Exploring zinc oxide morphologies for aqueous solar cells by a photoelectrochemical, computational, and multivariate approach.

Dye-sensitized solar cells assembled with aqueous electrolytes are emerging as a sustainable photovoltaic technology suitable for safe indoor and portable electronics use. While the scientific community is exploring unconventional materials for preparing electrodes and electrolytes, this work presents the first study on zinc oxide as a semiconductor material to fabricate photoanodes for aqueous solar cells. Different morphologies (i.e., nanoparticles, multipods, and desert roses) are synthesized, characterized, and tested in laboratory-scale prototypes. This exploratory work, also integrated by a computational study and a multivariate investigation on the factors that influence electrode sensitization, confirms the possibility of using zinc oxide in the field of aqueous photovoltaics and opens the way to new morphologies and processes of functionalization or surface activation to boost the overall cell efficiency.

Mammals' sperm microbiome: current knowledge, challenges, and perspectives on metagenomics of seminal samples.

Bacterial growth is highly detrimental to sperm quality and functionality. However, during the last few years, using sequencing techniques with a metagenomic approach, it has been possible to deepen the study of bacteria-sperm relationships and describe non-culturable species and synergistic and antagonistic relationships between the different species in mammalian animals. We compile the recent metagenomics studies performed on mammalian semen samples and provide updated evidence to understand the importance of the microbial communities in the results of sperm quality and sperm functionality of males, looking for future perspectives on how these technologies can collaborate in the development of andrological knowledge.

Measuring the effect of climate change in Antarctic microbial communities: toward novel experimental approaches.

The Antarctic continent is undergoing a rapid warming, affecting microbial communities throughout its ecosystems. This continent is a natural laboratory for studying the effect of climate change, however, assessing the microbial communities' responses to environmental changes is challenging from a methodological point of view. We suggest novel experimental designs, including multivariable assessments that apply multiomics methods in combination with continuous environmental data recording and new warming simulation systems. Moreover, we propose that climate change studies in Antarctica should consider three main objectives, including descriptive studies, short-term temporary adaptation studies, and long-term adaptive evolution studies. This will help us to understand and manage the effects of climate change on the Earth.

New Amino Naphthoquinone Derivatives as Anti-Trypanosoma cruzi Agents Targeting Trypanothione Reductase.

To develop novel chemotherapeutic alternatives for the treatment of Chagas disease, in this study, a set of new amino naphthoquinone derivatives were synthesised and evaluated in vitro on the epimastigote and trypomastigote forms of Trypanosoma cruzi strains (NINOA and INC-5) and on J774 murine macrophages. The design of the new naphthoquinone derivatives considered the incorporation of nitrogenous fragments with different substitution patterns present in compounds with activity on T. cruzi, and, thus, 19 compounds were synthesised in a simple manner. Compounds 2e and 7j showed the lowest IC50 values (0.43 µM against both strains for 2e and 0.19 µM and 0.92 µM for 7j). Likewise, 7j was more potent than the reference drug, benznidazole, and was more selective on epimastigotes. To postulate a possible mechanism of action, molecular docking studies were performed on T. cruzi trypanothione reductase (TcTR), specifically at a site in the dimer interface, which is a binding site for this type of naphthoquinone. Interestingly, 7j was one of the compounds that showed the best interaction profile on the enzyme; therefore, 7j was evaluated on TR, which behaved as a non-competitive inhibitor. Finally, 7j was predicted to have a good pharmacokinetic profile for oral administration. Thus, the naphthoquinone nucleus should be considered in the search for new trypanocidal agents based on our hit 7j.

Antibiotic Prescribing in Children Hospitalized With COVID-19 and Multisystem Inflammatory Syndrome in Spain: Prevalence, Trends, and Associated Factors.

The SARS-CoV-2 pandemic has caused an increase in antibiotic use in different settings. We describe the antibiotic prescribing prevalence, associated factors and trends, as well as concomitant bacterial infections in children hospitalized with COVID-19 or multisystemic inflammatory syndrome related to SARS-CoV-2 in Spain.

Spatial co-occurrence patterns of benthic microbial assemblage in response to trace metals in the Atacama Desert Coastline.

Taxonomic and functional microbial communities may respond differently to anthropogenic coastal impacts, but ecological quality monitoring assessments using environmental DNA and RNA (eDNA/eRNA) in response to pollution are poorly understood. In the present study, we investigated the utility of the co-occurrence network approach's to comprehensively explore both structure and potential functions of benthic marine microbial communities and their responses to Cu and Fe fractioning from two sediment deposition coastal zones of northern Chile via 16S rRNA gene metabarcoding. The results revealed substantial differences in the microbial communities, with the predominance of two distinct module hubs based on study zone. This indicates that habitat influences microbial co-occurrence networks. Indeed, the discriminant analysis allowed us to identify keystone taxa with significant differences in eDNA and eRNA comparison between sampled zones, revealing that Beggiatoaceae, Carnobacteriaceae, and Nitrosococcaceae were the primary representatives from Off Loa, whereas Enterobacteriaceae, Corynebacteriaceae, Latescibacteraceae, and Clostridiaceae were the families responsible for the observed changes in Mejillones Bay. The quantitative evidence from the multivariate analyses supports that the benthic microbial assemblages' features were linked to specific environments associated with Cu and Fe fractions, mainly in the Bay. Furthermore, the predicted functional microbial structure suggested that transporters and DNA repair allow the communities to respond to metals and endure the interacting variable environmental factors like dissolved oxygen, temperature, and salinity. Moreover, some active taxa recovered are associated with anthropogenic impact, potentially harboring antibiotic resistance and other threats in the coastal zone. Overall, the method of scoping eRNA in parallel with eDNA applied here has the capacity to significantly enhance the spatial and functional understanding of real-time microbial assemblages and, in turn, would have the potential to increase the acuity of biomonitoring programs key to responding to immediate management needs for the marine environment.

1,5-Benzodiazepin-2(3H)-ones: In Vitro Evaluation as Antiparkinsonian Agents.

A new series of twenty-three 1,5-benzodiazepin-2(3H)-ones were synthesized and evaluated in the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays as a new chemotype with antioxidant and good drug-like properties. All of the derivatives showed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y and the human hepatoma HepG2 cell lines. Experimental solubility in bio-relevant media showed a good relationship with melting points in this series. Five compounds with the best antioxidant properties showed neuroprotectant activity against H2O2-induced oxidative stress in the SH-SY5Y cell line. From them, derivatives 4-phenyl-1H-1,5-benzodiazepin-2(3H)-one (18) and 4-(3,4,5-trimethoxyphenyl)-1H-1,5-benzodiazepin-2(3H)-one (20) yielded good neuroprotection activity in the same neuronal cell line under 6-OHD and MPP+ insults as in vitro models of mitochondrial dysfunction and oxidative stress in Parkinson's disease (PD). Both compounds also demonstrated a significant reduction of intracellular Reactive Oxygen Species (ROS) and superoxide levels, in parallel with a good improvement of the Mitochondrial Membrane Potential (ΔΨm). Compared with curcumin, compound 18 better reduced lipid peroxidation levels, malondialdehyde (MDA), in SH-SY5Y cells under oxidative stress pressure and recovered intracellular glutathione synthetase (GSH) levels. Apoptosis and caspase-3 levels of SH-SY5Y under H2O2 pressure were also reduced after treatment with 18. Neuroprotection in neuron-like differentiated SH-SY5Y cells was also achieved with 18. In summary, this family of 1,5-benzodiazepin-2-ones with an interesting antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitutes a new promising chemical class with high potential for the development of new therapeutic agents against PD.

A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo.

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

Benthic microbial diversity trends in response to heavy metals in an oxygen-deficient eutrophic bay of the Humboldt current system offshore the Atacama Desert.

Mejillones Bay is a coastal ecosystem situated in an oxygen-deficient upwelling area impacted by mining activities in the coastal desert region of northern Chile, where conspicuous microbial life develops in the sediments. Herein, heavy metal (loid)s (HMs) such as Cu, Pb, As, Zn, Al, Fe, Cd, Mo, Ni and V as well as benthic microbial communities were studied using spectrometry and iTag-16 S rRNA sequencing. Samples were taken from two contrasting sedimentary localities in the Bay named Punta Rieles (PR) and Punta Chacaya (PC) within 10-50 m water-depth gradient. PR sediments were organic matter rich (21.1% of TOM at 50 m) and overlaid with low-oxygen waters (<0.06 ml O2/L bottom layer) compared with PC. In general, HMs like Al, Ni, Cd, As and Pb tended to increase in concentration with depth in PR, while the opposite pattern was observed in PC. In addition, PR presented a higher number of unique families (72) compared to PC (35). Among the top ten microbial families, Desulfobulbaceae (4.6% vs. 3.2%), Flavobacteriaceae (2.8% vs. 2.3%) and Anaerolineaceae (3.3% vs. 2.3%) dominated in PR, meanwhile Actinomarinales_Unclassified (8.1% vs. 4.2%) and Sandaracinaceae (4.4% vs. 2.0%) were more abundant in PC. Multivariate analyses confirmed that water depth-related variation was a good proxy for oxygen conditions and metal concentrations, explaining the structure of benthic microbial assemblages. Cd, Ni, As and Pb showed uniformly positive associations with communities that represented the keystone taxa in the co-occurrence network, including Anaerolineaceae, Thiotrichaceae, Desulfobulbaceae, Desulfarculaceae and Bacteroidales_unclassified communities. Collectively, these findings provide new insights for establishing the ecological interconnections of benthic microorganisms in response to metal contamination in a coastal upwelling environment.

DNA repair, NFKß, and TP53 polymorphisms associated with potentially malignant disorders and oral squamous cell carcinoma in Argentine patients.

OBJECTIVE: An important strategy in cancer prevention is to identify individual susceptibilities for cancer development through the genomic profile. Developing countries such as Argentina have no data on genetic composition. The aim of this study was to evaluate the single nucleotide polymorphisms of genes related to DNA repair (XCCR3, XPD), cell cycle arrest/apoptosis (TP53), and inflammation (NFKß) of patients with precancer and oral cancer and to contribute to recognizing potential risk of developing these pathologies, and incorporate the risk patients into a clinical follow-up program in Córdoba, Argentina. STUDY DESIGN: A cross-sectional study was performed on 140 patients with oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMDs), and controls. Genotyping of single nucleotide polymorphisms was performed using allele-specific polymerase chain reaction or restriction fragment length polymorphism techniques. The variables were evaluated by bivariate and multivariate statistical methods, with P < .05 statistically significant. RESULTS: The multiple correspondence analyses showed that patients with OSCC are clustered with the T allele of XRCC3 T241 M and the C allele of TP53 R72 P, and patients with OPMDs are clustered with the T allele of NFKß-519. CONCLUSION: Our preliminary results showed that the C allele of the Pro72 variant of TP53 was related to OSSC and OPMD, and the T allele of NFKß-519 is related to OPMDs in Argentine patients.

Connectivity of bacterial assemblages along the Loa River in the Atacama Desert, Chile.

The Loa River is the only perennial artery that crosses the Atacama Desert in northern Chile. It plays an important role in the ecological and economic development of the most water-stressed region, revealing the impact of the mining industry, which exacerbate regional water shortages for many organisms and ecological processes. Despite this, the river system has remained understudied. To our knowledge, this study provides the first effort to attempt to compare the microbial communities at spatial scale along the Loa River, as well as investigate the physicochemical factors that could modulate this important biological component that still remains largely unexplored. The analysis of the spatial bacterial distribution and their interconnections in the water column and sediment samples from eight sites located in three sections along the river catchment (upper, middle and lower) was conducted using 16S rRNA gene-based Illumina MiSeq sequencing. Among a total of 543 ASVs identified at the family level, over 40.5% were cosmopolitan in the river and distributed within a preference pattern by the sediment substrate with 162 unique ASVs, while only 87 were specific to the column water. Bacterial diversity gradually decreased from the headwaters, where the upper section had the largest number of unique families. Distinct groupings of bacterial communities often associated with anthropogenic disturbance, including Burkholderiaceae and Flavobacteriaceae families were predominant in the less-impacted upstream section. Members of the Arcobacteraceae and Marinomonadaceae were prominent in the agriculturally and mining-impacted middle sector while Rhodobacteraceae and Coxiellaceae were most abundant families in downstream sites. Such shifts in the community structure were also related to the influence of salinity, chlorophyll, dissolved oxygen and redox potential. Network analyses corroborated the strong connectivity and modular structure of bacterial communities across this desert river, shedding light on taxonomic relatedness of co-occurring species and highlighting the need for planning the integral conservation of this basin.

Grow well/Crecer bien: a protocol for research on infant feeding practices in low-income families.

BACKGROUND: The prevalence of obesity among children remains high. Given obesity's significant lifelong consequences, there is great interest in preventing obesity early in life. There is a need to better understand the relation of common infant feeding styles and practices to obesity in infants using longitudinal study designs. There is also an urgent need to understand the role of caregivers other than mothers in feeding. A better understanding of variation in feeding styles and practices can inform the identification of risk groups and the tailoring of interventions to them. METHODS: In partnership with Early Head Start programs across four counties in southern California, mothers and infants will be enrolled in a two-year longitudinal study collecting survey and anthropometric data. A subsample of mothers and their selected other caregivers will participate in qualitative research involving feeding diaries and dyadic interviews. The results will be used to develop and test an enhanced nutrition education program. DISCUSSION: We outline a study methodology to examine feeding styles and practices and their association with early childhood obesity risk and enhance an existing intervention to promote healthy infant feeding and growth among children in low-income families.

Protein quantification by bicinchoninic acid (BCA) assay follows complex kinetics and can be performed at short incubation times.

Amongst the available methodologies for protein determination, the bicinchoninic acid (BCA) assay highlights for its simplicity, sensitivity, repeatability and reproducibility. Nevertheless, in spite that the general principle behind this methodology is known, there are still unanswered questions regarding the chemistry behind the assay and the experimental conditions commonly employed. The present work explored the kinetics, and the analytical response of the assay to free amino acids, peptides (containing tryptophan and tyrosine), and proteins. Results revealed kinetic profiles characterized by the absence of plateaus, with behaviors depending on the type of the sample. The latter, along with contribution to the BCA index elicited by oxidation products generated at the side chain of tryptophan and tyrosine, as well as pre-oxidized ß-casein, evidenced the presence of complex reaction mechanisms. In spite of such complexity, our results showed that the BCA index is not modulated by the incubation time. This applies for responses producing absorbance intensities (at 562 nm) higher than 0.1. Therefore, we propose that the assay can be applied at shorter incubation times (15 min) than those indicated in manufactures specifications, and usually used by researches and industry (30 min at 37 °C).

Formation and characterization of crosslinks, including Tyr-Trp species, on one electron oxidation of free Tyr and Trp residues by carbonate radical anion.

Dityrosine and ditryptophan bonds have been implied in protein crosslinking. This is associated with oxidative stress conditions including those involved in neurodegenerative pathologies and age-related processes. Formation of dityrosine and ditryptophan derives from radical-radical reactions involving Tyr˙ and Trp˙ radicals. However, cross reactions of Tyr˙ and Trp˙ leading to Tyr-Trp crosslinks and their biological consequences have been less explored. In the present work we hypothesized that exposure of free Tyr and Trp to a high concentration of carbonate anion radicals (CO3˙-), under anaerobic conditions, would result in the formation of Tyr-Trp species, as well as dityrosine and ditryptophan crosslinks. Here we report a simple experimental procedure, employing CO3˙- generated photochemically by illumination of a Co(iii) complex at 254 nm, that produces micromolar concentrations of Tyr-Trp crosslinks. Analysis by mass spectrometry of solutions containing only the individual amino acids, and the Co(iii) complex, provided evidence for the formation of o,o'-dityrosine and isodityrosine from Tyr, and three ditryptophan dimers from Trp. When mixtures of Tyr and Trp were illuminated in an identical manner, Tyr-Trp crosslinks were detected together with dityrosine and ditryptophan dimers. These results indicate that there is a balance between the formation of these three classes of crosslinks, which is dependent on the Tyr and Trp concentrations. The methods reported here allow the generation of significant yields of isolated Tyr-Trp adducts and their characterization. This technology should facilitate the detection, and examination of the biological consequences of Tyr-Trp crosslink formation in complex systems in future investigations.

New aryloxy-quinone derivatives with promising activity on Trypanosoma cruzi.

Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy-quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modifications in three specific moieties on the aryloxy-quinone core were considered for developing new anti-T. cruzi agents. The majority of our new quinones showed higher potency (IC50 values of <0.70 µM) than nifurtimox, a known pharmaceutical used as a baseline drug (IC50 values of 7.00 µM); however, only two of them elicited higher selectivity than nifurtimox against Vero cells. A structure-activity relationship analysis provided information about the stereoelectronic features of these compounds, which are responsible for an increase in trypanosomicidal activity. Using a pharmacophore model, we mapped the substitution patterns of the five pharmacophoric features of trypanosomicidal activity. We chose the Epc1 compounds and found no relationship with the trypanosomicidal effects. These results provided useful information about the structural characteristics for developing new aryloxy-quinones with higher potency against the protozoan parasite T. cruzi.

New 2,6,9-trisubstituted purine derivatives as Bcr-Abl and Btk inhibitors and as promising agents against leukemia.

Bcr-Abl and Btk kinases are among the targets that have been considered for the treatment of leukemia. Therefore, several strategies have focused on the use of inhibitors as chemotherapeutic tools to treat these types of leukemia, such as imatinib (for Bcr-Abl) or ibrutinib (for Btk). However, the efficacy of these drugs has been reduced due to resistance mechanisms, which have motivated the development of new and more effective compounds. In this study, we designed, synthesized and evaluated 2,6,9-trisubstituted purine derivatives as novel Bcr-Abl and Btk inhibitors. We identified 5c and 5d as potent inhibitors of both kinases (IC50 values of 40 nM and 0.58/0.66 µM for Abl and Btk, respectively). From docking and QSAR analyses, we concluded that fluorination of the arylpiperazine system is detrimental to the activity against two kinases, and we also validated our hypothesis that the substitution on the 6-phenylamino ring is important for the inhibition of both kinases. In addition, our studies indicated that most compounds could suppress the proliferation of leukemia and lymphoma cells (HL60, MV4-11, CEM, K562 and Ramos cells) at low micromolar concentrations in vitro. Finally, we preliminarily demonstrated that 5c inhibited the downstream signaling of both kinases in the respective cell models. Therefore, 5c or 5d possessed potency to be further optimized as anti-leukemia drugs by simultaneously inhibiting the Bcr-Abl and Btk kinases.

Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays.

We designed, synthesized, and evaluated novel 2,6,9-trisubstituted purine derivatives for their prospective role as antitumor compounds. Using simple and efficient methodologies, 31 compounds were obtained. We tested these compounds in vitro to draw conclusions about their cell toxicity on seven cancer cells lines and one non-neoplastic cell line. Structural requirements for antitumor activity on two different cancer cell lines were analyzed with SAR and 3D-QSAR. The 3D-QSAR models showed that steric properties could better explain the cytotoxicity of compounds than electronic properties (70% and 30% of contribution, respectively). From this analysis, we concluded that an arylpiperazinyl system connected at position 6 of the purine ring is beneficial for cytotoxic activity, while the use of bulky systems at position C-2 of the purine is not favorable. Compound 7h was found to be an effective potential agent when compared with a currently marketed drug, cisplatin, in four out of the seven cancer cell lines tested. Compound 7h showed the highest potency, unprecedented selectivity, and complied with all the Lipinski rules. Finally, it was demonstrated that 7h induced apoptosis and caused cell cycle arrest at the S-phase on HL-60 cells. Our study suggests that substitution in the purine core by arylpiperidine moiety is essential to obtain derivatives with potential anticancer activity.

Study of the TP53 codon 72 polymorphism in oral cancer and oral potentially malignant disorders in Argentine patients.

The aim of this work was to evaluate the prevalence of TP53Arg72Pro mutations and their possible relationship with oral carcinoma and oral potentially malignant disorders in Argentine patients. A cross-sectional study was performed on 111 exfoliated cytologies from patients with oral cancer (OC), oral potentially malignant disorders (OPMD) and controls. The TP53Arg72Pro mutations were determined using conventional PCR. We evaluated univariate and multivariate study variables, setting p < 0.05. We found: (a) a low frequency of Pro72 variant in control group and a high frequency in OC and OPMD, as well in OC and oral leukoplakia (OL) diagnosis; (b) multivariate association among the TP53CC genotype and females over 45 years with no tobacco nor alcohol habits with oral lichen planus pathology; (c) multivariate association between the TP53GC genotype and males with alcohol and tobacco habits and OC and OL pathologies. Our results showed that the wild-type Arg72variant was related to control patients and Pro72variant was related to OC and OPMD, in Argentine patients.

Burkholderia tropica as a Potential Microalgal Growth-Promoting Bacterium in the Biosorption of Mercury from Aqueous Solutions.

The use of microalgal biomass is an interesting technology for the removal of heavy metals from aqueous solutions owing to its high metal-binding capacity, but the interactions with bacteria as a strategy for the removal of toxic metals have been poorly studied. The goal of the current research was to investigate the potential of Burkholderia tropica co-immobilized with Chlorella sp. in polyurethane discs for the biosorption of Hg(II) from aqueous solutions and to evaluate the influence of different Hg(II) concentrations (0.041, 1.0, and 10 mg/l) and their exposure to different contact times corresponding to intervals of 1, 2, 4, 8, 16, and 32 h. As expected, microalgal bacterial biomass adhered and grew to form a biofilm on the support. The biosorption data followed pseudo-second-order kinetics, and the adsorption equilibrium was well described by either Langmuir or Freundlich adsorption isotherm, reaching equilibrium from 1 h. In both bacterial and microalgal immobilization systems in the coimmobilization of Chlorella sp. and B. tropica to different concentrations of Hg(II), the kinetics of biosorption of Hg(II) was significantly higher before 60 min of contact time. The highest percentage of biosorption of Hg(II) achieved in the co-immobilization system was 95% at pH 6.4, at 3.6 g of biosorbent, 30 ± 1°C, and a mercury concentration of 1 mg/l before 60 min of contact time. This study showed that co-immobilization with B. tropica has synergistic effects on biosorption of Hg(II) ions and merits consideration in the design of future strategies for the removal of toxic metals.

Design, synthesis, biological evaluation and binding mode modeling of benzimidazole derivatives targeting the cannabinoid receptor type 1.

A series of N-acyl-2,5-dimethoxyphenyl-1H-benzimidazoles were designed based on a CoMFA model for cannabinoid receptor type 1 (CB1) ligands. Compounds were synthesized and radioligand binding affinity assays were performed. Eight novel benzimidazoles exhibited affinity for the CB1 receptor in the nanomolar range, and the most promising derivative compound 5 displayed a K(i) value of 1.2 nM when compared to CP55,940. These results confirm our previously reported QSAR model on benzimidazole derivatives, providing new information for the development of small molecules with high CB1 affinity.