. The complete sequences of dsRNAs 1 to 3, with the sizes of 10316, 5511, and 631 bp, were determined by random cloning together with a RACE protocol. Sequence analyses support that dsRNA1 is a genome of a novel hypovirus belonging to genus Alphahypovirus of the family Hypoviridae, tentatively named Pestalotiopsis fici hypovirus 1 (PfHV1); dsRNA2 is a defective RNA (D-RNA) generating from dsRNA1 with septal deletions; and dsRNA3 is the satellite component of PfHV1 since it could be co-precipitated with other dsRNA components in the same sucrose fraction by ultra-centrifuge, suggesting that it is encapsulated together with PfHV1 genomic dsRNAs. Moreover, dsRNA3 shares an identical stretch (170 bp) with dsRNAs 1 and 2 at their 5' termini and the remaining are heterogenous, which is distinct from a typical satellite that generally has very little or no sequence similarity with helper viruses. More importantly, dsRNA3 lacks a substantial open reading frame (ORF) and a poly (A) tail, which is unlike the known satellite RNAs of hypoviruses, as well as unlike those in association with Totiviridae and Partitiviridae since the latters are encapsidated in coat proteins. As up-regulated expression of RNA3, dsRNA1 was significantly down-regulated, suggesting that dsRNA3 negatively regulates the expression of dsRNA1, whereas dsRNAs 1 to 3 have no obvious impact on the biological traits of the host fungus including morphologies and virulence. This study indicates that PfHV1 dsRNA3 is a special type of satellite-like nucleic acid that has substantial sequence homology with the host viral genome without encapsidation in a coat protein, which broadens the definition of fungal satellite.

Insulin modified Decellularized Adipose Tissue/Tremella Polysaccharide hydrogel loaded with ADSCs for skin wound healing.

Full-thickness skin wounds still represent a challenge for clinical treatment. Adipose-derived stem cells (ADSCs) therapy is a promising approach to achieve efficient healing in skin wounds. The excellent cell scaffold can promote proliferation, differentiation and paracrine of ADSCs in wound microenvironment, and is a key factor in ADSCs application. Herein, we first prepared the composite hydrogel with decellularized adipose tissue (DAT) and tremella polysaccharide (TPS), and loaded insulin (INS) into the DAT/TPS composite hydrogel (DAT/TPS-gel) to fabricate an efficient carrier for ADSCs in treating skin wound. Our study showed that INS modified DAT/TPS-gel (INS-DAT/TPS-gel) can promote the proliferation, differentiation and paracrine of ADSCs. INS-DAT/TPS-gel laden with ADSCs (ADSCs/INS-DAT/TPS-gel) effectively facilitated the skin wound healing in SD rats. These findings indicated that INS-DAT/TPS-gel was an effective scaffold for ADSCs transplantation, and ADSCs/INS-DAT/TPS-gel provides a potential strategy for the treatment of skin wounds.

Cohort size required for prognostic genes analysis of stage II/III esophageal squamous cell carcinoma.

Background: Few overlaps between prognostic biomarkers are observed among different independently performed genomic studies of esophageal squamous cell carcinoma (ESCC). One of the reasons for this is the insufficient cohort size. How many cases are needed to prognostic genes analysis in ESCC? Methods: Here, based on 387 stage II/III ESCC cases analyzed by whole-genome sequencing from one single center, effects of cohort size on prognostic genes analysis were investigated. Prognostic genes analysis was performed in 100 replicates at each cohort size level using a random resampling method. Results: The number of prognostic genes followed a power-law increase with cohort size in ESCC patients with stage II and stage III, with exponents of 2.27 and 2.25, respectively. Power-law curves with increasing events number were also observed in stage II and III ESCC, respectively, and they almost overlapped. The probability of obtaining statistically significant prognostic genes shows a logistic cumulative distribution function with respect to cohort size. To achieve a 100% probability of obtaining statistically significant prognostic genes, the minimum cohort sizes required in stage II and III ESCC were approximately 95 and 60, respectively, corresponding to a number of outcome events of 33 and 36, respectively. Conclusion: In summary, the number of prognostic genes follows a power-law growth with the cohort size or events number in ESCC. The minimum events number required to achieve a 100% probability of obtaining a statistically significant prognostic gene is approximately 35.

A biotin-stabilized HKUST-1/ADM scaffold for facilitating MSC endothelial differentiation and vascularization in diabetic wound healing.

Inadequate angiogenesis in diabetic wound healing has been identified as one of the most difficult issues to treat. Copper ions (Cu2+) have been confirmed to stimulate angiogenesis; nevertheless, the rapid rise in non-physiological Cu2+ concentrations increases the danger of ion poisoning. For the first time, biotin was used to stabilize a copper-based metal-organic framework (HKUST-1) to change its hydrophobicity and achieve sustained release of Cu2+. The inability to offer a suitable area for the dynamic interaction between cells and growth factors still restricts the use of nanomaterials for the regeneration of injured skin in diabetes. Acellular dermal matrix (ADM) scaffolds are collagen fibers with natural spatial tissue that can create a biological "niche" for cell attachment and growth. In this study, biotin-stabilized HKUST-1 (B-HKUST-1) nanoparticles were modified with an ADM to form a novel scaffold (ADM-B-HKUST-1). Notably, Cu2+ and mesenchymal stem cells (MSCs) released by the composite scaffold may synergistically promote MSC adhesion, proliferation and endothelial differentiation by upregulating the expression of transforming growth factor-ß (TGF-ß), vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA). Overall, the ADM-B-HKUST1 scaffold combines the dual advantages of the sustained release of Cu2+ and creating a biological "niche" can provide a potential strategy for enhancing angiogenesis and promoting diabetic wound healing.

Novel Viroid-Like RNAs Naturally Infect a Filamentous Fungus.

To date, viroids have been found to naturally infect only plants, resulting in substantial losses for some crops. Whether viroids or viroid-like RNAs naturally infect non-plant hosts remains unknown. Here the existence of a set of exogenous, single-stranded circular RNAs, ranging in size from 157 to 450 nucleotides, isolated from the fungus Botryosphaeria dothidea and nominated B. dothidea RNAs (BdcRNAs) is reported. BdcRNAs replicate autonomously in the nucleus via a rolling-circle mechanism following a symmetric pathway. BdcRNA infection induces symptoms, because BdcRNAs can apparently modulate, to different degrees, specific biological traits (e.g., alter morphology, decrease growth rate, attenuate virulence, and increase or decrease tolerance to osmotic and oxidative stress) of the host fungus. Overall, BdcRNAs have genome characteristics similar to those of viroids and exhibit pathogenic effects on fungal hosts. It is proposed that these novel fungus infecting RNAs should be termed mycoviroids. BdcRNA(s) may be considered additional inhabitants at the frontier of life in terms of genomic complexity, and represent a new class of acellular entities endowed with regulatory functions, and novel epigenomic carriers of biological information.

PLGA@IL-8 nanoparticles-loaded acellular dermal matrix as a delivery system for exogenous MSCs in diabetic wound healing.

Diabetic chronic wounds are not only accompanied by inflammation and ulcers but also cause amputation when they develop into severe diabetic foot. Mesenchymal stem cells (MSCs) have been proven to ameliorate diabetic wound healing, however, the low survival rate of exogenous MSCs after transplantation into the highly proteolytic wound environment is a major obstacle to effective stem cell therapy. Herein, to improve the proliferation, differentiation, and anti-apoptosis ability of transplanted MSCs, we prepared Poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulated with anti-inflammatory and angiogenic cytokine IL-8, then loaded the nanospheres on acellular dermal matrix to fabricate an efficient delivery medium (PLGA@IL-8/ADM) for exogenous MSCs. It was observed that, in the PLGA@IL-8-loaded ADM, MSCs presented significant proliferation and endothelial differentiation with a great survival rate. In addition, PLGA@IL-8/ADM laden with MSCs effectively induced the capillary construction, collagen deposition and wound healing in cutaneous wounds of streptozotocin-induced diabetic mice. Further immunofluorescence analysis indicated that proangiogenic factors (VEGF and α-SMA) were upregulated in regenerated tissue. Overall, our findings indicated that PLGA@IL-8/ADM-MSCs was a potential therapeutic dressing that may contribute to the therapy of diabetic wounds and the PLGA@IL-8/ADM scaffold would be a novel delivery system for exogenous cells for tissue regeneration.

Clinical evaluation of percutaneous endovascular radiofrequency ablation for portal vein tumor thrombus: experience in 120 patients.

BACKGROUND: Portal vein tumor thrombosis (PVTT) secondary to primary liver carcinoma (PLC) is commonly associated with poor prognosis and poses great challenge. This study was to evaluate the efficacy and safety of percutaneous endovascular radiofrequency ablation (RFA) in treatment of PVTT. METHODS: Consecutive patients who were performed endovascular RFA because of PVTT in single-institution in recent 8 years were retrospectively reviewed, compared with patients who underwent only sequential transcatheter arterial chemoembolization (TACE) during the contemporary period. Patency of portal vein, complications, and overall survival (OS) were investigated. RESULTS: One hundred and 20 patients who underwent endovascular RFA and 96 patients who underwent only sequential TACE were included. No severe complications happened in both groups. Except the higher rates of severe fever and moderate pain in the study group, no difference was found in the incidence of side effects and complications. The effective rate in the study group was (78.3%, 94/120) significantly higher than the comparison group (35.4%, 34/96). The median survival time and 1-3 years cumulative survival rates in the study group were 15.7 months and 42.5%, 21.7%, 2.5%, respectively, and 11.3 months, 21.9%, 9.4%, 0 correspondingly in the comparison group, without significant difference. Type of PVTT and Child-Pugh classification of liver function were independent risk factors, and OS was significantly improved by endovascular RFA and subsequent therapy. CONCLUSION: Endovascular RFA is technically safe and feasible for unresectable PLC and PVTT to improve the prognosis and quality of life.

Intra-tumor heterogeneity and prognostic risk signature for hepatocellular carcinoma based on single-cell analysis.

Intra-tumor heterogeneity poses a serious challenge in the treatment of cancer, including hepatocellular carcinoma (HCC). Recent developments in single-cell RNA sequencing (scRNA-seq) make it possible to examine the heterogeneity of tumor cells. The Gene Expression Omnibus (GEO) database was retrieved to obtain scRNA-seq data of 13 HCC and 8 para cancer samples, and the cells were clustered using FindNeighbors and FindClusters functions. Cell subsets were defined using the "Enricher" function of the clusterProfiler package. Monocle was used to predict cell developmental trajectory. The LIMMA package included in the R program was utilized to detect differentially expressed genes (DEGs) between HCC and paracancerous tissues. Univariate Cox analysis and Least Absolute and Selection Operator (Lasso) Cox regression analysis were conducted to establish a risk assessment model. Thirteen cell subpopulations were identified from the sequencing data of 64,634 single cells. Four cell subgroups (dendritic cells, hepatocytes, liver bud hepatic cells, and liver progenitor cells) in tumor tissues were highly enriched. Between HCC and para cancer tissues, 3024 DEGs were identified, and 641 were specific markers of four cell subgroups. To develop a prognostic risk model, 9 genes among the 641 genes were selected. In the training and validation sets, the model demonstrated a higher 5-year AUC and independently served as a prognostic marker as confirmed by multivariate and univariate Cox analyses. This study revealed the characteristics of different cell subpopulations of immune cells and tumor cells from the HCC microenvironment. We established a novel nine-gene prognostic model to determine the death risk of HCC patients. The discoveries in this research improved the current knowledge of HCC heterogeneity and may inspire future research.

Abnormal dynamic functional network connectivity in male obstructive sleep apnea with mild cognitive impairment: A data-driven functional magnetic resonance imaging study.

Objective: The purpose of this study was to investigate the dynamic functional network connectivity (FNC) and its relationship with cognitive function in obstructive sleep apnea (OSA) patients from normal cognition (OSA-NC) to mild cognitive impairment (OSA-MCI). Materials and methods: Eighty-two male OSA patients and 48 male healthy controls (HC) were included in this study. OSA patients were classified to OSA-MCI (n = 41) and OSA-NC (n = 41) based on cognitive assessments. The independent component analysis was used to determine resting-state functional networks. Then, a sliding-window approach was used to construct the dynamic FNC, and differences in temporal properties of dynamic FNC and functional connectivity strength were compared between OSA patients and the HC. Furthermore, the relationship between temporal properties and clinical assessments were analyzed in OSA patients. Results: Two different connectivity states were identified, namely, State I with stronger connectivity and lower frequency, and State II with lower connectivity and relatively higher frequency. Compared to HC, OSA patients had a longer mean dwell time and higher fractional window in stronger connectivity State I, and opposite result were found in State II, which was mainly reflected in OSA-MCI patients. The number of transitions was an increasing trend and positively correlated with cognitive assessment in OSA-MCI patients. Compared with HC, OSA patients showed extensive abnormal functional connectivity in stronger connected State I and less reduced functional connectivity in lower connected State II, which were mainly located in the salience network, default mode network, and executive control network. Conclusion: Our study found that OSA patients showed abnormal dynamic FNC properties, which was a continuous trend from HC, and OSA-NC to OSA-MCI, and OSA patients showed abnormal dynamic functional connectivity strength. The number of transformations was associated with cognitive impairment in OSA-MCI patients, which may provide new insights into the neural mechanisms in OSA patients.

Abnormal cerebellar-prefrontal cortical pathways in obstructive sleep apnea with/without mild cognitive impairment.

Obstructive sleep apnea (OSA), a common respiratory sleep disorder, is often associated with mild cognitive impairment (MCI), which is a precursor stage to Alzheimer's disease (AD). However, the neuroimaging changes in patients with OSA with/without MCI are still under discussion. This study aimed to investigate the temporal variability of spontaneous brain activity in OSA. Fifty-two OSA patients (26 with OSA with MCI (OSA-MCI), 26 OSA without MCI (OSA-nMCI), and 26 healthy controls (HCs) underwent MRI scans and scale questionnaires. A dynamic amplitude of low-frequency fluctuation (dALFF) evaluation was performed to examine the time-varying nature of OSA-MCI and OSA-nMCI. Compared with OSA-MCI, OSA-nMCI had increased dALFF in the posterior cerebellar and right superior frontal gyrus; compared with HCs, OSA-nMCI patients showed increased dALFF in the right posterior cerebellum. A positive correlation between the bilateral posterior cerebellar lobes and right superior frontal gyrus was observed in OSA-MCI patients; however, in OSA-nMCI patients, a positive correlation was observed only between the bilateral posterior cerebellar lobes. The dALFF value of the left posterior cerebellar lobe was positively correlated with the apnea-hypopnea index (AHI), epworth sleepiness scale (ESS) score, and arousal index in OSA-nMCIs, while the dALFF value of the right posterior cerebellum was positively correlated with the AHI and negatively correlated with the lowest oxygen saturation (SaO2). This study argues that OSA-nMCIs and OSA-MCIs exhibit different temporal variabilities in dynamic brain functions, OSA-nMCIs may have variable intermediate states. We concluded that the functional abnormalities of the cerebellar-prefrontal cortex pathway in OSA-MCIs may cause cognitive impairment with OSA.

Frequency-specific alterations in intrinsic low-frequency oscillations in newly diagnosed male patients with obstructive sleep apnea.

Purpose: Previous studies found abnormal low-frequency spontaneous brain activity related to cognitive impairment in patients with obstructive sleep apnea (OSA). However, it is unclear if low-frequency spontaneous brain activity is related to specific frequency bands in OSA patients. In this study, we used the amplitude of low-frequency fluctuation (ALFF) method in patients with OSA to explore characteristics of spontaneous brain activity in the classical (0.01-0.1 Hz) and five sub-frequency bands (slow-2 to slow-6) and analyzed the relationship between spontaneous brain activity and clinical evaluation was analyzed. Patients and methods: Resting-state magnetic resonance imaging data and clinical assessments were collected from 52 newly-diagnosed OSA patients and 62 healthy controls (HCs). We calculated the individual group ALFF values in the classical and five different sub-frequency bands. A two-sample t-test compared ALFF differences, and one-way analysis of variance explored interactions in frequency bands between the two groups. Results: ALFF values in the OSA group were lower than those in the HC group in the bilateral precuneus/posterior cingulate cortex, bilateral angular gyrus, left inferior parietal lobule, brainstem, and right fusiform gyrus. In contrast, ALFF values in the OSA group were higher than those in the HC group in the bilateral cerebellum posterior lobe, bilateral superior frontal gyrus, bilateral middle frontal gyrus, left inferior frontal gyrus, left inferior temporal gyrus, and left fusiform gyrus. Some ALFF values in altered brain regions were associated with body mass index, apnea-hypopnea index, neck circumference, snoring history, minimum SaO2, average SaO2, arousal index, oxygen reduction index, deep sleep period naming, abstraction, and delayed recall in specific frequency bands. Conclusion: Our results indicated the existence of frequency-specific differences in spontaneous brain activity in OSA patients, which were related to cognitive and other clinical symptoms. This study identified frequency-band characteristics related to brain damage, expanded the cognitive neuroimaging mechanism, and provided additional OSA neuroimaging markers.

New perspective of ceria nanodots for precise tumor therapy via oxidative stress pathway.

Ceria-based nanomaterials have aroused major attentions among the biomedical application research field in recent years. Most of the researches have mainly focused on promoting the functional healing therapies of normal cells/organs with cerium oxide compounds, while the applications of ceria-based materials employed on cancer curing processes have been merely mentioned. To explore the possible capabilities of cerium oxide nanomaterials exterminating tumor cells, innovatively, we synthesized the eco-friendly pure cerium oxide nanodots (CNDs), proving the prominent ability of CNDs used in tumor chemotherapy (CDT) via Fenton reaction with the highly presence of H2O2 (acidic pH) in tumor tissues. CNDs reacted with the self-produced H2O2 of tumor cells, which generated piled up toxic hydroxyl radical (·OH). The accumulated virulent ·OH restrained the growth of cancer cells intensively. This peroxidase-like activity, provided a distinguished paradigm for effective cancer curing treatment. We also verified the biosafety of CNDs applied on normal cells. Notably, not only did CNDs be harmless to normal cells, but also it protected them from the damages of reactive oxygen species (ROS). In normal cells/tissues, under the microenvironment of neutral pH and low level of H2O2, the CNDs could effectively function as an annihilator inhibiting ROS. They reduced the damages caused by ROS, exhibiting catalase-like activity. The research we studied, which estimated CNDs thoroughly, has provided a new perspective to the future researches of the cerium oxide biomaterial applications.

Effects of 3-month CPAP therapy on brain structure in obstructive sleep apnea: A diffusion tensor imaging study.

White matter (WM) fiber alterations in patients with obstructive sleep apnea (OSA) is associated with cognitive impairment, which can be alleviated by continuous positive airway pressure (CPAP). In this study, we aimed to investigate the changes in WM in patients with OSA at baseline (pre-CPAP) and 3 months after CPAP adherence treatment (post-CPAP), and to provide a basis for understanding the reversible changes after WM alteration in this disease. Magnetic resonance imaging (MRI) was performed on 20 severely untreated patients with OSA and 20 good sleepers. Tract-based spatial statistics was used to evaluate the fractional anisotropy (FA), mean diffusion coefficient, axial diffusion coefficient, and radial diffusion coefficient (RD) of WM. To assess the efficacy of treatment, 20 patients with pre-CPAP OSA underwent MRI again 3 months later. A correlation analysis was conducted to evaluate the relationship between WM injury and clinical evaluation. Compared with good sleepers, patients with OSA had decreased FA and increased RD in the anterior thalamic radiation, forceps major, inferior fronto-occipital tract, inferior longitudinal tract, and superior longitudinal tract, and decreased FA in the uncinate fasciculus, corticospinal tract, and cingulate gyrus (P < 0.05). No significant change in WM in patients with post-CPAP OSA compared with those with pre-CPAP OSA. Abnormal changes in WM in untreated patients with OSA were associated with oxygen saturation, Montreal cognitive score, and the apnea hypoventilation index. WM fiber was extensively alteration in patients with severe OSA, which is associated with cognitive impairment. Meanwhile, cognitive recovery was not accompanied by reversible changes in WM microstructure after short-term CPAP therapy.

Abnormal Spontaneous Brain Activity and Cognitive Impairment in Obstructive Sleep Apnea.

Purpose: This study aimed to explore the alterations in spontaneous brain activity in obstructive sleep apnea (OSA) using percent amplitude of fluctuation (PerAF) and investigate the relationship between abnormal spontaneous brain activity and cognitive impairment in OSA. Patients and Methods: Overall, 52 patients with moderate to severe OSA and 61 healthy controls (HCs) were eventually enrolled in this study. All participants underwent resting-state functional magnetic resonance (rs-fMRI) and T1-weighted imaging. The PerAF was calculated and compared between patients with OSA and HCs, with voxel level P < 0.001 and cluster level P < 0.05 corrected with Gaussian Random Field was be considered statistically different. A partial correlation analysis was used to assess the relationship between altered PerAF and clinical assessments in patients with OSA. Results: Compared to HCs, patients with OSA had significantly lower PerAF values in the right rectal gyrus and left superior frontal gyrus, but higher PerAF values in the right cerebellum posterior lobe and left middle frontal gyrus. The PerAF values of some specific regions in patients with OSA correlated with sleep efficiency and Montreal Cognitive Assessment scores. Additionally, support vector machine analysis showed that PerAF values in all differential brain regions could differentiate patients with OSA from HCs with good accuracy. Conclusion: Specific brain areas in OSA patients may exhibit aberrant neuronal activity, and these anomalies may be linked to decreased cognitive performance. This discovery offers fresh perspectives on these patients' neurocognition.