Custom-tailored hole transport layer using oxalic acid for high-quality tin-lead perovskites and efficient all-perovskite tandems.

All-perovskite tandem solar cells (TSCs) have exhibited higher efficiencies than single-junction perovskite solar cells (PSCs) but still suffer from the unsatisfactory performance of low-bandgap (LBG) tin-lead (Sn-Pb) subcells. The inherent properties of PEDOT:PSS are crucial to high-performance Sn-Pb perovskite films and devices; however, the underlying mechanism has not been fully explored and revealed. Here, we report a facile oxalic acid treatment of PEDOT:PSS (OA-PEDOT:PSS) to precisely regulate its work function and surface morphology. OA-PEDOT:PSS shows a larger work function and an ordered reorientation and fiber-shaped film morphology with efficient hole transport pathways, leading to the formation of more ideal hole-selective contact with Sn-Pb perovskite for suppressing interfacial nonradiative recombination losses. Moreover, OA-PEDOT:PSS induces (100) preferred orientation growth of perovskite for higher-quality Sn-Pb films. Last, the OA-PEDOT:PSS-tailored LBG PSC yields an impressive efficiency of up to 22.56% (certified 21.88%), enabling 27.81% efficient all-perovskite TSC with enhanced operational stability.

Biomarkers of Autologous Whole Blood Injection Efficacy in Patients with Chronic Spontaneous Urticaria with Autoreactivity: A Preliminary Study.

INTRODUCTION: Chronic spontaneous urticaria (CSU) with autoreactivity is often resistant to antihistamines. Autologous whole blood injection (AWBI) has shown potential efficacy in the treatment of this disease, but it is controversial. It is necessary to screen patients who are suitable for this therapy in advance. This study aimed to identify biomarkers that predict the efficacy of AWBI treatment in CSU patients with autoreactivity. METHODS: A total of 30 patients with autologous serum skin test-positive CSU treated with AWBI were included in this study; urticaria activity score (UAS7) was recorded and the treatment response was judged based on it. Levels of total serum IgE, anti-high-affinity IgE receptor (FcεRI) IgG, and basophils CD63 and FcεRI expressions, and D-dimer of all patients were determined and analyzed. RESULTS: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed good correlations with UAS7 variations. D-dimer, basophil FcεRI and CD63 expressions changed significantly before and after AWBI treatment in AWBI responders, and the basophil FcεRI and CD63 expressions consistently and dynamically decreased in AWBI responders during the treatment. Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed certain predictive values for AWBI response. CONCLUSIONS: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions could be biomarkers of predicting AWBI efficacy in patients with CSU with autoreactivity.

Improving interface quality for 1-cm2 all-perovskite tandem solar cells.

All-perovskite tandem solar cells provide high power conversion efficiency at a low cost1-4. Rapid efficiency improvement in small-area (<0.1 cm2) tandem solar cells has been primarily driven by advances in low-bandgap (approximately 1.25 eV) perovskite bottom subcells5-7. However, unsolved issues remain for wide-bandgap (> 1.75 eV) perovskite top subcells8, which at present have large voltage and fill factor losses, particularly for large-area (>1 cm2) tandem solar cells. Here we develop a self-assembled monolayer of (4-(7H-dibenzo[c,g]carbazol-7-yl)butyl)phosphonic acid as a hole-selective layer for wide-bandgap perovskite solar cells, which facilitates subsequent growth of high-quality wide-bandgap perovskite over a large area with suppressed interfacial non-radiative recombination, enabling efficient hole extraction. By integrating (4-(7H-dibenzo[c,g]carbazol-7-yl)butyl)phosphonic acid in devices, we demonstrate a high open-circuit voltage (VOC) of 1.31 V in a 1.77-eV perovskite solar cell, corresponding to a very low VOC deficit of 0.46 V (with respect to the bandgap). With these wide-bandgap perovskite subcells, we report 27.0% (26.4% certified stabilized) monolithic all-perovskite tandem solar cells with an aperture area of 1.044 cm2. The certified tandem cell shows an outstanding combination of a high VOC of 2.12 V and a fill factor of 82.6%. Our demonstration of the large-area tandem solar cells with high certified efficiency is a key step towards scaling up all-perovskite tandem photovoltaic technology.

Improved Carrier Management via a Multifunctional Modifier for High-Quality Low-Bandgap Sn-Pb Perovskites and Efficient All-Perovskite Tandem Solar Cells.

All-perovskite tandem solar cells (TSCs) hold great promise in terms of ultrahigh efficiency, low manufacturing cost, and flexibility, stepping forward to the next-generation photovoltaics. However, their further development is hampered by the relatively low performance of low-bandgap (LBG) tin (Sn)-lead (Pb) perovskite solar cells (PSCs). Improving the carrier management, including suppressing trap-assisted non-radiative recombination and promoting carrier transfer, is of great significance to enhance the performance of Sn-Pb PSCs. Herein, a carrier management strategy is reported for using cysteine hydrochloride (CysHCl) simultaneously as a bulky passivator and a surface anchoring agent for Sn-Pb perovskite. CysHCl processing effectively reduces trap density and suppresses non-radiative recombination, enabling the growth of high-quality Sn-Pb perovskite with greatly improved carrier diffusion length of >8 µm. Furthermore, the electron transfer at the perovskite/C60 interface is accelerated due to the formation of surface dipoles and favorable energy band bending. As a result, these advances enable the demonstration of champion efficiency of 22.15% for CysHCl-processed LBG Sn-Pb PSCs with remarkable enhancement in both open-circuit voltage and fill factor. When paired with a wide-bandgap (WBG) perovskite subcell, a certified 25.7%-efficient all-perovskite monolithic tandem device is further demonstrated.

Pure 2D Perovskite Formation by Interfacial Engineering Yields a High Open-Circuit Voltage beyond 1.28 V for 1.77-eV Wide-Bandgap Perovskite Solar Cells.

Surface post-treatment using ammonium halides effectively reduces large open-circuit voltage (VOC ) losses in bromine-rich wide-bandgap (WBG) perovskite solar cells (PSCs). However, the underlying mechanism still remains unclear and the device efficiency lags largely behind. Here, a facile strategy of precisely tailoring the phase purity of 2D perovskites on top of 3D WBG perovskite and realizing high device efficiency is reported. The transient absorption spectra, cross-sectional confocal photoluminescence mapping, and cross-sectional Kelvin probe force microscopy are combined to demonstrate optimal defect passivation effect and surface electric-field of pure n = 1 2D perovskites formed atop 3D WBG perovskites via low-temperature annealing. As a result, the inverted champion device with 1.77-eV perovskite absorber achieves a high VOC of 1.284 V and a power conversion efficiency (PCE) of 17.72%, delivering the smallest VOC deficit of 0.486 V among WBG PSCs with a bandgap higher than 1.75 eV. This enables one to achieve a four-terminal all-perovskite tandem solar cell with a PCE exceeding 25% by combining with a 1.25-eV low-bandgap PSC.

An integrated RNA sequencing and network pharmacology approach reveals the molecular mechanism of dapagliflozin in the treatment of diabetic nephropathy.

Dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), is a new type of oral hypoglycemic drugs which can promote glucose excretion in the kidney. Studies have shown that dapagliflozin has renoprotective effect in the treatment of type 2 diabetes. However, the underlying mechanism remains unclear. Here, we combined integrated RNA sequencing and network pharmacology approach to investigate the molecular mechanism of dapagliflozin for diabetic nephropathy (DN). Dapagliflozin significantly relieved glucose intolerance, urinary albumin/creatinine ratio (UACR) and renal pathological injuries of db/db mice. The LncRNA and mRNA expression in kidney tissues from control group (CR), db/db group (DN) and dapagliflozin group (DG) were assessed by RNA sequencing. We identified 7 LncRNAs and 64 mRNAs common differentially expressed in CR vs DN and DN vs DG, which were used to construct co-expression network to reveal significantly correlated expression patterns in DN. In addition, network pharmacology was used to predict the therapeutic targets of dapagliflozin and we constructed component-target-pathway network according to the results of RNA sequencing and network pharmacology. We found that SMAD9, PPARG, CD36, CYP4A12A, CYP4A12B, CASP3, H2-DMB2, MAPK1, MAPK3, C3 and IL-10 might be the pivotal targets of dapagliflozin for treating DN and these genes were mainly enriched in pathways including TGF-ß signaling pathway, PPAR signaling pathway, Chemokine signaling pathway, etc. Our results have important implication and provide novel insights into the protective mechanism of dapagliflozin for treating DN.

Folic acid and zinc improve hyperuricemia by altering the gut microbiota of rats with high-purine diet-induced hyperuricemia.

A high-purine diet can cause hyperuricemia and destroy the microbial composition of the gut microbiota. Both folic acid and zinc significantly reduce uric acid levels and alleviate hyperuricemia. However, whether the underlying mechanisms are associated with the regulation of the gut microbiota remain unknown. To explore alterations of the gut microbiota related to folic acid and zinc treatment in rats with hyperuricemia in our study. A hyperuricemic rat model was established with a high-purine diet. The effects of folic acid and zinc on uric acid levels were evaluated. Alterations of the gut microbiota related to hyperuricemia and the treatments were evaluated by sequencing using the Illumina MiSeq system. The results demonstrated that uric acid levels dropped observably, and the activities of adenosine deaminase (ADA) and xanthine oxidase (XOD) were downregulated after folic acid or zinc intervention. 16S rRNA gene sequencing-based gut microbiota analysis revealed that folic acid and zinc enhanced the abundance of probiotic bacteria and reduced that of pathogenic bacteria, thus improving intestinal barrier function. PICRUST analysis indicated that folic acid and zinc restored gut microbiota metabolism. These findings indicate that folic acid and zinc ameliorate hyperuricemia by inhibiting uric acid biosynthesis and stimulating uric acid excretion by modulating the gut microbiota. Thus, folic acid and zinc may be new and safe therapeutic agents to improve hyperuricemia.

A lactate-induced Snail/STAT3 pathway drives GPR81 expression in lung cancer cells.

Highly expressed G protein-coupled receptor 81 (GPR81), a receptor for lactate, is emerging as a critical regulator of tumor growth and metastasis. However, the mechanistic basis for its highly expression in cancer cells remains elusive. Here we report that tumor-derived lactate transcriptionally regulates GPR81 expression. We demonstrated that the transcriptional response of GPR81 to lactate is mediated by Signal transducer and activator of transcription 3 (STAT3). Mechanistically, lactate upregulates transcriptional factor Snail and induces the assembly of Snail/EZH2/STAT3 complex. Within this ternary complex, STAT3 activity is strongly enhanced. Consequently, the activated STAT3 by lactate directly binds GPR81promoter and activates its expression. These findings shed light on the transcriptional mechanism by which GPR81 expression is regulated in cancer cells, and provides mechanistic insight into how aberrant signaling and continually high lactate levels due to metabolic switch may yield a feed-forward/self-enabling loop to promote tumor progression.

Knockdown of Trnau1ap inhibits the proliferation and migration of NIH3T3, JEG-3 and Bewo cells via the PI3K/Akt signaling pathway.

The tRNA selenocysteine 1 associated protein 1 (Trnau1ap, initially named SECp43) is involved in Selenocysteine (Sec) biosynthesis and incorporation into selenoproteins, which play a key role in biological processes, such as embryonic development. We previously reported that downregulation of Trnau1ap inhibited proliferation of cardiomyocyte-like H9c2 cells. However, the effects of Trnau1ap on cell proliferation and migration of embryonic development are not known, and the mechanisms remain elusive. Herein, lentiviral shRNA vectors were transfected in NIH3T3, JEG-3 and Bewo cells (embryonic, trophoblast and placental cells). We found that knockdown of Trnau1ap resulted in reduced expression levels of selenoproteins. The data of Cell Count Kit-8 (CCK-8) assay and wound scratch assay revealed the proliferation and migration rates were reduced in the Trnau1ap-shRNA groups. Furthermore, western blot analysis showed that the phosphorylation level of Akt in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was attenuated. These results indicate that Trnau1ap plays an important role in regulation of cell proliferation and migration through the PI3K/Akt signaling pathway, as well as being essential for embryonic development by regulating the expression of selenoproteins.

Selenoprotein K Mediates the Proliferation, Migration, and Invasion of Human Choriocarcinoma Cells by Negatively Regulating Human Chorionic Gonadotropin Expression via ERK, p38 MAPK, and Akt Signaling Pathway.

Selenoprotein K (SelK), a member of selenoprotein family, is identified as a single endoplasmic reticulum (ER) transmembrane protein. Although over-expression of SelK inhibits adherence and migration of human gastric cancer BGC-823 cells, the effects of SelK in human choriocarcinoma (CCA) are not well understood. In this study, the expression levels of SelK in three CCA cell lines, BeWo, JEG-3, and JAR, were examined. The effects of silencing or over-expressing SelK on expression of human chorionic gonadotropin beta subunit (ß-hCG) were detected by western blotting. The results show that the protein level of ß-hCG was reciprocally regulated by down- or up-regulation of SelK (*P < 0.05; #P < 0.05). The proliferative, migratory, and invasive capabilities of JEG-3 cells with reduced or over-expressed SelK were then tested using the cell counting kit-8 (CCK-8), wound healing, and transwell chamber assays. We found that these cellular activities were markedly increased by the loss of SelK in JEG-3 cells. Conversely, over-expressing SelK in JEG-3 cells suppressed these phenotypes. In addition, SelK expression after down- or up-regulation of ß-hCG was also measured. Surprisingly, we found that level of SelK was affected by ß-hCG (*P < 0.05; #P < 0.05). The proliferation, migration, and invasion were determined in JEG-3 cells after each over-expression and reduction of ß-hCG. The results confirmed that ß-hCG functions as a promoter of human choriocarcinoma. Furthermore, ERK/p38 MAPK and Akt signaling pathways were found to involve in these cellular functions. This work suggests that SelK may act as a tumor suppressor in human choriocarcinoma cells by negatively regulating ß-hCG expression via ERK, p38 MAPK, and Akt signaling pathways. These findings revealed that selenoprotein K may serve as a novel target for human choriocarcinoma therapy in vitro.

Loss of selenocysteine insertion sequence binding protein 2 suppresses the proliferation, migration/invasion and hormone secretion of human trophoblast cells via the PI3K/Akt and ERK signaling pathway.

INTRODUCTION: Selenocysteine insertion binding protein 2 (SECISBP2) plays a vital role in selenocysteine incorporation into selenoprotein in many creatures. However, the impact of SECISBP2 in development of trophoblast cells remains unclear. The aim of this study was to investigate the roles of SECISBP2 in human trophoblast cells and the underlying molecular mechanism. METHODS: Low-expression of SECISBP2 in trophoblast cells was achieved by transfection with siRNAs. Then protein levels of selenoproteins and MDA content were performed to evaluate the levels of oxidative stress. CCK-8 assays, transwell chamber assay and wound healing assay were used to assess the trophoblast proliferation, migration/invasion. Production of ß-hCG and progesterone was quantified to estimate the effect of SECISBP2 on hormone secretion. The underlying mechanisms were also examined in two trophoblast cell lines. RESULTS: Knockdown of SECISBP2 clearly reduced the levels of some selenoproteins, including GPx1, SelK, Dio2 (p < 0.05). On the contrary, the levels of oxidative stress presented as MDA content markedly increased in two cell lines (p < 0.05). In addition, proliferative, migratory and invasive abilities of trophoblast cells were significantly suppressed when SECISBP2 was partially deleted (p < 0.05). Furthermore, silencing SECISBP2 reduced the expression of ß-hCG at mRNA and protein levels (p < 0.05), and inhibited the production of progesterone (p < 0.01). The PI3K/Akt and ERK signaling pathway were found to involve in the progress (p < 0.05). DISCUSSION: Our results suggest that the decreased SECISBP2 impaired trophoblast proliferation, migration/invasion and hormone secretion through inactivation of the PI3K/Akt and ERK signaling pathway may provide an insight into the preeclampsia and miscarriage induced by selenium deficiency.

MicroRNA-328 is involved in the effect of selenium on hydrogen peroxide-induced injury in H9c2 cells.

Oxidative stress induces apoptosis in cardiac cells, and antioxidants attenuate the injury. MicroRNAs (miRNAs) are also involved in cell death; therefore, this study aimed to investigate the role of miRNAs in the effect of selenium on oxidative stress-induced apoptosis. The effects of sodium selenite were analyzed via cell viability, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) concentration. Flow cytometry was used to evaluate cell apoptosis. Fura-2AM was used to calculate intracellular Ca2+ concentration. Sodium selenite could ameliorate hydrogen peroxide (H2 O2 )-induced cell apoptosis and improve expression levels of glutathione peroxidase and thioredoxin reductase. Pretreatment with sodium selenite improved SOD activity and reduced MDA concentration. Treatments with H2 O2 or sodium selenite decreased miR-328 levels. MiR-328 overexpression enhanced cell apoptosis, reduced ATP2A2 levels, and increased intracellular Ca2+ concentration, while inhibition produced opposite effects. MiR-328 might be involved in the effect of sodium selenite on H2 O2 -induced cell death in H9c2 cells.

Role of tRNA selenocysteine 1 associated protein 1 in the proliferation and apoptosis of cardiomyocyte­like H9c2 cells.

Transfer RNA selenocysteine 1 associated protein 1 (Trnau1ap) serves an essential role in the synthesis of selenoproteins, which have critical functions in numerous biological processes. Selenium deficiency results in a variety of diseases, including cardiac disease. However, the mechanisms underlying myocardial injury induced by selenium deficiency remain unclear. The present study examined the effects of Trnau1ap under­ and overexpression in cardiomyocyte­like H9c2 cells, by transfection with small interfering RNA and an overexpression plasmid, respectively. Expression levels of glutathione peroxidase, thioredoxin reductase and selenoprotein K were decreased in Trnau1ap­underexpressing cells, and increased in Trnau1ap­overexpressing cells. Using MTT, proliferating cell nuclear antigen, annexin V and caspase­3 activity assays, it was demonstrated that reducing Trnau1ap expression levels inhibited the proliferation of H9c2 cells and induced apoptosis. Conversely, increasing Trnau1ap expression levels promoted cell growth. Western blot analysis revealed that the phosphoinositide 3­kinase/protein kinase B signaling pathway was activated in Trnau1ap­underexpressing cells. Furthermore, the apoptotic pathway was activated in these cells, evidenced by relatively greater expression levels of B­cell lymphoma (Bcl­2)­associated X protein and reduced expression levels of Bcl­2. Taken together, these findings suggest that Trnau1ap serves a key role in the proliferation and apoptosis of H9c2 cells. The present study provides insight into the underlying mechanisms of myocardial injury induced by selenium deficiency.