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1.
Nature ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379225

RESUMO

The open circuit voltage (VOC) deficit in perovskite solar cells (PSCs) is greater in wide bandgap (>1.7 eV) cells than in ~1.5 eV perovskites.1,2 Quasi-Fermi level splitting (QFLS) measurements reveal VOC-limiting recombination at the electron transport layer (ETL) contact.3-5 This, we find, stems from inhomogeneous surface potential and poor perovskite-ETL energetic alignment. Common monoammonium surface treatments fail to address this; instead we introduce diammonium molecules to modify the perovskite surface states and achieve a more uniform spatial distribution of surface potential. Using 1,3-propane diammonium (PDA), QFLS increases by 90 meV, enabling 1.79 eV PSCs with a certified 1.33 V VOC, and > 19% power conversion efficiency (PCE). Incorporating this layer into a monolithic all-perovskite tandem, we report a record VOC of 2.19 V (89% of the detailed balance VOC limit) and > 27% PCE (26.3% certified quasi-steady-state). These tandems retain more than 86% of their initial PCE after 500 hrs operation.

2.
Front Oncol ; 12: 1009673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248964

RESUMO

Purpose: Our study aims to examine the clinicopathological features, disease progression, management, and outcomes of gallbladder sarcomatoid carcinoma (GBSC) patients. Methods: Between January 2000 and December 2020, 50 gallbladder cancer (GBC) patients who received surgical treatment and were pathologically verified as GBSC at our institution were enrolled. The clinical and pathological features and survival of these patients were retrospectively reviewed. Results: The median overall survival (OS) of GBSC patients was 14.5 months, and the 1-, 2- and 3-year OS rates were 68.0%, 32.0%, and 10.0%, respectively. The median progression-free survival (PFS) was 10.0 months, and the 1-, 2-, and 3-year PFS rates were 42.0%, 16.0%, and 2.0%, respectively. Patients who received radical resection had obviously better OS (18.0 vs. 7.0 months, P<0.001) and PFS (12.0 vs. 5.0 months, P<0.001) than those who underwent palliative resection. Multivariate analysis revealed that vascular invasion (P=0.033), curative operation (P<0.001) and postoperative chemotherapy (P=0.033) were independent risk factors for PFS. We further identified postoperative chemotherapy (P=0.010) and curative operation (P<0.001) as independent prognostic factors affecting the OS of GBSC patients. After curative surgery, patients who underwent S-1-based chemotherapy showed significantly longer recurrence-free survival (RFS) than those who underwent other chemotherapy regimens (20.0 vs 11.0 months, P=0.028). Conclusion: GBSC patients always have aggressive biological behaviors and remarkably poor prognoses. Most GBSC patients are diagnosed in advanced stages, and timely radical operation together with postoperative chemotherapy is important. S-1-based chemotherapy may be a selectively efficient regimen to prolong the survival of GBSC patients.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 286: 121994, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36283205

RESUMO

The molecular conformation evolution of Hexanitrostilbene (HNS) under high pressure was systematically investigated using Raman and Fourier transform infrared (FTIR) spectroscopy. The vibration modes of HNS associated with C-H, nitro groups, CC and the ring have been analyzed and clarified in detail under ambient conditions. trans-HNS is symmetrically distributed about -CHCH-, and six nitro groups are symmetrically distributed under ambient conditions. Two molecular conformation changes of HNS were observed at 1.4 GPa and 5 GPa due to the variations of hydrogen-bond interaction between C-H (in the ring) and N-O and the distortion of trans olefin, respectively. The hydrogen-bond interaction between C-H (in the ring) and N-O strengthened at 1.4 GPa. It induced the degenerated symmetry of the nitro groups and the Raman changes of νas (NO2), ν(CC), ν(C-C) and ν(C-H). In addition, the nonplanarity property of HNS and the sensitivity of trans olefin to pressure promoted the deformation of trans olefin, as well as the hydrogen bond interaction between C-H (in trans olefin) and N-O at about 5 GPa. When further loading pressure on HNS, the variations in the hydrogen-bond interaction between C-H and N-O restricted the vibrations of C-H, NO2 and the ring. It blocked the nonradiative pathway and activated the strong fluorescent background in the Raman spectra as the pressure increased above 5.7 GPa. These current results reveal that there is no structural transformation and only conformational changes under high pressure for HNS.

4.
Inorg Chem ; 61(39): 15408-15415, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36126270

RESUMO

For the famous functional REF3 family, there exist two typical structures, that is, orthorhombic phase and hexagonal phase. In the present work, high pressure behaviors of the orthorhombic phase REF3 (RE = Sm to Lu and Y) were investigated by experimental methods and first-principles calculations. The pressure-induced phase transitions of GdF3, TbF3, YbF3, and LuF3 were studied by using in situ photoluminescence measurements in the diamond anvil cell. At room temperature, all these four compounds follow the phase transition route from orthorhombic to hexagonal phase at 5.5-20.6 GPa. The pressure ranges of phase transition are 5.5-9.3, 8.4-11.9, 13.5-20.3, and 14.8-20.6 GPa for GdF3, TbF3, YbF3, and LuF3, respectively. In combination with first-principles calculations, we infer that all orthorhombic REF3 members from Sm-Lu and Y obey the same orthorhombic-to-hexagonal phase transition rules under high pressures. For lanthanide trifluorides, the transition pressures increase as zero pressure volumes of REF3 in the orthorhombic phase become smaller. As the calculation results show, this is because the difference in value of energy from the two structures is larger. This work not only provides precise structural change but also benefits the understanding of two typical structures for rare-earth trifluorides, which may play a significant role in the applications of REF3.

5.
World J Clin Cases ; 10(19): 6385-6398, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35979313

RESUMO

BACKGROUND: The intestinal mucosal barrier is the first line of defense against numerous harmful substances, and it contributes to the maintenance of intestinal homeostasis. Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases. However, no study thoroughly evaluated this barrier in patients with functional constipation (FC). AIM: To investigate the intestinal mucosal barrier in FC, including the mucus barrier, intercellular junctions, mucosal immunity and gut permeability. METHODS: Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital. The colonic mucus barrier, intercellular junctions in the colonic epithelium, mucosal immune state and gut permeability in FC patients were comprehensively examined. Goblet cells were stained with Alcian Blue/Periodic acid Schiff (AB/PAS) and counted. The ultrastructure of intercellular junctional complexes was observed under an electron microscope. Occludin and zonula occludens-1 (ZO-1) in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction. Colonic CD3+ intraepithelial lymphocytes (IELs) and CD3+ lymphocytes in the lamina propria were identified and counted using immunofluorescence. The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay. RESULTS: Compared to healthy controls, the staining of mucus secreted by goblet cells was darker in FC patients, and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients (control, 18.67 ± 2.99; FC, 22.42 ± 4.09; P = 0.001). The intercellular junctional complexes in the colonic epithelium were integral in FC patients. The distribution of mucosal occludin and ZO-1 was not altered in FC patients. No significant differences were found in occludin (control, 5.76E-2 ± 1.62E-2; FC, 5.17E-2 ± 1.80E-2; P = 0.240) and ZO-1 (control, 2.29E-2 ± 0.93E-2; FC, 2.68E-2 ± 1.60E-2; P = 0.333) protein expression between the two groups. The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls (P = 0.145, P = 0.451, respectively). No significant differences were observed in the number of CD3+ IELs per 100 epithelial cells (control, 5.62 ± 2.06; FC, 4.50 ± 2.16; P = 0.070) and CD3+ lamina propria lymphocytes (control, 19.69 ± 6.04/mm2; FC, 22.70 ± 11.38/mm2; P = 0.273). There were no significant differences in serum D-lactic acid [control, 5.21 (4.46, 5.49) mmol/L; FC, 4.63 (4.31, 5.42) mmol/L; P = 0.112] or zonulin [control, 1.36 (0.53, 2.15) ng/mL; FC, 0.94 (0.47, 1.56) ng/mL; P = 0.185] levels between FC patients and healthy controls. CONCLUSION: The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.

6.
Gastroenterology ; 163(5): 1267-1280.e7, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35718227

RESUMO

BACKGROUND & AIMS: The stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms. METHODS: A murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-programmed cell death protein 1 (PD-1) antibody, and stromal hyaluronan (HA) degradation by PEGylated recombinant human hyaluronidase (PEGPH20) to assess immune and stromal modulating effects of these agents and their combinations. RESULTS: The results showed that HA degradation by PEGPH20 and reduction in phosphorylated FAK expression by FAKi leads to improved survival in PDAC-bearing mice treated with anti-PD-1 antibody. HA degradation in combination with FAKi and anti-PD-1 antibody increases T-cell infiltration and alters T-cell phenotype toward effector memory T cells. FAKi alters the expression of T-cell modulating cytokines and leads to changes in T-cell metabolism and increases in effector T-cell signatures. HA degradation in combination with anti-PD-1 antibody and FAKi treatments reduces granulocytes, including granulocytic- myeloid-derived suppressor cells and decreases C-X-C chemokine receptor type 4 (CXCR4)-expressing myeloid cells, particularly the CXCR4-expressing granulocytes. Anti-CXCR4 antibody combined with FAKi and anti-PD-1 antibody significantly decreases metastatic rates in the PDAC liver metastasis model. CONCLUSIONS: This represents the first preclinical study to identify synergistic effects of targeting both intracellular and extracellular components within the PDAC stroma and supports testing anti-CXCR4 antibody in combination with FAKi as a PDAC treatment strategy.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Neoplasias Pancreáticas/patologia , Adenocarcinoma/patologia , Hialuronoglucosaminidase/farmacologia , Hialuronoglucosaminidase/uso terapêutico , Ácido Hialurônico , Carcinoma Ductal Pancreático/genética , Neoplasias Hepáticas/tratamento farmacológico , Proteína-Tirosina Quinases de Adesão Focal , Citocinas/farmacologia , Morte Celular , Polietilenoglicóis/uso terapêutico , Microambiente Tumoral
7.
Small ; 18(22): e2200824, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523735

RESUMO

Constructing high-order DNA nano-architectures in large sizes is of critical significance for the application of DNA nanotechnology. Robust and flexible design strategies together with easy protocols to construct high-order large-size DNA nano-architectures remain highly desirable. In this work, the authors report a simple and versatile one-pot strategy to fabricate DNA architectures with the assistance of spherical gold nanoparticles modified with thiolated oligonucleotide strands (SH-DNA-AuNPs), which serve as "power strips" to connect various DNA nanostructures carrying complementary ssDNA strands as "plugs". By modulating the plug numbers and positions on each DNA nanostructure and the ratios between DNA nanostructures and AuNPs, the desired architectures are formed via the stochastic co-assembly of different modules. This SH-DNA-AuNP-mediated plug-in assembly (SAMPA) strategy offers new opportunities to drive macroscopic self-assembly to meet the demand of the fabrication of well-defined nanomaterials and nanodevices.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , DNA/química , Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , Nanotecnologia/métodos
8.
Cancer Lett ; 539: 215722, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35533951

RESUMO

Pancreatic ductal adenocarcinoma(PDAC) does not respond to single-agent immune checkpoint inhibitor therapy, including anti-PD-1 antibody(aPD-1) therapy. Higher plasma levels of IL-8 are associated with poorer outcomes in patients who receive aPD-1 therapies, providing a rationale for combination immunotherapy with an anti-IL-8 antibody(aIL-8) and aPD-1. We thus investigated whether human aIL-8 therapy can potentiate the antitumor activity of aPD-1 and further investigated how the combination affects the immune response by regulating myeloid cells in the tumor microenvironment in a humanized murine model of PDAC with a reconstituted immune system consisting of human T cells and a combination of CD14+ and CD16+ myeloid cells. The results show that the combination of aIL-8 and aPD-1 treatment significantly enhanced antitumor activity following the infusion of myeloid cells. Our results further showed that the target of IL-8 is mainly present in CD16+ myeloid cells and is likely to be granulocytes. FACS analysis showed that aIL-8 treatment increased granulocytic myeloid cells in tumors. Consistently, single-nuclear RNA-sequencing analysis of tumor tissue showed that the innate immune response and cytokine response pathways in the myeloid cell cluster were activated by aIL-8 treatment. This is the first preclinical study using a humanized mouse model for new combination immunotherapeutic development and supports the further clinical testing of aIL-8 in combination with aPD-1 for PDAC treatment. This study also suggests that peripherally derived myeloid cells can potentiate the antitumor response of T cells, likely through the innate immune response, and aIL-8 re-educates tumor-infiltrating myeloid cells by activating the innate immune response.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Modelos Animais de Doenças , Humanos , Interleucina-8 , Camundongos , Células Mieloides/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Microambiente Tumoral
9.
Asian J Surg ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35422386

RESUMO

BACKGROUND: Gallbladder mucinous adenocarcinoma (GBMAC) is a rare type of gallbladder malignant tumor, whereas little is known regarding the clinicopathological features and surgical outcomes of GBMAC. METHODS: From January 2000 till December 2015, 54 GBMAC patients who underwent curative-intent surgical resection at our institution were retrospectively reviewed. We compared the clinicopathological features and surgical outcomes of these GBMAC patients with a relatively large cohort of surgically resected conventional gallbladder adenocarcinoma (GBAC) patients without existence of mucinous components. RESULTS: The clinicopathological features of GBMAC were significantly different from conventional GBAC, including poorer tumor differentiation (P < 0.001), higher CA19-9 levels (P < 0.001), larger tumor sizes (P = 0.020), advanced AJCC tumor stage (P = 0.002), higher frequency of liver parenchyma invasion (P = 0.020), portal vein invasion (P = 0.003), lymph node metastasis (P = 0.016), lympho-vascular invasion (P < 0.001) and perineural invasion (P = 0.025). Relative to conventional GBAC patients, GBMAC patients showed significantly worse overall survival (OS) (29.0 vs 15.0 months; P < 0.001). Multivariate analysis confirmed the surgical margin (P = 0.046), tumor differentiation grade (P = 0.018), lymph node metastasis (P = 0.024), and presence of signet-ring cell component (P = 0.005) as independent prognostic factors influencing OS of patients with GBMAC. CONCLUSION: GBMAC always had more aggressive biological behaviors and poor survival outcomes even after curative surgery. GBMAC patients with the presence of signet-ring cell component showed even worse survival outcome.

10.
J Exp Med ; 219(5)2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35404390

RESUMO

The resistance of pancreatic ductal adenocarcinoma (PDAC) to immune checkpoint inhibitors (ICIs) is attributed to the immune-quiescent and -suppressive tumor microenvironment (TME). We recently found that CCR2 and CCR5 were induced in PDAC following treatment with anti-PD-1 antibody (αPD-1); thus, we examined PDAC vaccine or radiation therapy (RT) as T cell priming mechanisms together with BMS-687681, a dual antagonist of CCR2 and CCR5 (CCR2/5i), in combination with αPD-1 as new treatment strategies. Using PDAC mouse models, we demonstrated that RT followed by αPD-1 and prolonged treatment with CCR2/5i conferred better antitumor efficacy than other combination treatments tested. The combination of RT + αPD-1 + CCR2/5i enhanced intratumoral effector and memory T cell infiltration but suppressed regulatory T cell, M2-like tumor-associated macrophage, and myeloid-derived suppressive cell infiltration. RNA sequencing showed that CCR2/5i partially inhibited RT-induced TLR2/4 and RAGE signaling, leading to decreased expression of immunosuppressive cytokines including CCL2/CCL5, but increased expression of effector T cell chemokines such as CCL17/CCL22. This study thus supports the clinical development of CCR2/5i in combination with RT and ICIs for PDAC treatment.


Assuntos
Adenocarcinoma , Antagonistas dos Receptores CCR5 , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Receptores CCR2 , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Animais , Antagonistas dos Receptores CCR5/farmacologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/radioterapia , Camundongos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/radioterapia , Receptores CCR2/antagonistas & inibidores , Receptores CCR5 , Microambiente Tumoral
11.
ACS Appl Mater Interfaces ; 14(14): 16497-16504, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35352932

RESUMO

Interface layers used for electron transport (ETL) and hole transport (HTL) often significantly enhance the performance of organic solar cells (OSCs). Surprisingly, interface engineering for hole extraction has received little attention thus far. By finetuning the chemical structure of carbazole-based self-assembled monolayers with phosphonic acid anchoring groups, varying the length of the alkane linker (2PACz, 3PACz, and 4PACz), these HTLs were found to perform favorably in OSCs. Compared to archetypal PEDOT:PSS, the PACz monolayers exhibit higher optical transmittance and lower resistance and deliver a higher short-circuit current density and fill factor. Power conversion efficiencies of 17.4% have been obtained with PM6:BTP-eC9 as the active layer, which was distinctively higher than the 16.2% obtained with PEDOT:PSS. Of the three PACz derivatives, the new 3PACz consistently outperforms the other two monolayer HTLs in OSCs with different state-of-the-art nonfullerene acceptors. Considering its facile synthesis, convenient processing, and improved performance, we consider that 3PACz is a promising interface layer for widespread use in OSCs.

12.
Transpl Immunol ; 71: 101547, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35121160

RESUMO

BACKGROUND: Eosinophilic gastroenteritis is a rare gastrointestinal disease that is characterized by diffuse or localized eosinophil infiltration in the gastrointestinal tract, and is accompanied by increased peripheral blood eosinophils. Herein, a case of plasma membrane lesion-type total intestinal eosinophil enteritis is reported. CASE PRESENTATION: We report on a 20-year-old male patient who was admitted to the hospital with "abdominal distension for 15 days". The infiltration of a large number of eosinophils was found by conducting an intestinal biopsy, routine ascites examination, blood routine, smear test, and a bone marrow puncture. A special feature of this patient was that a large number of eosinophils were found in the duodenum, small intestine, and colon. The final diagnosis was plasma membrane lesion type total intestinal eosinophilic enteritis. After four weeks of prednisone treatment, the symptoms disappeared completely and the entire intestinal mucosa was endoscopically observed as smooth. CONCLUSION: Clinical practitioners must pay attention to gastrointestinal endoscopy and biopsy pathology results for patients presenting with abdominal distention and ascites. Combined with an abnormal increase of eosinophils in ascites, bone marrow, and peripheral blood, clinical practitioners must be highly vigilant against plasma membrane lesion type total intestinal eosinophilic enteritis.


Assuntos
Enterite , Eosinofilia , Adulto , Ascite/complicações , Membrana Celular/patologia , Enterite/complicações , Enterite/diagnóstico , Enterite/tratamento farmacológico , Eosinofilia/complicações , Eosinofilia/patologia , Gastrite , Humanos , Masculino , Adulto Jovem
14.
Phys Chem Chem Phys ; 24(4): 2396-2402, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35019913

RESUMO

Thermal mechanical responses under high temperature and high pressure are basic information to understand the performance of energetic materials. In this work, the pressure effects on the thermal decay of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) are explored. Up to the initial pressure of 4.6 GPa, the pressure dependent decomposition boundary is built and no phase transition occurs until the decomposition of the LLM-105 crystal. The decomposition temperature is significantly lifted via a weak loading pressure. The experimental measurement confirms the decomposition products, including NO2, CO2 and NH3, which are predicted by the density functional tight-binding molecular dynamics method. The calculation described the details of thermal decay in the initial stages under high pressure. The sudden drop in the shifts of the Raman modes associated with hydrogen bonds under high pressure indicates the strengthening of the intermolecular hydrogen bonds and the occurrence of intermolecular hydrogen transfer prior to crystal decomposition. The simulation supported the existence of intermolecular hydrogen transfer and provided the transfer path and decomposition mechanism. All of these jobs not only contribute significantly to the understanding of thermal decomposition of energetic materials as a function of pressure, but also contribute to the understanding of sensitivity mechanisms and safety issues.

15.
Environ Sci Pollut Res Int ; 29(9): 13478-13490, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34595713

RESUMO

The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP.


Assuntos
Dietilexilftalato , Testículo , Animais , Dietilexilftalato/toxicidade , Perfilação da Expressão Gênica , Masculino , Camundongos , Ratos Sprague-Dawley , Transcriptoma
16.
J Hazard Mater ; 426: 127807, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34863575

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is an extensively used plasticizer and has been shown to cause reproductive dysfunction in humans and model animals. However, the exact mechanisms of testicular injury induced by DEHP exposure have not been fully clarified. Using gas chromatography-mass spectrometry, we found that mono-2-ethylhexyl ester (MEHP, a major biometabolite of DEHP) and DEHP concentrations were elevated in mouse serum after DEHP exposure. Using RNA-seq, we found that ferroptosis and HIF-1 signaling pathways might be involved in testicular injury due to prepubertal DEHP exposure. Subsequent Western blotting, ferrous iron and MDA measurements, and immunofluorescence of testicular sections verified the RNA-seq findings. Consistently, based on the RNA-seq findings, we found that ferroptosis and HIF-1 signaling pathways might play crucial roles in Leydig and Sertoli cell injury due to MEHP exposure in vitro. Further experiments also confirmed ferroptosis in Leydig and Sertoli cells. Using Western blotting, cellular immunofluorescence and ChIP-qPCR, we found that MEHP exposure caused HIF-1α accumulation and stabilization, resulted in HIF-1α translocation into the nucleus, and induced HIF-1α/Hmox1 binding in Leydig and Sertoli cells. To clarify whether HIF-1α plays a pivotal role in MEHP-induced ferroptosis, we knocked out Hif-1α using the CRISPR/Cas9 technique. We found that Hif-1α knockout rescued MEHP-induced ferroptosis. In summary, our findings certified that prepubertal DEHP exposure led to ferroptosis in mouse testes via the HIF-1α/HO-1 signaling pathway.


Assuntos
Dietilexilftalato , Ferroptose , Animais , Dietilexilftalato/toxicidade , Masculino , Camundongos , Ácidos Ftálicos , Transdução de Sinais , Testículo
17.
Adv Mater ; 34(11): e2110053, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34965005

RESUMO

Perovskite-based multijunction solar cells are a potentially cost-effective technology that can help surpass the efficiency limits of single-junction devices. However, both mixed-halide wide-bandgap perovskites and lead-tin narrow-bandgap perovskites suffer from non-radiative recombination due to the formation of bulk traps and interfacial recombination centers which limit the open-circuit voltage of sub-cells and consequently of the integrated tandem. Additionally, the complex optical stack in a multijunction solar cell can lead to losses stemming from parasitic absorption and reflection of incident light which aggravates the current mismatch between sub-cells, thereby limiting the short-circuit current density of the tandem. Here, an integrated all-perovskite tandem solar cell is presented that uses surface passivation strategies to reduce non-radiative recombination at the perovskite-fullerene interfaces, yielding a high open-circuit voltage. By using optically benign transparent electrode and charge-transport layers, absorption in the narrow-bandgap sub-cell is improved, leading to an improvement in current-matching between sub-cells. Collectively, these strategies allow the development of a monolithic tandem solar cell exhibiting a power-conversion efficiency of over 23%.

19.
Chemosphere ; 286(Pt 3): 131844, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34392196

RESUMO

The etiology of hypospadias and cryptorchidism, which are the two most common genital anomalies in males, has not been elucidated. Although prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase the risks of hypospadias and cryptorchidism, the associations have not been confirmed. Therefore, we performed a meta-analysis to establish the relationships between prenatal exposure to EDCs and male genital anomalies. A systematic search of PubMed, EMbase, and Cochrane Library CENTRAL for relevant published studies providing quantitative data on the associations between prenatal EDCs exposure and hypospadias/cryptorchidism in humans was conducted. In total, sixteen case-controlled studies were included. Prenatal exposure to overall EDCs was associated with an increased risk of hypospadias in males (OR, 1.34, 95 % CI 1.12 to 1.60). Although there was no statistically significant association between overall EDCs exposure and cryptorchidism (OR, 1.11, 95 % CI 0.99 to 1.24), exposure to phenol substances was associated with an increased risk of cryptorchidism (OR, 1.81, 95 % CI, 1.12 to 2.93). Using the GRADE tool, we found the overall evidence to be of moderate certainty. In conclusion, the current evidence suggests prenatal EDCs exposure may increase the risk of hypospadias in males.


Assuntos
Criptorquidismo , Disruptores Endócrinos , Hipospadia , Estudos de Casos e Controles , Criptorquidismo/induzido quimicamente , Criptorquidismo/epidemiologia , Disruptores Endócrinos/toxicidade , Feminino , Genitália , Humanos , Hipospadia/induzido quimicamente , Hipospadia/epidemiologia , Masculino , Gravidez
20.
Environ Pollut ; 292(Pt A): 118264, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606968

RESUMO

Preterm birth is the second most common cause of death in children under 5 years of age. The etiology of preterm birth has not yet been elucidated. Although maternal exposure to endocrine disrupting chemicals (EDCs) may increase the risk for preterm birth, associations have not been confirmed. We performed a meta-analysis to elucidate the relationships between maternal exposure to EDCs and preterm birth. A systematic search of PubMed, Ovid-EMBASE, and the Cochrane Library (CENTRAL) for relevant published studies providing quantitative data on the association between maternal EDC exposure and preterm birth in humans was conducted in July 2021. To calculate the overall estimates, we pooled the adjusted regression coefficients with 95% confidence intervals (CIs) from each study by the inverse variance method. A total of 59 studies were included. The pooled results indicated that maternal exposure to metals (OR, 1.23; 95% CI, 1.17 to 1.29) and phthalates (OR, 1.31; 95% CI, 1.21 to 1.42) was related to an increased risk for preterm birth. Specifically, maternal exposure to lead, cadmium, chromium, copper and manganese appeared to be correlated with an elevated risk for preterm birth. Additionally, maternal exposure to monoethyl phthalate (MEP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), monobenzyl phthalate (MBzP), and di (2-ethylhexyl) phthalate (DEHP) was also associated with preterm birth. In conclusion, maternal exposure to metals and phthalates may increase the risk for preterm birth based on current evidence.


Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Ácidos Ftálicos , Nascimento Prematuro , Criança , Pré-Escolar , Exposição Ambiental , Feminino , Humanos , Recém-Nascido , Exposição Materna , Ácidos Ftálicos/toxicidade , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Análise de Regressão
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