Identification of highly selective SIK1/2 inhibitors that modulate innate immune activation and suppress intestinal inflammation.

The salt-inducible kinases (SIK) 1-3 are key regulators of pro- versus anti-inflammatory cytokine responses during innate immune activation. The lack of highly SIK-family or SIK isoform-selective inhibitors suitable for repeat, oral dosing has limited the study of the optimal SIK isoform selectivity profile for suppressing inflammation in vivo. To overcome this challenge, we devised a structure-based design strategy for developing potent SIK inhibitors that are highly selective against other kinases by engaging two differentiating features of the SIK catalytic site. This effort resulted in SIK1/2-selective probes that inhibit key intracellular proximal signaling events including reducing phosphorylation of the SIK substrate cAMP response element binding protein (CREB) regulated transcription coactivator 3 (CRTC3) as detected with an internally generated phospho-Ser329-CRTC3-specific antibody. These inhibitors also suppress production of pro-inflammatory cytokines while inducing anti-inflammatory interleukin-10 in activated human and murine myeloid cells and in mice following a lipopolysaccharide challenge. Oral dosing of these compounds ameliorates disease in a murine colitis model. These findings define an approach to generate highly selective SIK1/2 inhibitors and establish that targeting these isoforms may be a useful strategy to suppress pathological inflammation.

Epistemic misalignments in microbiome research.

We argue that microbiome research should be more reflective on the methods that it relies on to build its datasets due to the danger of facing a methodological problem which we call "epistemic misalignment." An epistemic misalignment occurs when the method used to answer specific scientific questions does not track justified answers, due to the material constraints imposed by the very method. For example, relying on 16S rRNA to answer questions about the function of the microbiome generates epistemic misalignments, due to the different temporal scales that 16S rRNA provides information about and the temporal scales that are required to know about the functionality of some microorganisms. We show how some of these exist in contemporary microbiome science and urge microbiome scientists to take some measures to avoid them, as they may question the credibility of the field as a whole.

Scrutinizing microbiome determinism: why deterministic hypotheses about the microbiome are conceptually ungrounded.

This paper addresses the topic of determinism in contemporary microbiome research. I distinguish two types of deterministic claims about the microbiome, and I show evidence that both types of claims are present in the contemporary literature. First, the idea that the host genetics determines the composition of the microbiome which I call "host-microbiome determinism". Second, the idea that the genetics of the holobiont (the individual unit composed by a host plus its microbiome) determines the expression of certain phenotypic traits, which I call "microbiome-phenotype determinism". Drawing on the stability of traits conception of individuality (Suárez in Hist Philos Life Sci 42:11, 2020) I argue that none of these deterministic hypotheses is grounded on our current knowledge of how the holobiont is transgenerationally assembled, nor how it expresses its phenotypic traits.

Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine.

Cutaneous melanoma is a type of cancer with an inherent potential for lymph node colonization, which is generally preceded by neolymphangiogenesis. However, sentinel lymph node removal does not necessarily extend the overall survival of patients with melanoma. Moreover, lymphatic vessels collapse and become dysfunctional as melanomas progress. Therefore, it is unclear whether (and how) lymphangiogenesis contributes to visceral metastasis. Soluble and vesicle-associated proteins secreted by tumours and/or their stroma have been proposed to condition pre-metastatic sites in patients with melanoma. Still, the identities and prognostic value of lymphangiogenic mediators remain unclear. Moreover, our understanding of lymphangiogenesis (in melanomas and other tumour types) is limited by the paucity of mouse models for live imaging of distal pre-metastatic niches. Injectable lymphatic tracers have been developed, but their limited diffusion precludes whole-body imaging at visceral sites. Vascular endothelial growth factor receptor 3 (VEGFR3) is an attractive 'lymphoreporter' because its expression is strongly downregulated in normal adult lymphatic endothelial cells, but is activated in pathological situations such as inflammation and cancer. Here, we exploit this inducibility of VEGFR3 to engineer mouse melanoma models for whole-body imaging of metastasis generated by human cells, clinical biopsies or endogenously deregulated oncogenic pathways. This strategy revealed early induction of distal pre-metastatic niches uncoupled from lymphangiogenesis at primary lesions. Analyses of the melanoma secretome and validation in clinical specimens showed that the heparin-binding factor midkine is a systemic inducer of neo-lymphangiogenesis that defines patient prognosis. This role of midkine was linked to a paracrine activation of the mTOR pathway in lymphatic endothelial cells. These data support the use of VEGFR3 reporter mice as a 'MetAlert' discovery platform for drivers and inhibitors of metastasis.

Potent Phenylpyridine and Oxodihydrofuran Inhibitors of Cyclooxygenase-2: Optimization toward a Long Residence Time with Balanced Internal Energetics.

Long residence time enzyme inhibitors with a two-step binding mechanism are characterized by a high internal energy barrier for target association. This raises the question of whether optimizing residence time via further increasing this internal energy barrier would inevitably lead to insufficient target occupancy in vivo due to slow, time-dependent binding. We attempted to address this question during optimization of cyclooxygenase-2 (COX-2) inhibitors. Defining long residence time drugs with acceptable association and dissociation rate constants required for sufficient target occupancy and sustained efficacy, which we termed "balanced internal energetics", provides an important criterion for successful progression during lead optimization. Despite the advancement of several COX-2 inhibitors to marketed drugs, their detailed inhibition kinetics have been surprisingly limiting especially during the structure-activity relationship process mainly due to the lack of robust kinetic assays. Herein, we describe a reoptimized COX enzymatic assay and a novel MS-based assay enabling detailed mechanistic studies for identifying long residence time COX-2 inhibitors with balanced internal energetics. These efforts led to the discovery of promising leads possessing dissociation half-lives of ≤40 h, much greater than the values of 6 and 0.71 h for two marketed drugs, etoricoxib and celecoxib, respectively. Importantly, the inhibition rate constants remain comparable to those of the marketed drugs and above the lower limits set by the criteria of balanced internal energetics, predicting sufficient target occupancy required for efficacy. Taken together, this study demonstrates the feasibility of increasing the internal energy barrier as a viable approach for lead optimization toward discovering long residence time drug candidates.

Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study.

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.

Impact of the COVID-19 pandemic during Spain's state of emergency on the diagnosis of colorectal cancer.

INTRODUCTION: We evaluate the impact of COVID-epidemic in colorectal cancer (CRC) diagnosis during Spain's state of emergency. METHODS: We compared newly diagnosed patients with patients diagnosed in the same period of 2019. RESULTS: A new diagnosis of CRC decreased 48% with a higher rate of patients diagnosed in the emergency setting (12.1% vs. 3.6%; p = .048) and a lower rate diagnosed in the screening program (5.2% vs. 33.3%; p = .000). CONCLUSIONS: Fewer patients have been diagnosed with CRC, with a higher rate of patients diagnosed in an emergency setting.

Descriptive understanding and prediction in COVID-19 modelling.

COVID-19 has substantially affected our lives during 2020. Since its beginning, several epidemiological models have been developed to investigate the specific dynamics of the disease. Early COVID-19 epidemiological models were purely statistical, based on a curve-fitting approach, and did not include causal knowledge about the disease. Yet, these models had predictive capacity; thus they were used to ground important political decisions, in virtue of the understanding of the dynamics of the pandemic that they offered. This raises a philosophical question about how purely statistical models can yield understanding, and if so, what the relationship between prediction and understanding in these models is. Drawing on the model that was developed by the Institute of Health Metrics and Evaluation, we argue that early epidemiological models yielded a modality of understanding that we call descriptive understanding, which contrasts with the so-called explanatory understanding which is assumed to be the main form of scientific understanding. We spell out the exact details of how descriptive understanding works, and efficiently yields understanding of the phenomena. Finally, we vindicate the necessity of studying other modalities of understanding that go beyond the conventionally assumed explanatory understanding.

Pharmacologic Characterization of JNJ-42226314, [1-(4-Fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a Reversible, Selective, and Potent Monoacylglycerol Lipase Inhibitor.

The serine hydrolase monoacylglycerol lipase (MAGL) is the rate-limiting enzyme responsible for the degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. Inhibition of 2-AG degradation leads to elevation of 2-AG, the most abundant endogenous agonist of the cannabinoid receptors (CBs) CB1 and CB2. Activation of these receptors has demonstrated beneficial effects on mood, appetite, pain, and inflammation. Therefore, MAGL inhibitors have the potential to produce therapeutic effects in a vast array of complex human diseases. The present report describes the pharmacologic characterization of [1-(4-fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone (JNJ-42226314), a reversible and highly selective MAGL inhibitor. JNJ-42226314 inhibits MAGL in a competitive mode with respect to the 2-AG substrate. In rodent brain, the compound time- and dose-dependently bound to MAGL, indirectly led to CB1 occupancy by raising 2-AG levels, and raised norepinephrine levels in cortex. In vivo, the compound exhibited antinociceptive efficacy in both the rat complete Freund's adjuvant-induced radiant heat hypersensitivity and chronic constriction injury-induced cold hypersensitivity models of inflammatory and neuropathic pain, respectively. Though 30 mg/kg induced hippocampal synaptic depression, altered sleep onset, and decreased electroencephalogram gamma power, 3 mg/kg still provided approximately 80% enzyme occupancy, significantly increased 2-AG and norepinephrine levels, and produced neuropathic antinociception without synaptic depression or decreased gamma power. Thus, it is anticipated that the profile exhibited by this compound will allow for precise modulation of 2-AG levels in vivo, supporting potential therapeutic application in several central nervous system disorders. SIGNIFICANCE STATEMENT: Potentiation of endocannabinoid signaling activity via inhibition of the serine hydrolase monoacylglycerol lipase (MAGL) is an appealing strategy in the development of treatments for several disorders, including ones related to mood, pain, and inflammation. [1-(4-Fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone is presented in this report to be a novel, potent, selective, and reversible noncovalent MAGL inhibitor that demonstrates dose-dependent enhancement of the major endocannabinoid 2-arachidonoylglycerol as well as efficacy in models of neuropathic and inflammatory pain.

"Whole" vs. "fragmented" approach to EAACI pollen season definitions: A multicenter study in six Southern European cities.

BACKGROUND: The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe. OBJECTIVE: To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa. METHODS: As part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility. RESULTS: The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days). CONCLUSION: The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.

Depixelation and enhancement of fiber bundle images by bundle rotation.

Fiber bundles have become widely adopted for use in endoscopy, live-organism imaging, and other imaging applications. An inherent consequence of imaging with these bundles is the introduction of a honeycomb-like artifact that arises from the inter-fiber spacing, which obscures features of objects in the image. This artifact subsequently limits applicability and can make interpretation of the image-based data difficult. This work presents a method to reduce this artifact by on-axis rotation of the fiber bundle. Fiber bundle images were first low-pass and median filtered to improve image quality. Consecutive filtered images with rotated samples were then co-registered and averaged to generate a final, reconstructed image. The results demonstrate removal of the artifacts, in addition to increased signal contrast and signal-to-noise ratio. This approach combines digital filtering and spatial resampling to reconstruct higher-quality images, enhancing the utility of images acquired using fiber bundles.

Relative Entropy and Minimum-Variance Pricing Kernel in Asset Pricing Model Evaluation.

Recent literature shows that many testing procedures used to evaluate asset pricing models result in spurious rejection probabilities. Model misspecification, the strong factor structure of test assets, or skewed test statistics largely explain this. In this paper we use the relative entropy of pricing kernels to provide an alternative framework for testing asset pricing models. Building on the fact that the law of one price guarantees the existence of a valid pricing kernel, we study the relationship between the mean-variance efficiency of a model's factor-mimicking portfolio, as measured by the cross-sectional generalized least squares (GLS) R 2 statistic, and the relative entropy of the pricing kernel, as determined by the Kullback-Leibler divergence. In this regard, we suggest an entropy-based decomposition that accurately captures the divergence between the factor-mimicking portfolio and the minimum-variance pricing kernel resulting from the Hansen-Jagannathan bound. Our results show that, although GLS R 2 statistics and relative entropy are strongly correlated, the relative entropy approach allows us to explicitly decompose the explanatory power of the model into two components, namely, the relative entropy of the pricing kernel and that corresponding to its correlation with asset returns. This makes the relative entropy a versatile tool for designing robust tests in asset pricing.

The stability of traits conception of the hologenome: An evolutionary account of holobiont individuality.

Bourrat and Griffiths (Hist Philos Life Sci 40(2):33, 2018) have recently argued that most of the evidence presented by holobiont defenders to support the thesis that holobionts are evolutionary individuals is not to the point and is not even adequate to discriminate multispecies evolutionary individuals from other multispecies assemblages that would not be considered evolutionary individuals by most holobiont defenders. They further argue that an adequate criterion to distinguish the two categories is fitness alignment, presenting the notion of fitness boundedness as a criterion that allows divorcing true multispecies evolutionary individuals from other multispecies assemblages and provides an adequate criterion to single out genuine evolutionary multispecies assemblages. A consequence of their criterion is that holobionts, as conventionally defined by hologenome defenders, are not evolutionary individuals except in very rare cases, and for very specific host-symbiont associations. This paper is a critical response to Bourrat and Griffiths' arguments and a defence of the arguments presented by holobiont defenders. Drawing upon the case of the hologenomic basis of the evolution of sanguivory in vampire bats (Nat Ecol Evol 2:659-668, 2018), I argue that Bourrat and Griffiths overlook some aspects of the biological nature of the microbiome that justifies the thesis that holobionts are evolutionarily different to other multispecies assemblages. I argue that the hologenome theory of evolution should not define the hologenome as a collection of genomes, but as the sum of the host genome plus some traits of the microbiome which together constitute an evolutionary individual, a conception I refer to as the stability of traits conception of the hologenome. Based on that conception I argue that the evidence presented by holobiont defenders is to the point, and supports the thesis that holobionts are evolutionary individuals. In this sense, the paper offers an account of the holobiont that aims to foster a dialogue between hologenome advocates and hologenome critics.

Circulating Tumor Cells in Patients Undergoing Resection of Colorectal Cancer Liver Metastases. Clinical Utility for Long-Term Outcome: A Prospective Trial.

BACKGROUND: Patients with resected colorectal cancer liver metastases display heterogeneous clinical behavior. The identification of new prognostic factors would help in making more accurate decisions. OBJECTIVE: The aim of this study was to evaluate the survival impact of circulating tumor cells (CTCs) in this setting. METHODS: We conducted a prospective study of patients with resected liver metastases of colorectal cancer. Patients were included in the study from February 2009 to January 2013. The CellSearch System™ was employed for the detection of pre- and postsurgery CTCs. A positive test was defined as two or more CTCs/7.5 mL of blood. Recurrence rate, disease-free survival, and overall survival were calculated, and univariate and multivariate analyses were performed. RESULTS: Forty-four patients were included in our study. After a median follow-up of 60 months (range 28-74), 32 patients experienced recurrence (72.7%). The CTCs number was determined and the test was positive in 8 patients (18.6%) before surgery and 13 patients (29.5%) after surgery. The postoperative detection of CTCs was not related to any clinical outcome; however, the preoperative detection of CTCs was significantly related to behavior. All patients in the preoperative CTC-positive group relapsed, versus 65% in the CTC-negative group (p = 0.051). Disease-free survival was 19 months in the preoperative CTC-negative group versus 7 months in the CTC-positive group (p = 0.01). Additionally, overall survival was 69 months in the preoperative CTC-negative group versus 17 months in the CTC-positive group (p = 0.004). Preoperative CTC count remained significant in multivariate analysis. CONCLUSIONS: In this cohort of colorectal cancer liver metastases patients, the presence of two or more preoperative CTCs was associated with disease progression and poor survival despite complete resection.

Impact of specific modes of circumferential resection margin involvement in rectal cancer local recurrence: A retrospective study.

PURPOSE: To compare the local recurrence rate and overall survival between patients with circumferential resection margin (CRM) involvement by direct tumor spread and by a tumor within a lymph node. METHODS: A total of 776 patients diagnosed with rectal cancer underwent rectal resection. Patients with CRM involvement by direct tumor spread were named group A. CRM involvement by tumor within a lymph node formed group B. Patient data, including sex, age, pT, pN, stage I-III versus IV, neoadjuvant radiotherapy, adjuvant chemotherapy, carcinoembryonic antigen, primary tumor location, lymph node retrieval, and need for abdominoperineal resection, were compared between both groups. RESULTS: In total, 10.5% of the patients had CRM involvement. Of these, in 57 cases (7.3%), it was by direct tumor spread and in 19 cases (2.4%) by tumor within a lymph node. Other types of CRM involvement were found in six patients. With a mean follow-up of 32.9 months, 18 patients from group A (31.5%) and one patient from group B (5.2%) suffered a local recurrence. Local recurrence-free survival was significantly higher in patients from group B (P = 0.049). Patients in stage I-III (P = 0.037) and from group B ( P = 0.049) had better overall survival. CONCLUSION: Patients with CRM involvement by tumor within a lymph node have a low risk of local recurrence and better overall survival than patients with CRM involvement by direct tumor spread.

Improving the activity of gold nanoparticles for the water-gas shift reaction using TiO2-Y2O3: an example of catalyst design.

In the last ten years, there has been an acceleration in the pace at which new catalysts for the water-gas shift reaction are designed and synthesized. Pt-based catalysts remain the best solution when only activity is considered. However, cost, operation temperature, and deactivation phenomena are important variables when these catalysts are scaled in industry. Here, a new catalyst, Au/TiO2-Y2O3, is presented as an alternative to the less selective Pt/oxide systems. Experimental and theoretical techniques are combined to design, synthesize, characterize and analyze the performance of this system. The mixed oxide demonstrates a synergistic effect, improving the activity of the catalyst not only at large-to-medium temperatures but also at low temperatures. This effect is related to the homogeneous dispersion of the vacancies that act both as nucleation centers for smaller and more active gold nanoparticles and as dissociation sites for water molecules. The calculated reaction path points to carboxyl formation as the rate-limiting step with an activation energy of 6.9 kcal mol-1, which is in quantitative agreement with experimental measurements and, to the best of our knowledge, it is the lowest activation energy reported for the water-gas shift reaction. This discovery demonstrates the importance of combining experimental and theoretical techniques to model and understand catalytic processes and opens the door to new improvements to reduce the operating temperature and the deactivation of the catalyst.

Isotope-specific and amino acid-specific heavy atom substitutions alter barrier crossing in human purine nucleoside phosphorylase.

Computational chemistry predicts that atomic motions on the femtosecond timescale are coupled to transition-state formation (barrier-crossing) in human purine nucleoside phosphorylase (PNP). The prediction is experimentally supported by slowed catalytic site chemistry in isotopically labeled PNP (13C, 15N, and 2H). However, other explanations are possible, including altered volume or bond polarization from carbon-deuterium bonds or propagation of the femtosecond bond motions into slower (nanoseconds to milliseconds) motions of the larger protein architecture to alter catalytic site chemistry. We address these possibilities by analysis of chemistry rates in isotope-specific labeled PNPs. Catalytic site chemistry was slowed for both [2H]PNP and [13C, 15N]PNP in proportion to their altered protein masses. Secondary effects emanating from carbon-deuterium bond properties can therefore be eliminated. Heavy-enzyme mass effects were probed for local or global contributions to catalytic site chemistry by generating [15N, 2H]His8-PNP. Of the eight His per subunit, three participate in contacts to the bound reactants and five are remote from the catalytic sites. [15N, 2H]His8-PNP had reduced catalytic site chemistry larger than proportional to the enzymatic mass difference. Altered barrier crossing when only His are heavy supports local catalytic site femtosecond perturbations coupled to transition-state formation. Isotope-specific and amino acid specific labels extend the use of heavy enzyme methods to distinguish global from local isotope effects.

Stent placement prior to initiation of chemotherapy in patients with obstructive, nonoperative left sided tumors is associated with fewer stomas.

BACKGROUND AND OBJETIVES: Due to the potential risks associated with stent placement, European Society Gastrointestinal Endoscopy does not recommend prophylactic insertion of stents in patients without symptoms. The aim was to compare complication rates, need of surgery, colostomy formation, and survival between stent placement prior to start of chemotherapy (SEMS group) and upfront ChT (ChT group) in patients with endoscopically non-transverable metastatic left-sided colorectal cancer. METHODS: Gender, age, CEA, tumor location, sites of metastatic disease, peritoneal involvement, liver involvement, and angiogenesis inhibitors administration, were recorded. Complication rates, need of surgery, stoma creation, and survival were compared between both groups by univariate and multivariate test. Complications of SEMS placement in both groups were compared. RESULTS: We studied 75 men and 40 women, with a mean age of 66.3 years. Overall complication and perforation rates were similar but patients in the ChT group had a significant higher need of surgery and subsequent stoma creation. Perforation after SEMS placement rates were higher in patients receiving ChT than in patients without ChT. Survival was related to peritoneal carcinomatosis and administration of biological agents. CONCLUSIONS: SEMS placement prior to ChT administration dismissed the need of subsequent surgery and decreased the rates of permanent stoma formation.

Effects of the capping ligands, linkers and oxide surface on the electron injection mechanism of copper sulfide quantum dot-sensitized solar cells.

Quantum dot-sensitized solar cells, QDSCs, are a clean and effective alternative to fossil fuels to reduce CO2 emissions. However, the different components that constitute the QDSCs and the difficulty of isolating experimentally their effects on the performance of the whole system slow down the development of more efficient devices. In this work, DFT calculations are combined with a bottom-up approach to differentiate the effect of each component on the electronic structure and absorption spectra. First, Cu2S QDs were built including a U parameter to effectively describe the localization of electrons. The effect of capping agents is addressed using ligands with different electron-donating/withdrawing groups. The role of linkers and their adsorption on the oxide surface are also examined. Finally, we propose a main indirect electron injection mechanism based on the position of the peaks of the spectra.

Ag2S Quantum Dot-Sensitized Solar Cells by First Principles: The Effect of Capping Ligands and Linkers.

Quantum dots solar cells, QDSCs, are one of the candidates for being a reliable alternative to fossil fuels. However, the well-studied CdSe and CdTe-based QDSCs present a variety of issues for their use in consumer-goods applications. Silver sulfide, Ag2S, is a promising material, but poor efficiency has been reported for QDSCs based on this compound. The potential influence of each component of QDSCs is critical and key for the development of more efficient devices based on Ag2S. In this work, density functional theory calculations were performed to study the nature of the optoelectronic properties for an anatase-TiO2(101) surface sensitized with different silver sulfide nanoclusters. We demonstrated how it is possible to deeply tune of its electronic properties by modifying the capping ligands and linkers to the surface. Finally, an analysis of the electron injection mechanism for this system is presented.