Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.

[Pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration].

This study aims to establish a rapid and sensitive UPLC-MS/MS method for simultaneously determining the content of strychnine and paeoniflorin in plasma and brain tissue of rats, and compare the pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration. Compared with those in the toxic-dose strychnine group, the AUC_(0-t), AUC_(0-∞), and C_(max) of strychnine decreased by 51.51%, 45.68%, and 46.03%, respectively(P<0.01), and the corresponding values of paeoniflorin increased by 91.41%, 102.31%, and 169.32%, respectively(P<0.01), in the compatibility group. Compared with the normal-dose strychnine group, the compatibility group showed insignificantly decreased C_(max), AUC_(0-t), and AUC_(0-∞) of strychnine, increased C_(max) and T_(max) of paeoniflorin(P<0.01), 66.88% increase in AUC_(0-t), and 70.55% increase in AUC_(0-∞) of paeoniflorin. In addition, the brain tissue concentration of strychnine decreased and that of paeoniflorin increased after compatibility. The combination of paeoniflorin with normal dose and toxic dose of strychnine can inhibit the percutaneous absorption of strychnine, and greatly promote the percutaneous penetration of paeoniflorin, whereas the interaction mechanism remains to be explored. The UPLC-MS/MS method established in this study is easy to operate and has good precision. It is suitable for in vivo study of pharmacokinetic behavior and brain tissue distribution of paeoniflorin and strychnine after percutaneous administration in rats, which provides reference for the safe and rational clinical use of strychnine and the combined use of drugs, and lays a solid foundation for the development of external preparations containing Strychni Semen.

Relationship between sleep duration and sociodemographic characteristics, mental health and chronic diseases in individuals aged from 18 to 85 years old in Guangdong province in China: a population-based cross-sectional study.

BACKGROUND: Sleep is vital for maintaining individual's physical and mental health. Prior studies have reported close relationships between sleep duration and chronic diseases. However, in China, the prevalence of aberrant sleep duration and the associations between sleep duration and chronic conditions still merit studying in Guangdong province. This study aimed at examining the relationship between sleep duration and multiple dimensions of sociodemographic characteristics, mental health and chronic diseases in Guangdong province in China, with a large population-based data of individuals aged from 18 to 85 years old. METHODS: This study aimed at analyzing the sociodemographic and clinical characteristics of the population in Guangdong province. Multistage stratified cluster sampling was applied for this study. 13,768 participants from Guangdong province were interviewed with standardized assessment tools, including Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder (GAD-7). Basic socio-demographic information, mental health and chronic diseases information were collected. Self-reported sleep duration was classified as three types: short (< 7 h), normative (7-9 h) and long (≥9 h). RESULTS: The mean sleep duration was 6.75 ± 1.11 h. Short sleepers had a higher prevalence of chronic diseases, including anemia (6.2%, p = 0.024), gout (2.8%, p = 0.010), hyperlipidemia (3.9%, p = 0.003) and low back pain (5.6%, p = 0.020) than other types of sleeper. Multinomial logistic regression analysis revealed that short sleepers were more likely to have low income level, have depressive symptoms, be ex- or current drinkers and be overweight. Anemia, hyperlipidemia and low back pain were all risk factors for short sleep, while malignant tumor was risky for long sleep. CONCLUSIONS: Low income level, drinking status, being overweight, and chronic conditions may be associated with aberrant sleep duration in Guangdong province general population. Short sleepers have a higher risk of suffering from anemia, hyperlipidemia, and low back pain, while long sleepers are more likely to have malignant tumor. Health professionals should value the sleep patterns in general health care and attach importance to conduct further epidemiologic surveys to explore the relationship between sleep duration and health.

KRT1 gene silencing ameliorates myocardial ischemia-reperfusion injury via the activation of the Notch signaling pathway in mouse models.

Myocardial ischemia and reperfusion injury (MIRI) includes major drawbacks, such as excessive formation of free radicals and also overload of calcium, which lead to cell death, tissue scarring, and remodeling. The current study aims to explore whether KRT1 silencing may ameliorate MIRI via the Notch signaling pathway in mouse models. Myocardial tissues were used for the determination of the positive rate of KRT1 protein expression, apoptosis of myocardial cells, creatine kinase (CK) and lactate dehydrogenase (LDH) expression, expression of related biomarkers as well as myocardial infarction area. The transfected myocardial cells were treated with KRT1-siRNA, Jagged1, and DAPT (inhibitor of Notch-1 signaling pathway). The expression of KRT1, NICD, Hes1, Bcl-2, and Bax protein was detected. The MTT assay was applied for cell proliferation and flow cytometry was used for cell apoptosis. Mice with MIRI had a higher positive rate of KRT1 protein expression, apoptosis of myocardial cells, CK and LDH expression, myocardial infarction area, increased expression of MDA, NO, SDH, IL-1, IL-6, TNF-α, CRP, KRT1, Bax protein, CK, and LDH, and decreased expression of SOD, NICD, Hes1, and Bcl-2. The downregulation of KRT1 led to decreased expression of KRT1 and Bax protein, increased expression of NICD, Hes1, and Bcl-2, decreased cell apoptosis, and improved cell proliferation. The inhibition of the Notch signaling pathway leads to reduced expression of Bax, increased expression of NICD, Hes1, and Bcl 2, and also decreased cell apoptosis and increased cell proliferation. Our data conclude that KRT1 silencing is able to make MIRI better by activating the Notch signaling pathway in mice.

Dietary supplementation with polypeptides improved growth performance, antibacterial immune and intestinal microbiota structure of Litopenaeus vannamei.

Antibacterial peptides (AMPs) are expected to replace some or all of the antibiotics and become a new feed additive. However, the high production cost and unclear mechanism limited the application of AMPs. In this research, the effects of a commercial polypeptide (Polypeptide S100) whose main components are AMPs on the growth, antibacterial immune and intestinal microbial of Litopenaeus vannamei were study. L. vannamei (initial weight of 0.16 ±â€¯0.03 g) were fed for 123 days with basal diet added Polypeptide S100 at two levels each (0.5% and 1%) as experimental groups, and a basal diet as control. Dietary inclusion of Polypeptide S100 at 1% level significantly increased the weight gain (WG) and specific growth rate (SGR) of L. vannamei. The survival rates of L. vannamei in 0.5% and 1% Polypeptide S100 groups were significantly higher than the control when infected by Vibrio harveyi but not Vibrio parahaemolyticus. The activities of total superoxide dismutase (T-SOD) and lysozyme (LZM) in the two experimental groups were all significantly higher than the control. Differently, the activities of amylase (AMS) and lipase (LPS) were significantly higher in 0.5% Polypeptide S100 group but lower in 1.0% Polypeptide S100 group. Illumina MiSeq high-throughput sequencing showed that the dominant phyla in the intestine of L. vannamei were Proteobacteria, followed by Actinobacteria, Bacteroidetes, Chloroflexi, Cyanobacteria, Fusobacteria and Tenericutes, and the abundance of predominant phyla Cyanobacteria were upregulated significantly in the experimental groups. At the family level, significant increase was observed in Pseudomonadaceae and Xanthomonadaceae but decrease in Vibrionaceae in the 1.0% Polypeptide S100 group. The abundance of predominant genus Photobacterium were obviously downregulated in the two experimental groups. Unlikely, the abundance of Pseudomonas and Stenotrophomonas were distinctly increased in the 1.0% Polypeptide S100 group but not significantly different from the control in 0.5% Polypeptide S100 group. All these results suggested that Polypeptide S100 could improve the growth performance, antibacterial immune and intestinal microbiota structure of L. vannamei.

Current Treatment Patterns of Aplastic Anemia in China: A Prospective Cohort Registry Study.

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.

Sexual dysfunction in Chinese rural patients with schizophrenia.

BACKGROUND: Sexual dysfunction is common in patients with schizophrenia, however it is poorly studied in China, especially in primary health care institutions in rural areas. We investigated the prevalence of sexual dysfunction and its correlates including quality of life (QoL), in schizophrenia patients treated in primary care in a rural area in China. METHOD: By using a random numbers table, 21 small town primary care service centers (from 63 totally) were selected in the study. Data of 720 community-dwelling patients with schizophrenia in rural area with diagnoses according to DSM -IV or ICD-10 were collected by interviews. Data on socio-demographic and clinical characteristics including sexual dysfunction and quality of life (QoL) were collected using a standardized protocol and data collection procedure. Data were analyzed using chi-square tests, t-tests, U-tests, ANCOVA and multiple logistic regression as appropriate by SPSS 21.0.The level of significance was set at 0.05 (two-tailed). RESULTS: In this sample, sexual dysfunction was found in 71.3% of the whole sample, 82.7% of female patients and 64.5% of male patients. Multiple logistic regression analysis showed that older age (OR = 1.06, P<0.001, 95%CI: 1.04-1.09) and higher Brief Psychotic Rating Scale (negative domain) score (OR = 1.16, P = 0.01, 95%CI: 1.02-1.31) were significantly associated with sexual dysfunction. Contrary to previous findings, sexual dysfunction was not associated with quality of life after controlling for confounding variables. CONCLUSIONS: More than 2/3 of schizophrenia patients living in a rural area complained of sexual dysfunction, which was associated with older age and more negative psychotic symptoms. Primary care physicians should pay attention to sexual dysfunction during the assessment and treatment of patients with schizophrenia in rural areas in China.

The role of microRNA-1 targeting of MAPK3 in myocardial ischemia-reperfusion injury in rats undergoing sevoflurane preconditioning via the PI3K/Akt pathway.

Recent studies have uncovered the vital roles played by microRNAs in regulating cardiac injury. Among them, the cardiac enriched microRNA-1 (miR-1) has been extensively studied and proven to be detrimental to cardiac myocytes. Hence, the current study aimed to explore whether miR-1 affects myocardial ischemia-reperfusion injury (MIRI) in rats undergoing sevoflurane preconditioning and the underlying mechanism. After successful model establishment, rats with MIRI were transfected with mimics or inhibitors of miR-1, or siRNA against MAPK3, and then were injected with sevoflurane. A luciferase reporter gene assay was conducted to evaluate the targeting relationship between miR-1 and MAPK3. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were employed to evaluate the expressions of miR-1, MAPK3, phosphatidylinositol 3-kinase (PI3K), and Akt. Additionally, the concentration of lactate dehydrogenase (LDH) was determined. Cell apoptosis and viability were assessed using TUNEL and cell counting kit-8 assays, and the ischemic area at risk and infarct size were detected using Evans blue and triphenyltetrazolium chloride staining. MAPK3 was found to be the target gene of miR-1. miR-1 expressed at a high level whereas MAPK3 expressed at a low level in MIRI rats. Overexpressing miR-1 or silencing MAPK3 blocked the PI3K/Akt pathway to increase cell apoptosis, ischemic area at risk, and infarct area but decreased cell viability and increased LDH concentration. In contrast, miR-1 downregulation abrogated the effects induced by miR-1 mimics or siRNA against MAPK3. These findings indicate that inhibition of miR-1 promotes MAPK3 to protect against MIRI in rats undergoing sevoflurane preconditioning through activation of the PI3K/Akt pathway.

A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial in Northwest China.

The nasal type of extranodal natural killer/T-cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol-asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T-cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2-year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression-free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment-related deaths. These results will require confirmation in larger prospective trials.

Essential role of miR-200c in regulating self-renewal of breast cancer stem cells and their counterparts of mammary epithelium.

BACKGROUND: Breast cancer stem cells (BCSCs) have been reported as the origin of breast cancer and the radical cause of drug resistance, relapse and metastasis in breast cancer. BCSCs could be derived from mutated mammary epithelial stem cells (MaSCs). Therefore, comparing the molecular differences between BCSCs and MaSCs may clarify the mechanism underlying breast carcinogenesis and the targets for gene therapy. Specifically, the distinct miRNome data of BCSCs and MaSCs need to be analyzed to find out the key miRNAs and reveal their roles in regulating the stemness of BCSCs. METHODS: MUC1(-)ESA(+) cells were isolated from normal mammary epithelial cell line MCF-10A by fluorescence-activated cell sorting (FACS) and tested for stemness by clonogenic assay and multi-potential differentiation experiments. The miRNA profiles of MaSCs, BCSCs and breast cancer MCF-7 cells were compared to obtain the candidate miRNAs that may regulate breast tumorigenesis. An miRNA consecutively upregulated from MaSCs to BCSCs to MCF-7 cells, miR-200c, was chosen to determine its role in regulating the stemness of BCSCs and MaSCs in vitro and in vivo. Based on bioinformatics, the targets of miR-200c were validated by dual-luciferase report system, western blot and rescue experiments. RESULTS: In a 2-D clonogenic assay, MUC1(-)ESA(+) cells gave rise to multiple morphological colonies, including luminal colonies, myoepithelial colonies and mixed colonies. The clonogenic potential of MUC1(-)ESA(+) (61.5 ± 3.87 %) was significantly higher than that of non-stem MCF-10A cells (53.5 ± 3.42 %) (P < 0.05). In a 3-D matrigel culture, MUC1(-)ESA(+) cells grew into mammospheres with duct-like structures. A total of 12 miRNAs of interest were identified, 8 of which were upregulated and 4 downregulated in BCSCs compared with MaSCs. In gain- and lost-of-function assays, miR-200c was sufficient to inhibit the self-renewal of BCSCs and MaSCs in vitro and the growth of BCSCs in vivo. Furthermore, miR-200c negatively regulated programmed cell death 10 (PDCD10) in BCSCs and MaSCs. PDCD10 could rescue the tumorigenesis inhibited by miR-200c in BCSCs. DISCUSSION: Accumulating evidence shows that there is a milignant transformation from MaSCs into BCSCs. The underlying mechanism remains unclear. In present study, miRNA profiles between MaSCs and BCSCs were obtained. Then miRNA-200c, downregulated in both MaSCs and BCSCs, were verified as anti-oncogene, and played essential role in regulating self-renewal of both kinds of stem-like cells. These findings reveal a novel insights of breast tumorigenesis. CONCLUSIONS: PDCD10 is a target gene of miR-200c and also a possible mechanism by which miR-200c plays a role in regulating the stemness of BCSCs and MaSCs.

Space-bound optical source for satellite-ground decoy-state quantum key distribution.

Satellite-ground quantum key distribution has embarked on the stage of engineering implementation, and a global quantum-secured network is imminent in the foreseeable future. As one payload of the quantum-science satellite which will be ready before the end of 2015, we report our recent work of the space-bound decoy-state optical source. Specialized 850 nm laser diodes have been manufactured and the integrated optical source has gotten accomplished based on these LDs. The weak coherent pulses produced by our optical source feature a high clock rate of 100 MHz, intensity stability of 99.5%, high polarization fidelity of 99.7% and phase randomization. A series of space environment tests have been conducted to verify the optical source's performance and the results are satisfactory. The emulated final secure keys are about 120 kbits during one usable pass of the low Earth orbit satellite. This work takes a significant step forward towards satellite-ground QKD and the global quantum-secured network.

Increased 14-3-3ζ expression in the multidrug-resistant leukemia cell line HL-60/VCR as compared to the parental line mediates cell growth and apoptosis in part through modification of gene expression.

BACKGROUND: Acute myeloid leukemia (AML) recurrence is largely a result of multidrug resistance (MDR). We aimed to examine the role of 14-3-3ζ in AML chemosensitivity using HL-60 and vincristine-resistant HL-60/VCR cells. METHODS: The effects of 14-3-3ζ siRNA on the growth and cell cycle progression of HL-60 and HL-60/VCR cells were determined. The effect of 14-3-3ζ siRNA on topotecan (TPT)-induced apoptosis was evaluated by several assays. RESULTS: Compared to HL-60 cells, HL-60/VCR cells had increased 14-3-3ζ mRNA and protein expression. Increased mdr-1 mRNA as well as mdr-1, Bcl-2 and Mcl-1 protein expression were observed in HL-60/VCR cells. In both HL-60 and HL-60/VCR cells, 14-3-3ζ was observed in the cytoplasm and nuclear compartments. 14-3-3ζ siRNA significantly reduced HL-60 and HL-60/VCR cell growth after 48 h and increased the proportion of cells in the G0/G1 phase. Moreover, 14-3-3ζ siRNA significantly increased the sensitivity of both HL-60 and HL-60/VCR cells to TPT, possibly through the inhibition of Bcl-2, Mcl-1 and mdr-1 protein expression. CONCLUSIONS: Silencing of 14-3-3ζ increased the sensitivity of both sensitive and resistant HL-60 cells to TPT-induced apoptosis, possibly through altering the expression of apoptosis-associated proteins, suggesting that it may be a potential target for MDR AML.

Retinitis pigmentosa and stem cell therapy.

Retinitis pigmentosa (RP) is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium (RPE) cells. Its main clinical manifestations include night blindness and progressive loss of peripheral vision, making it a prevalent debilitating eye disease that significantly impacts patients' quality of life. RP exhibits significant phenotypic and genetic heterogeneity. For instance, numerous abnormal genes are implicated in RP, resulting in varying clinical presentations, disease progression rates, and pathological characteristics among different patients. Consequently, gene therapy for RP poses challenges due to these complexities. However, stem cells have garnered considerable attention in the field of RPE therapy since both RPE cells and photoreceptors can be derived from stem cells. In recent years, a large number of animal experiments and clinical trials based on stem cell transplantation attempts, especially cord blood mesenchymal stem cell (MSC) transplantation and bone marrow-derived MSC transplantation, have confirmed that stem cell therapy can effectively and safely improve the outer retinal function of the RP-affected eye. However, stem cell therapy also has certain limitations, such as the fact that RP patients may involve multiple types of retinal cytopathia, which brings great challenges to stem cell transplantation therapy, and further research is needed to solve various problems faced by this approach in the clinic. Through comprehensive analysis of the etiology and histopathological changes associated with RP, this study substantiates the efficacy and safety of stem cell therapy based on rigorous animal experimentation and clinical trials, while also highlighting the existing limitations that warrant further investigation.

Chinese self-report version of biological rhythms interview for assessment in neuropsychiatry (C-BRIAN-SR) - psychometric properties and prospective follow-up in patients with non-seasonal depression.

This study examined the psychometric properties and longitudinal changes of the self-reporting Traditional Chinese version of Biological Rhythms Interview for Assessment in Neuropsychiatry (C-BRIAN-SR) among healthy controls (HC) and patients with major depressive episode (MDE). Eighty patients with a current MDE and 80 HC were recruited. Assessments were repeated after two weeks in HC, and upon the discharge of MDE patients to examine the prospective changes upon remission of depression. The C-BRIAN-SR score was significantly higher in the MDE than HC group. The concurrent validity was supported by a positive correlation between scores of C-BRIAN-SR, Insomnia Severity Index and the Hospital Anxiety Depression Scale. C-BRIAN-SR negatively correlated MEQ in the MDE group (r = .30, p = 0.009), suggesting higher rhythm disturbances were associated with a tendency toward eveningness. A moderate test-retest reliability was found (r = .61, p < 0.001). A cut-off of 38.5 distinguished MDE subjects from HC with 82.9% of sensitivity and 81.0% of specificity. C-BRIAN-SR score normalized in remitted MDE patients but remained higher in the non-remitted. The C-BRIAN-SR is a valid and reliable scale for measuring the biological rhythms and may assist in the screening of patients with MDE.

Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study.

BACKGROUND: Invasive fungal infection (IFI) is common in neutropenic patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is a broad-spectrum triazole antifungal drug with efficacy in prevention of IFI; however, it has not been previously studied as prophylaxis in a Chinese population. METHODS: This multicenter, randomized study in China enrolled AML and MDS patients with persistent chemotherapy-induced neutropenia. Prophylaxis with posaconazole or fluconazole was administered for a maximum of 12 weeks, or until patients recovered from neutropenia and achieved complete remission or an IFI occurred. The primary endpoint was incidence of proven, probable, or possible IFI during treatment. Clinical failure rate, all-cause mortality and time to first systemic antifungal treatment were secondary endpoints. RESULTS: Patients were randomized to receive posaconazole (n = 129) or fluconazole (n = 123); 117 patients in each group were included in the statistical analysis. The incidence of proven, probable or possible IFI was 9.4% (11/117) and 22.2% (26/117) in the posaconazole and fluconazole groups, respectively (p = 0.0114). The clinical failure rate was numerically lower in the posaconazole group (37/117 (31.6%; 95%CI: 23.3 - 40.9)) than in the fluconazole group (49/117 (41.88%; 95% CI: 32.8 - 51.4)) (p = 0.168). Patients receiving posaconazole had a later onset of first systematic antifungal treatment than those receiving fluconazole (p = 0.0139). The most common important adverse events were liver function abnormalities (11 patients (8.8%) on posaconazole and 6 (5.0%) on fluconazole (p = 0.221)). CONCLUSIONS: Posaconazole demonstrates efficacy as prophylaxis against IFI in high-risk neutropenic Chinese patients and is well tolerated during long-term use (ClinicalTrials. gov number, NCT00811928).

Differences in urban heat island and its driving factors between central and new urban areas of Wuhan, China.

Urban heat island (UHI) is one of the important effects of urbanization on built environment. Land surface temperature data was taken from moderate-resolution imaging spectroradiometer (MODIS) to investigate the long-term spatiotemporal patterns of UHI in Wuhan during 2001~2018 and, the UHI intensity changes of built-up land in 13 administrative regions in Wuhan were analyzed. Furthermore, 34 spatial error models and 34 ordinary least squares models were established and compared. Spatial error models showed good fitting effect, which were used to determine the influence of normalized difference vegetation index (NDVI), normalized difference building index (NDBI), and social-economic factors (population and nighttime light) on UHI intensity in central urban area and new urban area. The explanatory power changes of these four indicators during 2001~2018 were explored as well. The average UHI intensity in 2014~2018 has increased by about 0.45 °C compared to that in 2001~2005. NDBI is the most dominant factor contributing to the increase in temperature. The impact of NDVI on UHI intensity changes from negative to positive, and the impact of NDBI on UHI intensity in central urban area is weakened during 2001-2018. Social-economic factors have a greater impact on new urban area than on central urban area. These findings show the effects and the explanatory power changes of driving factors during 18 years, which can provide a better understanding of the formation and development of UHI and support for the future urban planning of Wuhan.

Network Bursts in 3D Neuron Clusters Cultured on Microcontact-Printed Substrates.

Microcontact printing (CP) is widely used to guide neurons to form 2D networks for neuroscience research. However, it is still difficult to establish 3D neuronal cultures on the CP substrate even though 3D neuronal structures are able to recapitulate critical aspects of native tissue. Here, we demonstrate that the reduced cell-substrate adhesion caused by the CP substrate could conveniently facilitate the aggregate formation of large-scale 3D neuron cluster networks. Furthermore, based on the quantitative analysis of the calcium activity of the resulting cluster networks, the effect of cell seeding density and local restriction of the CP substrate on network dynamics was investigated in detail. The results revealed that cell aggregation degree, rather than cell number, could take on the main role of the generation of synchronized network-wide calcium oscillation (network bursts) in the 3D neuron cluster networks. This finding may provide new insights for easy and cell-saving construction of in vitro 3D pathological models of epilepsy, and into deciphering the onset and evolution of network bursts in developmental nerve systems.

Correlation of preclinical and clinical biomarkers with efficacy and toxicity of cancer immunotherapy.

Immune checkpoint inhibitors (ICIs) have revealed significant clinical values in different solid tumors and hematological malignancy, changing the landscape for the treatment of multiple types of cancer. However, only a subpopulation of patients has obvious tumor response and long-term survival after ICIs treatment, and many patients may experience other undesirable clinical features. Therefore, biomarkers are critical for patients to choose exact optimum therapy. Here, we reviewed existing preclinical and clinical biomarkers of immunotherapeutic efficacy and immune-related adverse events (irAEs). Based on efficacy prediction, pseudoprogression, hyperprogressive disease, or irAEs, these biomarkers were divided into cancer cell-derived biomarkers, tumor microenvironment-derived biomarkers, host-derived biomarkers, peripheral blood biomarkers, and multi-modal model and artificial intelligence assessment-based biomarkers. Furthermore, we describe the relation between ICIs efficacy and irAEs. This review provides the overall perspective of biomarkers of immunotherapeutic outcome and irAEs prediction during ICIs treatment.

An Overview of In Vitro Biological Neural Networks for Robot Intelligence.

In vitro biological neural networks (BNNs) interconnected with robots, so-called BNN-based neurorobotic systems, can interact with the external world, so that they can present some preliminary intelligent behaviors, including learning, memory, robot control, etc. This work aims to provide a comprehensive overview of the intelligent behaviors presented by the BNN-based neurorobotic systems, with a particular focus on those related to robot intelligence. In this work, we first introduce the necessary biological background to understand the 2 characteristics of the BNNs: nonlinear computing capacity and network plasticity. Then, we describe the typical architecture of the BNN-based neurorobotic systems and outline the mainstream techniques to realize such an architecture from 2 aspects: from robots to BNNs and from BNNs to robots. Next, we separate the intelligent behaviors into 2 parts according to whether they rely solely on the computing capacity (computing capacity-dependent) or depend also on the network plasticity (network plasticity-dependent), which are then expounded respectively, with a focus on those related to the realization of robot intelligence. Finally, the development trends and challenges of the BNN-based neurorobotic systems are discussed.

Development and validation of an interpretable machine learning model-Predicting mild cognitive impairment in a high-risk stroke population.

Background: Mild cognitive impairment (MCI) is considered a preclinical stage of Alzheimer's disease (AD). People with MCI have a higher risk of developing dementia than healthy people. As one of the risk factors for MCI, stroke has been actively treated and intervened. Therefore, selecting the high-risk population of stroke as the research object and discovering the risk factors of MCI as early as possible can prevent the occurrence of MCI more effectively. Methods: The Boruta algorithm was used to screen variables, and eight machine learning models were established and evaluated. The best performing models were used to assess variable importance and build an online risk calculator. Shapley additive explanation is used to explain the model. Results: A total of 199 patients were included in the study, 99 of whom were male. Transient ischemic attack (TIA), homocysteine, education, hematocrit (HCT), diabetes, hemoglobin, red blood cells (RBC), hypertension, prothrombin time (PT) were selected by Boruta algorithm. Logistic regression (AUC = 0.8595) was the best model for predicting MCI in high-risk groups of stroke, followed by elastic network (ENET) (AUC = 0.8312), multilayer perceptron (MLP) (AUC = 0.7908), extreme gradient boosting (XGBoost) (AUC = 0.7691), and support vector machine (SVM) (AUC = 0.7527), random forest (RF) (AUC = 0.7451), K-nearest neighbors (KNN) (AUC = 0.7380), decision tree (DT) (AUC = 0.6972). The importance of variables suggests that TIA, diabetes, education, and hypertension are the top four variables of importance. Conclusion: Transient ischemic attack (TIA), diabetes, education, and hypertension are the most important risk factors for MCI in high-risk groups of stroke, and early intervention should be performed to reduce the occurrence of MCI.