Understanding the effects of sub-inhibitory antibiotic concentrations on the development of ß-lactamase resistance based on quantile regression analysis.

AIMS: Quantile regression is an alternate type of regression analysis that has been shown to have numerous advantages over standard linear regression. Unlike linear regression, which uses the mean to fit a linear model, quantile regression uses a data set's quantiles (or percentiles), which leads to a more comprehensive analysis of the data. However, while relatively common in other scientific fields such as economic and environmental modeling, it is infrequently used to understand biological and microbiological systems. METHODS AND RESULTS: We analyzed a set of bacterial growth rates using quantile regression analysis to better understand the effects of antibiotics on bacterial fitness. Using a bacterial model system containing 16 variant genotypes of the TEM ß-lactamase enzyme, we compared our quantile regression analysis to a previously published study that uses the Tukey's range test, or Tukey honestly significantly difference (HSD) test. We find that trends in the distribution of bacterial growth rate data, as viewed through the lens of quantile regression, can distinguish between novel genotypes and ones that have been clinically isolated from patients. Quantile regression also identified certain combinations of genotypes and antibiotics that resulted in bacterial populations growing faster as the antibiotic concentration increased-the opposite of what was expected. These analyses can provide new insights into the relationships between enzymatic efficacy and antibiotic concentration. CONCLUSIONS: Quantile regression analysis enhances our understanding of the impacts of sublethal antibiotic concentrations on enzymatic (TEM ß-lactamase) efficacy and bacterial fitness. We illustrate that quantile regression analysis can link patterns in growth rates with clinically relevant mutations and provides an understanding of how increasing sub-lethal antibiotic concentrations, like those found in our modern environment, can affect bacterial growth rates, and provide insight into the genetic basis for varied resistance.

Environmental radiological baseline in unconventional oil and gas areas of Mexico.

Environmental radioactivity study was performed in unconventional hydrocarbons areas for the first time in Mexico, where four unconventional hydrocarbon exploratory wells (UHEW) are planned. This study assesses natural radiological conditions in areas around UHEW. Equivalent dose rate distribution displayed in Geographic Information System (GIS) had a maximum of 1.83 mSv a-1 and minimum of 0.04 mSv a-1, GIS was also used for introducing land usage, water resources and population occupancy. Measurements of gross alpha and gross beta in water were below the national permissible limits for drinking water 0.5 and 1.0 Bq L-1 respectively, even though samples do not correspond to drinking water. Evaluation of 238U and 226Ra in groundwater were below minimum detectable concentration 1.3 and 1.0 Bq L-1, respectively. This study provides a radiological baseline for the impact of future industrial activities, especially if exploitation of unconventional hydrocarbons produces naturally occurring radioactive material.

Sociodemographic factors associated with immediate puerperal control: A cross-sectional study based on the Peruvian demographic and health survey, 2019.

Introduction: Peru is the fifth country in Latin America with the highest maternal mortality. In Peru, immediate puerperal control (IPC) was established in 2013 as a measure to improve postnatal control, with a view in reducing maternal mortality. This study aimed to evaluate the frequency and sociodemographic factors associated with compliance with IPC in Peru, 2019. Methods: We conducted an analytical cross-sectional study based on the Demographic and Family Health Survey (ENDES, for its acronym in Spanish) of Peru, 2019. The dependent variable was compliance with IPC (control in the first 2 h) in women aged 15-49 years who had delivered within the last five years preceding the survey. To evaluate the associated factors, Poisson family generalized linear models were used to calculate crude (cPR) and adjusted (aPR) prevalence ratios, with their respective 95% confidence intervals (95%CI). Results: Data from 11,854 women were analyzed. The frequency of IPC was 59.6% (95%CI: 58.3-60.9). We found a lower proportion of IPC in urban areas (58.8%) and in the highlands (57%) and jungle (57.2%) of Peru. Residing in rural areas (aPR:1.13; 95%CI:1.08-1.19), having undergone appropriate antenatal care (ANC) (aPR:1.05; 95%CI:1.01-1.10) and having delivered a low-birth-weight newborn (aPR:1.20; 95%CI:1.12-1.29) were associated with a higher frequency of IPC, while living in the highlands (aPR:0.86; 95%CI:0.80-0.92) or jungle (aPR:0.86; 95%CI:0.80-0.92) was associated with a lower frequency of IPC. Conclusions: Approximately four out of ten women did not have IPC. There was a lower proportion of IPC in urban areas and in the highland and jungle regions.

Enhancing Thermomechanical Strength and Thermal Stability of Poly(dicyclopentadiene) Composites through Cost-Effective Fly Ash Reinforcement for Structural and Impact Applications.

Poly(dicyclopentadiene) (poly-DCPD) is a thermoset with potential for high-performance applications. In this research, epoxy resin was blended with different concentrations of fly ash class F particles at 0.0, 1.0, 10.0, and 50.0 wt.%, aiming to improve its use as a high-volume structural material by decreasing costs and reducing its negative environmental impact through using fly ash particles. A planetary Thinky mixer was used to initially mix the resin with the curing agent, followed by incorporating a Grubbs catalyst. The microstructures were analyzed using scanning electron microscopy (SEM), where particles were found to be homogeneously distributed over the polymer matrix. The thermomechanical behavior was evaluated via curing, compression, dynamic mechanical analysis (DMA), and thermo-gravimetric analysis (TGA). Nanoindentation tests were also conducted. Fly ash was found to decelerate the curing of the resin through the release of calcium ions that enhanced the exothermic reaction.

Improving interfacial shear strength of fique fibres using an acrylic coating.

Natural fibres have proven to be a potential alternative to replace synthetic fibres in some composite materials applications. However, drawbacks such as impregnation difficulties and the poor fibre-matrix interface limit the use of natural fibres in high-performance applications. This work proposes using an acrylic resin to coat the fibre surface to enhance the interfacial compatibility among fique fibres and polyester resin. Pull-out tests revealed an improvement in the interfacial shear strength of about 110% for coated fibres. Furthermore, nanoindentation test, Micro Raman spectroscopy and scanning electronic microscopy indicated that the acrylic resin eliminates the gap at the fibre/matrix interface seen in the uncoated fibres. Observed behaviour could be attributed to a better chemical bonding between the fibre and matrix and is also hypothesised that the elastic characteristic of the coating helps to transfer loads effectively from the matrix to the fibre.

Impacto de la morfología espermática en las tasas de embarazo con inseminación intrauterina / Impact of sperm morphology on pregnancy rates after intrauterine insemination

Introducción y objetivo: La morfología espermática se ha utilizado como factor pronóstico en fertilización in vitro; sin embargo, en inseminación intrauterina (IIU) su rol predictivo es controversial. El objetivo de este estudio fue determinar el impacto que tiene la morfología espermática como parámetro aislado del espermiograma en la probabilidad de embarazo de parejas que son tratadas con IIU. Material y métodos: Estudio retrospectivo de los ciclos de IIU realizados en la Unidad de Medicina Reproductiva de Clínica Las Condes entre enero del 2016 y diciembre del 2018. Regresión logística de las siguientes variables: morfología espermática agrupada en 0-1%, 2-3% y≥4%, recuento total de espermatozoides con motilidad progresiva inseminados, edad de la mujer y del hombre. Resultados: Se incluyeron 385 casos, diagnosticándose embarazo clínico en 85 de ellos. Al separar en grupos de morfología espermática<4% y≥4% la tasa de embarazo fue de 22% en ambos grupos. La edad de la mujer fue el único factor estadísticamente significativo en la regresión logística. El área bajo la curva de ROC de morfología espermática como predictor de embarazo fue de 0,53. Conclusiones: Nuestro estudio concluye que la morfología espermática no debe ser considerada como parámetro único a la hora de decidir si una pareja puede ser tratada o no con IIU, eliminando la teratozoospermia aislada como indicación directa de fertilización in vitro. No fue posible determinar un punto de corte de morfología espermática que sirva como predictor de embarazo. (AU)

Introduction and objective: Sperm morphology has been used as a prognostic factor in in vitro fertilization, however, in intrauterine insemination (IUI) its predictive role is controversial. The aim of this study was to determine the impact of sperm morphology as isolated parameter of the spermiogram has on the probability of pregnancy in couples that are treated with IUI. Material and methods: Retrospective study of IUI cycles performed in the Reproductive Medicine Unit of Clínica Las Condes between January 2016 and December 2018. Logistic regression of the following variables: sperm morphology grouped in 0-1%, 2-3% and≥4%, total progressively motile sperm count inseminated, age of the woman and the man. Results: A total of 385 cases were included and clinical pregnancy was diagnosed in 85 of them. When separating into groups of sperm morphology<4% and≥4%, the pregnancy rate was 22% in both groups. The age of the woman was the only statistically significant factor in the logistic regression. The area under the ROC curve of sperm morphology as a predictor of pregnancy was 0.53. Conclusions: Our study concludes that sperm morphology should not be considered as a single parameter when deciding whether or not a couple can be treated with IUI, eliminating isolated teratozoospermia as a direct indication for in vitro fertilization. It was not possible to determine a cut-off point for sperm morphology that serves as a predictor of pregnancy. (AU)

[Impact of sperm morphology on pregnancy rates after intrauterine insemination]. / Impacto de la morfología espermática en las tasas de embarazo con inseminación intrauterina.

INTRODUCTION AND OBJECTIVE: Sperm morphology has been used as a prognostic factor in in vitro fertilization, however, in intrauterine insemination (IUI) its predictive role is controversial. The aim of this study was to determine the impact of sperm morphology as isolated parameter of the spermiogram has on the probability of pregnancy in couples that are treated with IUI. MATERIAL AND METHODS: Retrospective study of IUI cycles performed in the Reproductive Medicine Unit of Clínica Las Condes between January 2016 and December 2018. Logistic regression of the following variables: sperm morphology grouped in 0-1%, 2-3% and≥4%, total progressively motile sperm count inseminated, age of the woman and the man. RESULTS: A total of 385 cases were included and clinical pregnancy was diagnosed in 85 of them. When separating into groups of sperm morphology<4% and≥4%, the pregnancy rate was 22% in both groups. The age of the woman was the only statistically significant factor in the logistic regression. The area under the ROC curve of sperm morphology as a predictor of pregnancy was 0.53. CONCLUSIONS: Our study concludes that sperm morphology should not be considered as a single parameter when deciding whether or not a couple can be treated with IUI, eliminating isolated teratozoospermia as a direct indication for in vitro fertilization. It was not possible to determine a cut-off point for sperm morphology that serves as a predictor of pregnancy.

Antidiabetic and Toxicological Effects of the Tea Infusion of Summer Collection from Annona cherimola Miller Leaves.

Annona cherimola Miller (Ac) is a plant used in Mexican traditional medicine for the treatment of diabetes. In this work, the tea infusion extracts obtained from 1.5 g of leaf powder from Ac collected in May (AcMa), June (AcJun), July (AcJul), and August (AcAu) were evaluated on streptozocin-induced diabetic (STID) mice and for subchronic toxicity in STID and non-diabetic (ND) mice. In addition, extracts were subjected to high-performance liquid chromatography with diode array detection (HPLC-DAD). Results showed that the tea infusion extract of the sample collected in August (AcAu) exhibited the most significant antihyperglycemic activity during all acute assays. The analysis of the extracts (AcMa, AcJu, AcJul, and AcAu) by HPLC-DAD revealed that flavonoid glycosides, rutin, narcissin, and nicotiflorin were the major components. In addition, the sample AcAu contained the best concentration of flavonoids. In the case of subchronic oral toxicity, the AcAu sample did not cause mortality in STID mice, and histopathological analysis revealed significant improvement in the changes associated with diabetes in the liver and kidneys. These findings suggest that the Ac leaves collected in August may be a source of flavonoids such as rutin, with antidiabetic potential. In addition, these findings support the use of Ac to treat diabetes in traditional medicine.

Membrane fluidity, composition, and charge affect the activity and selectivity of the AMP ascaphin-8.

Ascaphins are cationic antimicrobial peptides that have been shown to have potential in the treatment of infectious diseases caused by multidrug-resistant pathogens (MDR). However, to date, their principal molecular target and mechanism of action are unknown. Results from peptide prediction software and molecular dynamics simulations confirmed that ascaphin-8 is an alpha-helical peptide. For the first time, the peptide was described as membranotrophic using biophysical approaches including calcein liposome leakage, Laurdan general polarization, and dynamic light scattering. Ascaphin-8's activity and selectivity were modulated by rearranging the spatial distribution of lysine (Var-K5), aspartic acid (Var-D4) residues, or substitution of phenylalanine with tyrosine (Var-Y). The parental peptide and its variants presented high affinity toward the bacterial membrane model (≤2 µM), but lost activity in sterol-enriched membranes (mammal and fungal models, with cholesterol and ergosterol, respectively). The peptide-induced pore size was estimated to be >20 nm in the bacterial model, with no difference among peptides. The same pattern was observed in membrane fluidity (general polarization) assays, where all peptides reduced membrane fluidity of the bacterial model but not in the models containing sterols. The peptides also showed high activity toward MDR bacteria. Moreover, peptide sensitivity of the artificial membrane models compared with pathogenic bacterial isolates were in good agreement.

CD4+/IL­4+ lymphocytes of the lamina propria and substance P promote colonic protection during acute stress.

Life stress may influence symptom onset and severity in certain gastrointestinal disorders in association with a dysregulated intestinal barrier. It has been widely accepted that stress triggers the hypothalamus­pituitary­adrenal (HPA) axis, releasing corticosterone, which promotes intestinal permeability. In response, colonic inflammation alters mucosal immune homeostasis and destroys the colonic architecture, leading to severe intestinal diseases. Endogenous substance P (SP) does not inhibit the initial extent of the HPA axis response to restraint stress, but it reduces the duration of the stress, suggesting that SP plays an important role in the transition between acute and chronic stress. The present study aimed to investigate the effect of two groups of mice exposed to stress, including acute and chronic stress. The corticosterone was evaluated by ELISA, colon samples were obtained to detected polymorphonuclear cells by hematoxylin and eosin staining, goblet and mast cells were identified by immunocytochemistry and cytokine­producing CD4+ T cells were analyzed by flow cytometry assays, adhesion proteins in the colon epithelium by western blotting and serum SP levels by ELISA. The results demonstrated an increase in the number of polymorphonuclear, goblet and mast cells, a decrease in claudin­1 expression and an elevation in E­cadherin expression during acute stress. Increased E­cadherin expression was also detected during chronic stress. Moreover, it was found that acute stress caused a shift towards a predominantly anti­inflammatory immune response (T helper 2 cells), as shown by the increase in the percentage of CD4+/IL­6+ and CD4+/IL4+ lymphocytes in the lamina propria and the increase in serum SP. In conclusion, this response promoted colonic protection during acute stress.

Insights into the Molecular Inhibition of the Oncogenic Channel KV10.1 by Globular Toxins.

Inhibition of the expression of the human ether-à-go-go (hEAG1 or hKV10.1) channel is associated with a dramatic reduction in the growth of several cancerous tumors. The modulation of this channel's activity is a promising target for the development of new anticancer drugs. Although some small molecules have shown inhibitory activity against KV10.1, their lack of specificity has prevented their use in humans. In vitro studies have recently identified a limited number of peptide toxins with proven specificity in their hKV10.1 channel inhibitory effect. These peptide toxins have become desirable candidates to use as lead compounds to design more potent and specific hKV10.1 inhibitors. However, the currently available studies lack the atomic resolution needed to characterize the molecular features that favor their binding to hKV10.1. In this work, we present the first attempt to locate the possible hKV10.1 binding sites of the animal peptide toxins APETx4, Aa1a, Ap1a, and k-hefutoxin 1, all of which described as hKV10.1 inhibitors. Our studies incorporated homology modeling to construct a robust three-dimensional (3D) model of hKV10.1, applied protein docking, and multiscale molecular dynamics techniques to reveal in atomic resolution the toxin-channel interactions. Our approach suggests that some peptide toxins bind in the outer vestibule surrounding the pore of hKV10.1; it also identified the channel residues Met397 and Asp398 as possible anchors that stabilize the binding of the evaluated toxins. Finally, a description of the possible mechanism for inhibition and gating is presented.

Phthalates in the diet of Mexican children of school age. Risk analysis.

Phthalates are widely used as plasticizers, additives, or solvents. Its extensive use has generated environmental and food contamination, which implies continuous population exposure. The aim of this work was to determine the probability of health risk of Mexican children exposed to phthalates through the consumption of contaminated food. A survey was applied to 384 Mexican school-age children (between 6 and 12 years old), to find out the type of food they eat most frequently, based on this, a research was made to know the concentration of phthalates contained in these foods. The daily intake had been calculated with the concentration of phthalates reported in food, obtaining: DEHP (19.50 µg/kg body weight/day), DnBP (5.52 µg/kg body weight/day) y for DEP (1.12 µg/kg body weight/day). The hazard index (HI) for DEP y DEHP was 0.49 to 42.5 for internal organs damage reported. HI for reproductive health damage due to exposure to DnBT and DEHP was of 0.04 to 5.58, so that there is a high probability that children's health is at risk. Therefore, it is necessary to a quantitative analysis of phthalates in food consumed in Latin American countries and establish the TDI of phthalates especially, to DEHP, which was obtained the higher HI.

Restraint stress increased the permeability of the nasal epithelium in BALB/c mice.

Stress seems to affect the onset and evolution of diverse illnesses with an inflammatory substrate. Whether physiological or psychological, stress increases epithelial permeability. In the mucosa of the nasal cavity and upper respiratory tract, the epithelial barrier is regulated in large part by bicellular and tricellular tight junctions (bTJs and tTJs, respectively). The junctional complexes are composed of multiple membrane proteins: claudins, tight-junction-associated MARVEL proteins (TAMs: occludin, tricellulin and marvelD3), and scaffolding proteins such as ZO-1, -2 and -3. The aim of the present study was to examine the possible modification of nasal permeability and TJ protein expression in a mouse model of acute psychological stress (a 4-h immobility session). Serum corticosterone was quantified from plasma samples to verify the onset of stress. Evaluation was made of the relative concentration of key proteins in nasal mucosa by using Western blot, and of changes in permeability by analyzing FITC-Dextran leakage from the nose to the blood. Compared to the control, the stressed group showed a greater epithelial permeability to FITC-Dextran, a reduced expression of occludin and tricellulin, and an elevated expression of ZO-2 and claudin-4. This evidence points to increased paracellular flow of large molecules through an altered structure of tTJs. Apparently, the structure of bTJs remained unchanged. The current findings could provide insights into the relation of stress to the onset/exacerbation of respiratory infections and/or allergies.

Evaluating the effect of low dose rate of gamma rays in germ cells of Drosophila melanogaster.

Purpose: Evaluation of genetic risk in germ cells is still matter of research, mainly due to their role in the transmission of genetic information from one generation to another. Although numerous experiments have been carried out in Drosophila in order to study the effect of radiation on germ cells, the role of dose rate (DR) has not been fully explored. The purpose of this study was to evaluate the action of DR on the radioprotection induction on male germ cell of D. melanogaster.Material and method: The productivity and the sex-linked recessive lethal (SLRL) tests were used to evaluate the radio-sensitivity of different states of the germ line of males. Two-day-old males of Canton-S wild type strain were pretreated with 0.2 Gy at 5.4 or 34.3 Gy/h of gamma rays from a 60Co source, three hours later, they were irradiated with 20 Gy at 907.7 Gy/h. Thereafter, each single male was crossed with 3 five-day old Basc virgin females, that were replaced every other day by new females. This procedure was conducted three times, to test the whole germ cell stages.Results: Females crossed with males irradiated with 0.2 Gy at both DR tested, laid a higher number of eggs than control, but egg-viability was reduced. On the other hand, in the group of 0.2 Gy + 20 Gy -combined treatments- the total number of eggs laid decreased only when 0.2 Gy were delivered at 34.3 Gy/h however, the egg-viability increased. The dose of 0.2 Gy at both DR did not modify the baseline frequency of SLRL. A tendency to decrease in the frequency of lethals in brood III was found in combined treatments at both DR.Conclusion: The fact that 0.2 Gy at 5.4 or 34.3 Gy/h induced an increase in the egg-viability and a tendency to decrease the genetic damage in pre-meiotic cells provoked by 20 Gy, might indicate the induction of any mechanism that could be interpreted as radioprotection in male germ cells of D. melanogaster. Results emphasize the need to carry out more studies on the effect of the DR on the induction of genetic damage in germ cells.

Growth rate assays reveal fitness consequences of ß-lactamases.

NON-TECHNICAL SUMMARY: Antibiotic resistance is a global human health problem. We partnered with Dignity Health Mercy Medical Center to study antibiotic resistance in clinical isolates. We tested whether growth rates, a sensitive assay used to measure the fitness of bacterial samples, correlate with a clinical test to measure antibiotic resistance. We found a strong correlation between these two methods suggesting that growth rates could be reliably applied to evolutionary studies of clinically relevant problems. Moreover, the sensitivity of the growth rates assay enabled us to identify fitness effects of specific antibiotic resistance genes.

Tratamiento multidisciplinario actual por etapas del síndrome de Paget-Schroetter: a propósito de 2 casos y revisión de la literatura / Current multidisciplinary treatment by stages of the Paget-Schroetter syndrome: in relation to 2 cases and review of the literatura

El síndrome de opérculo torácico se debe a la compresión de los vasos subclavios y/o plexo braquial. Puede ser de tipo neurológico (95%), venoso (< 4%) y arterial (1%). Se conoce como síndrome de Paget-Schroetter al síndrome de opérculo torácico que se asocia a trombosis de la vena subclavia, más común en la extremidad superior dominante y en pacientes jóvenes. El tratamiento de elección para el síndrome de Paget-Schroetter consiste en la trombólisis de la vena subclavia y en la resección de la primera costilla de forma temprana para descomprimir el paquete neurovascular subclavio, disminuyendo el riesgo de retrombosis o síntomas recurrentes. En este artículo describimos dos casos de tratamiento para el síndrome de Paget-Schroetter con resección por cirugía toracoscópica video asistida de la primera costilla y realizamos una revisión de la literatura al respecto

The thoracic outlet compression is due to the compression of the subclavian vessels and / or brachial plexus, which can be neurological (95%), venous (< 4%) and arterial (1%). Paget-Schroetter syndrome is when thoracic outlet compression is associated with subclavian vein thrombosis, being more common in the dominant upper limb and in young patients. The treatment of choice for Paget-Schroetter syndrome consists of thrombolysis of the subclavian vein and resection of the first rib early, to decompress the subclavian neurovascular bundle, decreasing the risk of rethrombosis or recurrent symptoms. In this article, we describe 2 cases of treatment for Paget-Schroetter syndrome with video-Assisted Thoracoscopic Surgery resection of the first rib, carrying out a review of the literature in this regard

Trehalose Mediated Inhibition of Lactate Dehydrogenase from Rabbit Muscle. The Application of Kramers' Theory in Enzyme Catalysis.

Lactate dehydrogenase (LDH) catalyzes the reduction of pyruvate to lactate by using NADH. LDH kinetics has been proposed to be dependent on the dynamics of a loop over the active site. Kramers' theory has been useful in the study of enzyme catalysis dependent on large structural dynamics. In this work, LDH kinetics was studied in the presence of trehalose and at different temperatures. In the absence of trehalose, temperature increase raised exponentially the LDH Vmax and revealed a sigmoid transition of Km toward a low-affinity state similar to protein unfolding. Notably, LDH Vmax diminished when in the presence of trehalose, while pyruvate affinity increased and the temperature-mediated binding site transition was hindered. The effect of trehalose on kcat was viscosity dependent as described by Kramers' theory since Vmax correlated inversely with the viscosity of the medium. As a result, activation energy ( Ea) for pyruvate reduction was dramatically increased by trehalose presence. This work provides experimental evidence that the dynamics of a structural component in LDH is essential for catalysis, i.e., the closing of the loop on the active site. While the trehalose mediated-increased of pyruvate affinity is proposed to be due to the compaction and/or increase of structural order at the binding site.

Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer.

BACKGROUND: Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response. RESULTS: Here we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV365 nm irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells. CONCLUSIONS: This work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer.