RNA polymerase III transcription as a disease factor.

RNA polymerase (Pol) III is responsible for transcription of different noncoding genes in eukaryotic cells, whose RNA products have well-defined functions in translation and other biological processes for some, and functions that remain to be defined for others. For all of them, however, new functions are being described. For example, Pol III products have been reported to regulate certain proteins such as protein kinase R (PKR) by direct association, to constitute the source of very short RNAs with regulatory roles in gene expression, or to control microRNA levels by sequestration. Consistent with these many functions, deregulation of Pol III transcribed genes is associated with a large variety of human disorders. Here we review different human diseases that have been linked to defects in the Pol III transcription apparatus or to Pol III products imbalance and discuss the possible underlying mechanisms.

Structures of Respiratory Supercomplex I+III2 Reveal Functional and Conformational Crosstalk.

The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII2. CI shows a transition between "closed" and "open" conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII2, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.

lncRNA BC200 is processed into a stable Alu monomer.

The noncoding RNA BC200 is elevated in human cancers and is implicated in translation regulation as well as cell survival and proliferation. Upon BC200 overexpression, we observed correlated expression of a second, smaller RNA species. This RNA is expressed endogenously and exhibits cell-type-dependent variability relative to BC200. Aptamer-tagged expression constructs confirmed that the RNA is a truncated form of BC200, and sequencing revealed a modal length of 120 nt; thus, we refer to the RNA fragment as BC120. We present a methodology for accurate and specific detection of BC120 and establish that BC120 is expressed in several normal human tissues and is also elevated in ovarian cancer. BC120 exhibits remarkable stability relative to BC200 and is resistant to knockdown strategies that target the 3' unique sequence of BC200. Combined knockdown of BC200 and BC120 exhibits greater phenotypic impacts than knockdown of BC200 alone, and overexpression of BC120 negatively impacts translation of a GFP reporter, providing insight into a potential translational regulatory role for this RNA. The presence of a novel, truncated, and stable form of BC200 adds complexity to the investigation of this noncoding RNA that must be considered in future studies of BC200 and other related Alu RNAs.

Cryo-EM structure of the four-subunit Rhodobacter sphaeroides cytochrome bc1 complex in styrene maleic acid nanodiscs.

Cytochrome bc1 complexes are ubiquinol:cytochrome c oxidoreductases, and as such, they are centrally important components of respiratory and photosynthetic electron transfer chains in many species of bacteria and in mitochondria. The minimal complex has three catalytic components, which are cytochrome b, cytochrome c1, and the Rieske iron-sulfur subunit, but the function of mitochondrial cytochrome bc1 complexes is modified by up to eight supernumerary subunits. The cytochrome bc1 complex from the purple phototrophic bacterium Rhodobacter sphaeroides has a single supernumerary subunit called subunit IV, which is absent from current structures of the complex. In this work we use the styrene-maleic acid copolymer to purify the R. sphaeroides cytochrome bc1 complex in native lipid nanodiscs, which retains the labile subunit IV, annular lipids, and natively bound quinones. The catalytic activity of the four-subunit cytochrome bc1 complex is threefold higher than that of the complex lacking subunit IV. To understand the role of subunit IV, we determined the structure of the four-subunit complex at 2.9 Å using single particle cryogenic electron microscopy. The structure shows the position of the transmembrane domain of subunit IV, which lies across the transmembrane helices of the Rieske and cytochrome c1 subunits. We observe a quinone at the Qo quinone-binding site and show that occupancy of this site is linked to conformational changes in the Rieske head domain during catalysis. Twelve lipids were structurally resolved, making contacts with the Rieske and cytochrome b subunits, with some spanning both of the two monomers that make up the dimeric complex.

Structure and function of the S. pombe III-IV-cyt c supercomplex.

The respiratory chain in aerobic organisms is composed of a number of membrane-bound protein complexes that link electron transfer to proton translocation across the membrane. In mitochondria, the final electron acceptor, complex IV (CIV), receives electrons from dimeric complex III (CIII2), via a mobile electron carrier, cytochrome c. In the present study, we isolated the CIII2CIV supercomplex from the fission yeast Schizosaccharomyces pombe and determined its structure with bound cyt. c using single-particle electron cryomicroscopy. A respiratory supercomplex factor 2 was found to be bound at CIV distally positioned in the supercomplex. In addition to the redox-active metal sites, we found a metal ion, presumably Zn2+, coordinated in the CIII subunit Cor1, which is encoded by the same gene (qcr1) as the mitochondrial-processing peptidase subunit ß. Our data show that the isolated CIII2CIV supercomplex displays proteolytic activity suggesting a dual role of CIII2 in S. pombe. As in the supercomplex from S. cerevisiae, subunit Cox5 of CIV faces towards one CIII monomer, but in S. pombe, the two complexes are rotated relative to each other by ~45°. This orientation yields equal distances between the cyt. c binding sites at CIV and at each of the two CIII monomers. The structure shows cyt. c bound at four positions, but only along one of the two symmetrical branches. Overall, this combined structural and functional study reveals the integration of peptidase activity with the CIII2 respiratory system and indicates a two-dimensional cyt. c diffusion mechanism within the CIII2-CIV supercomplex.

Rat Models of Hormone Receptor-Positive Breast Cancer.

Hormone receptor-positive (HR+) breast cancer (BC) is the most common type of breast cancer among women worldwide, accounting for 70-80% of all invasive cases. Patients with HR+ BC are commonly treated with endocrine therapy, but intrinsic or acquired resistance is a frequent problem, making HR+ BC a focal point of intense research. Despite this, the malignancy still lacks adequate in vitro and in vivo models for the study of its initiation and progression as well as response and resistance to endocrine therapy. No mouse models that fully mimic the human disease are available, however rat mammary tumor models pose a promising alternative to overcome this limitation. Compared to mice, rats are more similar to humans in terms of mammary gland architecture, ductal origin of neoplastic lesions and hormone dependency status. Moreover, rats can develop spontaneous or induced mammary tumors that resemble human HR+ BC. To date, six different types of rat models of HR+ BC have been established. These include the spontaneous, carcinogen-induced, transplantation, hormone-induced, radiation-induced and genetically engineered rat mammary tumor models. Each model has distinct advantages, disadvantages and utility for studying HR+ BC. This review provides a comprehensive overview of all published models to date.

Identification of hydrogen bonding network for proton transfer at the quinol oxidation site of Rhodobacter capsulatus cytochrome bc1.

Cytochrome bc1 catalyzes electron transfer from quinol (QH2) to cytochrome c in reactions coupled to proton translocation across the energy-conserving membrane. Energetic efficiency of the catalytic cycle is secured by a two-electron and two-proton bifurcation reaction leading to oxidation of QH2 and reduction of the Rieske cluster and heme bL. The proton paths associated with this reaction remain elusive. Here, we used site-directed mutagenesis and quantum mechanical calculations to analyze the contribution of protonable side chains located at the heme bL side of the QH2 oxidation site in Rhodobacter capsulatus cytochrome bc1. We observe that the proton path is effectively switched off when H276 and E295 are simultaneously mutated to the nonprotonable residues in the H276F/E295V double mutant. The two single mutants, H276F or E295V, are less efficient but still transfer protons at functionally relevant rates. Natural selection exposed two single mutations, N279S and M154T, that restored the functional proton transfers in H276F/E295V. Quantum mechanical calculations indicated that H276F/E295V traps the side chain of Y147 in a position distant from QH2, whereas either N279S or M154T induce local changes releasing Y147 from that position. This shortens the distance between the protonable groups of Y147 and D278 and/or increases mobility of the Y147 side chain, which makes Y147 efficient in transferring protons from QH2 toward D278 in H276F/E295V. Overall, our study identified an extended hydrogen bonding network, build up by E295, H276, D278, and Y147, involved in efficient proton removal from QH2 at the heme bL side of QH2 oxidation site.

PANoptosis: a potential new target for programmed cell death in breast cancer treatment and prognosis.

Breast cancer is a prevalent and severe form of cancer that affects women all over the world. The incidence and mortality of breast cancer continue to rise due to factors such as population growth and the aging of the population. There is a growing area of research focused on a cell death mechanism known as PANoptosis. This mechanism is primarily regulated by the PANoptosome complex and displays important characteristics of cell death, including pyroptosis, apoptosis, and/or necroptosis, without being strictly defined by the cell death pathway. PANoptosis acts as a defensive response to external stimuli and pathogens, contributing to the maintenance of cellular homeostasis and overall stability. Increasing evidence suggests that programmed cell death (PCD) plays an important role in the development of breast cancer, and PANoptosis, as a novel form of PCD, may be a crucial factor in the development of breast cancer, potentially leading to the identification of new therapeutic strategies. Therefore, the concept of PANoptosis not only deepens our understanding of PCD, but also opens up new avenues for treating malignant diseases, including breast cancer. This review aims to provide an overview of the definition of PANoptosis, systematically explore the interplay between PANoptosis and various forms of PCD, and discuss its implications for breast cancer. Additionally, it delves into the current progress and future directions of PANoptosis research in the context of breast cancer, establishing a theoretical foundation for the development of molecular targets within critical signaling pathways related to PANoptosis, as well as multi-target combination therapy approaches, with the goal of inducing PANoptosis as part of breast cancer treatment.

Breast cancer genomic analyses reveal genes, mutations, and signaling networks.

Breast cancer (BC) is the most commonly diagnosed cancer and the predominant cause of death in women. BC is a complex disorder, and the exploration of several types of BC omic data, highlighting genes, perturbations, signaling and cellular mechanisms, is needed. We collected mutational data from 9,555 BC samples using cBioPortal. We classified 1174 BC genes (mutated ≥ 40 samples) into five tiers (BCtier_I-V) and subjected them to pathway and protein‒protein network analyses using EnrichR and STRING 11, respectively. BCtier_I possesses 12 BC genes with mutational frequencies > 5%, with only 5 genes possessing > 10% frequencies, namely, PIK3CA (35.7%), TP53 (34.3%), GATA3 (11.5%), CDH1 (11.4%) and MUC16 (11%), and the next seven BC genes are KMT2C (8.8%), TTN (8%), MAP3K1 (8%), SYNE1 (7.2%), AHNAK2 (7%), USH2A (5.5%), and RYR2 (5.4%). Our pathway analyses revealed that the five top BC pathways were the PI3K-AKT, TP53, NOTCH, HIPPO, and RAS pathways. We found that BC panels share only seven genes. These findings show that BC arises from genetic disruptions evident in BC signaling and protein networks.

Neoadjuvant anthracycline-based (5-FEC) or anthracycline-free (docetaxel/carboplatin) chemotherapy plus trastuzumab and pertuzmab in HER2 + BC patients according to their TOP2A: a multicentre, open-label, non-randomized phase II trial.

PURPOSE: Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status. METHODS: Open-label, multicentre, phase II study. Eligible patients were aged ≥ 18 with untreated, operable, histologically confirmed HER2 + BC. After centralized review of TOP2A status, TOP2A-amplified (TOP2A+) patients received FEC100 for 3 cycles then 3 cycles of Trastuzumab (8 mg/kg then 6 mg/kg), Pertuzumab (840 mg/kg then 420 mg/kg), and Docetaxel (75mg/m2 then 100mg/m2). TOP2A-not amplified (TOP2A-) patients received 6 cycles of Docetaxel (75mg/m2) and Carboplatin (target AUC 6 mg/ml/min) plus Trastuzumab and Pertuzumab. Primary endpoint was pathological Complete Response (pCR) using Chevallier's classification. Secondary endpoints included pCR (Sataloff), Progression-Free Survival (PFS), Overall Survival (OS), and toxicity. RESULTS: Out of 74 patients, 41 and 33 were allocated to the TOP2A + and TOP2A- groups respectively. pCR rates (Chevallier) were 74.4% (95%CI: 58.9-85.4) vs. 71.9% (95%CI: 54.6-84.4) in the TOP2A + vs. TOP2A- groups. pCR rates (Sataloff), 5-year PFS and OS were 70.6% (95%CI: 53.8-83.2) vs. 61.5% (95%CI: 42.5-77.6), 82.4% (95%CI: 62.2-93.6) vs. 100% (95%CI: 74.1-100), and 90% (95%CI: 69.8-98.3) vs. 100% (95%CI: 74.1-100). Toxicity profile was consistent with previous reports. CONCLUSION: Our results showed high pCR rates with Trastuzumab and Pertuzumab associated to chemotherapy. They were similar in TOP2A + and TOP2A- groups and the current role of neoadjuvant anthracycline-based chemotherapy remains questioned. TRIAL REGISTRATION NUMBER: NCT02339532 (registered on 14/12/14).

Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.

BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC. METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy. RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis. CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.

LncRNA S100PBP promotes proliferation and steroid hormone synthesis of granulosa cells by sponging MiR-2285bc-BMPR2 in bovine†.

In bovine follicular development, the proliferation of bovine granulosa cells affects follicular selection, atresia, and cystic follicle formation. When cystic follicles appear on the ovaries, granulosa cells stop proliferating, resulting in the reduction of granulosa cells layer. In our previous study, the whole transcriptome sequencing revealed that Bone morphogenetic protein receptor 2 (BMPR2) was differentially expressed between cystic and normal follicular granulosa cells. We speculated that long noncoding RNA may act as competing endogenous RNA targeting microRNAs and then regulating the expression of BMPR2 and the function of granulosa cells, thereby affecting follicular development and cyst formation. In this study, the results elucidated that long noncoding RNA S100PBP (NONBTAT011846.2) directly bound miR-2285bc, which targeted in the BMPR2 3'-UTR. miR-2285bc suppresses granulosa cells proliferation by downregulating BMPR2 expression. Furthermore, long noncoding RNA S100PBP was silenced by small interfering RNA, and long noncoding RNA S100PBP regulated BMPR2 expression by sponging miR-2285bc investigated through cross-verification. When small interfering RNA of long noncoding RNA S100PBP was transfected into granulosa cells, the results revealed similar molecular changes as those transfected with miR-2285bc mimics. Silencing long noncoding RNA S100PBP or overexpressing miR-2285bc altered the expressions of some follicular development-related genes, which could be related to follicular cyst occurrence. In conclusion, our findings support that long noncoding RNA S100PBP regulates the expression of BMPR2 through sponge miR-2285bc, promotes the proliferation of granulosa cells, inhibits their apoptosis, and increases the synthesis and secretion of follicular steroid hormones, thus promoting the development of bovine follicles.

Deep learning radiomics under multimodality explore association between muscle/fat and metastasis and survival in breast cancer patients.

Sarcopenia is correlated with poor clinical outcomes in breast cancer (BC) patients. However, there is no precise quantitative study on the correlation between body composition changes and BC metastasis and survival. The present study proposed a deep learning radiomics (DLR) approach to investigate the effects of muscle and fat on distant metastasis and death outcomes in BC patients. Image feature extraction was performed on 4th thoracic vertebra (T4) and 11th thoracic vertebra (T11) on computed tomography (CT) image levels by DLR, and image features were combined with clinical information to predict distant metastasis in BC patients. Clinical information combined with DLR significantly predicted distant metastasis in BC patients. In the test cohort, the area under the curve of model performance on clinical information combined with DLR was 0.960 (95% CI: 0.942-0.979, P < 0.001). The patients with distant metastases had a lower pectoral muscle index in T4 (PMI/T4) than in patients without metastases. PMI/T4 and visceral fat tissue area in T11 (VFA/T11) were independent prognostic factors for the overall survival in BC patients. The pectoralis muscle area in T4 (PMA/T4) and PMI/T4 is an independent prognostic factor for distant metastasis-free survival in BC patients. The current study further confirmed that muscle/fat of T4 and T11 levels have a significant effect on the distant metastasis of BC. Appending the network features of T4 and T11 to the model significantly enhances the prediction performance of distant metastasis of BC, providing a valuable biomarker for the early treatment of BC patients.

B(C6F5)3/CPA-Catalyzed Aza-Diels-Alder Reaction of 3,3-Difluoro-2-Aryl-3H-indoles and Unactivated Dienes.

Here we report B(C6F5)3/CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.

Bacterial cellulose as an ideal potential treatment for burn wounds: A comprehensive review.

Burn wound regeneration is a complex process, which has many serious challenges such as slow wound healing, secondary infection, and inflammation. Therefore, it is essential to utilise appropriate biomaterials to accelerate and guide the wound healing process. Bacterial cellulose (BC), a natural polymer synthesised by some bacteria, has attracted much attention for wound healing applications due to its unique properties including excellent physicochemical and mechanical properties, simple purification process, three-dimensional (3D) network structure similar to extracellular matrix, high purity, high water holding capacity and significant permeability to gas and liquid. BC's lack of antibacterial activity significantly limits its biomedical and tissue engineering application, but adding antimicrobial agents to it remarkably improves its performance in tissue regeneration applications. Burn wound healing is a complex long-lasting process. Using biomaterials in wound treatment has shown that they can satisfactorily accelerate wound healing. The purpose of this review is to elaborate on the importance of BC-based structures as one of the most widely used modern wound dressings in the treatment of burn wounds. In addition, the combination of various drugs, agents, cells and biomolecules with BC to expand its application in burn injury regeneration is discussed. Finally, the main challenges and future development direction of BC-based structures for burn wound repair are considered. The four most popular search engines PubMed/MEDLINE, Science Direct, Scopus and Google Scholar were used to help us find relevant papers. The most frequently used keywords were bacterial cellulose, BC-based biocomposite, wound healing, burn wound and vascular graft.

Role of low-density cholesterol and Interleukin-17 interaction in breast cancer pathogenesis and treatment.

Breast cancer (BC) has become the most prevalent cancer worldwide, and further research is being conducted to deepen our understanding of its pathogenesis and treatment. Lipid metabolism disorder is a significant alteration in cancer cells, and the investigation into the role of Interleukin-17 (IL-17) in malignant tumors has emerged as a research focus in recent years. Thus, exploring changes in lipid metabolism and inflammatory factors in BC cells is crucial in identifying potential therapeutic targets. This article summarizes the progress made in the research on the main low-density cholesterol (LDL) transporter and IL-17 in lipid metabolism, and their potential involvement in the development of BC. The article aims to establish a theoretical foundation for the development of BC-related therapies.

Serum exosomal miR-200c is a potential diagnostic biomarker for breast cancer.

BACKGROUND: Breast cancer (BC) is one of the most common malignancies in women. Exosomes are widely found in body fluids and carry microRNAs (miRNAs) that reflect the biological properties of the parental cells. Our study aimed to investigate the differential expression of miR-200c in BC serum exosomes and its diagnostic value. METHODOLOGY: miRNA profiles in culture supernatant exosomes of normal mammary epithelial cells MCF-10A and BC cells (MCF-7, MDA-MB-231, MCF-7 Taxol) were examined by miRNA deep sequencing to screen for significantly differentially expressed miRNAs; Transmission electron microscopy (TEM), Nanoparticle tracking analysis (NTA), and Western blot were used to identify exosomes; qPCR was used to detect the expression level of miR-200c in cellular exosomes and serum exosomes; The efficacy of individual and combined tests of each indicator to diagnose BC was evaluated using receiver operating characteristic (ROC) curves. RESULTS: We identified typical exosome features by TEM, NTA and Western blot, indicating successful exosome extraction. Then our miRNA sequencing results and qRT-PCR experiments showed that miR-200c was significantly down-regulated in BC cell exosomes. In addition, we divided the clinical serum samples into two cohorts according to region, and in independent cohort I, the serum exosomal miR-200c levels of BC patients were significantly lower than those of healthy controls. In cohort II, serum exosomal miR-200c expression was significantly lower in the BC group than in the control and benign breast disease (BBD) groups, whereas miR-200c expression in the BBD group was not statistically different from that in the control group. ROC analyses in both independent cohorts confirmed that serum exosomal miR-200c could differentiate between patients with and without BC disease and could be used as an early diagnostic marker for BC disease. CONCLUSION: Serum exosome miR-200c can be used as a potential biomarker for the diagnosis of BC, and combined with conventional serum diagnostic markers AFP, CA125 and CA153 can help to improve diagnostic efficiency.

TNFRSF11B promotes the progression of bladder cancer through PI3K/AKT signaling pathway.

TNFRSF11B contributes to tumorigenesis in many malignancies. Nevertheless, its function and underlying tumorigenic mechanism in bladder cancer (BC) has been rare. The clinical significance and relevant signaling pathway of TNFRSF11B in BC were assessed using bioinformatic analysis. The determination of TNFRSF11B expression was conducted in bladder tissues and BC cells. BC cells were subjected to functional experiments to evaluate their ability to proliferate, migrate, and invade. Cell apoptosis experiments were conducted. The protein levels of markers associated with epithelial-mesenchymal transition (EMT) and molecules linked to the PI3K/AKT pathway were assessed. To evaluate the effect of the PI3K/AKT pathway on TNFRSF11B, LY294002, a PI3K/AKT pathway inhibitor, was utilized. TNFRSF11B exhibited significant upregulation in both BC tissues and various cell lines. Inhibited TNFRSF11B expression impeded the growth, movement, infiltration of BC cells. Conversely, the ultimate outcome varied when TNFRSF11B was overexpressed. In vivo assay further confirmed the above results. Furthermore, TNFRSF11B promoted malignant traits by controlling the PI3K/AKT pathway. In BC, TNFRSF11B exhibits elevated expression levels and has a substantial tumor-promoting role in BC via the PI3K/AKT pathway. Importantly, TNFRSF11B may represent a valuable prognostic tumor marker for BC treatment.

Covalent surface modification of single-layer graphene-like BC6N nanosheets with reactive nitrenes for selective ammonia sensing via DFT modeling.

Novel graphene-like nanomaterials with a non-zero bandgap are important for the design of gas sensors. The selectivity toward specific targets can be tuned by introducing appropriate functional groups on their surfaces. In this study, we use first-principles simulations, in the form of density functional theory (DFT), to investigate the covalent functionalization of a single-layer graphitized BC6N with azides to yield aziridine-functionalized adducts and explore their possible use to realize ammonia sensors. First, we determine the most favorable sites for physical adsorption and chemical reaction of methylnitrene, arising from the decomposition of methylazide, onto a BC6N monolayer. Then, we examine the thermodynamics of the [1 + 2]-cycloaddition reaction of various phenylnitrenes and perfluorinated phenylnitrenes para-substituted with (R = CO2H, SO3H) groups, demonstrating favorable energetics. We also monitor the effect of the functionalization on the electronic properties of the nanosheets via density of states and band structure analyses. Finally, we test four dBC6N to gBC6N substrates in the sensing of ammonia. We show that, thanks to their hydrogen bonding capabilities, the functionalized BC6N can selectively detect ammonia, with interaction energies varying from -0.54 eV to -1.37 eV, even in presence of competing gas such as CO2and H2O, as also confirmed by analyzing the change in the electronic properties and the values of recovery times near ambient temperature. Importantly, we model the conductance of a selected substrate alone and in presence of NH3to determine its effect on the integrated current, showing that humidity and coverage conditions should be properly tuned to use HO2C-functionalized BC6N-based nanomaterials to develop selective gas sensors for ammonia.

Factors Determining Black Carbon Exposures among Pregnant Women Enrolled in the HAPIN Trial.

Residential biomass burning is an important source of black carbon (BC) exposure among rural communities in low- and middle-income countries. We collected 7165 personal BC samples and individual/household level information from 3103 pregnant women enrolled in the Household Air Pollution Intervention Network trial. Women in the intervention arm received free liquefied petroleum gas stoves and fuel throughout pregnancy; women in the control arm continued the use of biomass stoves. Median (IQR) postintervention BC exposures were 9.6 µg/m3 (5.2-14.0) for controls and 2.8 µg/m3 (1.6-4.8) for the intervention group. Using mixed models, we characterized predictors of BC exposure and assessed how exposure contrasts differed between arms by select predictors. Primary stove type was the strongest predictor (R2 = 0.42); the models including kerosene use, kitchen location, education, occupation, or stove use hours also provided additional explanatory power from the base model adjusted only for the study site. Our full, trial-wide, model explained 48% of the variation in BC exposures. We found evidence that the BC exposure contrast between arms differed by study site, adherence to the assigned study stove, and whether the participant cooked. Our findings highlight factors that may be addressed before and during studies to implement more impactful cookstove intervention trials.