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A simple strategy is developed to simultaneously release tensile strain and passivate defects in an FA-based perovskite using CsPbI3 QDs, achieving a PCE of 23.3%.

A self-assembled nanofibrillar conjugated polymer film is used to optimize the CsPbIBr2/hole-transporting layer interface. The obtained CsPbIBr2 solar cell demonstrates an efficiency of 11.05% with excellent long-term stability.

A simple anion modification strategy was developed to inhibit MeOH absorption in CsPbBr3 QDs. The CsPbBr3 QD solar cell yielded a PCE of 7.04%, which is the highest PCE reported for CsPbBr3 QD solar cells to date.

Organic–inorganic hybrid perovskite has achieved great success in the field of solar cells. The charge-transporting layers (CTLs) play an important role on the performance of perovskite solar cells (PSCs). In order to elucidate the influence of the doping density of CTLs on the current–voltage characteristics and power conversion efficiencies (PCEs) of PSCs, numerical simulation was performed for both n-i-p and p-i-n configurations. The simulated results suggest that the doping density of CTLs must maintain a certain value from the aspect of efficient built-in electric field. The reasonable value of the doping density of CTLs is mainly related to their dielectric constant. Effects of the doping density of charge-transporting layers on perovskite solar cells were elucidated by numerical simulations

Inorganic lead halide perovskite CsPbIBr2 possesses good stability with a suitable band gap for tandem solar cells. Decreasing the defect concentration and improving the film quality is crucial to further increase the power conversion efficiency of CsPbIBr2 solar cells. Here, the crystallization dynamics of CsPbIBr2 films is regulated by introducing the volatile organic salt, formamidinium acetate (FAAc) into the precursor solution. It is found that FAAc slows the crystallization process of CsPbIBr2 films and pinhole-free films with large grains and smooth surfaces are obtained. The defect concentration of the films is decreased and the nonradiative recombination is significantly inhibited. By improving the film quality, the FAAc remarkably enhances the efficiency of CsPbIBr2 solar cells. The champion device delivers a power conversion efficiency of 9.44% and exhibits higher stability than the reference device. This finding provides an effective strategy for reducing defects, suppressing the recombination, and improving the performance of CsPbIBr2 solar cells.

Approximately 70% of the HIV-1 latent reservoir originates from infections of CD4 T cells that occur in the months near the time of ART initiation, raising the possibility that interventions during this period might prevent reservoir seeding and reduce reservoir size. We identify class 1 histone deacetylase inhibitors (HDACi) as potent agents of latency prevention. Inhibiting HDACs in productively infected cells caused extended maintenance of HIV expression and this activity was associated with persistently elevated H3K9 acetylation and reduced H3K9 methylation at the viral LTR promoter region. HDAC inhibition in HIV-infected CD4 T cells during effector-to-memory transition led to striking changes in the memory phenotype of infected cells. Proviral silencing is accomplished through distinct activities of HDAC1/2 and HDAC3. Thus HDACs regulate a critical gateway process for HIV latency establishment and are required for the development of CD4 T-cell memory subsets that preferentially harbor long-lived, latent provirus.

Calcium influx from depolarized CaV1.2 calcium channels triggers the contraction of vascular smooth muscle cells (VSMCs), which is important for maintaining vascular myogenic tone and blood pressure. The function of CaV1.2 channel can be subtly modulated by alternative splicing (AS), and its aberrant splicing involves in the pathogenesis of multiple cardiovascular diseases. The RNA-binding protein Rbfox1 is reported to regulate the AS events of CaV1.2 channel in the neuronal development, but its potential roles in vascular CaV1.2 channels and vasoconstriction remain undefined. Here, we detect Rbfox1 is expressed in rat vascular smooth muscles. Moreover, the protein level of Rbfox1 is dramatically decreased in the hypertensive small arteries from spontaneously hypertensive rats in comparison with normotensive ones from Wistar-Kyoto rats. In VSMCs, Rbfox1 could dynamically regulate the AS of CaV1.2 exons 9* and 33. By whole-cell patch clamp, we identify knockdown of Rbfox1 induces the hyperpolarization of CaV1.2 current–voltage relationship curve in VSMCs. Furthermore, siRNA-mediated knockdown of Rbfox1 increases the K+-induced constriction of rat mesenteric arteries. In summary, our results indicate Rbfox1 modulates vascular constriction by dynamically regulating CaV1.2 alternative exons 9* and 33. Therefore, our work elucidates the underlying mechanisms for CaV1.2 channels regulation and provides a potential therapeutic target for hypertension.

Endometrial cancer, a type of primary epithelial malignant tumor in the endometrium, is one of the three most common malignant tumors of the female reproductive system. While the incidence of endometrial cancer has been recently rising, its etiology remains unclear. In this study we found that EM2D9, an independently developed monoclonal antibody, specifically recognized endometrial cancer cells; we further determined that EM2D9 target protein was α5β1. In vitro and in vivo experiments showed that EM2D9 inhibited the migration of endometrial cancer cells. Real-time quantitative PCR results showed that the expression of CD151 mRNA in endometrial carcinoma cells significantly decreased after EM2D9 treatment. We also found that EM2D9 affected the FAK signaling pathway. Collectively, these results shed light on a new mechanism for the development of endometrial carcinoma.

Objective: The study objective was to investigate whether endogenous glucocorticoids directly impact the functions and proliferation/apoptosis of ovarian granulosa cells. Methods: Primary rat ovarian granulosa cells were cultured and treated with graded concentrations of corticosterone either alone or in the presence of the indicated drugs. After 48 h of treatment, the cells and growth media were collected to measure intracellular and extracellular progesterone/estradiol concentrations, and steroid secretion ratios were obtained by parameter calculation. The number of granulosa cells was determined by Cell Counting Kit-8. To determine the impact on cell numbers, granulosa cell proliferation was detected using the BrdU incorporation method and cell apoptosis was detected by flow cytometry. Results: First, high corticosterone concentrations significantly stimulated progesterone synthesis/secretion and inhibited estradiol synthesis in cultured granulosa cells. Second, accompanied by follicle-stimulating hormone, high corticosterone concentrations promoted progesterone synthesis/release and estradiol release. Last, high corticosterone concentrations increased the cell number and suppressed apoptosis but did not induce cell proliferation. Conclusions: These indicate that high glucocorticoid concentrations may play luteotropic roles in the functions and number of corpora lutea.

Cs2AgBiBr6 solar cells have the advantages of non-toxicity and high stability and are regarded as one of the most promising novel solar cells. The crystallization kinetics of the films play a crucial role on the film microstructure and the optoelectronic properties. Herein, thiourea is introduced into the Cs2AgBiBr6 precursor solution as an additive. Fourier transform infrared spectroscopy characterization confirms that thiourea acts as a Lewis base to form an adduct with Ag+, Bi3+. The modified Cs2AgBiBr6 film is used to fabricate solar cells. As a result, the power conversion efficiency and the open-circuit voltage of the optimized device are 1.65% and 1.07 V, significantly higher than the control device (1.04% and 0.89 V). Dark current–voltage, electrochemical impedance spectroscopy, etc, reveal that defects and recombination in the solar cells are inhibited. This work provides an effective method to regulate the crystallization kinetics of Cs2AgBiBr6 film and is helpful for further enhancement of the photovoltaic performance of Cs2AgBiBr6 solar cells.

Purpose Radical prostatectomy (RP) is a common treatment for prostate cancer, but a fraction of patients may experience PSA recurrence after surgery, manifesting as an elevation in prostate specific antigen (PSA). Vast literature has reported different prognostic factors for PSA recurrence without reaching a consensus. This retrospective study investigated the efficacy of a new indicator in predicting PSA recurrence in patients after RP. Patients and methods From October 2000 to December 2015, 102 PCa patients who underwent laparoscopic prostatectomy in the Urology Department of Peking Union Medical College Hospital were analyzed. We calculated PSApostd3/PSApre, defined as the ratio of the PSA on day 3 postop as the numerator and the pre-operative PSA as the denominator, in these patients to represent PSA decrement after surgery, and investigated its relationship with PSA recurrence during follow-up. Results The receiver operating characteristic (ROC) curve of PSApostd3/PSApre derived a cut-off at 0.453 (sensitivity=0.704, specificity=0.853, P

Photovoltaic power generation, as a rapidly growing new energy source, is a technology that uses a semiconductor to convert light energy into electrical energy. Sb2S3 solar cells possess the advantages of simple binary components, abundant resources, nontoxicity, and excellent stability; they have recently attracted extensive investigation interest. Various strategies, such as solution and vacuum deposition, have been used to fabricate functional layers, including Sb2S3 photoactive layers, electron transport layers and hole transport layers. Here, we briefly review the preparation methodologies, morphologies, structures, optoelectronic properties and the corresponding solar cell performance of functional layers for both planar heterojunction solar cells and mesoporous sensitized solar cells. Some viewpoints of further improvement of Sb2S3 solar cell conversion efficiency from the aspect of material fabrication and modification are given.

Inorganic lead halide perovskite CsPbIBr

Chlamydia trachomatis (CT) is a common sexually transmitted bacterial infection, that in women can cause pelvic inflammatory disease and infertility. No preventative vaccine has been developed against CT. Immunity to CT is primarily mediated by Th1 CD4+ T cells. We are defining immunoprevalent CT proteins in a well-defined cohort of CT seropositive women with the goal of defining novel vaccine immunogens. We screened 30 women one month after a CT-positive test by cultured IFN-γ ELISpot. Ten-day short-term cell lines (STCL) were generated against overlapping peptides spanning 21 CT antigens. The threshold for a positive CT-specific T cell response (≥ 300 spot-forming cells, SFU, per 106 cells) was defined following a screening of 12 CT seronegative donors. CT− specific T cell responses were detected in 27/30 CT-seropositive women. On average, women harbored T cell responses to two CT proteins (range 0–6). Strikingly, CT858 (CPAF) elicited a T cell response in 16/30 women with an average of 966 IFN-g SFU/106 cells (range 300–3,633 SFU/106 cells). Data to date suggest CPAF-specific T cell responses are predominantly CD4-restricted. In preliminary studies, we have also detected CT-specific T cell responses in men with documented CT infection, including a T cell response to CPAF. We are currently mapping CPAF T cell epitopes and expanding our screen to other CT secreted proteins. In summary, CT858 (CPAF) is an immunoprevalent antigen in women and a promising vaccine immunogen. Supported by UNC Chlamydia Vaccine Initiative (U19AI144181)

CD8+ T cell immunity is essential to the control of HIV viremia. We examined the safety and immunogenicity of MVA-vectored vaccines expressing highly conserved HIV regions in a first-in-man Phase I study in people living with HIV on ART. Participants received a single intramuscular dose of MVA.tHIVconsv3 (M3), MVA.tHIVconsv4 (M4), combined M3+M4 or saline in a 7:7:7:3 ratio. M3 and M4 span the same 6 HIV regions but differ by approximately 10% of amino acids; a design to increase vaccine coverage of circulating HIV variants. We employed ex vivo IFN-g ELISpot assays to measure changes in HIV-specific T cell magnitude and breadth to M3 and/or M4 immunogens following vaccination. We also examined whether M3, M4 or M3+M4 vaccination increased the ability of CD8+ T cells inhibit HIV in vitro replication. The M&M study is fully enrolled but presently is blinded. Analysis of blinded data show that vaccination was safe and well tolerated. Vaccination induced strong increases in the T cell response to M3, M4 vaccine immunogens producing a 2- to 18-fold increase in magnitude in 16/20 participants tested to date. M3/M4-specific T cell breadth also increased across participants. Vaccine-associated T cell responses mostly remained elevated (>2-fold increase) for at least 70 days post-vaccination visit. Vaccination was also associated with clear and sustained increases in in vitro virus inhibition. The percentage of the total HIV T cell response targeting conserved HIV regions in participants increased on average from 40 to 60% post-vaccination, suggesting M3/M4/M3+4 vaccination successfully produced a sustained shift in T cell immunodominance. Unblinded data will be presented at this meeting. Supported by U01AI131310

Background. Diabetic endotoxemia has been recognized as one of the hallmarks of type 2 diabetes mellitus (T2DM). Recent findings suggest that gut leak plays a pivotal role in diabetic endotoxemia. Cortex Mori (CM) has been widely applied in China to ameliorate development of T2DM, but its effect on endotoxemia is unknown. Methods. The study was constructed with two parts: (1) in vivo study of CM on diabetic endotoxemia in db/db mice. Eight C57BL/6 mice were set as normal control; (2) in vitro study of mulberroside A (MBA) from CM on diabetic endotoxemia. Potential mechanism of MBA on ameliorating diabetic endotoxemia was also explored. Results. The present study found that CM water extract decreased levels of blood glucose, ameliorated liver and renal damage in db/db mice, and ameliorated diabetic endotoxemia ( p < 0.01 ). We also found that the water extract enhanced gut integrity and decreased gut inflammatory protein ICAM-1 expression in db/db mice as detected by H&E staining and immunohistochemistry methods. In the in vitro study, MBA decreased levels of MDA and ROS induced by LPS ( p < 0.01 ) and enhanced the integrity of gut epithelial barrier ( p < 0.01 ). Conclusions. We found that Cortex Mori and its active component mulberroside A could ameliorate diabetic endotoxemia by preserving gut integrity.

Background and aim: Urothelial bladder cancer (UBC) is a common malignant tumor of the urogenital system with a high rate of recurrence. Due to the sophisticated and largely unexplored mechanisms of tumorigenesis of UBC, the classical therapeutic approaches including transurethral resection and radical cystectomy combined with chemotherapy have remained unchanged for decades. However, with increasingly in-depth understanding of the microenvironment and the composition of tumor-infiltrating lymphocytes of UBC, novel immunotherapeutic strategies have been developed. Bacillus Calmette-Guerin (BCG) therapy, immune checkpoint blockades, adoptive T cell immunotherapy, dendritic cell (DC) vaccines, etc., have all been intensively investigated as immunotherapies for UBC. This review will discuss the recent progress in immune escape mechanisms and immunotherapy of UBC. Methods: Based on a comprehensive search of the PubMed and ClinicalTrials.gov database, this review included the literature reporting the immune escape mechanisms of UBC and clinical trials assessing the effect of immunotherapeutic strategies on tumor or immune cells in UBC patients published in English between 1999 and 2020. Results: Immune surveillance, immune balance, and immune escape are the three major processes that occur during UBC tumorigenesis. First, the role of immunosuppressive cells, immunosuppressive molecules, immunosuppressive signaling molecules, and DCs in tumor microenvironment is introduced elaborately in the immune escape mechanisms of UBC section. In addition, recent progress of immunotherapies including BCG, checkpoint inhibitors, cytokines, adoptive T cell immunotherapy, DCs, and macrophages on UBC patients are summarized in detail. Finally, the need to explore the mechanisms, molecular characteristics and immune landscape during UBC tumorigenesis and development of novel and robust immunotherapies for UBC are also proposed and discussed. Conclusion: At present, BCG and immune checkpoint blockades have been approved by the US Food and Drug Administration for the treatment of UBC patients and have achieved encouraging therapeutic results, expanding the traditional chemotherapy and surgery-based treatment for UBC. Relevance for patients: Immunotherapy has achieved desirable results in the treatment of UBC, which not only improve the overall survival but also reduce the recurrence rate and the occurrence of treatment-related adverse events of UBC patients. In addition, the indicators to predict the effectiveness and novel therapy strategies, such as combination regimen of checkpoint inhibitor with checkpoint inhibitor or chemotherapy, should be further studied.

Anisotropic films composed of aligned CsPbBr

B-site doping is an effective strategy to improve the performance of inorganic perovskite solar cells. Zinc halides (ZnX2, X I, Br, Cl) doped CsPbIBr2 solar cells were prepared by simply introducing ZnX2 salts into the precursor solution for one step spin-coating process. The doped inorganic perovskite films exhibit enhanced crystallinity and improved surface morphology. More over, the photoluminescence and single-carrier device characterizations confirm that the internal defect density of CsPbIBr2 films decreases remarkably after ZnX2 doping and the non-radiative recombination is suppressed. The CsPbIBr2 solar cells based on the ZnI2 doped films achieve a champion efficiency of 8.15%, outperforming that (6.93%) of the pristine counterpart.

Neurocan (NCAN), a secreted chondroitin sulfate proteoglycan, is one of the major inhibitory molecules for axon regeneration in nervous injury. However, its role in cancer is not clear. Here we observed that high NCAN expression was closely associated with the unfavorable outcome of neuroblastoma (NB). NCAN was also highly and ubiquitously expressed in the early lesions and terminal tumor of TH-MYCN mice, a NB model. Interestingly, exogenous NCAN (i.e., overexpression, recombinant protein and conditioned medium) transformed adherent NB cells into spheres whose malignancies in vitro (anchorage-independent growth and chemoresistance) and in vivo (xenograft tumor growth) were potentiated. Both chondroitin sulfate sugar chains and NCAN's core protein were essential for the sphere formation. The CSG3 domain was essential in the moiety of NCAN. Our comprehensive microarray analysis and RT-qPCR of mRNA expression suggested that NCAN treatment promoted cell division, and urged cells to undifferentiated state. The knockdown of NCAN in tumor sphere cells cultured from TH-MYCN mice resulted in growth suppression in vitro and in vivo. Our findings suggest that NCAN, which stimulates NB cells to promote malignant phenotypes, is an extracellular molecule providing a growth advantage to cancer cells.

Background The histone deacetylase (HDAC) inhibitor vorinostat (VOR) can increase HIV RNA expression in vivo within resting CD4+ T cells of aviremic HIV+ individuals. However, while studies of VOR or other HDAC inhibitors have reported reversal of latency, none has demonstrated clearance of latent infection. We sought to identify the optimal dosing of VOR for effective serial reversal of HIV latency. Methods In a study of 16 HIV-infected, aviremic individuals, we measured resting CD4+ T cell-associated HIV RNA ex vivo and in vivo following a single exposure to VOR, and then in vivo after a pair of doses separated by 48 or 72 hours, and finally following a series of 10 doses given at 72-hour intervals. Results Serial VOR exposures separated by 72 hours most often resulted in an increase in cell-associated HIV RNA within circulating resting CD4+ T cells. VOR was well tolerated by all participants. However, despite serial reversal of latency over 1 month of VOR dosing, we did not observe a measurable decrease (>0.3 log10) in the frequency of latent infection within resting CD4+ T cells. Conclusions These findings outline parameters for the experimental use of VOR to clear latent infection. Latency reversal can be achieved by VOR safely and repeatedly, but effective depletion of persistent HIV infection will require additional advances. In addition to improvements in latency reversal, these advances may include the sustained induction of potent antiviral immune responses capable of recognizing and clearing the rare cells in which HIV latency has been reversed. Trial registration Clinicaltrials.gov NCT01319383. Funding NIH grants U01 AI095052, AI50410, and P30 CA016086 and National Center for Advancing Translational Sciences grant KL2 TR001109.

Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc.

This study investigated the mechanistic basis behind the reported superior efficacy of high-avidity CD8 T cells. CMV and HIV are both chronic viral infections, but while CMV-specific CD8 T cells can mediate lifelong viral control, in untreated HIV infection HIV-specific CD8 T cells progressively lose function. Using in vitro studies of human cells, we show that avidity-dependent downregulation of the CD8 co-receptor directly programs metabolism, due to a novel association between CD8 and the glucose transporter GLUT1. We used flow cytometry to profile ex vivo and virus-specific CD8 T cells from HIV-infected individuals on antiretroviral therapy. Ex vivo, cells expressing low levels of CD8 (CD8dim) expressed more CD69 but less cell surface GLUT1, and took up less glucose (2-NBDG) than CD8bright T cells. Following antigen stimulation, CD3, CD8, and GLUT1 were downregulated from the cell surface in an avidity-dependent manner. CMV-specific CD8 T cells, which were of higher avidity, downregulated these proteins to a greater extent than lower-avidity HIV-specific CD8 T cells. GLUT1 downregulation strongly correlated with CD8 but not CD3 downregulation. Antibody-mediated downregulation of CD8 from the cell surface resulted in reduced glucose uptake and increased fatty acid (Bodipy) uptake, independent of CD3. Finally, CD3, CD8, and GLUT1 downregulation by HIV-specific CD8 T cells was impaired following viral escape mutations that reduced CD8 T cell avidity. We confirmed this finding in a transduction setting with a single clonal TCR. Our data reveal a novel function of the CD8 co-receptor, linking the avidity and metabolism of CD8 T cells.