New prospects of cancer therapy based on pyroptosis and pyroptosis inducers.

Pyroptosis is a gasdermin-mediated programmed cell death (PCD) pathway. It differs from apoptosis because of the secretion of inflammatory molecules. Pyroptosis is closely associated with various malignant tumors. Recent studies have demonstrated that pyroptosis can either inhibit or promote the development of malignant tumors, depending on the cell type (immune or cancer cells) and duration and severity of the process. This review summarizes the molecular mechanisms of pyroptosis, its relationship with malignancies, and focuses on current pyroptosis inducers and their significance in cancer treatment. The molecules involved in the pyroptosis signaling pathway could serve as therapeutic targets for the development of novel drugs for cancer therapy. In addition, we analyzed the potential of combining pyroptosis with conventional anticancer techniques as a promising strategy for cancer treatment.

NOS-like activity of CeO2 nanozymes contributes to diminishing the vascular plaques.

Ceria nanoparticles (CeO2NPs) exhibit great potential in cardiovascular disease and nonalcoholic fatty liver disease due to its excellent antioxidant capacity. However, the profitable effect of CeO2NPs on many diseases is almost all attributed to the regulation of ROS. Apart from the general antioxidant function, there seems to be no more distinct mechanism to reflect its unique multi-disease improvement effect. Here, we for the first time reveal a new discovery of CeO2NPs in mimicking nitric oxide synthase (NOS) by catalyzing L-arginine (L-Arg) to produce nitric oxide (NO) or the derivatives. NOS-like activity of CeO2NPs is original and associated with multiple factors like substrate concentration, pH, temperature and time, etc. where oxygen vacancy ratio plays a more critical role. Meanwhile, NOS-like activity of CeO2NPs successfully elevates NO secretion in endothelial cells and macrophages without expanding eNOS/iNOS expression. Importantly, NOS-like activity of CeO2NPs and the responsive endogenous NO promote the re-distribution of blood lipids and stabilize eNOS expression but suppress iNOS, thus collectively alleviate the accumulation of vascular plaque. Altogether, we provide a new angle of view to survey the outstanding potential of CeO2NPs, apart from the inevitable antioxidant capacity, the covert but possible and more critical NOS-like enzymatic activity is more noteworthy.

Clinical Characteristics and Detection Sensitivity of Cervical Cancer Screening in Vaginal Intraepithelial Neoplasia.

OBJECTIVE: This study aimed to investigate the characteristics and screening history of vaginal intraepithelial neoplasia (VaIN) or vaginal cancer and compare the sensitivity of cytology and human papillomavirus (HPV) tests on the cervix against vaginal and cervical high-grade squamous intraepithelial lesion or cancer. METHODS: This study included patients who underwent colposcopy-directed biopsy and were diagnosed with VaIN or vaginal cancer from February 2013 to November 2022. Clinical information was obtained from the medical records of the department. Statistical analysis was performed on SPSS 26.0 (IBM Corp, Armonk, NY) using t test, chi-square, and Fisher exact tests. RESULTS: A total of 1,166 patients were included in this study. The median age of VaIN2+ patients was 50.5 years, whereas VaIN1 reported a median age of 42.1 years old, p < .001. This study reported that VaIN was significantly and positively correlated with cervical lesions (r = 0.244). The high-risk HPV (hr-HPV) detection rate was 88.2% (858/973) in VaIN and 95.2% in VaIN2+. Human papillomavirus 16 was the most prevalent HPV type in VaIN2+, which accounted for 54.9%, followed by HPV58 (19.5%), HPV52 (15.2%), HPV51 (12.2%), and HPV18 (11.0%). The sensitivity of hr-HPV and cytology tests on the cervix for detecting VaIN2+ was 94.7% and 83.4%, respectively. Both tests were not significantly different from detecting cervical intraepithelial neoplasia 2+. CONCLUSIONS: Human papillomavirus 16 is the dominant HPV type in vaginal precancer lesions. Cervical cancer screening has similar sensitivity for VaIN2+ as for cervical intraepithelial neoplasia 2+, with hr-HPV testing showing higher sensitivity than cytology.

Dopant-Free Polymer Hole Transport Materials for Highly Stable and Efficient CsPbI3 Perovskite Solar Cells.

All-inorganic perovskite CsPbI3 contains no volatile organic components and is a thermally stable photoactive material for wide-bandgap perovskite solar cells (PSCs); however, CsPbI3 readily undergoes undesirable phase transitions due to the hygroscopic nature of the ionic dopants used in commonly used hole transport materials. In the current study, the popular donor material PM6 in organic solar cells is used as a hole transport layer (HTL). The benzodithiophene-based backbone-conjugated polymer requires no dopant and leads to a higher power conversion efficiency (PCE) than 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (Spiro-OMeTAD). Moreover, PM6 also shows priorities in hole mobility, hydrophobicity, cascade energy level alignment, and even defect passivation of perovskite films. With PM6 as the dopant-free HTL, the PSCs achieve a champion PCE of 18.27% with a competitive fill factor of 82.8%. Notably, the present PCE is based on the dopant-free HTL in CsPbI3 PSCs reported thus far. The PSCs with PM6 as the HTL retain over 90% of the initial PCE stored in a glovebox filled with N2 for 3000 h. In contrast, the PSCs with Spiro-OMeTAD as the HTL maintain ≈80% of the initial PCE under the same conditions.

Effect of different oxygen precursors on alumina deposited using a spatial atomic layer deposition system for thin-film encapsulation of perovskite solar cells.

An atmospheric-pressure spatial atomic layer deposition system operated in atmospheric-pressure spatial chemical vapor deposition conditions is employed to deposit alumina (AlOx) thin films using trimethylaluminum and different oxidants, including water (H2O), hydrogen peroxide (H2O2), and ozone (O3). The impact of the oxygen precursor on the structural properties of the films and their moisture-barrier performance is investigated. The O3-AlOxfilms, followed by H2O2-AlOx, exhibit higher refractive indexes, lower concentrations of OH- groups, and lower water-vapor-transmission rates compared to the films deposited using water (H2O-AlOx). The AlOxfilms are then rapidly deposited as thin-film-encapsulation layers on perovskite solar cells at 130 °C without damaging the temperature-sensitive perovskite and organic materials. The stability of thep-i-nformamidinium methylammonium lead iodide solar cells under standard ISOS-D-3 testing conditions (65 °C and 85% relative humidity) is significantly enhanced by the encapsulation layers. Specifically, the O3-AlOxand H2O2-AlOxlayers result in a six-fold increase in the time required for the cells to degrade to 80% of their original efficiency compared to un-encapsulated cells.

The increased prevalence of depression and anxiety in T2DM patients associated with blood glucose fluctuation and sleep quality.

BACKGROUND: Current evidence demonstrates that blood glucose fluctuation can be associated with depression and anxiety. The association among blood glucose fluctuation, traditional risk factors and emotional disorders in T2DM should be studied and clarified. METHODS: A total of 182 diabetic patients including 81 patients with depression or anxiety and 101 patients without emotional disorder were enrolled into this study. Data were obtained through medical history and questionnaire survey. Data were analyzed using appropriate statistical methods. RESULTS: The comparison results of basic information between the two groups showed that the differences of the proportion of female were statistically significant (p = 0.002). There was no statistical difference in laboratory examination indexes between the two groups, however, standard deviation of blood glucose (SDBG) and postprandial glucose excursion (PPGE) of the comorbidity group were significantly higher than that of control group (p = 0.032 and p = 0.037). The results of questionnaire survey showed that there were statistically significant differences in sleep quality, PSQI and dietary habit between the two groups (p < 0.001, p < 0.001 and p < 0.001). Stratified analysis results according to gender showed that the percentage of cognitive disorder, anxiety and depression in female group was significantly higher than that in male group (p = 0.001, p < 0.001 and p < 0.001). Mini-mental state examination (MMSE), self-rating anxiety scale (SAS) and patient health questionnaire (PHQ-9) score in female group were also higher than male group (p = 0.001, p < 0.001 and p < 0.001). Logistic regression analysis results showed that SDBG and sleep quality were associated with emotional disorders in T2DM (p = 0.040 and p < 0.001) and the OR values of these factors were 7.588 (1.097-52.069) and 4.428 (2.649-7.401). CONCLUSIONS: Blood glucose fluctuation and sleep quality are associated with the increased prevalence of depression and anxiety disorders in T2DM.

A Nonconjugated Zwitterionic Polymer: Cathode Interfacial Layer Comparable with PFN for Narrow-Bandgap Polymer Solar Cells.

A nonconjugated, alcohol-soluble zwitterionic polymer, poly(sulfobetaine methacrylate) (denoted by PSBMA), is employed as cathode interfacial layer (CIL) in polymer solar cells (PSCs) based on PTB7-Th:PC71 BM. Compared with the control device without CIL, PSCs with PSBMA CILs show significant enhancement on the resulting performance, and the highest power conversion efficiency (PCE) of 8.27% is achieved. Under parallel conditions, PSCs with PSBMA as CIL show comparable performance than those with widely used poly[(9,9-bis(30-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-ioctylfluorene)] as CIL. The polar groups of PSBMA not only provide a solvent orthogonal solubility in the process of preparation of the devices but also lead to interfacial dipole to the electrode, which promises a better energy level alignment. In addition, PSBMA-based devices show better abilities of hole blocking. These results indicate that the zwitterionic polymer PSBMA should be a promising CIL in PSC-based narrow-bandgap polymers.

MiR-124 Inhibits Growth and Enhances Radiation-Induced Apoptosis in Non-Small Cell Lung Cancer by Inhibiting STAT3.

BACKGROUND/AIMS: A growing body of evidence indicates that the abnormal expression of microRNAs (miRNAs) play an important role in sensitizing the cellular response to ionizing radiation (IR). The aim of this study was to investigate whether the expression of miR-124 correlated with radiosensitivity in the context of non-small-cell lung carcinoma (NSCLC). METHODS: Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to quantify miR-124 expression in NSCLC tissues and cell lines. The role of miR-124 in NSCLC proliferation and radiosensitivity was analyzed using CCK-8 and flow cytometry apoptosis assays. Luciferase activity assays, RT-PCR, and Western blot assays were performed to confirm the target gene of miR-124. RESULTS: In this study, we found that miR-124 was downregulated both in clinical NSCLC samples and in cell lines. miR-124 inhibited the proliferation of NSCLC cells and enhanced the apoptosis of NSCLC cells exposed to ionizing radiation. We identified signal transducer and activator of transcription 3 (STAT3) as a direct target of miR-124 by using target prediction algorithms and luciferase assays. Overexpression of STAT3 in A549 cell lines restored the enhanced radiosensitivity induced by miR-124. CONCLUSION: Taking these observations into consideration, we illustrated that miR-124 is a potential target for enhancing the radiosensitivity of NSCLC cells by targeting STAT3.

Association of Functional Genetic Variants of HOTAIR with Hepatocellular Carcinoma (HCC) Susceptibility in a Chinese Population.

BACKGROUND/AIMS: The HOX transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), plays an important role in the pathogenesis and progression of multiple tumors. The aim of the present study was to evaluate whether common single nucleotide polymorphisms (SNPs) in HOTAIR are related to hepatocellular carcinoma (HCC) susceptibility in a Chinese population. METHODS: We genotyped three SNPs of HOTAIR in a hepatocellular carcinoma (HCC) case-control study, including 482 cases and 520 control subjects. SNPs were genotyped using real-time polymerase chain reaction (RT-PCR). Associations between gene polymorphisms and HCC were evaluated using multiple logistic regression analysis. The allele-specific effects on HOTAIR expression in HCC were confirmed by real time quantitative PCR and luciferase activity assays. The influence of HOTAIR SNPs on the proliferation of HCC cells was evaluated using a CCK-8 assay. RESULTS: Significant associations were observed between the HOTAIR rs920778 C>T polymorphism and HCC risk (TT versus CC: OR = 1.634, 95% CI =1.028-2.598, P = 0.046) and the allelic model (allele T versus allele C: OR =1.293, 95% CI = 1.060-1.577, P = 0.011). However, no statistically significant differences of rs4759314 and rs1899663 genotypes were observed between patients and controls (both P > 0.05). The increased risk for rs920778 TT genotype carriers was more evident in a sub-group of drinkers (OR = 3.103, 95% CI = 1.151-8.368, p=0.025) and in people positive for HBV infection (OR = 2.885, 95% CI = 1.086-7.663, p=0.034). RT-PCR and luciferase activity assay confirmed that the rs920778 TT genotype induced significantly higher HOTAIR levels than did the CC genotype (P < 0.05). CCK-8 assays and colony formation assays demonstrated that the rs920778 TT genotype had a higher proliferation rate of HCC cells than did the CC genotype (P < 0.05). CONCLUSION: These results suggest that SNP rs920778 of HOTAIR acts as a potential biomarker for predicting hepatocellular carcinoma, and further studies are warranted to confirm these findings.

A Functional Variant at the miR-214 Binding Site in the Methylenetetrahydrofolatereductase Gene Alters Susceptibility to Gastric Cancer in a Chinese Han Population.

BACKGROUND AND AIMS: Single nucleotide polymorphisms in miRNA binding sites, which are located in mRNA 3' untranslated regions (3'-UTRs), were recently found to influence microRNA-target interactions. Specifically, such polymorphisms can modulatebinding affinity or create or destroy miRNA-binding sites; such variants have also been found to be associated with cancer risk. In this study, we explored the effect of a functional variant at the miR-214 binding site in the methylenetetrahydrofolate reductase gene (rs114673809) on gastric cancer (GC) risk in a hospital-based case-control study in a Chinese Han population. METHODS AND RESULTS: We genotyped the rs114673809 polymorphism in 345 gastric cancer patients and 376 cancer-free controls using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The functions of rs114673809 were investigated using a luciferase activity assay and validated by immunoblotting. We found that participants carrying the rs114673809 AA genotype or A allele had a significantly increased risk of gastric cancer (OR = 1.667, 95% CI = 1.044-2.660, P = 0.034; OR = 1.261, 95% CI = 1.017-1.563, P = 0.037, respectively) compared to those carrying the GG genotype and G allele. In addition, rs114673809 modified the binding of hsa-miR-214 to MTHFR as well as MTHFR protein levels in gastric cancer patients. CONCLUSION: Our data suggested that rs114673809, which is located at the miR-214 binding site in the 3'-UTR of MTHFR, may play an important role in the development of gastric cancer in a Chinese Han population.

Berberine Sensitizes Human Ovarian Cancer Cells to Cisplatin Through miR-93/PTEN/Akt Signaling Pathway.

BACKGROUND: Berberine, a well-known component of the Chinese herbal medicine Huanglian, has wide range of biochemical and pharmacological effects, including antineoplastic effect, but the exact mechanisms remain unclear. The aim of the present study was to evaluate the potential chemo-sensitization effect of berberine in ovarian cancer cell line A2780. METHODS: The expression of miR-93 was measure by RT-PCR. The target of miR-93 was confirmed by luciferase activity assay. Hoechst 33258 staining, Annexin V and PI double staining were used for apoptosis analysis. RESULTS: In this study, we found A2780/DDP cells that were incubated with berberine combined with cisplatin had a significantly lower survival than the control group. Berberine enhanced cisplatin induced apoptosis and induced G0/G1 cell cycle arrest in A2780 cells. Next, we observed that the miR-93 levels in cisplatin resistant cell lines were higher than that in cisplatin sensitive cell lines. Furthermore, our study found berberine could inhibit miR-93 expression and function in ovarian cancer, as shown by an increase of its target PTEN, an important tumor suppressor in ovarian cancer. A2780 cells that were treated with PTEN siRNA had increased survival compared to NC group and this could be partly alleviated by the AKT inhibitor Triciribine. More importantly, A2780 cells that were treated with PTEN siRNA had a survival pattern that is similar to cells with miR-93 overexpression. CONCLUSION: The results suggested that berberine modulated the sensitivity of cisplatin through miR-93/PTEN/AKT signaling pathway in the ovarian cancer cells.

Decreased expression of microRNA-21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis.

The imbalance of Th17/Treg cell populations has been suggested to be involved in the regulation of rheumatoid arthritis (RA) pathogenesis; however, the mechanism behind this phenomenon remains unclear. Recent studies have shown how microRNAs (miRNAs) are important regulators of immune responses and are involved in the development of a variety of inflammatory diseases, including RA. In this study, we demonstrated that the frequencies of CD3(+) CD4(+) IL-17(+) Th17 cells were significantly higher, and CD4(+) CD25(+) FOXP3(+) Treg cells significantly lower in peripheral blood mononuclear cells from RA patients. Detection of cytokines from RA patients revealed an elevated panel of pro-inflammatory cytokines, including IL-17, IL-6, IL-1ß, TNF-α and IL-22, which carry the inflammatory signature of RA and are crucial in the differentiation and maintenance of pathogenic Th17 cells and dysfunction of Treg cells. However, the level of miR-21 was significantly lower in RA patients, accompanied by the increase in STAT3 expression and activation, and decrease in STAT5/pSTAT5 protein and Foxp3 mRNA levels. Furthermore, lipopolysaccharide stimulation up-regulated miR-21 expression from healthy controls, but down-regulated miR-21 expression from RA patients. Therefore, we speculate that miR-21 may be part of a negative feedback loop in the normal setting. However, miR-21 levels decrease significantly in RA patients, suggesting that this feedback loop is dysregulated and may contribute to the imbalance of Th17 and Treg cells. MiR-21 may thus serve as a novel regulator in T-cell differentiation and homoeostasis, and provides a new therapeutic target for the treatment of RA.

MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells.

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for the advanced ovarian cancer, but resistance to cisplatin remains a major obstacle to successful treatment. MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in disease processes, including the development of drug resistance. In this study, we found miR-449a were significantly downregulated in the cisplatin-resistant ovarian cell lines SKOV3/DDP and A2780/DDP, compared with their sensitive parent line SKOV3 and A2780, respectively. The overexpression of miR-449a increased cisplatin sensitivity of SKOV3/DDP and A2780/DDP cells by inhibiting proliferation and promoting apoptosis. The luciferase assay confirmed that miR-449a functioned through suppressing NOTCH1 directly. Concordantly, BALB/c nude mice that were injected intraperitoneally with SKOV3/DDP cells transfected with miR-449a mimics exhibited enhanced cisplatin sensitivity in vivo. Taken together, these results suggest that the ectopic expression of miR-449a may be a promising therapeutic strategy for the management of cisplatin resistance in ovarian cancer.

miR-449a Regulates proliferation and chemosensitivity to cisplatin by targeting cyclin D1 and BCL2 in SGC7901 cells.

BACKGROUND: Recently, several miRNAs have been determined as tumor suppressors in various cancers, such as microRNA-449a. However, the exact molecular mechanisms underlying miR-449a regulated cell proliferation and chemosensitivity in gastric cancer cells have not been well documented. AIM: The present study was designed to test whether miR-449a mediates cell proliferation and chemosensitivity in gastric cancer cells via regulating cyclin D1 and BCL2. METHODS: In vitro, the ability of cell proliferation and cell viability were measured by MTT assay; cell cycle and cell apoptosis was detected by FCM. qRT-PCR was used to measure the expression of miR-449a. Western blot and real-time PCR assays were used to detect the expression of cyclin D1 and BCL2 in gastric cancer cell line SGC7901. RESULTS: miR-449a expression was downregulated in gastric cancer cell line SGC7901 and human gastric cancer tissues, compared to the gastric epithelial cell line GES-1 and matched non-tumor associated tissues. Upregulation of miR-449a reduced the proliferation of SGC7901 cells. Ectopic expression of miR-449a decreased the percentage of S phase cells, increased the percentage of G1/G0 phase cells and increased the apoptosis induced by cisplatin. Moreover, miR-449a inhibited SGC7901 cells proliferation and enhanced cisplatin chemosensitivity by downregulating expression of BCL2 and cyclin D1, respectively, via directly targeting the 3'-untranslated regions of BCL2 and cyclin D1 mRNA. CONCLUSIONS: This is the first report to provide evidence that miR-449a could modulate cell cycle and apoptosis through regulating cyclin D1 and BCL2 expression in SGC7901 cells.

Zinc Aluminum Oxide Encapsulation Layers for Perovskite Solar Cells Deposited Using Spatial Atomic Layer Deposition.

An atmospheric-pressure spatial atomic layer deposition system is used to rapidly deposit 60 nm zinc-aluminum oxide (Zn-AlOx ) thin-film-encapsulation layers directly on perovskite solar cells at 130 °C without damaging the temperature-sensitive perovskite and organic materials. Varying the Zn/Al ratio has a significant impact on the structural properties of the films and their moisture barrier performance. The Zn-AlOx films have higher refractive indexes, lower concentrations of OH─ groups, and lower water-vapor transmission rates (WVTR) than AlOx films without zinc. However, as the Zn/Al ratio increases beyond 0.21, excess Zn atoms segregate, leading to an increase in the number of available hydroxyl groups on the surface of the deposited film and a slight increase in the WVTR. The stability of the p-i-n formamidinium methylammonium lead iodide solar cells under standard ISOS-D-3 testing conditions (65 °C and 85% relative humidity) is significantly enhanced by the thin encapsulation layers. The layers with a Zn/Al ratio of 0.21 result in a seven-fold increase the time required for the cells to degrade to 80% of their original efficiency.

The Spatial Shifts and Vulnerability Assessment of Ecological Niches under Climate Change Scenarios for Betula luminifera, a Fast-Growing Precious Tree in China.

The spatial shifts and vulnerability assessments of ecological niches for trees will offer fresh perspectives for sustainable development and preservation of forests, particularly within the framework of rapid climate change. Betula luminifera is a fast-growing native timber plantation species in China, but the natural resources have been severely damaged. Here, a comprehensive habitat suitability model (including ten niche-based GIS modeling algorithms) was developed that integrates three types of environmental factors, namely, climatic, soil, and ultraviolet variables, to assess the species contemporary and future distribution of suitable habitats across China. Our results suggest that the habitats of B. luminifera generally occur in subtropical areas (about 1.52 × 106 km2). However, the growth of B. luminifera is profoundly shaped by the nuances of its local environment, the most reasonable niche spaces are only 1.15 × 106 km2 when limiting ecological factors (soil and ultraviolet) are considered, generally considered as the core production region. Furthermore, it is anticipated that species-suitable habitats will decrease by 10 and 8% with climate change in the 2050s and 2070s, respectively. Our study provided a clear understanding of species-suitable habitat distribution and identified the reasons why other niche spaces are unsuitable in the future, which can warn against artificial cultivation and conservation planning.

Enhancing the Humidity Stability of Perovskite Films through Interfacial Modification with Differentiated Hydrophilic Organics.

Preparing high-quality perovskite films is a decisive step toward realizing highly efficient and stable perovskite solar cells (Pero-SCs). Water is a key factor affecting the stability of the Pero-SCs. Here, the widely used water adsorbents chitosan, sorbitol, and sodium hyaluronate (NaHA) were used as hydrophilic layers on the upper interface of the perovskite to form a barrier against water. The water adsorbents also passivated defects on the surface of the perovskite active layer due to their -OH and -COOH functional groups. The NaHA-modified devices showed the best power conversion efficiency (PCE) (PCE = 21.74%). Although the NaHA-modified Pero-SCs showed optimal photovoltaic performance, the stability of the modified devices decreased due to the strong water adsorption ability of NaHA, while with moderate water adsorption ability sorbitol-modified devices exhibited good stability and PCE. The devices were tested in the dark and room temperature at different humidity levels for 800 h. At low humidity (25% ± 5% RH), the PCEs of the sorbitol- and NaHA-modified devices were maintained at 80% and 71% of the initial values, respectively. At high humidity (75% ± 5% RH), the PCE was maintained at 64% and 23% of the initial values, respectively. This work provides an avenue to select adsorbents with suitable water absorption ability as the interface modification layer, thus reducing the water erosion of perovskite films and obtaining highly stable inverted Pero-SCs.

Chirality-Induced Crystallization and Defect Passivation of Perovskites: Toward High-Performance Solar Cells.

As an additive for perovskites, in addition to functional groups, the steric configuration of molecules is worthy of consideration because it influences perovskite crystallization, thus determining whether defect passivation is effective without any side effects. In this work, the chiral molecules l- and d-pyroglutamic acid (l-PA and d-PA) were chosen as additives for perovskite passivators to reveal the reasons for the differences in passivation between amino acids with different steric configurations. Functional groups, such as the C═O groups and N-H groups of l-PA and d-PA, can passivate the perovskite defects. However, l-PA exhibited a more distorted steric configuration, while d-PA was more planar, leading to differences in the distances between the two C═O groups. Taking the Pb-Pb bond length as a reference, the shorter distance between the two C═O groups of l-PA distorts the perovskite lattice structure, which results in poor device stability. Conversely, the similar distance between the two C═O groups of d-PA promoted the preferred orientational growth of the perovskite. Finally, the d-PA-doped device accomplished an excellent efficiency of 24.11% with an improved open-circuit voltage of 1.17 V. Furthermore, the efficiency of the unencapsulated d-PA-doped device was maintained at 93% in N2 for more than 3000 h and 74% after 500 h of operation at maximum power point tracking under continuous illumination.

The Association between Obstructive Sleep Apnea and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study.

BACKGROUND: Despite previous observational studies linking obstructive sleep apnea (OSA) to venous thromboembolism (VTE), these findings remain controversial. This study aimed to explore the association between OSA and VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), at a genetic level using a bidirectional two-sample Mendelian randomization (MR) analysis. METHODS: Utilizing summary-level data from large-scale genome-wide association studies in European individuals, we designed a bidirectional two-sample MR analysis to comprehensively assess the genetic association between OSA and VTE. The inverse variance weighted was used as the primary method for MR analysis. In addition, MR-Egger, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for complementary analyses. Furthermore, a series of sensitivity analyses were performed to ensure the validity and robustness of the results. RESULTS: The initial and validation MR analyses indicated that genetically predicted OSA had no effects on the risk of VTE (including PE and DVT). Likewise, the reverse MR analysis did not find substantial support for a significant association between VTE (including PE and DVT) and OSA. Supplementary MR methods and sensitivity analyses provided additional confirmation of the reliability of the MR results. CONCLUSION: Our bidirectional two-sample MR analysis did not find genetic evidence supporting a significant association between OSA and VTE in either direction.

Vascular endothelial growth factor induces multidrug resistance-associated protein 1 overexpression through phosphatidylinositol-3-kinase /protein kinase B signaling pathway and transcription factor specificity protein 1 in BGC823 cell line.

Multidrug resistance (MDR) is one of the most important causes of chemotherapy failure and carcinoma recurrence. But the roles of the MDR-associated protein MRP1 in MDR remain poorly understood. Vascular endothelial growth factor (VEGF), one of the most active and specific vascular growth factors, plays a significant role in proliferation, differentiation, and metastasis of cancers. To explore the effect of VEGF on the expression of MRP1, we used recombinant human VEGF to stimulate K562 and BGC-823 cell lines. Quantitative real-time polymerase chain reaction and western blot analysis showed that the expression of MRP1 at both mRNA and protein levels was increased. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide results also showed that VEGF significantly enhanced the IC50 of the cells treated with adriamycin. To explore the underlying regulatory mechanisms, we constructed MRP1 promoter and the luciferase reporter gene recombinant vector. The luciferase reporter gene assay showed that the activity of the MRP1 promoter was markedly increased by VEGF stimulation, while LY294002, an inhibitor of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, reduced this effect. Transcription factor specificity protein 1 (SP1) binding site mutation partially blocked the up-regulation of MRP1 promoter activity by VEGF. In summary, our results demonstrated that VEGF enhanced the expression of MRP1, and the PI3K/Akt signaling pathway and SP1 may be involved in this modulation.