Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy.

LncRNA XLOC_032768 is reported to prevent renal tubular epithelial cells from cisplatin-induced apoptosis, suggesting its involvement in the development of kidney injury. The present study aimed to explore the role of XLOC_032768 in diabetic nephropathy (DN). The present study enrolled a total of 140 healthy controls (Control group) and 140 patients with type 2 diabetes (Diabetes group). Expression of XLOC_032768 in plasma from these participants was analyzed by performing RT-qPCR. The 140 diabetic patients were followed up for 5 years to monitor the occurrence of diabetic complications. The role of XLOC_032768 in predicting the occurrence of diabetic complications, including DN, diabetic cardiomyopathy (DC), diabetic retinopathy (DR), and diabetic foot (DF) were analyzed by plotting receiver operating characteristic curves and complication-free curves. On the day of admission, plasma levels of XLOC_032768 were not significantly different between Control and Diabetes groups. During follow-up, a total of 22, 15, 13, and 15 cases were diagnosed as DN, DC, DR, and DF, respectively. On the day of diagnosis, plasma levels of XLOC_032768 were only decreased in DN group, but not in other groups, compared to plasma levels of XLOC_032768 on the day of admission. Using plasma levels of XLOC_032768 on the day of admission as a biomarker, potential DN patients were effectively separated from patients with other potential complications and diabetic patients without complications. The 140 diabetic patients were grouped into high and low XLOC_032768 level groups. It was observed that low XLOC_032768 level group showed increased occurrence of DN, but not other complications, compared to high XLOC_032768 level group. Therefore, the downregulation of lncRNA XLOC_032768 in diabetic patients may predict the occurrence of DN.

External Stimuli-Responsive Strategies for Surface Modification of Orthopedic Implants: Killing Bacteria and Enhancing Osteogenesis.

Bacterial infection and insufficient osteogenic activity are the main causes of orthopedic implant failure. Conventional surface modification methods are difficult to meet the requirements for long-term implant placement. In order to better regulate the function of implant surfaces, especially to improve both the antibacterial and osteogenic activity, external stimuli-responsive (ESR) strategies have been employed for the surface modification of orthopedic implants. External stimuli act as "smart switches" to regulate the surface interactions with bacteria and cells. The balance between antibacterial and osteogenic capabilities of implant surfaces can be achieved through these specific ESR manifestations, including temperature changes, reactive oxygen species production, controlled release of bioactive molecules, controlled release of functional ions, etc. This Review summarizes the recent progress on different ESR strategies (based on light, ultrasound, electric, and magnetic fields) that can effectively balance antibacterial performance and osteogenic capability of orthopedic implants. Furthermore, the current limitations and challenges of ESR strategies for surface modification of orthopedic implants as well as future development direction are also discussed.

Chitosan/NH2-MIL-125 (Ti) scaffold loaded with doxorubicin for postoperative bone tumor clearance and osteogenesis: An in vitro study.

Surgical resection remains the primary treatment modality for bone tumors. However, it is prone to local bone defects and tumor recurrence. Therefore, there is an urgent need for multifunctional biomaterials that combine tumor treatment and bone repair after bone tumor surgery. Herein, a chitosan composite scaffold (CS/DOX@Ti-MOF) was designed for both tumor therapy and bone repair. Among them, the amino-functionalized Ti-based metal-organic framework (NH2-MIL-125 (Ti), Ti-MOF) has a high specific surface area of 1116 m2/g and excellent biocompatibility, and promotes osteogenic differentiation. The doxorubicin (DOX) loading capacity of Ti-MOF was 322 ± 21 mg/g, and DOX@Ti-MOF has perfect antitumor activity. Furthermore, the incorporation of DOX@Ti-MOF improved the physical and mechanical properties of the composite scaffolds, making the scaffold surface rough and favorable for cells to attach. CS/DOX@Ti-MOF retains the unique properties of each component. It responds to the release of DOX in the tumor microenvironment to remove residual tumor cells, followed by providing a site for cell attachment, proliferation, and differentiation. This promotes bone repair and achieves the sequential treatment of postoperative bone tumors. Overall, CS/DOX@Ti-MOF may be a promising substitute for postoperative bone tumor clearance and bone defect repair. It also provides a possible strategy for postoperative bone tumor treatment.

Efficacy and Cost-Effectiveness Analysis of Internet-Based Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder: Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common and chronic mental illness with a high rate of disability. Internet-based cognitive behavioral therapy (ICBT) makes online treatment available to patients and has been shown to be effective. However, 3-arm trials on ICBT, face-to-face cognitive behavioral group therapy (CBGT), and only medication are still lacking. OBJECTIVE: This study is a randomized, controlled, assessor-blinded trial of 3 groups for OCD: ICBT combined with medication, CBGT combined with medication, and conventional medical treatment (ie, treatment as usual [TAU]). The study aims to investigate the efficacy and cost-effectiveness of ICBT related to CBGT and TAU for adults with OCD in China. METHODS: In total, 99 patients with OCD were selected and randomly assigned to the ICBT, CBGT, and TAU groups for treatment for 6 weeks. The primary outcomes were the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and the self-rating Florida Obsessive-Compulsive Inventory (FOCI), compared at baseline, during treatment (3 weeks), and after treatment (6 weeks), to analyze efficacy. The secondary outcome was the EuroQol Visual Analogue Scale (EQ-VAS) scores of the EuroQol 5D Questionnaire (EQ-5D). The cost questionnaires were recorded to analyze cost-effectiveness. RESULTS: Repeated-measures ANOVA was used for data analysis, and the final effective sample size was 93 (ICBT: n=32, 34.4%; CBGT: n=28, 30.1%; TAU: n=33, 35.5%). After 6-week treatment, the YBOCS scores of the 3 groups significantly decreased (P<.001), and there were no significant differences among groups. The FOCI score of the ICBT (P=.001) and CBGT (P=.035) groups was significantly lower than that of the TAU group after treatment. The total cost of the CBGT group (renminbi [RMB] 6678.45, 95% CI 4460.88-8896.01 [US $1010.36, 95% CI 678.87-1345.84]) was significantly higher than that of the ICBT group (RMB 3308.81, 95% CI 2476.89-4140.73[US $500.58, 95% CI 374.72-626.43], P<.001) and the TAU group (RMB 2259.61, 95% CI 2074.16-2445.05 [US $341.85, 95% CI 313.79-369.90], P<.001) after treatment. The ICBT group spent RMB 303.19 (US $45.97) less than the CBGT group and RMB 11.57 (US $1.75) less than the TAU group for each unit reduction in the YBOCS score. CONCLUSIONS: Therapist-guided ICBT combined with medication is as effective as face-to-face CBGT combined with medication for OCD. ICBT combined with medication is more cost-effective than CBGT combined with medication and conventional medical treatment. It is expected to become an efficacious and economic alternative for adults with OCD when face-to-face CBGT is not available. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900023840; https://www.chictr.org.cn/showproj.html?proj=39294.

Inhibiting Osteolytic Breast Cancer Bone Metastasis by Bone-Targeted Nanoagent via Remodeling the Bone Tumor Microenvironment Combined with NIR-II Photothermal Therapy.

Bone is one of the prone metastatic sites of patients with advanced breast cancer. The "vicious cycle" between osteoclasts and breast cancer cells plays an essential role in osteolytic bone metastasis from breast cancer. In order to inhibit bone metastasis from breast cancer, NIR-II photoresponsive bone-targeting nanosystems (CuP@PPy-ZOL NPs) are designed and synthesized. CuP@PPy-ZOL NPs can trigger the photothermal-enhanced Fenton response and photodynamic effect to enhance the photothermal treatment (PTT) effect and thus achieve synergistic anti-tumor effect. Meanwhile, they exhibit a photothermal enhanced ability to inhibit osteoclast differentiation and promote osteoblast differentiation, which reshaped the bone microenvironment. CuP@PPy-ZOL NPs effectively inhibited the proliferation of tumor cells and bone resorption in the in vitro 3D bone metastases model of breast cancer. In a mouse model of breast cancer bone metastasis, CuP@PPy-ZOL NPs combined with PTT with NIR-II significantly inhibited the tumor growth of breast cancer bone metastases and osteolysis while promoting bone repair to achieve the reversal of osteolytic breast cancer bone metastases. Furthermore, the potential biological mechanisms of synergistic treatment are identified by conditioned culture experiments and mRNA transcriptome analysis. The design of this nanosystem provides a promising strategy for treating osteolytic bone metastases.

Successful chemotherapy with continuous immunotherapy for primary pulmonary endovascular epithelioid hemangioendothelioma: A case report.

RATIONALE: Epithelioid hemangioendothelioma (EHE) is a rare, low to moderate-grade malignancy, even less in pulmonary endovascular neoplasm. Patients with pulmonary EHE have no optimal treatment, resulting in poor prognoses. PATIENT CONCERNS: We reported a 42-year-old man with multiple mild metabolic uptakes in pulmonary endovascular filling defect with a maximum standardized uptake value of 4.5 by 18-fluorodeoxyglucose/fibroblast associated protein inhibitor-positron emission tomography/ computed tomography. Anticoagulant treatment was not effective with the diagnosis of acute pulmonary embolism. DIAGNOSES: A primary endovascular EHE pulmonary endovascular epithelioid hemangioendothelioma was diagnosed by endovascular biopsy with positive stains for molecular CD31, CD34 and CAMTA1, and it had low proliferative capacity characterized by Ki-67 of 5%. The mutation gene MSH2 (p.Y656 in exon 12) (mutation abundance of 0.07%) from peripheral blood indicates the potential benefit of an immune checkpoint inhibitor, pembrolizumab. INTERVENTIONS AND OUTCOMES: The patient was treated with tri-weekly paclitaxel (175mg/m2) and carboplatin (AUC 5) chemotherapy regimen. He exerted a remarkable response after 5 cycles (21 days per cycle) and Pembrolizumab (200mg once monthly) as maintenance treatment. LESSONS: This case highlights the diagnostic challenge of differentiating endovascular lesions and optimal therapy for pulmonary EHE. Importantly, it indicated that the mutation gene MSH2 (p.Y656) might influence the pathogenesis of EHE.

Aloe polymeric acemannan inhibits the cytokine storm in mouse pneumonia models by modulating macrophage metabolism.

The cytokine storm is highly associated with inflammatory-type disease severity and patients' survival. Plant polysaccharides, the main natural phytomedicine source, have a great potential to be an effective drug to treat cytokine storm. Herein we found that a polymeric acemannan (ABPA1) isolated from Aloe Vera Barbadensis extract C (AVBEC) exerted prominent inhibitory effects on inflammation-induced cytokine storm. The results displayed that ABPA1 effectively suppressed LPS-induced proinflammatory cytokines release in vitro. Moreover, ABPA1 treatment alleviated the cytokine storm and tissue damage in LPS- and IAV-induced mouse pneumonia models, and altered the phenotypic balance of macrophages in lung tissues. Functionally, ABPA1 enhanced macrophage M2 polarization and phagocytosis in RAW264.7 cells and inhibited LPS-induced M1 polarization. Mechanistically, ABPA1 enhanced mitochondrial metabolism and OXPHOS through activated PI3K/Akt/GSK-3ß signalling pathway. Overall, our findings suggest that ABPA1 may modulate macrophage activation and mitochondrial metabolism by targeting PI3K/Akt/GSK-3ß signalling pathway, thereby alleviating cytokine storm and inflammation.

An acetylated mannan isolated from Aloe vera induce colorectal cancer cells apoptosis via mitochondrial pathway.

The anti-cancer effects of Aloe vera barbadensis extract C (AVBEC) have been demonstrated in a previous study. However, the specific functional ingredient and mechanism remain undefined. This study aimed to evaluate the function and associated mechanisms of purified polysaccharide (ABPA1) from AVBEC on colorectal cancer. Here, we identify that ABPA1 can induce colorectal cancer apoptosis. In vivo, ABPA1 significantly suppressed tumor growth in an orthotopic colon cancer model. Mechanistically, ABPA1 alters mitochondrial membrane permeability by promoting Bax translocation while causing cytochrome-c release, which initiates the caspase cascade reaction. Additionally, we found that ABPA1 exerted distinct impacts on the mitochondrial metabolism of colorectal cancer cells. Our study elucidated the mechanism by which the polysaccharide ABPA1 induces apoptosis in colorectal cancer cells through the regulation of Bax and cytochrome-c mediated mitochondrial pathway, indicating that ABPA1 may be developed as a mitochondrial-targeting anti-cancer drug.

Development and validation of a novel mitophagy-related gene prognostic signature for glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most malignant tumors in brain with high morbidity and mortality. Mitophagy plays a significant role in carcinogenesis, metastasis, and invasion. In our study, we aim to construct a mitophagy-related risk model to predict prognosis in GBM. METHODS: RNA-seq data combined with clinical information were downloaded from TCGA. The 4-gene risk model and nomograph was then constructed and validated in external cohort. Evaluation of immune infiltration, functional enrichment and tumor microenvironment (TME) were then performed. RESULT: A mitophagy-related risk model was established and patients in TCGA and CGGA were classified into low-risk and high-risk groups. In both cohorts, patients in low-risk group had improved survival, while high-risk group had poor prognosis. Also, the risk model was identified as an independent factor for predicting overall survival via Cox regression. Furthermore, a prognostic nomogram including mitophagy signatures was established with excellent predictive performance. In addition, the risk model was closely associated with regulation of immune infiltration as well as TME. CONCLUSION: In conclusion, our study constructed a mitophagy-related risk model, which can be utilized for the clinical prognostic prediction in GBM.

Ag nanoparticles/PbTiO3 with in-situ photocatalytic process and its application in an ultra-sensitive molecularly imprinted hemoglobin detection.

An electrochemical sensor based on loading molecularly imprinted polymers (MIP) on the material surface can improve the specificity towards the object. In this work, a T-shaped PbTiO3 with a high active-exposed (110) facet was prepared by a hydrothermal process. Then, Ag nanoparticles (Ag NPs) modified T-shaped PbTiO3 was obtained by in-situ photocatalytic reduced method under UV irradiation, where a hetero-junction was formed with a well lattice matching between the (111) facet of Ag0 and the (110) facet of PbTiO3. A MIPs modified by Ag nanoparticles (NPs)/PbTiO3 (MAP) electrodes was prepared via electro polymerization process by o-Phenylenediamine (o-PD) in the presence of the template molecule, bovine hemoglobin (BHb), i.e., the detected molecule. The response peak current and concentration of BHb is demonstrated with a good linear relationship in the range of 0.00294-0.41 nM (R2 =0.98), and the detection limit at 0.23 pM (S/N = 3). A heterojunction between Ag NPs and high- active facet of PbTiO3 is beneficial to oxidizing electroactive material ([Fe (CN)6]3-/4-), generating more BHb-imprinting cavities on the modified electrode and improving the sensitivity of sensor. The electrochemical sensor is with a simple, stable structure and high sensitivity to BHb detection. Furthermore, the sensor was successfully applied to detect BHb in the bovine serum samples.

Copper fumarate with high-bifunctional nanozyme activities at different pH values for glucose and epinephrine colorimetric detection in human serum.

Metal-organic frameworks (MOFs) have attracted extensive attention for the development of colorimetric detection methods due to their ease of modification and high density of active sites. However, most of the reported colorimetric sensors based on MOFs show only a single nanozyme activity. Herein, the bifunctional enzyme activities of a hexagonal prism Cu MOF with fumaric acid as the ligand (Cu FMA), namely laccase-like activity under alkaline conditions (pH = 8) and peroxidase-like activity under acidic conditions (pH = 4), were verified. The specificity of Cu FMA at different pH values may be due to the presence of the Cu+ active center introduced by the weak reducibility of FMA. At pH = 8, Cu+ active centers are beneficial for dissociating the H-O bonds of phenolic compounds for the laccase system. In contrast, the dissociation of H-O is weakened at pH = 4, which prompts the breaking of the O-O bonds of H2O2 as a Fenton-like reaction for the peroxidase system. Based on the dual enzyme activities, Cu FMA sensors exhibit outstanding detectability for epinephrine and glucose with linear ranges of 2.7-54.6 µM and 0.01-0.8 mM and detection limits of 1.1 µM and 2.28 × 10-7 M, respectively. The Cu FMA colorimetric sensor can be applied for detecting and measuring glucose and epinephrine in human serum samples. This work paves the way for Cu MOFs to be used as the basis for rational regulation of the activity of dual nanozymes and for multifunctional applications under completely independent conditions.

Study of differences between patients with schizophrenia and healthy people in semantic processing.

Semantic processing is important in language comprehension and production, and context can facilitate understanding and accelerate processing speed by pre-activating semantically related words. There are many studies suggesting that patients with schizophrenia have inferior language ability. This study was aimed to examine the differences between patients with schizophrenia and healthy people in semantic processing with Chinese classifier-noun pairs rating tasks. Participants were required to finish rating tasks to judge acceptability of classifier-noun pairs. Also, the Positive and Negative Syndrome Scale (PANSS) was conducted in the schizophrenia group. According to results of variance analysis, schizophrenic patients' accuracy of judgment on the acceptability of classifier-noun pairs differed from the control group (F = 4.13, p < .05), and the contextual effect of classifier constraint could be observed in healthy people (F(1, 31) = 5.38, p < .05) but not in patients with schizophrenia (F(1, 25) = 3.55, p = .07), indicating that they failed to use the contextual information to facilitate language comprehension as healthy people. Stepwise linear regression analysis found that hostility, poor impulse control and suspiciousness/persecution and preoccupation in the PANSS may have contributed to the reduced sensitivity in the rating in patients (t = -2.38-3.80, p < .05).

Meso-tetra(4-sulfonatophenyl)porphyrin silver/Ag nanoparticles/graphene-phase C3N4 with a sandwich-like structure and double-faced active centers via two-step room-temperature photocatalytic synthesis for ractopamine detection.

Photochemical synthesis under visible light irradiation is a novel approach in the field of green chemistry, and composites with abundant active centers for electrochemical detection are highly attractive. Herein, a meso-tetra(4-sulfonatophenyl)porphyrin silver/Ag nanoparticles/graphene phase C3N4 nanosheets (Ag2TPPS4/AgNPs/ng-C3N4) material with a sandwich-like structure was synthesized using a two-step photocatalytic reaction at room temperature (25 °C). In the first visible light irradiation step and in the presence of a hole capture agent, Ag+ ions were photocatalytically reduced onto the surface of ng-C3N4 that was used as a photocatalyst. Then, the protons (H+) in the core of H2TPPS4 were substituted in situ by photo-oxidized Ag+ during the second visible light irradiation step and in the presence of an electron capture agent. The electrochemical response of Ag2TPPS4 and ng-C3N4 to ractopamine (RAC) results in the unique double-faced active centers of Ag2TPPS4/AgNPs/ng-C3N4, and the cores (AgNPs) are beneficial as bridges for the connection between Ag2TPPS4 and ng-C3N4 and for high-efficiency electron transfer. Hence, as-synthesized Ag2TPPS4/AgNPs/ng-C3N4 exhibits high sensitivity (a low detection limit of 5.1 × 10-8 M, S/N = 3.0), a wide linear range (1 × 10-7 to 1.2 × 10-5 M), and long-term stability. Based on the experimental verification of the electrochemical dynamics and electrostatic attraction at the interface between the dual-active-center surface and RAC, the electrochemical mechanism has been clarified. Specifically, in the multi-cycle oxidation of RAC, the blue shift of specific UV-vis peaks also confirms the electrocatalytic oxidation of the two terminal hydroxyl groups of RAC. In brief, Ag2TPPS4/AgNPs/ng-C3N4 with a sandwich-like structure and double-faced active centers enhances the detection sensitivity and electrocatalytic efficiency towards RAC.

Family caregivers' experiences of interaction with people with mild-to-moderate dementia in China: A qualitative study.

AIM: This study aimed to explore the experiences of family caregivers interacting with people with dementia. BACKGROUND: A majority of people with mild-to-moderate dementia live at home with family caregivers. This interaction creates positive experiences and challenges for these caregivers. DESIGN: Descriptive phenomenological qualitative inquiry guided this study. METHODS: This qualitative study involved semi-structured interviews with the caregivers of people with mild-to-moderate dementia (n = 10). Data were collected from June to September 2018, and then data were thematically analysed. RESULTS: Six categories of themes were identified from the interviews: (1) unexpected things often happen; (2) positive coping strategies; (3) sense of accomplishment because people with dementia actively participate in activities; (4) sense of frustration because of the reluctance of people with dementia to participate in activities; (5) hope for the happiness of people with dementia; and (6) want to have their own life. CONCLUSIONS: This study reveals that caregivers could positively interact with people with dementia through creating opportunities and arranging meaningful activities. Future research should focus on family management and training on how to help caregivers interact effectively with people with dementia.

Bone marrow-mesenchymal stem cells modulate microglial activation in the peri-infarct area in rats during the acute phase of stroke.

AIM: Bone marrow-mesenchymal stem cells (BM-MSCs) possess immunomodulatory properties in the brain. However, it remains unclear whether intravenously transplanted BM-MSCs have a neuromodulator effect on the activation of microglias after ischemic stroke. This study aimed to investigate the immunomodulatory effect of BM-MSCs on the regulation of brain microglial inactivation during the acute phase of stroke. METHODS: A rat model of middle cerebral artery occlusion (MCAO) was established. Rat BM-MSCs were transplanted through the tail vein at 12 h after MCAO. CD200 Receptor 1 (CD200R1) antibody was injected into the peri-infarct area of the rat brain at 3 h prior to BM- MSCs transplantation. Protein expression was determined by immunofluorescence staining and Western blot. The volume of the infarct area was determined by TTC (2,3,5-triphenyltetrazolium hydrochloride) staining. Neuron apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: In vitro study showed that co-culture with BM-MSCs significantly decreased LPS-induced iNOS expression in the microglial cells. Immunofluorescence and Western blot consistently revealed that BM-MSC transplantation significantly reduced the IBA-expressing microglial cells and IBA protein levels in the peri-infarct area. The inhibitory effect of BM-MSC on IBA expression was significantly attenuated by pretreatment of CD200R1 neutralizing antibody in the peri-infarct zone. BM-MSC transplantation significantly reduced the infarct volume, protected neuron apoptosis, and increased neuronal CD200 expression in the peri-infarct area. CONCLUSION: The transplanted BM-MSCs exerted immunomodulatory effect by inactivating the microglias in the peri-infarct area, at least partially, via the CD200-CD200R1 signaling.

Smoke suppression properties of Si-Al mesoporous structure on medium density fiberboard.

In this article, smoke suppression of Si-Al mesoporous structure on medium density fiberboard (MDF) was investigated by cone calorimeter test (CCT), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and fourier transform infrared spectrometry (FTIR). The CCT results show that the Si-Al mesoporous structure can effectively decrease heat release rate (HRR), total heat release (THR), smoke production rate (SPR), total smoke production (TSP), smoke rate (SR), CO and CO2 concentration, etc. Particularly, the SR curves of MDF present that Si-Al mesoporous structure are considered to be a filter, which can net the solid particles and volatile flammable components in the smoke and fix onto wood fiber. Remarkably, the CO and CO2 concentration curves of MDF indicate that the Si-Al mesoporous structure has an excellent adsorption property, which can rapidly absorb CO and CO2 that generated in wood combustion process. On the other hand, the FTIR and TGA results reveal that the Si-Al mesoporous structure can significantly improve the structure of char residue.