This article analyses the possibility of using fly ash from the combustion of wood–sunflower biomass in a fluidized bed boiler as an additive to concrete. The research shows that fly ash applied in an amount of 10–30% can be added as a sand substitute for the production of concrete, without reducing quality (compression strength and low-temperature resistance) compared to control concrete. The 28-day compressive strength of concrete with fly ash increases with the amount of ash added (up to 30%), giving a strength 28% higher than the control concrete sample. The addition of fly ash reduces the extent to which the compression strength of concrete is lowered after low-temperature resistance tests by 22–82%. The addition of fly ash in the range of 10–30% causes a slight increase in the water absorption of concrete. Concretes containing the addition of fly ash from biomass combustion do not have a negative environmental impact with respect to the leaching of heavy metal ions into the environment. The development of industry causes a systematic increase in the amount of generated waste. Some of the wastes produced, such as fly ashes and slags from the combustion of conventional fuels , are used to produce composite materials with a cement matrix, such as cement mortars or concretes ,7,8,9,10There have also been reports of the possibility of using fly ashes from the co-combustion of hard coal and biomass in conventional or fluidized bed boilers for this purpose. Mortars and concretes with the addition of such ash usually achieve similar or lower strength values after 28 days of maturation  is presented in Fly ash from the combustion process in a boiler with a circulating fluidized bed of biomass consisting of 80% waste wood and 20% sunflower was used for the research. Fly ash came from a power plant  in the Świętokrzyskie Voivodeship and was tested in accordance with PN EN 450 1:2012. Ash roasting losses amounted to 2.9%. According to the PN-EN 451-2:2017-06 standard, the fineness of the samples as a residue on the 0.045 mm sieve is 7.9%, and the fly ash density is 2.35 g/cmFly ash consists mainly of silicon oxide (50.2%), aluminium oxide (12%), calcium oxide (11.82%) and almost 8% potassium oxide. The remaining compounds constitute less than 4%, which traces include Zn, Ba, CR, Sr, Zr, Cu, Rb, Ni and Pb, among other materials. The microstructure of the fly ash used for the tests  is presented in The TGA-DTA thermal analysis was also conducted for the fly ash used in the research .3/min. Up to a temperature of approximately 100 °C, the fly ash sample lost approximately 0.3% weight, which is related to the evaporation of water. At a temperature of about 350 °C, a peak was noticeable, which may have resulted from the transformation of Fe compounds. The peak was seen at a temperature of about 580–600 °C and corresponded to the conversion of α-quartz to β-quartz and the reaction between unreacted particles and activator trapped in the pores. Decomposition of aluminum hydroxide (Al(OH)3) also took place in the same temperature range. At temperatures of 700 °C, endothermic or exothermic reactions occurred, which corresponded to the decomposition of CaCO3, Ti(OH)4 and Mg(OH)2. The exothermic effect at about 900 °C may be related to the crystallization of amorphous ash phases. Observed changes were similar to those presented in [The test was carried out in a Jupiter STA 449 F5  in the range from 30 to 1000 °C with a temperature increase rate of 10 °C/min in air with a gas flow rate of 100 cmTwo types of cements by CEMEX with high early strength were used for the tests: CEM I 42.5 R Portland cement and CEM II/A-V 42.5 R Portland ash cement.3 of concrete is presented in Two types of coarse aggregate, i.e., gravel and basalt, as well as one type of fine aggregate, which was arenaceous quartz, were used for concrete tests. The composition of the control concrete with a gravel–sand (B1-0) and sand–basalt (B2-0) mixture of aggregates and CEM I cement, as well as that of a gravel–sand mixture of aggregates and CEM II per 1 mSamples for the concrete mix tests were taken in accordance with the PN EN 12350 1:2011 standard. The air content in the concrete mixture was tested using the manometer method in accordance with the PN-EN 12350-7 standard.Compressive strength tests of concretes were conducted  on 12 cubic samples with a side of 150 mm in accordance with PN EN 12390-3. A constant load speed of 1.0 MPa/s was chosen. The load was applied to the specimen and continuously increased until the highest load was obtained. After the test, the testing machine, based on the entered dimensions of the sample, gave the compressive strength in MPa.Concrete water absorption was tested in accordance with PN B 06250:1988. The tests were performed on six cubic samples (each series) with sides of 150 mm. The samples were disassembled after 24 h and were kept in water for the next 7 days, and then the samples were kept in the air for 21 days. The tested concrete samples were placed in a vessel on a grate at a distance of 15 mm from the bottom of the vessel. After obtaining a constant mass, the samples were placed in a laboratory dryer and dried at 105 °C to a constant mass, i.e., until the next weighings showed differences below 0.2% of the mass of the samples. The water absorption by weight is defined as the ratio of the mass of water penetrating into the saturated material to its dry mass and is given as a percentage.The low-temperature resistance of concrete was tested on the basis of the PN-B-06250:1988 standard using a Toropol K-010 chamber . 12 samples with a side of 100 mm were taken from each series of concretes. Samples saturated with water were weighed and then subjected to frost resistance testing. Six samples were left in water at 18 ± 2 °C throughout the test, and the remaining six were wiped of water and weighed with an accuracy of 0.2%. These concrete samples were frozen in air at (−18 ± 2 °C) for 4 h and then thawed in water (at +18 ± 2 °C), also for 4 h. After 150 cycles of freezing and thawing the samples were reweighed and subjected to a compressive strength test.Penetration of concrete with water under pressure was tested on the basis of the PN EN 12390-8 standard with the RatioTec WU60M apparatus , and three cubic samples with sides of 150 mm for each series were used for the tests. A water pressure of 500 kPa was applied to the samples for 72 h. After this time, the samples were taken out of the device and split in half. After the fracture surface had dried to a visible range of water, the maximum depth of water penetration was measured with an accuracy of 1 mm.3 to 1 kg. The closed vessel was placed in a mixing device (roller table) for 24 ± 0.5 h. The vessel was then allowed to sit for 15 ± 5 min to allow the suspension to settle. The effluent was filtered through a membrane filter with a pore diameter of 0.045 µm. The concentrations of selected metal ions were determined by induction plasma atomic emission spectrophotometry (with an ICP-AES spectrometer) and the effluent pH was determined. Two samples were tested from the selected series.As part of the tests, a leaching analysis was also conducted based on the PN-EN-12457-2:2006 standard. For the test, samples containing 95% of grains smaller than 4 mm were prepared. For this purpose, the concrete samples were crushed in a jaw crusher and passed through a sieve with a mesh size of 4 mm. From the sample prepared in this way, an analytical sample (S) weighing 0.090 ± 0.005 kg was taken and placed in a vessel (bottle), and then distilled water (L) with electrical conductivity of 0.45 mS/m in the amount of 0.9 dm3 was added to it. According to the standard, the ratio of the washing liquid (L) to the solid phase (S) should be 10 dmDuring the preparation of concrete mixes, samples were taken to test the consistency as well as the air content in the mixes. The fall of the cone for the B1-0 control concrete mix was 145 mm, which qualifies it as belonging to the S3 consistency class. The air content in this concrete mix was 3.4%. B1 concrete mixes containing fly ash used as part of the sand were denser than the B1-0 mix. The air content in the concrete mix decreased with the increase of the amount of added ash and amounted to 2.7% for the B1 mix containing 30% ash . Mixes wThe concrete samples shaped into cubes with side dimensions of 150 mm were tested for compressive strength after 7, 28 and 56 days. After 7 days, the control concrete (B1-0) was marked by a compressive strength of 43.4 MPa. B1-0 concrete was the control concrete for the B1 series samples. All the concretes in the series with the addition of fly ash from biomass combustion in a fluidized bed boiler in the amounts of 10%, 20% and 30% of the weight of cement used instead of sand showed higher compressive strength after 7 days compared to the corresponding control concretes without the addition of ash .B1 series concretes with a sand–gravel mixture of aggregates containing up to 30% ash additive achieved a higher average compressive strength than the control concrete. The highest compressive strength was achieved by B1-3 concretes containing 30% fly ash and it was approximately 24% higher than the strength obtained with the sample from the control series (B1-0). On the other hand, the addition of ash in the amount of 40% caused a decrease in the compressive strength of the tested concretes by approximately 3% compared to the control concrete. The compressive strength results for B2 series concretes with a basalt–sand mixture of aggregates and the addition of fly ash obtained after 7 days confirmed the tendency observed for the B1 series concretes. The increase in strength for the B2-3 series was 45% compared to the B2-0 control concrete. For concrete samples of the B3 series, in which fly ash was used as an additive to concrete made on the basis of CEM II/A-V 42.5 R cement, the highest compressive strength was also obtained by samples containing 30% fly ash, achieving an average compressive strength 28% higher than the B3-0 control series. The addition of fly ash from biomass increased the compressive strength of concrete from 12% to over 45%. The smallest standard deviation for samples tested after 7 days was 0.55 for samples from series B2-0 and the highest was 1.79 for samples from series B3-3.Compressive strength tests were also conducted for concrete samples after the standard time of 28 days of maturation. The control concrete (B1-0) with a sand–gravel mixture of aggregates obtained an average compressive strength of 49.7 MPa, while all concretes with the addition of fly ash in the amounts of 10%, 20%, 30% and 40% obtained higher compressive strength results than the control concrete .The highest value of compressive strength was achieved by B1-3 concrete series with the addition of 30% fly ash as a substitute for part of the sand. As shown in the figure, the ash content at the level of 30% of the cement mass is the limit, leading to an increase in the compressive strength of concrete; higher amounts of added ash caused a decrease in the value of this parameter. The obtained test results for the B2 and B3 concrete series showed a similar tendency to concrete samples from the B1 series and increased this parameter by approximately 28%. The smallest standard deviation for samples tested after 28 days was 0.65 for samples from series B2-3 and the highest was 1.72 for samples from series B3-1.Compressive strength tests of concretes after 56 days of maturation were also conducted . At thisAnother property of the concretes tested was their water absorption, which was determined in accordance with the PN-B-06250 standard. Cubic samples with a side of 150 mm were prepared for the test. In the case of the B1-0 control concrete, the water absorption of the samples was 4.6%. The B1 series concretes, in which the fly ash from biomass combustion was added, showed a slightly higher water absorption, which increased along with the increase in the amount of added ash .The B2 series concretes also showed an increase in water absorption along with the increase of the added ash, however, the difference between the control concrete and the concrete containing 30% ash added was only 0.35%. The water absorption of B3 series concretes, in which CEM II ash cement was used, was higher than in the case of concretes made with CEM I cement. Additionally, in these series of concretes, an increase in the water absorption of the tested concretes was observed along with an increase in the amount of added ash. The water absorption of concrete should not exceed 5% in the case of concretes directly exposed to atmospheric conditions and 9% in the case of concretes sheltered from direct atmospheric conditions. According to these guidelines, the B1-0 control concrete and all B1 and B2 series concretes could be used outside, while the B3 series concretes could be used inside. The smallest standard deviation for samples was 0.03 for samples from series B1-0 and the highest was 0.11 for samples from series B3-0.Low-temperature resistance tests of synthesized concretes were also conducted in accordance with the PN-B-06250:1988 standard. Closed pores play a key role in this, as they increase the resistance of concrete to freeze–thaw cycles. During freezing, ice is formed in open capillaries and the volume of the ice increases, the frozen water creating high hydrodynamic pressure and internal stresses. The decrease in compression strength in the control concretes after the freeze–thaw cycles was less than 19% .In the case of the B1 series of concretes containing the addition of 10%, 20%, 30% and 40% of fly ash, a decrease in compressive strength was obtained by 12.5%, 10%, 8% and 9%, respectively. An addition of 30% fly ash can be considered optimal, due to this proportion being associated the lowest strength drop. All B1 series concrete samples had no visible damage or cracks after visual inspection. The low-temperature resistance test did not cause a large loss of mass, which was in the range of 0.01–0.03%. The B2 series concretes, in which crushed basalt aggregate was used, showed even smaller drops in compression strength after low-temperature resistance tests than the B1 series concretes. The addition of 30% of ash reduced the decrease in compression strength to a value of only 1.8%. The B3 series concretes also had no visible damage or cracks, and in all samples the use of fly ash was associated with a lower decrease in compression strength after low-temperature resistance tests. The best result was obtained for the concrete containing 30% of fly ash (strength decrease approximately 8.5%). To sum up, on the basis of the obtained test results, it can be concluded that the use of ashes from the combustion of wood–sunflower biomass in a fluidized bed boiler as substitutes for a part of the sand content in concrete reduces the decrease in the compression strength of concrete after low-temperature resistance tests. In each series of concrete containing ash, the decrease in compression strength was lower than for the control concrete. This addition reduced the decrease in compression strength by up to 80% compared to the control samples.The B1-0 control concrete, influenced by water pressure, obtained an average water penetration depth of 42 mm . The B1 The test for the leaching of metal ions from concrete was conducted in accordance with the PN EN 12457 2:2006 standard. The leaching test was performed only for the control concrete (B1-0) and for concretes produced with the addition of fly ash in the amount of 30% of the cement mass (samples from the B1-3 series), assuming that the highest content in the eluate will occur for them. Two determinations were made for the tested concrete, maintaining the ratio of the volume of the liquid phase (L) to the mass of the solid phase (S) equal to 10:1. Calculations were made according to the standard assuming no moisture in the samples. After the process of leaching ions from the B1-0 control concrete, the pH of the solution was 10.10, while in the case of B1-3 concretes it was 9.67. The data presented in The tests were performed on broken surfaces of concrete samples. EDS analysis of the concrete surface performed in the area visible in the photo showed, apart from the presence of calcium , a significant content of silicon , aluminium  and iron . Sodium (1.56%) and potassium (0.39%) are present in lesser amounts. The remaining components  are present in a small amount (less than 0.7%). In the case of the B1-3 concrete samples containing 30% fly ash from biomass combustion, microscopic photos show a very similar structure to concrete without the addition of ash, which results from very fine granulation of the ash. The aggregate grains distributed evenly in the concrete are also clearly visible in these concretes. EDS analysis of the B1-3 concrete surface confirmed similar amounts of elements compared to the control concrete. In the B2-0 control concrete, in which sand was used as fine aggregate and a basalt mixture as coarse aggregate, microscopic photos showed basalt grains with irregular and sharp edges and the present fine aggregate with oval shapes; the largest share in the chemical composition is calcium (18.91%) and silicon (18.36%). In the case of the B2-3 concrete with 30% ash added, coarse basalt aggregate and quartz sand are also visible, and in terms of chemical composition, ash-free concrete (B2-0 series) and concrete with 30% fly ash added (B2-3 series) do not differ significantly from each other. The analysis of the B3 series surfaces showed that the microstructure of the B3-0 concrete, made on the basis of CEM II cement, has a very similar microstructure and appearance to the B1-0 concrete made on the basis of CEM I cement. The B3-3 concrete containing 30% fly ash under the microscope did not differ noticeably in structure from the B3-0 concrete. The EDS analysis of the B3-0 series concrete surfaces made on the basis of CEM II ash cement is also marked by a similar chemical composition. This concrete consists of approximately 23% calcium and 17% silicon, and similar results were obtained for samples with the addition of the B3-3 ash. The obtained results are not very precise guides, as only a few measuring points on the surface were anyalysed. In addition, the concrete structure is not homogenous throughout the sample volume. However, it can be concluded that non-destructive research methods using modern techniques for testing material structures are a way to effectively assess the impact of structure on the strength of concrete.The conducted tests of the properties and structure of composite materials with a cement matrix containing waste fluidized ashes from the combustion of wood–sunflower biomass (in the proportion of 80% wood waste and 20% sunflower waste) and the analysis of the obtained results enabled the conclusion that this ash, in the amount of 10% and up to 30%, can be added as a sand replacement for the production of composite materials with a cement matrix, such as concretes (made on the basis of CEM I or CEM II/A-V 42.5R cement), without reducing their quality (compression strength and low-temperature resistance) in relation to materials produced without the addition of waste ash.The microstructure of concretes made on the basis of CEM I 42.5R cement containing fly ash from biomass combustion in the amount of 10–30% is marked by a microstructure very similar to the control concrete made without the addition of waste ash.The addition of fly ash in the amount of 10–30% causes the concrete mix to condense and reduce its air content. The compression strength of concrete samples with sand–gravel and sand–basalt mixtures of aggregates made with the tested additive is higher than that obtained for the control samples.The use of fly ash in the range of 10–30% causes a slight increase in the water absorption of concrete samples made with both sand–gravel and sand–basalt mixes of aggregates. The addition of waste ashes increases the depth of water penetration of the samples of all tested concrete series.The addition of fly ash from biomass to concretes in amounts up to 30% reduces the decrease in compression strength of these concretes after low-temperature resistance tests and does not cause the formation of fragments, cracks and defects in the sample. In addition, concrete composites containing the addition of ash from biomass combustion, taking into account the crack of the composite and the penetration of water, do not show a negative impact on the natural environment related to the leaching (release) of heavy metals into the environment.3, i.e., by about 15–20%.The use of waste ash has a positive effect on the natural environment by reducing the demand for natural resources. The use of fly ash in the amount of 30% of the cement mass as a sand substitute, depending on the type of aggregate mixture, reduces sand usage by 115–120 kg/mThe use of fly ash from the wood–sunflower biomass combustion process in a circulating fluidized bed boiler for the production of building materials is a desirable solution in terms of sustainable construction.


Immunotherapy with immune checkpoint inhibitors has recently brought a paradigm shift in the treatment of non-small cell lung cancer (NSCLC), but until now, most clinical benefits of immunotherapy have been demonstrated in the setting of advanced or metastatic disease. However, there has been a recent explosion in trial development and research focus exploring whether the benefits of immunotherapy can extend to the neoadjuvant setting for patients with resectable NSCLC. The aim of this review is to thoroughly outline the preclinical rationale for neoadjuvant immunotherapy research. In addition, we summarize and analyze the published interim results as well as results presented at major conferences from the initial early phase trials. An overview of the current and upcoming randomized clinical trials in this field is also provided. Finally, we highlight future challenges and questions that need to be addressed in upcoming research to clarify the role of neoadjuvant immunotherapy in the treatment of NSCLC.While lung cancer remains the leading cause of cancer death worldwide, lung cancer mortality has notably decreased in the past decade. Immunotherapy with immune checkpoint inhibitors have played a noteworthy role in contributing to this improved survival, particularly for patients with non-small cell lung cancer (NSCLC). However, until now the benefits have primarily been seen in patients with advanced or metastatic disease. Several recent early phase and ongoing phase III trials have been assessing whether the treatment benefit of immunotherapy in NSCLC can extend to the neoadjuvant setting for resectable diseases. In this comprehensive narrative review, we evaluate the most recent efficacy and safety data from these studies. We also outline questions that will need to be further examined to legitimate neoadjuvant immunotherapy’s role in NSCLC treatment, including the best surrogate marker of response, the incorporation of liquid biopsy for disease monitoring, the ability to be combined with other treatment modalities, the need for further adjuvant therapy, and potential future treatment combinations. Lung cancer continues to be the leading cause of cancer-associated death worldwide . In the The references to complete this review were identified by literature search utilizing databases including PubMed, Google Scholar, and Clinical Key. Abstracts from major clinical conferences including the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer, American Association for Cancer Research, European Society for Medical Oncology, and American Society of Clinical Oncology were also included. Included articles and abstracts were from database inception to 1 November 2021. The literature search was performed using the following search terms: (1) neoadjuvant, (2) immunotherapy, (3) resectable lung cancer, (4) non-small cell lung cancer, (5) checkpoint inhibitors. Only articles and abstracts published in English were included in this review. The results of various trials and studies accordingly were summarized narratively.Neoadjuvant therapy is a treatment approach that has been practiced in oncologic care for over fifty years. It comprises any form of treatment—chemotherapy, radiation therapy, endocrine therapy, or immunotherapy—that is given for cancer before the definitive treatment with curative intent, usually surgery, is conducted. A key advantage for neoadjuvant therapy is providing treatment at the earliest opportunity to minimize the chance for micrometastases to grow when patients receive and recover from local therapy . It alsoAs early as 1956, neoadjuvant therapy was proposed for the treatment of choriocarcinoma . PeriopeImmunotherapies with immune checkpoint inhibitors targeting the interaction of programmed death 1 (PD-1) with its ligands PD-L1 and PD-L2 or the cytotoxic T lymphocyte–associated protein 4 (CTLA-4) pathway, have recently become vital treatment components for a variety of malignancies. While immunotherapy’s initial key clinical benefits and tumor activity were seen in the metastatic setting, burgeoning research attention is now being placed in exploring these agents for benefits in the neoadjuvant setting.The preclinical rationale for evaluating neoadjuvant immunotherapy is varied. Neoadjuvant chemotherapy is thought to primarily decrease or debulk tumors preoperatively, but neoadjuvant immunotherapy may better target and eliminate micrometastatic disease and the subsequent chance of recurrence by enhancing systemic immunity against tumor antigens ,18. TherThese hypotheses have been tested in several preclinical studies. Liu et al. utilized two spontaneously metastasizing transplantable mouse breast cancer models, in which various combination immunotherapies were administered in either a neoadjuvant or adjuvant setting before or after primary tumor resection . They suConsequently, the authors suggested blood sampling for tumor-specific CD8+ T-cells before and after surgery may provide a predictive biomarker from neoadjuvant immunotherapy ,18,19. ONSCLC is a particular malignancy that has seen an explosion of recent trials as well as ongoing trials evaluating neoadjuvant immunotherapy whether alone or in combination with chemotherapy. Forde et al. conducted the first of these early phase trials . This siGao et al. conducted a single-center, single-arm, phase 1b study that evaluated the administration of two doses of weekly sintilimab, a PD-1 inhibitor approved in the People’s Republic of China, as neoadjuvant treatment in 40 enrolled patients with stage IA to IIIB NSCLC . PrimaryThe Lung Cancer Mutation Consortium 3 (LCMC3) trial is the largest monotherapy trial of immunotherapy in resectable NSCLC ,26. It iThe first interim analysis for the NEOMUN trial were also recently reported . This inA neoadjuvant immunotherapy trial that was recently presented at the ESMO Virtual Congress 2020 was the IONESCO trial. This phase II trial analyzed the administration of neoadjuvant durvalumab, 750 mg, for 3 courses  prior to surgical resection, which followed between 2 to 14 days after their last durvalumab infusion, in patients with stage IB (tumor > 4 cm)-IIIA resectable NSCLC. Fifty patients were enrolled in the study with 46 receiving surgical resection. The primary endpoint was the rate of complete surgical resection (R0), with secondary endpoints including MPR, overall survival (OS), and disease-free survival (DFS). Forty-one patients (90%) were seen to achieve R0, with MPR 18.6% and pCR 7%, but enrollment for this study was stopped prematurely due excess in 90-day postoperative mortality with 4 deaths (9%) observed. However, the authors of the study did not attribute any of these deaths to durvalumab toxicities, but rather they were thought to be due to pre-existing comorbidities highlighting the importance of caution with comorbidities in neoadjuvant immunotherapy trials [The ESMO Virtual Congress 2020 also showcased the interim results of the PRINCEPS trial . In thisAbove mentioned neoadjuvant studies using single agent anti-PD-1/L1 are summarized in To further explore the potential for neoadjuvant immunotherapy in NSCLC, trials are being conducted that analyze the effect of immune checkpoint inhibitor combinations. The NEOSTAR study is a Phase II randomized clinical trial that evaluated two parallel, randomized arms, with arm A utilizing neoadjuvant nivolumab  and arm B utilizing a combination of neoadjuvant nivolumab and ipilimumab  for resectable stage IA to IIIA NSCLC . This siReuss et al., also performed a multicenter, open-label, single-arm phase Ib/II study evaluating combination immunotherapy for patients with resectable Stage IB (≥4 cm)–IIIA NSCLC . EnrolleBased off the initial promising results from neoadjuvant immunotherapy trials in NSCLC, researchers have begun developing trials to examine whether the benefits of immunotherapy can be enhanced through its concurrent use with other neoadjuvant modalities such as chemotherapy, radiotherapy, or novel agents. Neoadjuvant chemoimmunotherapy is a combined treatment approach that has several current reported results, which are outlined in Upon review, it appears that the combination of neoadjuvant immunotherapy and chemotherapy may lead to increased antitumor activity as increased MPR and pCR rates, ranging from 27–86% and 9–63%, respectively, are seen in most of these trials in comparison to MPR and pCR rates with solely immunotherapy, ranging from 12–50% and 0–38% ,42,43,44p < 0.0001). The observed improvement in pCR was observed across all major subgroups including disease stage  and PD-L1 status . MPR rates were also significantly improved with nivolumab + chemotherapy (36.9% vs. 8.9%) [One such current phase III trial evaluating between neoadjuvant immunotherapy and neoadjuvant chemoimmunotherapy is the Checkmate-816 trial (NCT02998528). While initial reported results from this trial focused on evaluating between neoadjuvant nivolumab plus platinum-doublet chemotherapy and neoadjuvant platinum-doublet alone, another experimental arm of this study is looking at neoadjuvant combination immunotherapy with nivolumab plus ipilimumab. These initial reported results showed that the study’s first primary endpoint was achieved as the addition of nivolumab to a platinum-doublet chemotherapy preoperatively produced a decisively significant increased pCR rate compared to platinum doublet chemotherapy alone, in the intention to treat the population (ITT) at 24.0% vs. 2.2%  ,39.Radiotherapy is another treatment modality that is suggested and currently being evaluated to be a potent partner to immunotherapy in the neoadjuvant setting. This combination is believed to be potentially efficacious as immunotherapy has been hypothesized to accentuate the abscopal effect of radiotherapy, which is its ability to generate immune-mediated anti-tumor effects leading to deterioration of non-irradiated metastases that are distant from the primary irradiated site ,46,47.Altorki et al. recently reported data of a single-center, randomized, controlled, phase 2 trial, comparing neoadjuvant durvalumab alone with neoadjuvant durvalumab plus stereotactic radiotherapy in patients with resectable NSCLC . Sixty eAnother notable clinical question regarding neoadjuvant immunotherapy treatment is whether further immunotherapy in the adjuvant setting is needed, especially for those patients who have achieved pCR. It has not yet been determined if further adjuvant immunotherapy helps better eradicate micrometastatic disease or simply leads to increased treatment toxicity. Most of the major current phase III trials evaluating neoadjuvant chemoimmunotherapy, as outlined in In the clinical evaluation of neoadjuvant therapy, the ultimate goal is to demonstrate improved survival over that attained by adjuvant therapy. Consequently, overall survival (OS) should be the vital end point in neoadjuvant trials including those with neoadjuvant immunotherapy. However, determining OS can be a quite lengthy and difficult process, especially for neoadjuvant treatment, due to the amount of observed time and the large number of patients needed to ascertain differences in survival. These problems can lead to delays in conducting later stage trials, as well as the development of new therapies. Thus, researchers have recognized the significance of identifying surrogate markers that can be determined in a timely fashion, as well as accurately predict OS.Disease free survival (DFS) has been one such surrogate marker that has been utilized for other malignancies, such as breast cancer or colorectal cancer ,50. HoweAs a result, evaluations of pathologic responses to neoadjuvant therapy have been the focus of most recent trials as they can be discerned at the time of surgery. pCR, defined by the absence of residual invasive and in situ cancer in a resected specimen and all sampled lymph nodes on hematoxylin and eosin evaluation after neoadjuvant systemic treatment, has been seen as appropriate surrogate marker for OS in NSCLC ,55,56. USeveral studies have suggested that MPR after neoadjuvant therapy may reliably predict OS in NSCLC ,57,58,59To further consider the potential for mechanism-focused biomarkers as surrogate end points, recent research has focused on analyzing circulating tumor DNA (ctDNA) though liquid biopsy as a future predictor for recurrence and OS. ctDNA is DNA released from damaged or apoptotic tumor cells present in blood plasma. There are several malignancies, in particular colorectal cancer and hematological malignancies, that have an observed presence of ctDNA, correlating with an increased risk of recurrence ,63,64. HCheckmate-816 is another recent prospective trial that evaluated the potential relationship between ctDNA and clinical response. In this study, ctDNA analyses were performed on plasma samples collected on day 1 before each of the 3 planned treatment cycles. The rate of ctDNA clearance was the primary component examined, which was defined as change from detectable levels of ctDNA at cycle 1 to undetectable ctDNA at cycle 3. An exploratory subset analysis revealed a notably higher ctDNA clearance rate was seen in the nivolumab plus chemotherapy group versus chemotherapy alone, at 56% to 34%. This corresponded with the increased pCR and objective response rate observed with nivolumab plus chemotherapy .The results of the Checkmate-816 trial appear to further demonstrate the need for additional research focused on evaluating ctDNA as a potential response biomarker for neoadjuvant immunotherapy. It may also be important to look into the dynamic change of ctDNA at different time points during and after neoadjuvant treatment. In addition, the potential value of integrating immune biomarkers such as peripheral blood and/or intratumoral immune cell repertoire and cytokine levels, as well as gut and intratumoral microbiomes, may also need to be explored.Immunotherapy with immune checkpoint inhibitors has proven to be a novel integral component of NSCLC care in recent years. To further identify the scope of immunotherapy’s clinical utility, a significant number of recent and current trials are exploring if immunotherapy’s benefits can extend to the neoadjuvant setting for resectable NSCLC. The initial results of preclinical and early phase trials suggest further research focus to this treatment approach is warranted by exhibiting the safety, feasibility, and versatility of neoadjuvant immunotherapy. Neoadjuvant immunotherapy additionally has been seen to be a rather potent tumor debulking agent in these studies with MPRs ranging up to 45% when used alone, and even higher, up to around 80–85%, when used in conjunction with chemotherapy.2 = 73%) of patients who underwent surgery following neoadjuvant immunotherapy achieved MPR, 24%  achieved pCR of the primary lesion, and 20%  achieved pCR of both the primary lesion as well as sampled lymph nodes. With this finding, Cao et al., prudently recognized that there were discrepancies in how trials reported endpoints of MPR and pCR, with only some of the trials addressing whether the resected lymph nodes were also assessed. The variations in endpoint reporting from these trials compromises the ability to assess clinical outcomes from neoadjuvant immunotherapy and should be standardized in future studies.As more and more data have recently been reported from neoadjuvant immunotherapy trials, it will be important to analyze the major trends and associations within these results to better identify future research needs. Cao et al. recently helped address this need by conducting a systemic review and meta-analysis of sixteen studies with eighteen publications evaluating neoadjuvant immunotherapy in resectable NSCLC . The revAnother key discovery from the meta-analysis is that neoadjuvant immunotherapy appears to be safe and feasible, as 96% of patients received intended surgery after systemic neoadjuvant treatment, mortality within 30 days of surgical resection was 0.6%, and only 2.0% of patients were delayed from their intended time of operation after treatment with neoadjuvant immunotherapy. Surgical morbidities within the analysis were also seen to be similar to studies evaluating thoracic resections without neoadjuvant immunotherapy ,67.Several crucial questions and challenges remain that still need to be addressed before neoadjuvant immunotherapy can be regarded as a recommended treatment strategy. The ideal administration of neoadjuvant immunotherapy is still yet to be determined, including the optimal patient population for the consideration of a single agent immune checkpoint inhibitor vs. combination therapy, the number of preoperative cycles needed, and timing with respect to surgery. Surgical procedures have been noted to be more challenging after neoadjuvant immunotherapy, with increased adhesions and fibrosis in surgical fields observed ,44. ThusA review of the initial trials with neoadjuvant immunotherapy highlights several limitations of these studies that need to be considered and addressed in future trials. There is much heterogeneity in the patient populations, trial designs, types of immunotherapy provided, and endpoints evaluated in early phase trials within this field. This heterogeneity limits the ability to compare results across trials and develop improved future studies. More collaboration is needed amongst investigators to identify common standards necessary for trials to enable greater focus on their intended variables and increase external validity.The significant heterogeneity of these trials also limits the ability to form reliable conclusions in this review. The risk of biases in this review is recognized, particularly publication bias as most of the studies included were those which reported preliminary results. Therefore, revisions and updates to this review will be needed as further data from these trials are published.Despite the challenges and limitations noted, the promising results from the early clinical trials with neoadjuvant immunotherapy demonstrate that it is a safe and feasible approach that merits further study. The use of neoadjuvant immunotherapy alone or in combination with other therapies may soon revolutionize the standard of care for resectable NSCLC, such as the Checkmate 816 regimen. Consequently, the results of ongoing randomized trials to determine if and how this novel approach can be utilized optimally to treat NSCLC patients are eagerly awaited.


Background/Aim: Macrophage polarization and phenotypic switching of smooth muscle cells (SMCs) are multi-faceted events dominating atherosclerosis (AS) progression. TGF-β was proved to been one of the bridge on the crosstalk between macrophage and SMC. ShenLian (SL) was extracted from a potent anti-atherosclerotic formula. However, its exact mechanism rebalancing inflammatory microenvironment of AS remain largely unknown. Within the entirety of macrophage and SMC, this study investigated the pharmacological effects of SL on stabilizing atherosclerotic plaques.Methods: The main components of SL were examined by high performance liquid chromatography. Co-culture and conditioned medium models of macrophage/SMC interactions were designed to identify the relationship between macrophage polarization and switching of SMC phenotypes. Flow cytometry, immunofluorescent staining, RT-PCR, western blotting, and ELISA were used to determine the expression of molecules relating to AS progression. An atherosclerosis animal model, established by placing a perivascular collar on the right common carotid artery in ApoE−/− mice, was used to investigate whether TGF-β is the key molecular mediator of SL in crosstalk between macrophage and SMC. Plaque size was defined by nuclear magnetic resonance imaging. Key markers related to phenotypic transformation of macrophage and SMC were determined by immunohistochemical staining.Results: Results revealed that, accompanied by rebalanced M2 macrophage polarization, SL supported SMC phenotypic transformation and functionally reconstruct the ECM of plaques specifically in macrophage-SMC co-cultural model. Molecularly, such activity of SL closely related to the activation of STAT3/SOCS3 pathway. Furthermore, in co-culture system, up-regulation of α-SMA induced by SL could neutralized by 1D11, a TGF-β neutralizing antibody, indicating that SL mediated Macrophage-SMC communication by enhancing TGF-β. In the AS model constructed by ApoE−/− mice, effects of SL on phenotypic transformation of macrophage and SMC has been well verified. Specific blocking of TGF-β largely attenuated the aforementioned effects of SL.Conclusion: Our findings highlighted that TGF-β might be the responsive factor of SL within macrophage and SMC communication. This study revealed that crosstalk between macrophage and SMC forms a holistic entirety promoting atherosclerotic plaque stability. Cardiovascular diseases (CVDs) caused by atherosclerosis (AS) are the top-ranking global disease in terms of annual mortality . During As the main cellular component of the plaque fibrous cap, SMC often show a physiological trend to adopt a contractile phenotype, thus leading to normal vasoconstrictive activity . HoweverMacrophage is involved in all stages of AS and perform a dual role in that they can regulate both anti- and pro-inflammatory signals . M1 macrSalvia miltiorrhiza Bunge and Andrographis paniculata which are the fully proved anti-atherosclerotic TCM formula  considers atherosclerosis as the“chest bi-impediment” or “cardiac pain” induced by “Blood Heat” and “Blood Stasis” . After A formula . Salvia d stasis . Androgrof blood . These fof blood . In our of blood . Notablystration . Modern stration . This stSalvia miltiorrhiza Bunge and Andrographis paniculata were obtained from Beijing Tongrentang Co., Ltd. The taxonomic authenticity was identified by Professor Xirong He, who worked in the Institute of Chinese Materia Medica of the China Academy of Chinese Medical Sciences. The SL extract is composed of Salvia miltiorrhiza Bunge extract and Andrographis paniculata extract at a ratio of 15:9. The Salvia miltiorrhiza Bunge extract included two components, one extracted with ethanol (EtOH) under percolation and was then concentrated under reduced pressure, and the other was prepared by soaking in dilute EtOH, and purified using macroporous resins SP825. The Andrographis paniculata extract was prepared by soaking in dilute EtOH, and purified using macroporous resins SP825. The extraction rates of the water-soluble partial extract of Salvia miltiorrhiza Bunge was 2.27% and that of the fat-soluble extract was 1.31%. The extraction rate of Andrographis paniculata was 2.11%. The components from SL extract were Tanshinone IIA (3%), salvianolic acid B (38%), and andrographolide (20%) and were detected by HPLC ( by HPLC .Rosuvastatin(P), as positive control drug, was purchased from AstraZeneca Pharmaceuticals (China) Co., Ltd. Phorbol-12-myristate-13-acetate (PMA) was obtained from Beijing Solarbio Technology Co., Ltd. Oxidized low density lipoprotein (ox-LDL) was purchased from Shenzhen Angyubio Co., Ltd. JSI-124 (Cucurbitacin I hydrate), the JAK2/STAT3 blocker, was purchased from Sigma Co., Ltd. (United States). 1D11, a murine antibody that neutralizes all three major active TGF-β isoforms, was also provided by Genzyme .−/− mice , and male C57BL/6 J mice  were purchased from HFK Bioscience Co. . All mice were housed under specific pathogen-free conditions. The animal experiments were performed in accordance with the Guidelines for the Care and Use of Laboratory Animals and were approved by the local Laboratory Animal Ethics Committee of the Institute of Chinese Materia Medica of the China Academy of Chinese Medical Sciences . All mice were allowed to acclimatize with a standard laboratory diet for 1 week.Male ApoE−/− mice. Meanwhile, the right common carotid artery of the control C57BL/6 J mice were isolated without positioning the constrictive collar. All mice were anesthetized by peritoneal injection of pentobarbital sodium (at a dose of 50 mg kg−1) during surgery.The atherosclerotic model was established using perivascular constrictive silastic collars (0.3 mm in the inner diameter) that were positioned on the right carotid arteries of ApoE−/− mice were randomly divided by weight into six groups (10 mice/group). Each group was treated orally: the model group (0.5% carboxymethylcellulose sodium); positive control ; SL extract low, medium, and high groups ; the TGF-β blocking group ; and the combination group . Based on the pharmacodynamics study results in our previous studies, we chose 95, 190, 380 mg kg−1 d−1 as the low, medium, and high doses  was chosen as a positive control drug because it is a commonly used anti-atherosclerotic drug , and penicillin (100 units ml−1) and incubated at 37°C in a 5% CO2 atmosphere.The human acute monocytic leukemia cell line THP-1 obtained from the American Type Culture Collection (United States) was cultured in RPMI 1640. The mice monocytic macrophage cell line RAW264.7 was purchased from China Infrastructure of Cell Line Resource (China) and human aortic smooth muscle cells  were cultured in DMEM, supplemented with 10% of FBS, 1% L-glutamine, streptomycin (100 μg ml6·per well) were seeded into six-well plates with 1 ml fresh medium and washed three times with PBS before treatment.Three days before the extraction of peritoneal macrophage, 8-week-old C57BL/6 J mice were injected with 1 ml of 3% thioglycolate medium . Peritoneal macrophage was isolated by washing the peritoneal cavity with endotoxin-free phosphate buffered saline  and cultured at 37°C in 5% CO2 in RPMI 1640 medium supplemented by 10% fetal bovine serum . Peritoneal macrophage cells  to induce their differentiation to mature macrophage. After full induction, the differentiated cells can adhere onto the upper chamber for the subsequent experiments.1) THP-1 culture: THP-1 cells were cultured in 24-well plates with the permeable support basket  and stimulated with PMA (50 μg ml2) HVASMC culture: HVASMC cells were seeded in 24-well plates and cultured for 24 h.3) Establishment of the co-culture system: the co-culture system was established 24 h after seeding by transferring the upper basket was lined with differentiated Thp1 cells into the wells containing HVASMC.−1) was added to the co-culture medium for 24 h in the absence or presence of ox-LDL (10 μg ml−1), and then the drug-containing medium was totally removed and replaced with the fresh medium (SL-free medium).4) Drug treatment: After the co-culture system were successfully established, the SL extract  and treated with SL  for 24 h in the absence or presence of ox-LDL (10 μg ml−1). Next, the SL-containing medium was replaced with fresh medium (SL-free medium) for 24 h and then transferred to the HVASMC plates. The SL-free medium and HVASMC ware collected for detection of indicators.To exclude the direct influence of SL on SMC, the conditional medium transfer model was established as The cells were collected by cell scraper and fixed with 100% methanol (5 min), and then incubated in 3% FBS in 0.1% PBS-Tween 20 for 1 h to permeabilize the cells and to block non-specific protein-protein interactions followed by the antibody  for 1 h at room temperature. The secondary antibody used was Fluorescein (FITC)-conjugated IgG (H + L)  at 1:500 dilution for 30 min at room temperature. After staining, the cells were analyzed with a CD206+gate by flow cytometry .As described previously , total pThe cytokines TGF-β, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β concentration from culture supernatants samples were measured by the enzyme-linked immunosorbent assay (ELISA)  method. The TNF-α, IL-1β, and TGF-β ELISA kits performed in this study were “Sandwich” kits which possess potent capacity for quantitatively measuring TNF-α, IL-1β, and TGF-β present in serum and culture media. The manufacturer’s instructions were precisely followed. The concentration of the target molecules in the sample was calculated, after making suitable correction for dilution, according to their standard curve.As described previously , mRNA leNuclear magnetic resonance (NMR) plays a significant role in the study of experimental atherosclerosis which can effectively assess luminal narrowing . In our The samples to be subjected to Sirius red staining and immunohistochemistry (IHC) included the RCA within 1 cm . RCAs were fixed in 4% paraformaldehyde (pH 7.0–7.4) and then sliced into 4 μm sections for pathological evaluation. Sirius red staining  was performed according to the manufacture’s instruction for collagen staining of vascular plaque fibrous cap. Images were collected by an optical microscope graphic analysis system . Quantification of collagen was determined with ImageJ 1.4u  of Sirius red staining to that of the aorta.RCAs were sliced into 4 μm paraffin sections for pathological evaluation. Samples for IHC were subjected to heat-induced epitope retrieval and incubated with corresponding antibodies including CD86 , CD206 , α-SMA , Fibronectin , MMP9 , at 4°C overnight, the samples for CD86 and CD206 subsequently labeled with HRP-conjugated immunoglobulin G (IgG), and α-SMA, Fibronectin, MMP9 labeled with biotin conjugated-second antibody at room temperature for 45 min. Finally, they were visualized by DAB and observed by upright microscopy .p < 0.05 was considered statistically significant.All imaging results were analyzed using ImageJ 2.0 . Data were presented as the mean ± standard deviations (SD) and were processed using the statistical analysis software SPSS 17.0 . Statistical analyses were performed by one-way analysis of variance (ANOVA), and an LSD post hoc test was used to show differences for each pair of factor levels. in vitro by flow cytometry. The results in Herein, we identified the effects of SL on transformation of macrophage phenotype in the inflammatory injury model. First, we examined the effects of SL on the expression of the M1 marker CD86 and M2 marker CD206 Based on the functional influences of SL on macrophage polarization and TGF-β, we focused on the main regulatory pathway, the STAT3/SOCS3 pathway. As shown in To clarify whether SL regulates the interaction between macrophage and SMC, we established the macrophage-SMC co-culture and conditioned medium models, as shown in To specifically demonstrate that the phenotypic changes of SMC induced by SL were based on the integrative influences on the macrophage-SMC unit rather than on the direct effects on SMC alone, the conditioned medium transfer model was designed. In this model, SL extracts were first used to treat the macrophage alone. By replacing the SL-containing medium with drug-free medium at 24 h after treatment, we ensured that the direct effects of SL on the SMC could be clearly excluded. In accordance with our hypothesis, the results showed that the SL possesses the effect of up-regulating the mRNA of Collagen1, SM-MHC, α-SMA as well as the protein expression of fibronectin and α-SMA, and down-regulating mRNA of OPN.Mechanistically, TGF-β/Smad2/3 is the primary pathway maintaining the SMC phenotypic balance and is responsible for the stability variation of AS plaques. In light of such recognition, our results indicated the activation states of this pathway in the presence of SL using the above-mentioned models. −/− mice to establish the atherosclerotic plaque model. The effects of SL on acrophage-SMC unit and plaque stability was verified in vitro. Specific blocking of TGF-βof ApoE−/− mice was used to investigate whether TGF-β is responsive molecular mediator of SL.The silastic collars were positioned to the right carotid arteries of ApoEPharmacologically, as NMR image described , in RCA in vitro experiments.In this model, to molecularly further identify the activity of SL on phenotypic transformation of macrophage and SMC. Representative factors of phenotypic transformation of macrophage and SMC were detected. As shown in Mechanistically, to further explore whether the TGF-β was the responsive molecular mediator of SL. Pirfenidone (Pi), the TGF-β blocker, was applied to the AS mice model. The Pi and SL-M combination group attenuated the effects of SL in regulating the RCA area of the arteries , TNF-α  and TGF-Collectively, above data consistently demonstrated that SL treatment functionnally promotes macrophage-SMC unit and stabilizes atherosclerotic plaques which shown high correlation with TGF-β.In vivo, our results further showed that the collagen in plaque was up-regulated by SL (The stability of the atherosclerotic plaques is characterized by both dynamicity and plasticity, which contribute significantly to the progression of AS . A denseed by SL , meanwhied by SL . These r−/− mice, we have evaluated the protein expression of phenotypic transformation of macrophage and SMC markers, which suggested that SL possesses a capacity for transferring phenotype of macrophage and SMC which would be beneficial for AS plaque stabilization (in vivo, we also have evaluated the protein expression of M1 and M2 makers in macrophage in vitro (Vulnerable plaque in AS was characterized by thin fibrous cap that is infiltrated by inflammatory cells and low VSMC density  Koga an reportedlization . Notablyin vitro , which cin vitro .in vivo (in vitro. Inspired by the interaction of macrophages and SMC and the effect of SL on macrophage, two co-culture systems were designed to identify whether SL regulate the crosstalk of the two cells to stabilize atherosclerotic plaque. The co-culture model represents an in vivo inflammatory microenvironment for SMC, while we excluded the direct influence of drugs on SMC by using the conditioned medium system. Confining within the macrophage-SMC communication, we observed the SL enhanced the bio-activity of macrophages to support the SMC phenotypic transformation and functionally reconstruct the ECM which would be beneficial for AS plaque stabilization. This pharmacological influence to macrophage of SL shares high similarity to and might be determined by M2 polarization in microenvironment from AS plaque.Although SL displayed the function on transformation SMC phenotype in vivo , SL had in vivo , a contrSMC often reside close to macrophage in vascular lesions and are most likely to be influenced by cytokines released from polarized macrophages . Among aThe crosstalk between macrophage and SMC is a complex communication network involved multiple factors, dominated by but not limited to TGF-β, including platelet-derived growth factor, fibrogenic connective tissue growth factor, macrophage colony stimulating factor, MCP-1, IL-6 and so on . As exemIn conclusion, the present study demonstrated that SL stabilized atherosclerotic plaques, in which TGF-β might be the bridge factor within macrophage-SMC unit. In the future studies, we need a more systematic analysis to determine how SL enhances this unit to pharmacologically stabilize vulnerable plaques.


The private versus public contribution to developing new health knowledge and interventions is deeply contentious. Proponents of commercial innovation highlight its role in late-stage clinical trials, regulatory approval, and widespread distribution. Proponents of public innovation point out the role of public institutions in forming the foundational knowledge undergirding downstream innovation. The rapidly evolving COVID-19 situation has brought with it uniquely proactive public involvement to characterize, treat, and prevent this novel health treat. How has this affected the share of research by industry and public institutions, particularly compared to the experience of previous pandemics, Ebola, H1N1 and Zika?any author identified as affiliated with industry or not. We placed all disease areas on a common timeline of the number of days since the WHO had declared a Public Health Emergency of International Concern with a six-month lookback window. We plotted the number and proportion of publications over time using a smoothing function and plotted a rolling 30-day cumulative sum to illustrate the variability in publication outputs over time.Using Embase, we categorized all publications for COVID-19, Ebola, H1N1 and Zika as having Industry-affiliated articles represented 2%  of publications over the 14 months observed for COVID-19, 7% (278 articles) over 7.1 years observed for Ebola, 5% (350 articles) over 12.4 years observed for H1N1, and 3% (160 articles) over the 5.7 years observed for Zika. The proportion of industry-affiliated publications built steadily over the time observed, eventually plateauing around 7.5% for Ebola, 5.5% for H1H1, and 3.5% for Zika. In contrast, COVID-19’s proportion oscillated from 1.4% to above 2.7% and then declined again to 1.7%. At this point in the pandemic , the proportion of industry-affiliated articles had been higher for the other three disease areas; for example, the proportion for H1N1 was twice as high.While the industry-affiliated contribution to the biomedical literature for COVID is extraordinary in its absolute number, its proportional share is unprecedentedly low currently. Nevertheless, the world has witnessed one of the most remarkable mobilizations of the biomedical innovation ecosystem in history. There has been extensive discussion about the contribution of the pharmaceutical industry to resolving the coronavirus pandemic, with some critics arguing that industry has profited from the support of government –4. This Within this context, numerous studies have used scientific publications to approximate the contribution of public versus private investments into the research enterprise, often finding that public contributions form the backbone of the innovation system with private industry playing a less substantial, but critical role in bringing health innovations to the marketplace –22. StudIn this study, we use bibliographic data to examine the role of industry in the global research enterprise during public health emergencies. Our objective was to quantify the role of industry in the wide-ranging mobilization of the biomedical science community, to understand the extent to which this evolves over time, and to assess how industry’s contribution during COVID-19 compares to previous pandemics, including Ebola, H1N1 and Zika.We used Embase to search for publications that mentioned either COVID-19, H1N1, Zika, or Ebola (or any variant of these terms) in the abstract, extracted bibliographic data, tabulated the results, and then compared the results across the four disease areas. We consider only articles with one of the following publication types: Article, Chapter, Review, Letter, Note, and Editorial. We chose these four epidemics because each had been designated a Public Health Emergency of International Concern (PHEIC) by the World Health Organization. This led us to select COVID-19 (designated a PHEIC on 30 January 2020 ), Ebola After extracting the publication data, the articles were categorized by reviewing the authors’ affiliations. Industry-affiliated articles were coded as those with one or more authors who listed a firm as their affiliation, such as a pharmaceutical or biotech company, rather than (or in addition to) another entity, such as a university, a governmental office, or a civil society organization. Therefore, the distinction of “industry-affiliated” includes articles that were either co-authored by one or more authors with a private affiliation or were entirely authored by authors with private affiliations. This approach was taken to establish a clear delineation rule for coding decisions that can be applied consistently across the diseases. There were a limited number of publication records in which no affiliation data were available. No affiliation data were available for a small fraction of publications. While these were not retained for our main analysis, we report on the distribution of these records across the four pandemics as well as their potential impact on our results.Our analysis reports descriptive statistics on the number of industry-affiliated articles as well as their proportional representation of all publications examined. We plotted the number and proportion of all publications over time using a smoothing function with confidence intervals. Additionally, we plotted a 30-day publication rate  using a cumulative sum function as well as a smooth with confidence intervals in order to more closely examine the variability in publication outputs over time. All plots were generated using the ggplot2 package in R.Table 1). The remaining 5%  of the publication records had no author affiliation data available. Of these 5,856 without affiliation data, the publications relevant to Ebola had the largest proportion of such records , followed by COVID-19 , Zika , and H1N1 .Our searches within the four disease areas collectively located 126,532 relevant publications. Affiliation data was available for 120,667 (95%) and was therefore retained in our final dataset for analysis. Of these, publications for COVID-19 represented 87%  of the literature (time observed: 14 months), followed by H1N1 with 5%  (time observed: 12.4 years), Zika with 4%  (time observed: 5.7 years), and Ebola with 3%  (time observed: 7.1 years) (Table 2). However, this proportion varied across the four pandemics with the highest level for Ebola at 7% (278 articles), followed by H1N1 with 5% (350 articles), Zika with 3% (160 articles), and COVID-19 with 2% . At this point in the pandemic (428 days after the pandemic), the cumulative sum of publications for COVID-19 was 1,773 for industry-affiliated versus for 103,693 non-industry-affiliated publications–a number far exceeding previously observed cumulative sums after the same amount of time following the PHEIC for both industry-affiliated publications (46 times larger as compared to Ebola) versus non-industry-affiliated publications (92 times higher as compared to Zika)  .Of the 120,667 publications with affiliation data available, 2%  had industry affiliations . The proportion of industry-affiliated publications built steadily over the time and eventually plateauing over the time observed for each of the three non-COVID pandemics with 7.5% for Ebola (after 7.1 years), 5.3% for H1H1 (after 12.4 years), and 3.3% for Zika (after 5.7 years). In contrast, COVID-19’s proportion oscillated from 1.4% at 4 weeks after the PHEIC, to 2.6% at 180 days after the PHEIC, and then declined back down to 1.7% at the end of the time observed (428 days). At this point in the pandemic , the proportion of industry-affiliated articles was higher for the three other diseases .The proportion of industry-affiliated publications varied over the total time observed for each pandemic . Based on the record of previous pandemics, there has been a peak in the publication rate per pandemic, but this may occur at different times for industry- and non-industry-affiliates . It remains possible that there may be an even larger surge in industry-affiliated publications which could regain greater proportional representation in the literature in the longer term that is more commensurate with prior experience.The proportional decline for COVID-19 occurred because industry-affiliated publications reached a peak 30-day rate of 296 publications on 26 August 2020 before declining to 77 publications on 14 January 2021. While this pace began to accelerate again in April 2021 with a last observed rate of 177 publications, non-industry-affiliated publications had been steadily climbing to a rate of 16,726 observed on that same day  at 14 months out from the PHEIC. This result is most surprising given unprecedented amount of public funding provided to industry during COVID-19 and given the levels of proportionate engagement in the biomedical scientific literature during previous pandemics.Similar to previous studies –30, we fOur findings regarding the proportion of industry-affiliated articles resonates with previous investigations, particularly in the sense that publicly funded research provides a platform from which industry can use applied research and commercialize. For example, one study  found NIThis is not to understate the critical and substantive role of industry which has been estimated to provide two-thirds of the total investment in life sciences in the United States , but ratOur study is subject to certain limitations. First, while our study is as current as possible, only 14 months of data is available for COVID. There may well (and hopefully will be) a second and larger wave of industry-affiliated publications that will bring its level to be more commensurate with the experience of previous pandemics. Second, in contrast to industry, the primary responsibility of academics who largely work for public or non-profit institutions is to publish; therefore, it is unsurprising that industry publications represent a small fraction of such publications. For this reason, our study has focused upon to the proportionate experience of prior pandemics for establishing a reasonable benchmark from which to compare. Third, our investigation broadly focused upon the entire biomedical enterprise using a single, yet important repository of scientific publications. It is possible that by isolating subsets of publications—such as by intervention type —the proportion of industry-affiliated articles would be higher. However, this would be at the exclusion of the context of the broader ecosystem of knowledge and innovation which made these interventions possible in the first place. Finally, our analysis applies the most inclusive approach to industry participation: if even one author lists an industry affiliation, then the article is categorized as industry-affiliated. This may overstate the share of industry participation.The absolute number of industry-affiliated scientific articles on COVID in the biomedical literature is unprecedented when compared to the previous experience of Ebola, H1N1, and Zika. However, the proportional share of industry-affiliated articles (versus non-industry-affiliated articles) on COVID is not. In fact, as of writing, its current level is extraordinarily low at below 2 percent, perhaps because the world has seen the most stunning mobilization of the biomedical innovation ecosystem in history. A possible learning that may emerge from the COVID pandemic in the long term is an appreciation for what can be achieved with a strong role for governments in driving innovation agendas and the advantages of this strategy over a market-driven model in which private industries are left to strategically respond to lower-risk business opportunities.S1 Appendix(DOCX)Click here for additional data file.


Epoxy resin coatings are commonly used to protect concrete structures due to their excellent chemical corrosion resistance and strong adhesion capacity. However, these coatings are susceptible to damage by surface abrasion and long-term contact with marine climate conditions, deteriorating their appearance and performance. This study aims to optimize the performance of cement-based epoxy resin coatings, bisphenol-A and polyol, in aggressive environments by functionalizing the selected systems with different nanoparticles such as activated carbon, surface modified nanoclay, silica and zinc oxide. Nanomodified coatings were applied to concrete specimens and subjected to three weeks in a spray salt chamber and three weeks in a QUV chamber. They were found to present improved thermal resistance and curing degree after the weathering test. Their water permeability, adhesion, and abrasion resistance properties were evaluated before and after this test. The results showed that the nature of the nanocomposites determined their water permeability; the bare resin presented the worst result. Additionally, nanomodified composites with activated carbon and silica showed the best adherence and abrasion resistance properties, due to the effect of this aging test on their thermal stability and curing degree. Concrete is extensively used in marine and coastal defense frames such as tunnels, quay walls, bridges, jetties, breakwaters, or sea walls, whose structural design is supposed to last more than 50 years. Thus, the durability and structural reliability of concrete structures are critical factors that require special attention, since they depend on a combination of environmental, design factors, and construction practices. In any case, concrete structures located in marine conditions suffer from continuous exposure to seawater, either in a direct or indirect way, which leads to a wide range of deterioration scenarios, e.g., functional, aesthetic, or structural problems.+ and Cl−  and Mg2+, Ca2+, K+, SO42− to a lesser extent, which enters the pores of concrete and chemically reacts with its components causing damage to the structure. Among the harmful substances present in a pore solution, magnesium sulfate may react with calcium hydroxide, resulting in calcium sulfate and magnesium hydroxide precipitation, or with hydrated calcium aluminate, forming calcium sulfo-aluminate, which are the main cause of expansion and leaching actions on concrete, affecting the strength of the structure. Chloride ions significantly contribute to the reduction of service life, but deterioration is also linked to the loss of part of the lime content of concrete due to leaching. Nevertheless, concrete structures are also subjected to contamination by gases, such as O2, N2, and CO2, which are dissolved in seawater and enter the pores, lowering the pH to below 7.5 . Consequently, these harmful effects induce the oxidation and degradation of reinforced concrete bars.Parameters such as temperature, pH, the type of cement, the number of harmful substances, and the permeability of concrete are found to be key for the chemical attack. Generally, seawater contains 3.5 wt.% of dissolved salts, mainly in form of NaOn the other hand, apart from chemical deterioration processes, physical degradation also takes place. Although the most damaged area of a concrete structure exposed to marine conditions is known to be above the high water mark due to the continuous direct impact of waves on that area, erosion and abrasion by direct contact of sand and silt with the concrete surface, especially in shallow waters, must be taken into consideration. As the outer paste of concrete wears, the inner aggregates are exposed to further abrasion, causing extra degradation. In addition, turbulent movements of water may generate vapor cavities that can implode when subjected to high pressure, inducing an intense shock wave, resulting in the delamination of the structure. Also, differences of temperature can cause different expansion coefficients for the aggregates and the cement matrix, leading to tensile stresses with crack risk. Furthermore, frost and de-icing in concrete pores provoke expansion, disruption, and a loss of durability.i.high pressure steam cured concrete elements,ii.the use of a suitable concrete specification, cover thickness, and compaction of construction joints;iii.the adoption of alternative materials to steel as reinforcement bars;iv.the use of concrete protective coatings; orv.cathodic barrier techniques.Therefore, the development of a method to mitigate degradation under highly aggressive environments is still a matter of interest. In this sense, different strategies can be followed to improve concrete durability:Considering the cost of replacement and repair for damaged concrete structures in coastal zones, the use of coatings may provide a cost-effective method to significantly extend service life. In this context, epoxy coatings seem to be a suitable alternative to increase the level of protection due to their feasibility for use with all kinds of concrete, excellent adhesion, environmentally friendly properties, and durable waterproofing . Althoug2 supplies good adhesive [In order to enhance the mechanical performance and introduce new functionalities different nanostructure materials such as iron-based nanoparticles , silica adhesive  and mechadhesive . Thus, eTherefore, this work aims to discuss the results obtained for the application of three different commercial epoxy-based coatings, i.e., cement epoxy resin (SE), bisphenol-a epoxy resin (S) and polyol epoxy resin (M), on the characteristics of a standard concrete specimen, and the subsequent selection of the most suitable one to prevent the deterioration of marine constructions. The influence of the incorporation of a certain load of nanoparticles to reinforce the selected epoxy resin-based coating was also explored. In that respect, NP loading and way of incorporation were firstly optimized. Then, the physicochemical properties of the as-prepared nanocomposites related to the addition of NPs of different nature  amine) were evaluated. NP wettability (in terms of the hydrophobic/hydrophilic behavior), as well as the surface chemistry and thermal stability of the different composites, were analyzed and compared to those obtained by the NP-free coated specimen. In a last stage, each coated concrete test specimen was subjected to a series of test: i) water permeability (absorption), ii) adhesion (by means of pull off), and iii) abrasion (Taber), before and after an accelerated weathering test simulating a marine environment in a salt chamber, which consisted of a three-week wetting cycle (35 °C), followed by another three weeks in a UV chamber (interchanging 4 h UV 340 nm radiation at 60 °C and 4 h of condensation at 50 °C).−3, and sand as fine aggregates were included in the mixtures. The main mixing equipment was the vertical axis forced concrete mixer. Coupons of different dimensions  were cured for 14 days before being removed from the formwork after pouring. Ambient conditions during casting and curing did not vary significantly. Then, the concrete structures were prepared to improve their performance. Concrete structures were coated with three different commercial coatings:i.a cement-based epoxy resin (SE);ii.a bisphenol-A based epoxy resin; andiii.a polyol-based epoxy resin.In this study, concretes with a nominal 28-day strength of 35 MPa and 110 mm slump were used as the base material. Different dosages of ordinary Portland cement, coarse aggregates with a maximum size of 20 mm and a density of 2.6 g·cmAccording to the recommendations of the supplier, a primer coating for S and M was needed in order to improve the adhesion and prevent the appearance of pinholes or bubbles in the hardened coating. More details of these coatings are given in 2) and zinc oxide with 99 wt.% purity (ZnO). AC and ZnO were purchased from PanReac , and NCSM and SiO2 were purchased from Sigma Aldrich .Four types of nanoparticles were used in this study to enhance the physicochemical properties of the resins: charcoal activated powder (AC), surface modified nanoclay with 35–45 wt.% dimethyl dialkyl (C14-18) amine (SMNC), silicon dioxide with 99.5 wt.% purity  previously described were considered in this optimization. To impregnate them, four film deposition methodologies were studied:−1. The fluorescent UV/condensation chamber was a QUV Accelerated Weathering Tester, from Q-Lab Corporation. To provide a more realistic marine weather exposure regime, the accelerated aging test consisted of cyclic exposure of UVA-340 light at 0.65 W·m−2 at 60 °C for 4 h and condensing humidity at 50 °C in the dark for 4 h. The radiation intensity was calibrated by a radiometer every 150 h. Water permeability tests of the coated concrete structures (127 mm × 76 mm × 30 mm) were carried out following the UNE EN 1062 [®)  was applied to the front face of the concrete structures, following the ASTM D 4541 [® Industries . Each specimen, with dimensions of 100 mm × 100 mm × 30 mm, was loaded for a total of 6000 cycles under an applied load of 1000 g in accordance with ASTM D 4060 [In the case of the spatula printing (i), SE coating was applied according to the recommendation of the supplier . First,  EN 1062 . The tesM D 4060 , with tw−1, with a resolution of 4 cm−1, and 100 scans per sample were recorded. Thermogravimetric analyses (TGA) were evaluated using a Mettler Toledo TGA/DSC 1 STARe under nitrogen and air atmospheres (90 NmL·min−1 flow rate) at a heating rate of 10 °C·min−1 from 25 °C to 1000 °C. Differential scanning calorimetry (DSC) experiments were performed using a Mettler Toledo DSC2 under nitrogen atmosphere with a gas flow of 50 NmL·min−1 and a heating rate of 10 °C·min−1 in the temperature range from 25 to 300 °C. Dispersion stability analyses of the NPs in Part B of the resin were determined by the Stability Index (TSI) provided by the TurbiscanTM Lab Expert stability analyzer, from Formulation Company, Toulouse, France. Samples were prepared in cylindrical vials with 1 wt.% of each type of NP. They were dispersed for 10 min in 20 mL of Part B using an ultrasonic bath  and rapidly placed into the analyzer. Stability experiments were performed at 30 °C for 24 h and data were collected every 30 s for the first 1.5 h and every 30 min for the rest of the experiment. The thickness of the resulting coatings was evaluated using a stereoscopic microscope optic loop with 7.5× zoom and 115 mm working distance, manufactured by Nikon . Density measurements were carried out using a pycnometer  with a medium cell size. Adsorption–desorption of nitrogen at −196 °C analyses were recorded in a Gemini VII . Samples were degassed at 120 °C overnight prior their measurement. Surface area values (SBET) were calculated using the Brunauer Emmett Teller equation.Contact angle micrographs were acquired by using an Attention Theta Optical Tensiometer from Biolin Scientific’s  with the OneAttension software  and accuracy of ±0.1° precision. Contact angle values were recorded instantaneously after the water droplet touched the surface of the materials to minimize evaporation errors. Analyses were performed in three equidistant points of the sample, with the final contact angle values being the average of three measurements. Micrographs of the different NPs were acquired using a GeminiSEM 500 High Resolution Scanning Electron Microscope (HRSEM) from ZEISS brand . The surface chemistry of the different materials was elucidated using a Spectrum Two Fourier transform infrared (FTIR) spectrometer, from PerkinElmer Inc. , with a zinc selenide (ZnSe) crystal. Spectra ranged from 4000 to 500 cm2, and ZnO nanoparticles were selected for this study. Two different NP concentrations were considered, i.e., 1 and 5 wt.%, to be dispersed in Part B of the resin. First, 5 wt.% of nanoparticles were dispersed in Part B (hardener) by sonication  for 10 min at room temperature, which was then vigorously mixed with Part A. After that, concrete structures were immersed in the resulting solution. The same procedure was carried out with 1 wt.% of NPs. In addition, this NP loading was dispersed in Part B via an ultrasonic bath  for 10 min.AC, SMNC, SiOIn i.type of resin;ii.coating time;iii.and number of the coating immersions;Water permeability and pull-off tests were carried out for the different coated concrete structures. For comparison purposes, these tests were also run with a raw concrete specimen as a blank. As shown in To understand these results, the thickness of both S and M coatings and their contact angle results were measured and are summarized in −3) > SiO2 (2.7 g·cm−3) > SMNC (1.7 g·cm−3) > AC (1.1 g·cm−3). The adsorption–desorption of nitrogen at −196 °C results evidenced that AC and SiO2 materials possessed higher surface area values, i.e., 954.8 and 533.3 m2·g−1, respectively, in comparison to SMNC (11.8 m2·g−1) and ZnO (5.4 m2·g−1). In 2 was composed of spherical particles, while ZnO displayed a hexagonal structure. The contact angle values obtained for these nanoparticles were lower than 90°, displaying a hydrophilic nature. Next, ATR-FTIR experiments were carried out to define the surface chemistry of the different NPs. Their spectra are shown in −1 were assigned to the stretching vibration of aliphatic groups (C-H) in organic matter [−1 could be assigned to aliphatic C-H deformation vibrations due to the presence of polymethylene [−1. The amine groups from the surface modification were detected at 3620 cm−1 and 917 cm−1. Si-O stretching vibration of orthosilicate anions and Si-O-Al groups were shown at about 1004 cm−1 [2, the absorption bands assigned to Si-O stretching vibrations appeared at 1069 cm−1, and Si-O bending vibrations at 814 cm−1 were also identified [−1 that clearly demonstrated the presence of stretching Zn-O bonds [The physical and textural properties of the different NPs are summarized in ethylene . The pre004 cm−1 ,36. For entified ,38,39. T-O bonds .2 NPs in the range of 1 to 5 wt.%, and Tomic et al. used a surface modified nanoclay in the range of 1 to 10 wt.% [2 was selected as an example NP for this optimization process. First, 5 wt.% of SiO2 was dispersed into Part B by sonication. In a similar way as in the studies by Bagherzadeh and Tomic, the incorporation of 5 wt.% of SiO2 into the coating presented visual agglomerations, resulting in a nonhomogeneous coating . In order to enhance the dispersion and diminish NP agglomeration, 1 wt.% of SiO2 was dispersed in Part B of the coating using the same procedure. In this case, there was no evidence of visual agglomeration of NPs . However, a nonuniformed coating was still observed. According to previous studies [2 were prepared using an ultrasonic bath as the dispersion technique to avoid the occurrence of such scissions. As a result, the obtained coated concrete structures presented a uniform coating without NP agglomeration . Therefore, 1 wt.% of NPs dispersed by ultrasonic bath was chosen as the optimal methodology for the incorporation of the different NPs into the coatings. As shown in Previous studies have investigated the effect of the incorporation of different NP concentrations into epoxy anticorrosive coatings. Bagherzadeh et al.  studied  studies ,43, highi.well dispersed materials (TSI < 5);ii.part of the material was deposited at the bottom of the flask and could be easily re-dispersed (5 < TSI < 20);iii.the material was mostly sedimented (TSI > 20) .To define the impact of NP incorporation into the coating, a characterization of the NPs in Part B was carried out. The stability of the different NPs in Part B of the epoxy resin was evaluated a by Turb2 (TSI = 10.5), ZnO (TSI = 16.5). This fact could be explained by its high porosity, as evidenced by HRSEM  in comparison to SMNC (TSI = 12.2) and SiOby HRSEM , and surby HRSEM . AC is l1 = 148 °C and T2 = 219 °C. The NP incorporation showed a positive effect on the thermal stability of the NPs-Part B composites. This effect was more pronounced after the incorporation of hydrophilic NPs, SiO2 (T1 = 193 °C and T2 = 251 °C) and ZnO (T1 = 191 °C and T2 = 251 °C) in comparison to hydrophobic NPs, SMNC (T1 = 175 °C and T2 = 243 °C) and AC (T1 = 183 °C and T 2= 246 °C).To determine the thermal effect of NP incorporation into Part B of the resin, TGA experiments in nitrogen atmosphere were carried out; the results are shown in AC-S10-1= 77.8° and θSMNC-S10-1= 88.7°, respectively, in comparison to θS10-1= 71.6°. The integration of SiO2 and ZnO promoted more hydrophilic composites, θSiO2-S10-1= 63.8° and θZnO-S10-1= 59.7°, respectively. After the weathering test, all composites displayed greater contact angle values in comparison to the S10-1 resin, i.e., ZnO-S10-1, which presented the least hydrophilic nature. As mentioned in research published elsewhere, ZnO could promote photocatalytic reactions in the resin upon exposure to UV-vis light that could make the composite less porous and more hydrophobic [The results from the characterization of the different S10-1 and NPs-S10-1 coatings (Part A + Part B) before and after the weathering test are summarized in rophobic ,48, indi1) values are summarized in 2-S10-1. Before the weathering test, the incorporation of different NPs promoted a more ordered composite and higher Tg1 values (SiO2-S10-1 (58.6 °C) > TgSMNC-S10-1 (57.6 °C) > TgAC-S10-1 (56.9 °C) > TgZnO-S10-1 (56.8 °C) > TgS10-1. This increment in the Tg could be attributed to the limited mobility of the epoxy chains due to the intense interactions between the NPs and the epoxy resin [2 led to a maximum Tg ~ 59 °C. Similar results were obtained by Rawaiz Khan et al. with the incorporation of 2 wt.% of SiO2 into an epoxy resin [1 was shifted to higher temperature values, especially for AC-S10-1 and SiO2-S10-1 composites, which could be associated with better thermal stability properties and curing degree of the coatings.Regarding the optical loop results before the weathering test , the inc1 values a, followxy resin ,51. In txy resin . After t−1, was attributed to the C-H in the methylene group of the epoxy group. The second one at 916 cm−1 was characteristic of C-O deformation from the oxirane group [−1, correlating with the O-H stretching mode of hydroxyl groups produced after the ring opening reaction, was detected [−1 to 850 cm−1), it can be observed that the incorporation of the NPs improved the curing process of the S10-1, in agreement with what was observed using DSC. The thermal stability of the different composites before and after the weathering test under nitrogen and air atmospheres was evaluated by TGA. The results of the bare coating, S10-1, and its composites, NPs-S10-1, are depicted in 5%) corresponds to the initial thermal degradation temperature. T5% values are summarized in 5% values in comparison to neat epoxy resin in nitrogen (40%) were recorded  than the neat epoxy resin (T5% = 201.7 °C). Otherwise, T40% results showed that these composites were the most thermally stable at higher temperature, i.e., T40% = 414.5 °C and T40% = 417.5 °C, respectively. In the case of air atmosphere, AC-S10-1 was the only composite which promoted higher temperatures (T5% = 177.1 °C) than the neat epoxy resin (T5% = 175.5 °C). The same trend was obtained with this composite for T40% results, meaning that this material yielded the best experiment results, T40% = 404.8 °C.Regarding nitrogen atmosphere results, the incorporation of nanoparticles into the coating promoted higher temperatures than the neat epoxy resin, especially for SMNC-S10-1. However, the results obtained in air showed that lower temperatures were found with NPs-S10-1, proving that the experimental atmosphere has an important effect on the degradation of the resin. Attending to results obtained after the weathering test b, highering test a. TherefAnalyzing in detail the different weight losses related to each composite during the heating process, the impact of NP incorporation at every stage of these thermal processes can be established. As previously explained, each weight loss was attributed to a different degradation reaction. All results and final residues at 1000 °C are compiled in 2-S10-1 promoted better adherence properties than S10-1, the best results were achieved with the least hydrophilic composites, i.e., AC-S10-1, and SMNC-S10-1. However, the latter was the only one that showed worse adherence than S10-1 after the weathering test. The best results were therefore achieved with AC-S10-1 and SiO2-S10-1 composites, with the latter showing superior performance. This behavior could be explained by taking into account the DSC results (The different coated concretes were subjected to an accelerated weathering test (fog/Uv-vis) to simulate the effect of hostile climate conditions. In this sense, the water permeability, adherence capacity and abrasion resistance of the different coatings were evaluated; the results are depicted in  results b, where Additionally, the Tg for both nanocomposites evidenced stronger interaction between the polymer network and these nanoparticles. Finally, abrasion resistances results, before and after the weathering test, are shown in 2-S10-1 were established as the only composites that promoted better Taber wear index values in comparison to S10-1 after the 6000 cycle abrasion test. These findings were in accordance with our previous pull-off results, since stronger adherence properties were developed with these materials, as evidenced by DSC experiments . The accelerated weathering test (fog/UV-vis) seemed to have an important impact on the physicochemical properties of the different coatings, and was most pronounced on their thermal properties and curing degree. Before the weathering test, the nature of the nanoparticle played an important role in the water permeability and adherence results, since less hydrophilic composites, i.e., SMNC-S10-1, and AC-S10-1, showed the lowest weight gain and best adherence in the water permeability and pull-off tests, respectively. Additionally, the latter composite presented the best abrasion resistance. After the accelerated weathering test, all composites presented a lower weight gain in comparison to the neat epoxy resin, especially ZnO-S10-1. The highest Tg values obtained with AC-S10-1 and SiOTo our knowledge, no other study has reported the incorporation of nanoparticles into epoxy resins and their abrasion and adherence properties after weathering tests. This research opens a new starting point for long-term coatings in concrete for future industrial applications.