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Decreasing ocean surface pH, called ocean acidification (OA), is among the major risks for marine ecosystems due to human-driven atmospheric pCO 2 increase. Understanding the molecular mechanisms of adaptation enabling marine species to tolerate a lowered seawater pH could support predictions of consequences of future OA scenarios for marine life. This study examined whether the ATP-binding cassette (ABC)-like gene slr2019 confers tolerance to the marine cyanobacterium Halomicronema metazoicum to low seawater pH conditions (7.7, 7.2, 6.5) in short- and long-term exposures (7 and 30 d). Photosynthetic pigment content indicated that the species can tolerate all three lowered-pH conditions. At day 7, slr2019 was up-regulated at pH 7.7 while no changes were observed at lower pH. After 30-d exposure, a significant decrease in slr2019 transcript levels was observed in all low-pH treatments. These first results indicate an effect of low pH on the examined transporter expression in H. metazoicum., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disorder among Caucasians. The improvement of genetic techniques has allowed the identification of an increasing number of genetic variants, including large rearrangements such as duplications. We report the first case of a whole CFTR gene duplication in a healthy newborn, who had normal sweat test, also carrying R74W and V855I variants on the same allele. Familial segregation analysis and the observed frequencies of all the CFTR gene variants, revealed that R74W and V855I were probably both present in a cis arrangement on the allele also containing the duplication (i.e., in a double complex allele). Since R74W is a "variant of varying clinical consequence" its arrangement in trans with one pathogenic variant may not be sufficient to cause a classic CF disease phenotype. Moreover, its duplication could even be an advantage that could compensate for the effect of the alteration., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

How Antarctic species are facing historical and new stressors remains under-surveyed and risks to wildlife are still largely unknown. Adélie penguins Pygoscelis adeliae are well-known bioindicators and sentinels of Antarctic ecosystem changes, a true canary in the coal mine. Immuno-haematological parameters have been proved to detect stress in wild animals, given their rapid physiological response that allows them tracking environmental changes and thus inferring habitat quality. Here, we investigated variation in Erythrocyte Nuclear Abnormalities (ENAs) and White Blood Cells (WBCs) in penguins from three clustered colonies in the Ross Sea, evaluating immuno-haematological parameters according to geography, breeding stage, and individual penguin characteristics such as sex, body condition and nest quality. Concentrations of mercury (Hg) and stable isotopes of carbon and nitrogen (as proxies of the penguin's trophic ecology) were analysed in feathers to investigate the association between stress biomarkers and Hg contamination in Adélie penguins. Colony and breeding stage were not supported as predictors of immuno-haematological parameters. ENAs and WBCs were respectively ∼30 % and ∼20 % higher in male than in female penguins. Body condition influenced WBCs, with penguins in the best condition having a ∼22 % higher level of WBCs than those in the worst condition. Nest position affected the proportion of micronuclei (MNs), with inner-nesting penguins having more than three times the proportion of MNs than penguins nesting in peripheral positions. Heterophils:Lymphocytes (H:L) ratio was not affected by any of the above predictors. Multiple factors acting as stressors are expected to increase prominently in Antarctic wildlife in the near future, therefore extensive monitoring aimed to assess the health status of penguin populations is mandatory., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Since the industrial revolution, fossil fuel combustion has led to a 30 %-increase of the atmospheric CO 2 concentration, also increasing the ocean partial CO 2 pressure. The consequent lowered surface seawater pH is termed ocean acidification (OA) and severely affects marine life on a global scale. Cellular and molecular responses of marine species to lowered seawater pH have been studied but information on the mechanisms driving the tolerance of adapted species to comparatively low seawater pH is limited. Such information may be obtained from species inhabiting sites with naturally low water pH that have evolved remarkable abilities to tolerate such conditions. This review gathers information on current knowledge about species naturally facing low water pH conditions and on cellular and molecular adaptive mechanisms enabling the species to survive under, and even benefit from, adverse pH conditions. Evidences derived from case studies on naturally acidified systems and on resistance mechanisms will guide predictions on the consequences of future adverse OA scenarios for marine biodiversity., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N -terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome. A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits. A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk. Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger prospective studies, it would identify a new class of skeletal-related irAEs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier GmbH.)

The presence of pharmaceutical residues in the aquatic environment is a known problem worldwide. Paracetamol is widely used as an analgesic and antipyretic. Its high consumption implies a continuous discharge in aqueous environments through industrial and domestic wastewater that requires mitigation and remediation strategies. The aim of the present study was to analyse the removal of the paracetamol from aqueous solutions using the adsorption technique. For this, three commercial adsorbents with different textural properties were used: two activated carbons (CAT and CARBOPAL) and silica gel. A series of batch adsorption experiments were conducted at different values of pH (3.0, 7.0 and 10.5) and ionic strength (0.01, 0.5 and 1 M) to investigate the effects on the removal of paracetamol from the aqueous solution. In addition, we investigated the adsorption mechanism using the density functional theory. Adsorption was found to be higher in the acidic pH range, as varying pH showed significant influence on the surface charge of the adsorbents and degree of ionization of the paracetamol. Adsorption capacity of the adsorbents increased with an increase in the ionic strength of solution. At 25 °C, pH 3, ionic strength 1 M, 167 mg L -1 of adsorbent and initial concentrations of paracetamol between 25 and 150 mg L -1 , the maximum adsorption capacity was 560 mg g -1 , 450 mg g -1 and 95 mg g -1 , for CAT, CARBOPAL and silica respectively. The experimental kinetic data fitted well the pseudo-second order model and the equilibrium isotherm data the Langmuir model. The functional density theory methods provided atomistic details about paracetamol adsorbed on the surface of carbon and silica through molecular modeling., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Ki67 is a prognostic and predictive marker in breast cancer (BC). However, manual scoring (MS) by visual assessment suffers from high inter-observer variability which limits its clinical use. Here, we developed a new digital image analysis (DIA) workflow, named KiQuant for automated scoring of Ki67 and investigated its equivalence with standard pathologist's assessment., Methods: Sequential immunohistochemistry of Ki67 and cytokeratin, for precise tumor cell recognition, were performed in the same section of 5 tissue microarrays containing 329 tumor cores from different breast cancer subtypes. Slides were digitalized and subjected to DIA and MS for Ki67 assessment. The intraclass correlation coefficient (ICC) and Bland-Altman plot were used to evaluate inter-observer reproducibility. The Kaplan-Meier analysis was used to determine the prognostic potential., Results: KiQuant showed an excellent correlation with MS (ICC:0.905,95%CI:0.878-0.926) with satisfactory inter-run (ICC:0.917,95%CI:0.884-0.942) and inter-antibody reproducibilities (ICC:0.886,95%CI:0.820-0.929). The distance between KiQuant and MS increased with the magnitude of Ki67 measurement and positively correlated with analyzed tumor area and breast cancer subtype. Agreement rates between KiQuant and MS within the clinically relevant 14% and 30% cut-off points ranged from 33% to 44% with modest interobserver reproducibility below the 20% cut-off (0.606, 95%CI:0.467-0.727). High Ki67 by KiQuant correlated with worse outcome in all BC and in the luminal subtype (P = 0.028 and P = 0.043, respectively). For MS, the association with survival was significant only in 1 out of 3 observers., Conclusions: KiQuant represents an easy and accurate methodology for Ki67 measurement providing a step toward utilizing Ki67 in the clinical setting., Competing Interests: Declaration of competing interest VP has received honoraria from Roche and Sismex; PN has consulted for Bayer, Novartis, MSD, and Targos, and received compensation. The other authors declare no potential conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this study, silica and functionalized silica materials (3-aminopropyl and 3-mercapto derivatives) were successfully used for the removal of the pesticides bentazone and imazapyc from aqueous solutions. Adsorbent materials were characterized by BET isotherms and FT-IR spectroscopy (confirming the functionalization), and their equilibrium adsorption capacity was evaluated at different ionic strengths. It is observed that the maximum adsorption capacities decrease in the order 3-aminopropyl-derivative > silica >3-mercaptopropyl derivative. An increase in ionic strength produces an enhancement in the removal of pesticides. All isotherms are Ib-type and follow the Langmuir model, suggesting a monolayer physical adsorption process., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, commercial activated carbons (GAB and CBP) were successfully used for the removal of two phenoxy acetic class-herbicides, 4-chloro-2-methyl phenoxy acetic acid and 2.4-dichlorophenoxy acetic acid (MCPA and 2.4-D) from aqueous solution. The adsorbent materials were characterized, and their equilibrium adsorption capacity was evaluated. The results suggest that the microporous properties of GAB activated carbon enhanced the adsorption capacity, in comparison to CBP carbon. Thus, the increasing in the ionic strength favored the adsorption removal of both pesticides, indicating that electrostatic interactions between the pollutant and the adsorbate surface are governing the adsorption mechanism, but increasing pH values decreased adsorption capacity. Experimental data for equilibrium was analyzed by two models: Langmuir and Freundlich. Finally, computational simulation studies were used to explore both the geometry and energy of the pesticides adsorption., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Silica based materials find applications as excipients and particularly as drug delivery agents for pharmaceutical drugs. Their performance can be crucially affected by surface treatments, as it can modify the adsorption (and release) of these formulations. The role of surface modification on the features of 4-formaminoantipyrine (FAA) adsorbed on β-cristobalite (001) surface is studied by means of simulations based on the Density Functional Theory (DFT). Starting from the results of FAA in interaction with a dehydroxylated surface; a fully hydroxylated surface and a functionalized surface with benzalkonium chloride (BC) surfactant have been added to study the configurational landscape. Calculations suggest that the trend for FAA preferential adsorption on silica surfaces is: dehydroxylated>hydroxylated>BC-functionalized. The potential for hydrogen bonding causes the main contribution to the bonding while dispersion forces present an additional contribution independently of whether the drug is hydrogen-bonded or BC-bonded to the surface. Adsorption takes mainly place through nitrogen atoms in the heterocyclic ring, the carbonyl and amine functional groups. Associated mode's shifts and concurrent changes in bond length are also observed showing accordance between electronic and geometrical structure results. BC surfactant reduces the number of formed H-bonds and lowers the attractive molecule-surface interaction being it useful to prevent particle agglomeration and could favor drug release in therapies that requires faster but controlled delivery., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Age-related differences in wound healing have been documented but little is known about the wound healing mechanism after burns. Our aim was to compare histological features and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9), collagen IV, K6 and CD44 in the burn wound healing process in aged and young rats. Following burns the appearance of the wound bed in aged rats had progressed but slowly, resulting in a delayed healing process compared to the young rats. At 21 days after injury, epithelial K6, MMP-9 and CD44 expression was significantly increased in aged rats with respect to young rats; moreover, in the aged rat group we observed a not fully reconstituted basement membrane. K6, MMP-9 and CD44 expression was significantly increased in wounded skin compared to unwounded skin both in young and aged rats. We hypothesise that delayed burn skin wound healing process in the aged rats may represent an age dependent response to injury where K6, MMP-9 and CD44 play a key role. It is therefore possible to suggest that these factors contribute to the delayed wound healing in aged skin and that modulation could lead to a better and faster recovery of skin damage in elderly., (Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.)

We analyzed immunohistochemically the expression of CD24 and spliced variants of CD44v5 and v9 in invasive micropapillary carcinoma (IMPC) of the breast that is a rather aggressive tumor characterized by alteration of cells adhesion molecules, early lymph node metastases and poor prognosis. We analyzed 31 high-grade IMPCs and compared their expression to 22 high grade (G3) invasive ductal carcinomas of the breast (IDCs). We found a higher expression of CD24 in high-grade IMPCs with a peculiar inverted apical localization, compared to IDCs, showing a strong cytoplasmic staining; normal breast tissue resulted completely negative. IMPCs showed reduced expression of CD44v5 and CD44v9 compared with IDCs, but without a statistical significant difference. This study demonstrated that IMPC represents a distinct entity of breast carcinoma with high expression of CD24 with a typical inverted apical membrane pattern and reduction of CD44 isoforms v5 and v9, compared to IDCs. These features could explain the high lymph-vascular invasion propensity and higher metastatic capability of these tumors and could be a useful tool for a future targeted therapy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Anti-sulfatide IgM antibodies have been recently associated with neuropathy but the clinical and electrophysiological correlations of this reactivity remains unclear. We reviewed the clinical and electrophysiological features of patients with high anti-sulfatide titers detected in our laboratory from 1991 to 1998. Of the 564 patients with different neurological diagnosis tested by enzyme-linked immunosorbent assay (ELISA), 11 had high anti-sulfatide IgM titers (>1/8000), 26 had titers of 1/8000 while 78 had titers of 1/4000. All patients with high anti-sulfatide IgM titers had a chronic, dysimmune, mostly sensorimotor neuropathy that in seven was associated with IgM monoclonal gammopathy. In most of these patients electrophysiological and morphological studies were consistent with a predominantly demyelinating neuropathy frequently associated with prominent axonal loss. Antibody titers of 1/8000, though always associated with neuropathy, did not correlate with a particular form or cause of neuropathy, while lower titers were equally distributed in patients with different neurological disorders. Our study indicate that high anti-sulfatide IgM titers (>1/8000) are highly predictive for a chronic, dysimmune, mostly demyelinating neuropathy often associated with IgM monoclonal gammopathy, and may therefore have potential diagnostic relevance.