Clopidogrel is one of the thienopyridine antiplatelet drugs commonly used as a prophylactic medication to prevent coagulation in vessels and cardiovascular events. The molecule of clopidogrel is metabolized in the liver via phase-I and phase-II metabolism pathways. The sulfenic acid clopidogrel metabolite undergoes phase-II metabolism through conjugation with glutathione by the glutathione-s-transferase (GST) to form a glutathione conjugate of clopidogrel (inactive metabolite). A glutaredoxin enzyme removes the glutathione conjugated with clopidogrel to form cis-thiol-clopidogrel. This review focused on the polymorphisms of genes related to phase-II metabolism during the clopidogrel bioactivation process. Overall, no well-controlled studies were done about the relationship between the clopidogrel bioactivation process and genes related to phase-II metabolism’s enzymes. Nevertheless, some polymorphisms of G6PD, GCLC, GCLM, GSS, GST, GSR, HK, and GLRX genes could be responsible for clopidogrel resistance due to low glutathione conjugate or glutaredoxin plasma levels. Studies needed to be concerned with the relationship between clopidogrel resistance and phase-II metabolism issues in the near future.

Iron is an essential nutrient for humans and microbes, such as bacteria. Iron deficiency occurs commonly in critically ill patients, but iron replacement therapy is not considered during the acute phase of critical illness, since it increases iron availability for invading microbes and oxidative stress. However, persistent iron deficiency in the recovery phase is harmful with potential adverse outcomes such as cognitive dysfunction, fatigue and cardiopulmonary dysfunction. Therefore, it is important to treat iron deficiency timely and efficiently. This article reviews current knowledge about iron-related biomarkers in critically ill patients and provides possible criteria to guide decision-making for iron supplementation in the recovery phase of critical illness.

As critical biocontrol agents, Trichoderma and Metarhizium have demonstrated vast potential in disease prevention and pest control respectively. Current applications, however, are predominantly confined to singular use or simplistic combinations of the two fungi. This study innovatively utilizes Metarhizium and Trichoderma as experimental subjects, employing non-targeted metabolomics to compare the differences in metabolites between co-culture and separate fermentation. The metabolite distinctions in co-culture are meticulously analyzed using sample correlation, least squares discriminant analysis, cluster analysis, and KEGG enrichment analysis. Metabolome sequencing analysis is then applied to compare the co-culture fermentation filtrate with Trichoderma atroviride and Metarhizium anisopliae. Differential metabolite analysis found that co-culture had significantly up-regulated or down-regulated metabolites compared to singular cultures.However,significant metabolite discrepancies are discovered in singular cultures, notably the up-regulated metabolites such as osthole and spirocyclic amine, which have documented antibacterial functions that may prove effective against Fusarium graminearum. Ultimately, the findings from this research contribute to the exploration of synergistic applications of biocontrol fungi and serve as a valuable reference for future development of bio-pesticides for disease and pest control.

Inflammation is implicated in the etiology of obesity-related diseases. Thromboxane-prostanoid receptor (TPR) is known to play a role in mediating an inflammatory response in a variety of cells. Gut-derived lipopolysaccharide (LPS), a TLR4 agonist, is elevated in obesity. Moreover, free fatty acids (FFAs) are important mediators of obesity-related inflammation. However, the role and mechanisms by which TPR regulates the inflammatory response in human immune cells remain unclear. We sought to determine the link between TPR and obesity and the role/mechanisms by which TPR alters LPS or stearic acid (SA)-induced inflammatory response in PBMCs. Cells were pre-treated with agents blocking TPR signaling, followed by treatment with LPS or stearic acid (SA). Our findings showed that TPR mRNA levels are higher in PBMCs from individuals with obesity. Blockade of TPR as well as ROCK which acts downstream of TPR, attenuated LPS and/or SA-induced pro-inflammatory response. On the other hand, TPR activation using its agonist enhanced the pro-inflammatory effects of LPS and/or SA. Of note, TPR agonist by itself elicits an inflammatory response which was attenuated by blocking TPR or ROCK. Our data suggest that TPR plays a key role in promoting an inflammatory response in human PBMCs and this effect is mediated via TLR4 and/or ROCK signaling.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Correlations among estrus cycle, pyometra, and canine diabetes mellitus (CDM) have been described since the late 1950s, and substantial progress in understanding mechanisms beyond was achieved nowadays. Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. Thus, a deep understanding of the physiopathological aspects involved is crucial to postulate treatment guidelines to improve the PRDM remission rate, as well as to inform preventive measures. This narrative review aims to provide relevant detailed information on 1) canine estrus cycle and its impact on CDM etiology and management, 2) the role of pyometra as a further cause of insulin resistance, and 3) useful individual therapeutic and preventive strategies. Pharmacological annulment of progesterone effects, as well as inflammatory and progesterone-related conditions resolution in association with adequate exogenous insulin therapy, and residual beta cell function, are key aspects to achieve remission, or at least to improve diabetic clinical control. In this way, spaying should be considered mandatory in most PRDM cases. Preventive measures against CDM can include spaying recommendations; however, individual-based recommendations should be considered since castration may be associated with some long-term health issues.

Introduction/Aim: Central sensitivity to thyroid hormones refers to the sensitivity of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). The relationship between fT4 levels and iodine intake is complex. The aim of the present study was to assess central sensitivity to thyroid hormones in pregnancy against iodine intake. Materials & Methods: One thousand one hundred two blood and urine samples were collected from pregnant women (with a mean age+SD of 30.4+4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH & fT4 and 24-hour urinary iodine excretion (UI) were measured in each trimester and at two months postpartum. The Thyroid Feedback Quantile-based Index (TFQI) was calculated to assess central sensitivity to thyroid hormones. For the statistical analysis of TFQI by time period, analysis of variance (ANOVA) was used, while Pearson's correlation was used to assess TFQI versus UI. Results: The mean TFQI index ranged from -0.06 (first trimester) to -0.07 (two months postpartum), while the corresponding UI was 141 and 172 μg/L, respectively. The TFQI-UI correlation was negative (Pearson r: -0.325, p: 0.04 and r: -0.399, p: 0.023), for UI values over 250 μg/L, in the first and the third trimester of pregnancy, respectively. Discussion: TFQI is a new index reflecting central sensitivity to thyroid hormones. Lower TFQI indicates higher sensitivity to thyroid hormones. In our sample TFQI was inversely related to iodine intake, in the first trimester of pregnancy (the critical period of organogenesis) and the third trimester (the critical period of fetal growth). Thus, the observed changes in TFQI may reflect different ways of central action of thyroid hormones, according to the phase of pregnancy. The negative association between maternal TFQI (indicative of central sensitivity to thyroid hormone) and urine iodine levels during the third trimester of pregnancy may reflect the combined influence of maternal and fetal thyroid function. Our results are intriguing and have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

Solar neutrinos have played a central role in the discovery of the neutrino oscillation mechanism. They still are proving to be a unique tool to help investigate the fusion reactions that power stars and further probe basic neutrino properties. The Borexino neutrino observatory has been operationally acquiring data at Laboratori Nazionali del Gran Sasso in Italy since 2007. Its main goal is the real-time study of low energy neutrinos (solar or originated elsewhere, such as geo-neutrinos). The latest analysis of experimental data, taken during the so-called Borexino Phase-II (2011-present), will be showcased in this talk - yielding new high-precision, simultaneous wide band flux measurements of the four main solar neutrino components belonging to the "pp" fusion chain (pp, pep, ⁷Be, ⁸B), as well as upper limits on the remaining two solar neutrino fluxes (CNO and hep).

Background: The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients treated with volanesorsen. The aim of the study is to evaluate platelet function and thrombin generation (TG) assessment in FCS patients receiving volanesorsen. We performed a cross-sectional study on FCS patients treated with volanesorsen. Methods: changes in PLC were assessed from baseline to Tw12 and Tw36. To assess TG, samples were processed by CAT (with PPP-reagent LOW). The results were expressed by the trombogram graphic (thrombin variation over time); lagTime; Endogenous Thormbin Potential(ETP); peak; time to reach peak(ttpeak), startTail e velocity Index. Platelet aggregation was assessed by testing different agonists using turbidimetry method. Results: Four FCS patients and 4 matched healthy controls were included in the present study. Changes in PLC at Tw12 was 30% and 34% at T36w. Thrombin generation results show values in normal range (for patients and controls respectively lagTime:10,42±4,40 and 9,25±0,99; ttPeak:14,33± 4,01 and 13,10±0,67; startTail:32,13±3,54 and 29,46±1,69; velocityIndex:20,21±3,63 and 33,05±13,21; ETP 599,80±73,47 and 900,2±210,99; peak value 76,84±1,07 and 123,30±39,45) and no significant difference between cases and controls. Platelet aggregation test showed values in range with no significant difference with healthy controls Conclusions: Our study showed for the first time that no significant changes in the general haemostasis assessed by TG and in platelet function have been observed in FCS patients receiving volanesorsen.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

Oritavancin is a novel long-acting lipoglycopeptide with in vitro activity against methicillin-resistant (MR) Gram-positive pathogens and a good bactericidal activity even in presence of biofilm forming bacteria. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, as for prosthetic joint infections (PJI), which, in more than half of cases, are caused by MR Gram positive organisms. We reported a case of a man in his eighties with a late shoulder PJI caused by methicillin resistant Staphyloccus epidermidis (MRSE) with contraindications for surgical replacement and few oral therapeutic options for a long term suppressive antibiotic therapy. The prosthesis was retained, and the patient received ten outpatient sequential doses of 1200 mg of oritavancin during 28 weeks, based on therapeutic drug monitoring (TDM) as a guide for correct timing of administration of each dose. During oritavancin administration, the patient achieved clinical cure, with disappearance of the pain and regaining pre-infection joint mobility, with no side effects reported and no further surgery or hospitalization needed. The treatment is ongoing as a long-lasting suppressive antimicrobial therapy. Oritavancin could represent an excellent solution for treating PJI caused by MR organism, especially in patients who need a long-term suppressive therapy.

Candida spondylodiscitis (CS) is a rare disease, for which therapeutic option are limited to fluconazole or echinocandins and the treatment should be administered up to 12 months. In case of reduced azole susceptibility, there is a scarcity of therapeutic options with adequate bone penetration and limited toxicity. We report the first case of successful use of rezafungin for a spondylodiscitis due to Candida parapsilosis with reduced susceptibility to azoles. The patient, affected by paraplegia and short bowel syndrome, was diagnosed with CS with culture on vertebral biopsy guided by a 18-FDG-PET/CT scan. He received rezafungin 200 mg weekly for 26 weeks, after 10 weeks of previous antifungal treatment. He had a full clinical, radiologic and biochemical response to the therapy with rezafungin, with no adverse effects. Rezafungin is a promising therapy for Candida osteomyelitis, especially when first line therapies are ineffective or contraindicated.

Childhood obesity is a public health problem and most of the interventions are focused on healthy habits as reducing energy intake, avoiding a sedentary lifestyle and increasing physical activity. However, usually they are based in individual programs, with few structured interventions in health systems without satisfactory results. PinPo aims to carry out an integral intervention in children with obesity, as well as in their parents and caregivers, to get motivation to change towards healthy lifestyle habits. The program contains 9 educational grupal sessions directed by a multidisciplinary expert team. 10 boys and girls, and another group with 10 family members and/or caregivers participate in sessions during 90 min biweekly. Moreover, there is an individual adaptation depending on the severity and comorbidities. At the beginning and at the end of the program, an integral evaluation for health status is developed including anthropometric, nutritional, physical activity, and psychologist and analytical measurements. Finally, a satisfaction survey is carried out on the participants.In conclusion, the implementation of PinPo could offer to paediatric patients with obesity and their families, an integral intervention to treat obesity and its complications. So, there are expectations of achieving favorable results that also allow to optimize its effectiveness.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

The aim of the present trial was to evaluate the growth performance of buffalo calves fed diets characterized by different forage/concentrate ratio with or without the Saccharomyces Cerevisiae supplementation (CBS 493.94, Yea-Sacc®). Twenty-four male buffalo calves (mean age 145.1 ± 16.1 days; mean weight 108.0 ± 18.7) were assigned randomly to 4 groups, homogeneous for age, fed four different diets: diet 1 F:C ratio 50:50; diet 2 F:C ratio 30:70; diet 3 F:C ratio 50:50 + Yea-Sacc® and diet 4 F:C ratio 30:70 + Yea-Sacc®. Buffalo calves were individually weighted before the start of the experiment and the data were used as a covariate, monthly until the end of the trial. Dry matter intake (DMI), daily weight gain (DWG) and feed conversion ratio (FCR) were calculated. The differences in diets’ composition significantly (p

The incremental sheet forming represents a relatively recent technology that guarantees high customization, thanks to the layered manufacturing principle typical of rapid prototyping, and cost-effectiveness, because it does not require dedicated equipment. Research has initially shown that this process is effective in metal materials capable of withstanding plastic deformation but, in recent years, the interest in this technique has been increasing for the manufacture of complex polymer sheet components as an alternative to the conventional technologies, based on heating-shaping-cooling manufacturing routes. Conversely, incremental formed polymer sheets can suffer from some peculiar defects, for example twisting. To reduce the risk of this phenomenon and the occurrence of failures, a viable way is to choose toolpath strategies that make the tool/sheet contact conditions less severe, and this represents the main goal of the present research. Polycarbonate sheets were worked by incremental forming; in detail, cone frusta with a fixed wall angle were manufactured with a reference and a stair toolpath strategy, and both the forming forces and the twist angle were monitored. The analysis of the results highlighted that a stair toolpath involving an alternation of diagonal up and vertical down steps represents a useful strategy to mitigate the forming forces and, with them, the occurrence of the twisting phenomenon in incremental formed thermoplastic sheets.

In late December 2019 a novel RNA beta-coronavirus was recognized as the causative agent of previously pneumonia cases of unknown origin. The virus was successively named Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) as well as the respiratory illness that it causes Coronavirus disease 19 (COVID-19) (1, 2). The global spread of SARS-CoV-2 and the thousands of deaths caused by COVID-19 led the World Health Organization (WHO) to declare a pandemic on 11 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. Indeed, even if most patients with COVID-19 are asymptomatic or experience mild self-limiting disease, 14% of them progress to severe disease and 5% to critical illness with complications, such as interstitial pneumonia, respiratory failure with acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndromes (MODS) (3). It is accepted that SARS-CoV-2 primarily affects the respiratory system, although other organs are also involved (4). The virus enters host cells by attaching its Spike like surface projections to the angiotensin-converting enzyme-2 (ACE2) receptor which is mainly expressed on alveolar epithelial cells and in nearly all human organs in varying degrees. Thus, although the central target of SARS-CoV-2 infection is the lung, the wide distribution of ACE2 receptors in other organs may lead to cardiovascular, gastrointestinal, kidney, liver, central nervous system and ocular damages that have to be closely monitored during the disease (5, 6). The virus then activates the innate and adaptive immune system resulting in a large number of cytokines release, known as “cytokine storm”, that is directly correlated with tissue injury and unfavourable prognosis of severe lung disease (7). In particular, interleukin (IL)-6 seems to plays an important role in driving this cytokine release so that its increased levels have been recognized as a hallmark inflammatory signature in sera of COVID-19 patients (8). IL-6 is a polyfunctional cytokine with both anti-inflammatory and pro-inflammatory properties which exerts its several functions through two main signal transduction pathways (9). In the classical signal transduction pathway, IL-6 binds to IL-6-trans membrane receptor (IL-6R) to form a complex that, then, binds to the trans membrane glycoprotein gp130, inducing its homo-dimerization and initiating intracellular signal transduction. This kind of signaling is limited to cells (hepatocytes, macrophages, neutrophils, T cells, etc.) that express IL-6R on their cell surface (10). Nevertheless, cells do not express IL- 6R, as stromal and epithelial cells, are able to still respond to IL-6 because the soluble form of the receptor (sIL-6R) binds to IL-6 in circle and then anchors to membrane gp130 receptor, initiating the trans-signaling pathway. For this reason, sIL-6R is able to increase the function of IL-6 and is considered the agonist form of its receptor. When the level of IL-6 increases, its effects are widely expressed because gp130 molecules are ubiquitous and, therefore, also present in cells without IL-6R in the membrane form. On the contrary, a soluble form of the glycoprotein 130 (sgp130) can complex with sIL-6R to prevent the sIL-6R from binding to the membrane-bound gp130. In this case sgp130 is able to decrease the function of IL-6 and is considered the antagonist form of IL-6 receptor system (11). Based on the central role of IL-6 in the inflammatory pathology of COVID-19 and the consistent association between elevated levels of the cytokine and severe disease outcomes found in the first phase of infection, we sought to analysis IL-6 and its soluble receptor complex behavior during the different waves of COVID-19 pandemic, in order to evaluate the possible differences which occur among them and to hypothesize if they might be used as prognostic markers of disease severity.

The aim of this paper is to establish a valid procedure for better understanding all the phenomena associated with the high-speed machining of Glass Fibre Reinforced Plastic (GFRP) composites. Both rectangular and circular specimens were machined at high speeds (up to 50 m/min) in order to understand what occurred for all values of fiber orientation angles during machining operations. An innovative testing methodology was proposed and studied to investigate the phenomenon of burr formation and thus understand how to avoid it during machining operations. To this end, the forces arising during the machining process and the roughness of the resulting surface, were carefully studied and correlated with the cutting angle. Additionally, the cutting surface and chip morphology formed during cutting tests were examined using a high-speed camera. Close correlations are found between the variations of the cutting forces' signals and the trends of the roughness and the morphology of the machined surface.

(1) Background: The aim of this investigation is to determine the effect of archwires’ deflection on the temperature transitions driving the austenite to martensite transformation (and vice versa) and the force released by NiTi and CuNiTi orthodontic wires. (2) Methods: Round cross-section archwires have been investigated. The calorimetric approach has been used for measuring transition temperatures occurring in the unstressed (e.g. undeflected) state of the wires. Static Thermo-mechanical analysis in a temperature controlled wet environment has been performed in the range of temperature between 5°C and 55°C for measuring temperature transitions occurring in highly deflected archwires in conjunction with the force released by these wires. (3) Results: Plateau forces investigated in Part I and those reported in the literature describes the wire’s behaviour only at deflection levels close to the end point of the force plateau extension detected at 37°C. Upon heating or cooling, the austenite finish (Af) transition temperature and the martensite start (Ms) temperature largely depends on the deflection level for both NiTi and CuNiTi. (4) Conclusions: The plateau force levels at 37°C, broadly reported in the literature, only represent the lower boundary force that a superelastic wire releases at 37°C above its elastic limit. For both NiTi and CuNiTi, plateau force levels at 37°C can be predicted by the static TMA profile matching the end point of the force plateau extension. Transition temperatures in largely deflected wires are significantly higher than those determined through the calorimetric approach.

Silencing of the fragile X mental retardation 1 (FMR1) gene and consequently lack of synthesis of FMR protein (FMRP) are associated with fragile X syndrome, which is one of the most prevalent inherited intellectual disabilities. FMRP is a multifunctional protein involved in many cellular functions in nearly all subcellular compartments under normal conditions and under conditions of cellular stress in both neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Introduction: Hospitalization in a COVID-19 unit represents a significant source of stress and psychological distress for patients. Our study aims to determine the factors of psychological distress in the therapeutic and psychosocial management of patients hospitalized with a COVID-19 infection. Methods: This cross-sectional study was carried out over 8 months at the COVID-19 zone of the CHU HASSAN II of FES. 99 patients were evaluated within days of diagnosis by psychometric scales of anxiety, depression, and post-traumatic stress. In the course of this follow-up, we found the presence of psychological impacts in these patients, and we tried to find correlating factors between the occurrence of psychiatric disorders and the set of factors related to sociodemographic data, hospitalization course and treatments taken, as well as family support. Results: 35% of patients had scores in favor of post-traumatic stress disorder, 37% of the patients had definite depression and 50% had anxiety. Post-traumatic stress, depression, and anxiety were correlated with sociodemographic factors, hospitalization, treatments received, and length of stay. Conclusion: The prevalence of anxiety-depressive disorders and post-traumatic stress disorder was high in patients with COVID-19, hence the interest in providing psychological and psychosocial care in the emergency department.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was done by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins and DNA. The cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extract contains catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile shows obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with IC50 of 4.86 ± 0.51 µg/mL and 8.33 ± 0.90 µg/mL in the ABTS assay for ELSR and ERSR, respectively. And in the DPPH• assay, the IC50 was 19.98 ± 1.96 µg/mL for ELSR and 13.37 ± 1.05 µg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 µg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 hours of treatment. After 48 h, results against the K562 cell line demonstrate IC50 of 242.54 ± 2.38 µg/mL and 223.00 ± 2.34 µg/mL for ELSR and ERSR , respectively. While against the Jurkat cell line, these extracts showed IC50 of 171.45 ± 2.25 µg/mL and 189.30 ± 2.27 µg/mL, respectively Results on PBMC viability, demonstrate that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions. This study expands the repertoire of identified chemical compounds and underscores their significant pharmacological potential in conditions related to oxidative stress and leukemia.

Background and Objectives: To investigate the relationship between the SII index and the micro-macro complications and death that develop in the first year and the following 3 years, following the calculation of the index in type 2 diabetic retinopathy patients. Materials and Methods: This study was performed retrospectively with 523 type 2 diabetic retinopathy patients admitted to the endocrinology outpatient clinic of our hospital between January 2019 and December 2019. The demographic, and clinical characteristics of the patients were evaluated using descriptive statistics. Shapiro-Wilk test was used for the normal distribution of quantitative data; Mann-Whitney U, Mc Nemar Chi-square, and Cochran's Q tests were used to analyze SII values between groups and complication rates by years; sensitivity and specificity were determined by ROC analysis and considered statistically significant with a significance level of P

Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine therapy is a cornerstone in DTC management, but sometimes it became useless when cancer cells develop refractoriness. Radioactive Iodine Refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. 18F-FDG PET/CT has been widely used, it has a demonstrated prognostic value, but 18F-FDG DTC avidity may remain low. FA-Pi, PSMA, SSTR tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed to re-induce RAI accumulation in DTC cells. Results appeared promising, despite not excellent. Conclusions: RAIR-DTC yet represent a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation with post-therapy whole body scan (PT-WBS) is the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents oblige physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

Energy metabolism regulates the proliferation of stem cells by regulating energy production and the production of substrates through biosynthetic pathways. It is an important target for cell regulation and stem cell applications, and is crucial for determining the pluripotency and cell fate of stem cells. In this context, this article focuses on reviewing the latest research progress on the association between glucose metabolism, amino acid metabolism, fatty acid metabolism, and mitophagy with stem cell function, elucidating how key energy metabolism pathways affect stem cell function by regulating signal transduction and epigenetic modifications. In this review, we discuss the key factors affecting energy metabolism and their association with stem cell function. The integration of energy metabolism and stem cell fate regulation will open up a new path for future regenerative medicine practices.

Urinary tract infections in kidney transplant patients are a real challenge. We conducted a retrospective observational study, enrolling all kidney transplant patients hospitalized for urinary tract infection (UTI), with the objective to evaluate the epidemiology, clinical sta-tus, therapeutic management, and clinical outcome of kidney transplant patients hospi-talized for urinary tract infection in a university hospital. From our real-life experience, infection with multidrug-resistant germs was confirmed as a risk factor for the severe evolution of the infection and at the same time the re-evaluation of immunosuppressive therapy could be an important therapeutic strategy in the course of infection. Prompt ini-tiation of empiric antibiotic therapy upon initiation of microbiological investigations could potentially reduce the risk of severe infection progression.

Background: Permanent tracheostomy because of total laryngectomy surgery entails great conse-quences for the patient regarding respiratory physiopathology such as the filtering, humidifying, and heating function of the air by the nose is lost. The use of special stomal filters can determine adequate protection of the trachea-broncho-pulmonary system with a reduction in respiratory pathologies. In fact, in most cases laryngectomee patients are first cigarette smokers who for this reason already have also respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, multiple times, as reported in the literature, the patient tends to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for the laryngectomee patient during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® Life™ Energy HME and Provox® Life™ Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomee patients, subjected to medi-um-high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT) which involves a sustained walk lasting six minutes, with evaluation , every 60 seconds, heart rate, oxygen saturation and meters travelled; furthermore, it examines two sub-jective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index.

Many risk-modifying factors affect cancer incidence and mortality rates. We present an ecological study of incidence and/or mortality rates for cancers during 2007–2016 of 17 anatomical sites with respect to solar ultraviolet-B (UVB) doses and obesity prevalence. Solar UVB reduces cancer risk by producing vitamin D, which has many mechanisms to reduce risk of cancer incidence, progression, and metastasis. Obesity increases cancer risk through several mechanisms, including increased systemic inflammation. Data were averaged for 12 geographical regions. Solar UVB doses were significantly inversely correlated with mortality rates for five cancers for males and four for females. Obesity prevalence was directly correlated with mortality rates for three cancers for males and seven for females. The population attributable fraction of cancer mortality rates ascribed to low solar UVB dose was 0.03 for both males and females, whereas that for obesity prevalence was 0.05 for males and 0.08 for females. Thus, cancer mortality rates in France could be reduced through vitamin D supplementation and reducing the prevalence of obesity. Doing so also could reduce risk of other adverse health outcomes.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nano-delivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nano-encapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nano-encapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nano-encapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

In marine ecosystems communication among microorganisms is crucial since the distance is significant if considered on a microbial scale. One of the ways used by microorganism cells to reduce this gap is the production of extracellular vesicles. Marine bacteria release extracellular vesicles (EVs), small membrane-bound structures of 50 to 250 nm diameter, into their surrounding environment. The vesicles contain various cellular compounds, including lipids, proteins, nucleic acids, and glycans. EVs may mediate the communication between microorganisms in aquatic environments thus influencing ecosystem function and determining the structure and composition of microbial populations. This review will focus on marine bacterial EVs analysing their structure, composition, functions, and applications.

Background/Objectives: Infectious Endocarditis often requires surgical intervention, with postoperative acute kidney injury (AKI) posing a significant concern. This retrospective study aimed to investigate AKI incidence, its impact on short-term mortality, and identify modifiable factors in patients with endocarditis scheduled for valve surgery. Methods: This single center study enrolled 130 consecutive endocarditis patients from 2013 to 2021 undergoing valve surgery. Creatinine levels were monitored pre- and postoperatively, and AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patient demographics, comorbidities, procedural details, and complications were recorded. Primary outcomes included AKI incidence, the relevance of creatinine levels for AKI detection, and the association of AKI with 30-, 60- and 180-day mortality. Modifiable factors contributing to AKI were explored as secondary outcomes. Results: Postoperatively, 35.4% developed AKI. The highest creatinine elevation occurred on the 2nd postoperative day. Best predictive value for AKI was a creatinine level of 1.35 mg/dl on the 2nd day (AUC: 0.901; sensitivity: 0.89, specificity: 0.79). Elevated creatinine levels on the 2nd day were robust predictors for short-term mortality at 30, 60 and 180 days postoperatively (AUC ranging from 0.708 to 0.789). CK-MB levels at 24 hours postoperatively and minimum hemoglobin during surgery were identified as independent predictors for AKI in logistic regression. Conclusions: This study highlights the crucial role of creatinine levels in predicting short-term mortality in surgical endocarditis patients. A specific threshold (1.35 mg/dl) provides a practical marker for risk stratification, offering insights for refining perioperative strategies and optimizing outcomes in this challenging patient population.

In the last decades we have experienced great social, cultural, and educational changes, spending more time performing tasks in near vision and less hours in outdoor activities, having more overexposure to digital screens, especially the youngest and increasingly from younger ages. It is common to see cases when performing tasks in near vision the posture or position of the head is not adequate, especially the youngest, being essential to have a correct posture of the head to avoid visual, muscular, or articular problems. We present a procedure to try to control the correct position of the head in real time when performing close-up activities. The aim is to detect the inclination of the head and to know if a bad position is adopted due to a visual problem or simply to inadequate visio-postural habits, warning us of the postural anomaly to correct it.

Knee osteoarthritis (KOA) is a progressive and multifactorial disease that leads to joint pain, muscle weakness, physical disability, and decreased quality of life. In KOA, hyaluronic acid (HA) quantity and molecular weight (MW) are decreased, leading to joint pain due to increased wear of the knee articular cartilage. Arthrogenic muscle inhibition, which is usually found in patients with KOA, is associated with joint inflammation, pain, and swelling, also causing muscle atrophy, primarily of the anterior thigh muscles, and hindering the rehabilitation process. The aim of our work was to determine if a single HA infiltration could minimize the effects of arthrogenic muscle inhibition in patients with KOA in the short term, using isokinetic dynamometry to evaluate the strength of the knee extensor and flexor muscles of the thigh. Thirty patients with KOA who underwent both clinical and isokinetic assessment, and that received a single injection of HA, were retrospectively included. Our results showed that a single intra-articular injection of HA significantly reduces pain and improves joint function at four weeks, while non-statistically significant improvements were observed for the reference isokinetic parameter (maximum torque) at both 90°/s and 180°/s. Further high-quality studies are necessary to confirm the results of our study.

This article presents a new input device for spastic patients and others with similar symptoms. The sensor consists of a disc used to determine positions and can replace standard joysticks in medical devices such as electric-powered wheelchairs. Using a standard joystick while operating a powered wheelchair can result in dangerous situations when spastic movements occur and extremities cramp making them uncontrollable. To avoid this, a disc was developed that can be controlled with any body part. By shifting weight (x- and y-axis) the disc can tilt in any direction creating a proportional output signal and can also be pushed down in the center (z-axis) to open a menu on a screen for example. When spasms occur it is impossible for users to get stuck on the input device because the disc is flat and can be mounted within a control panel. Body parts coming into contact with the disc would merely slide across the disc without triggering unintentional actions. The sensor presented here is also adaptive and can be adjusted to fit a user’s strength and range of motion. This proposal aims to develop an input device that enables spastic patients to operate sensitive systems safely.

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions but in case of copper(II) and nickel(II) the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ion but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relative low thermodynamic stability with these peptides. Copper(II) catalyzed oxidation of the peptides was also studied. In the presence of H2O2 the fragmentation of peptides can be detected in all cases. In the simultaneous presence of of H2O2 and ascorbic acid the extent of the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.

Cestrum parqui L'Herit. (Solanaceae family) is a species of forest shrub, self-incompatible and specialized in pollination, widespread in the subtropical area of the planet and now widely dis-tributed also in the Mediterranean area. The constituents of its leaves have antimicrobial, anti-cancer, insecticidal, antifeedant, and herbicidal properties. The spread of this species represents a valuable source of compounds with high biological value. Research on potential uses, under-standing of the nutritional and functional composition, and applications of C. parqui extracts is important and very promising for its commercial use. To date, there are some reports on the potential applications of C. parqui extracts as selective natural pesticides and for their potential phytotoxic role. Scientific knowledge and the use of extraction techniques for these components are essential for commercial applications. This article summarizes the research and recent studies available on the botany, phytochemistry, functional properties, and commercial applications of C. parqui as a biopesticide.

In recent decades, there has been a startling rise in the number of cancer patients worldwide, which has led to an amazing upsurge in the development of novel anticancer treatment candidates. On a positive note, arylpiperazines have garnered attention in cancer research due to their potential as scaffolds for developing anticancer agents. These compounds exhibit a diverse array of biological activities, including cytotoxic effects against cancer cells. Indeed, one of the key advantages of aryl piperazines lies in their ability to interact with various molecular targets implicated in cancer pathogenesis. Here, we focus on the chemical structures of several arylpiperazine derivatives, highlighting their anti-proliferative activity in different tumor cell lines. The modular structure, diverse biological activities, and potential for combination therapies of arylpiperazine com-pounds make them valuable candidates for further preclinical and clinical investigations in the fight against cancer. This review, providing a careful analysis of different arylpiperazine deriva-tives and their biological applications, allows researchers to refine the chemical structures to improve potency, selectivity, and pharmacokinetic properties, thus advancing their therapeutic potential in oncology.

Dementia, primarily caused by neurodegenerative diseases like Alzheimer’s disease (AD), affects millions worldwide, making detection and monitoring crucial. To enable these tasks, we propose encoding in-text pauses and filler words (i.e., “uh” and “um”) in text-based language models, and thoroughly evaluate their effect in performance. Additionally, we suggest using contrastive learning to improve performance in a multi-task framework. Our results demonstrated the effectiveness of our approaches in enhancing the model’s performance, achieving 87% accuracy and an 86% F1-score. Compared to the state-of-the-art, our approach has similar performance despite having significantly fewer parameters. This highlights the importance of pause and filler word encoding on the detection of dementia.

Two interesting compounds such as quaternary ammonium lignin(QAL) and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester (P507) were synthesized as ionic liquids(QP-ILs) for the extraction of metal ions. The extraction behavior of Co(II) and Ni(II) from chloride solution was compared between QP-ILs and P507. The results showed that the extraction rates of Co(II) and Ni(II) in the two solutions varied with the extraction conditions, but QP-ILs has stronger extractability for cobalt than P507, while Ni is on the contrary. Under the same conditions, the Co/Ni separation performance(βCo/Ni) in QP-ILs is superior to that in p507. At pH4.0, 55℃, concentration of 20%, extraction time of 10 minutes, the βCo/Ni of QP-ILs reached to 2703, while that of P507 was only 164. In conclusion, QP-ILs was more efficient than P507 for separating Co from mixed solutions.

Simple summary This reassessment of the findings from our Phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate-high risk prostate cancer in the absence of androgen-deprivation therapy due to patient’s refusal, with a median follow-up of 6.5 years. Our primary focus is on analysing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade 2 or higher, both genitourinary and gastrointestinal. Abstract Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intraprostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intraprostatic recurrences occurred in 7 patients (21%), with ≥ 75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patient. Notably, 5 patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intraprostatic recurrences. Extended follow-up revealed grade 2 or higher late GU and GI toxicity in 18% (n=6) and 6% (n=2) of the patients. Conclusions: Among patients with intermediate-high risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: focal dose escalated prostate SBRT prevented recurrences in the dominant nodule, however extra-prostatic recurrence sites were frequent.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

Allopolyploidy in plants involves the merging of two or more distinct parental genomes into a single nucleus, a significant evolutionary process in the plant kingdom. Transcriptomic analysis provides valuable insights into the fate of duplicated genes, evolutionary novelties, and environmental adaptations exhibited by allopolyploid plants. However, transcriptome profiling is challenging due to genomic redundancy, which is further complicated by the presence of multiple chromosomes sets and the variations among homoeologs and allelic genes. Prior to transcriptome analysis, sub-genome phasing and homoeology inference are essential for obtaining a comprehensive view of gene expression. This review aims to clarify the terminology in this field, identify the most challenging aspects of transcriptome analysis, explain their inherent difficulties, and suggest reliable analytic strategies. Furthermore, bulk RNA-seq is highlighted as a primary method for studying allopolyploid expression, with an emphasis on the critical steps of read mapping and normalization in differential gene expression analysis.

Epilepsy is a non-communicable neurological disease characterized by abnormal brain activity with conceivable peripheral implications. Few studies examine the role of peripheral and brain inflammation in the relationship between seizure predisposition and nonalcoholic fatty liver disease. Severe early-life infections leading to sepsis results in increased inflammation that can aggravate epilepsy and hepatic damage progression both associated with increased odds for hospital admissions in epileptic patients. Here, we examined the effect of early LPS challenge (1 mg/kg, i.p. at post-natal day3, PND3) in inducing hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45), evaluating the intra- and inter-gender differences on systemic and liver inflammation, hepatic lipid dysmetabolism and oxidative damage associated to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Early LPS challenge induced a major inflammatory and immune response in male epileptic rats than females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-insulted females showed a marked alteration in hepatic metabolic and lipid profile and the reduction in mitochondrial fatty acid oxidation. The two different gender-related mechanisms of LPS-induced liver injury converge in mitochondrial oxidative damage with intensified ROS production in both sexes, that notably induced a compensatory increase in antioxidant defense only in females. Our study with a translational potential points out that early postnatal infections predispose epileptic rats to develop or worsen hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

The COVID-19-medical emergency has ended worldwide, yet there is still a need to evaluate the psychological impact of these years of unprecedented changes on students’ life. Methods: This study aims to assess and compare COVID-19-related stressors (Relationships-and-Academic-Life; Isolation; Fear-of-Contagion) and psychophysical symptoms reported by university students in April-2020, April 2021, and April 2022. The predictive role of COVID-19-related stressors on psychophysical symptoms within each time was also tested. Data were collected among 637 university students in April-2020 (n = 197), April-2021 (n = 200), April-2022 (n = 240). Results: In April-2022, perceived Isolation and Fear-of-Contagion decreased from the peak registered in April-2021, but stress related to Relationships-and-Academic-Life remained noteworthy high. A sharp and ongoing increase in psychophysical symptoms was found, with more than 50% of students reporting clinical levels of Sleep-Disorders, Depression, Psychoticism, and Interpersonal-Sensitivity. In April-2022, students still perceiving stress related to Relationships-and-Academic-Life and Isolation were at risk for Anxiety, Somatization, and Sleep-Disorders, while those still perceiving stress related to Fear-of-Contagion were also at risk for Depression, Obsessive-Compulsive, and Psychoticism. Conclusion: Findings emphasized the long-lasting detrimental effects of the COVID-19-related stress. Interventions must pinpoint the complex post-pandemic adjustment process and their effects on university students' psychophysical health.

The theory and working principle of fabric phase sorptive extraction (FPSE) is presented that eloquently explains the mystery behind this new and powerful sample preparation technique. FPSE innovatively integrates the benefits of sol-gel coating technology and the rich surface chemistry of cellulose/polyester/fiberglass fabric, resulting in a microextraction device with very high sorbent loading in the form of an ultra-thin coating. This porous sorbent coating and the permeable substrate synergistically facilitate very fast extraction equilibrium. The flexibility of the FPSE device allows for direct insertion into original, unmodified samples of different origin. Strong chemical bonding between the sol-gel sorbent and the fabric substrate permits the exposure of FPSE devices to any organic solvent for analyte back-extraction/elution and to highly acidic or basic environments (pH 1-12) if required. A sol-gel derived sorbent, highly polar sol-gel poly(ethylene glycol) coating, was generated on cellulose substrates. Five cm2 segments of these coated fabrics were used as the FPSE devices for sample preparation using direct immersion. An important class of environmental pollutants, substituted phenols, was used as model compounds to evaluate the extraction performance of FPSE. The high primary contact surface area (PCSA) of the FPSE device and porous structure of the sol-gel coatings resulted in very high sample capacities and incredible extraction sensitivities for both the compound classes in a relatively short period of time. Different extraction parameters were evaluated and optimized. The new extraction devices demonstrated part per trillion level detection limits for substituted phenols, a wide range of detection linearity, and good performance reproducibility.

(1) Background: A wide literature based on loading and unloading bending tests has been carried out over the half past century for assessing the force released by superelastic wires. The aim of this investigation is not only to characterize a broadly described superelastic NiTi and a novel CuNiTi archwire, but also to provide novel insights into the load vs deflection profiles. A harmonic scenario for superelastic wires will be shown as temperature is kept constant at 37°C. However, a completely different picture will be highlighted as a temporary heating step up to 50°C is introduced within the force vs deflection profiles. (2) Methods: A variety of NiTi and a novel CuNiTi round and rectangular cross-section archwires have been investigated. Static 3-point bending tests up to a deflection level of 3.0 mm have been carried out for detecting the unloading force plateau levels occurring at 37°C. A hold deflection step of 5 min at deflection levels occurring along the unloading plateau extension is introduced. The effect of a temporary heating up to 50°C on the force plateau level released by the investigated wires is analyzed. (3) Results: Mechanical profiles suggest that the plateau force levels detected at 37°C are consistent with those broadly reported in the literature, but they only represent a single block puzzle of the force scenario that a superelastic wire releases during the orthodontic treatment. (4) Conclusions: Once a superelastic wire is bent and clinically applied, the effect of a temporary heating up to 50°C (e.g. hot food or drink ingestion) produces a significant plateau force increase whose magnitude depends on the deflection level. The highest force increase of about 50% and 40% have been detected at deflection levels located at the beginning of the unloading plateau extension for NiTi and CuNiTi wires, respectively.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

Approximately 20% of the world's population resides in coastal areas at risk of rising sea levels due to climate change. This could lead to severe weather events and ecological impact on critical infrastructure. To combat the effects of water-based environmental forces on the land, hard engineering methods such as seawalls have been utilized. However, a more sustainable solution is emerging in nature-based engineering, which involves growing vegetation. This approach can help extend the lifespan of existing technology and provide climate change adaptation and resilience for coastal and riverine communities. The following paper will review seaweed farms as an advanced nature-based mitigation approach. The paper also outlines the findings of experiments at RWTH Aachen University's hydraulic laboratory. These tests involved using seaweed as a natural solution to dampen waves in a model system to test a hypothesis. One result involving a system with two lines of seaweed revealed 15 percent wave damping. Using seaweed as a nature-based solution, a gentle engineering approach to designing future vegetated protection systems can extend the design life of existing coastal infrastructure. This can also provide protection against climate-induced sea level rise, promote coastal risk mitigation, restore ecosystems, and foster blue bio-economic development.

Hydroxamic acid (HA) derivates displayed antibacterial and antifungal activities. HA with various numbers of carbon atoms (C2, C6, C8, C10, C12 and C17), complexed to different metal ions Fe(II/III), Ni(II), Cu(II) and Zn(II) were evaluated for their antimycobacterial activities and their anti-biofilm activities. Some derivates, among others HA12Fe2, inhibited the development of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium marinum biofilms and could even attack pre-formed Pseudomonas aeruginosa biofilm. Proteomic profiles showed that the potential targets of HA10FeCl were mainly related to mycobacteria stress adaptation, involving cell wall lipid biosynthesis, drug resistance and tolerance, siderophore metabolism. This study provides new insights regarding the antimycobacterial activities of the HA and their complexes, especially about their potential antibiofilm activities.

In this work is proposed a new unsupervised method to evaluate the behavior of urban green areas in presence of heatwave scenarios analyzing the NDVI, NDMI and LST satellite data. To evaluate how these three indices characterize urban green areas during periods of heat waves, a reclassification of the data raster of each index is carried out. Rather than using standard classifications of the three indices, an unsupervised classification approach is proposed that uses the Elbow method to determine the optimal number of classes and the Jenks thematic classification method. Each class is assigned a Gaussian fuzzy set with means and standard deviations equal to that of the associated thematic class. The green urban areas are classified using zonal statistics operators and the degree of membership in the corresponding fuzzy set is used to assess the reliability of the classification. Finally, for each type of greenery the frequencies of belonging to the NDVI, NDMI and LST classes are analyzed to evaluate the behavior of the type of urban greenery during heatwaves. The framework was tested in an urban area consisting of the city of Naples (Italy). The results show that some types of greenery, such as deciduous forests and olive groves, are not very vulnerable to heatwave scenarios, unlike uncultivated areas which, instead, show critical behaviors during heatwaves.

Design process can be divided into stages of analysis and synthesis. This paper presents the application of the object-oriented technique to the synthesis as well as theoretical considerations concerning to design of gear size ranges. The synthesis consists in composition (aggregation) of single details into units – according to the rule: “from details up to general view”. The basics of the object-oriented synthesis were formulated. Furthermore, the consecutive stages of synthesis were formulated. The interactions between these stages were discussed. Some aspects were described in details e.g.: creation of interfaces for performance of the embodiment phase the designed artefact via CAD system drawing with specification (dimensions are still parametrically set). The final step of the procedure is creation of so called substantial (concrete) form of artifacts i.e. final assignment of dimensions which stored in the special data base. The final stage of the design process is issuing of technical documentation (technical drawings) created automatically via CAD system. The considerations are terminated by the list of advantages connected with the object-oriented approach to design (in comparison to the traditional way).

Lap joints were friction stir welded in AA 7075-T6 at 1320 rpm and using two welding speeds: 70 mm/min and 120 mm/min. The temperature profiles of the weld zone were registered during the process; furthermore, the microhardness, tensile strength, and microstructure of the joints produced were examined. This study brings new insights into the thermomechanical behavior of the material during the process. The peak temperature obtained with the lower welding speed (70 mm/min) is 10% higher than that obtained with the higher speed (120 mm/min). Moreover, a 5% increase in microhardness and a 6% increase in tensile strength were were observed increasing the welding speed. Addition-ally, the microstructure examination demonstrated that, by decreasing the welding speed, the larger interaction between the tool and the material results in a deeper stir zone due to the increased heat diffusion downwards to the material. This heat flow affects the thermal profile and influences the resulting mechanical properties of the welded joints.

Microalgae cultivation for biotechnological purposes is an expanding field. Their cultivation is usually performed on a liquid culture medium and require the presence of an energy source. Culture media are water-salt solutions containing nitrogen, sulfur, phosphate sources, with trace of transition metals. Light source supplies energy through photosynthesis process, resulting in metabolic reactions and cell growth. Thanks to the huge number of existing species and their diversity, it is possible to exploit alternative water sources with chemical and physical properties far from the commonly used freshwater media. Among these, oilfield or formation waters (AFW) are saline wastewater produced during oil drilling. They represent over 95 % of the total fluids collected from gas and oil wells during fuel extraction. This study exploits the adaptation capability of a Galdieria sulphuraria strain in different salinity conditions to build up a more feasible microalgae-based platform. Batch cultivation of G. sulphuraria was evaluated in a range from 0 to 20 g/L NaCl in terms of growth rate, metabolite content, photophysiology, and intracellular redox state. Moreover, the same strain has been tested for artificial formation water growth in semicontinuous cultivation mode. In these condition, NaCl preadaptation effect has been assessed too. Results clearly demonstrate that biomass composition is influenced from medium salinity. Strains preadapted in 0 to 20 g/L range of NaCl salinity show almost same cell growth profile and a slightly different ratio between lipids, carbohydrates, and proteins. Pigments content and photophysiology point out that variations of osmotic pressure and ionic strength in medium affect Photosystem II (PSII). Regulation of light harvesting is necessary to trigger metabolism shift toward synthesis of metabolites required in the adaptation process.

Background: Heart failure (HF) remains a challenging healthcare issue, necessitating innovative therapies like cardiac resynchronization-defibrillation therapy (CRT-D). However, defining CRT-D responders lacks uniformity, impeding effective clinical evaluation. This study explores diverse CRT-D responder definitions, encompassing functional, echocardiographic, and laboratory criteria. Materials & Methods: A single-center study involving 132 CRT-D patients scrutinized responder criteria, including NYHA stage, LVEF increase, and proBNP decrease. Statistical analyses, such as Kaplan–Meier curves and Cox hazard regression, were employed to evaluate responder characteristics and survival outcomes. Results: Responder rates varied across criteria, revealing nuanced patient profiles. CRT-D responders, defined by NYHA decrease, LVEF increase, or proBNP decrease, exhibit improved survival rates after 2 and 3 years (p < 0.050). Young age, absence of recent myocardial infarction, and normal right ventricular, echocardiographic parameters emerge as predictors for positive response. In part, drug-based HF therapy correlates with increased responder rates. Cox regression identified LVEF ≥ 5% and proBNP decrease ≥ 25% as independent predictors of extended survival. Conclusions: CRT-D responder definitions exhibit considerable variability, emphasizing the need for a nuanced, patient-centered approach. Factors like right ventricular function, drug therapy, atrial fibrillation, and renal function influence responses. The study enriches our understanding of CRT-D response, contributing to the foundation for personalized HF management.

The amino acid proline accumulates in plants during abiotic stresses such as drought and salinity and is considered a reliable marker of environmental stress. While its accumulation is well established, its precise role in stress tolerance and its underlying molecular mechanism remain less clear. To address these issues, we performed a meta-analysis - a robust statistical technique that synthesizes results from multiple independent studies while accounting for experimental differences. We focused on 16 physiological and morphological parameters affected by drought and salt stress in transgenic plants expressing proline metabolic genes. For each parameter, we calculated the effect size as the response ratio (RR), which represents the logarithm of the mean value in the transgenic group over the mean value of the control group (lnRR). Under stress, most parameters exhibited significantly higher response ratios in the transgenic group, confirming the beneficial effects of proline during drought and salt stress. Surprisingly, under non-stressed conditions, most stress markers showed no significant differences between transgenic and non-transgenic plants, despite elevated proline levels in the former. These results suggest that the benefits of proline may be related to proline catabolism or may only become apparent during stress, possibly due to interactions with reactive oxygen species (ROS), which accumulate predominantly under stress conditions.

This paper studies the Bondi-Metzner-Sachs group in homogeneous projective coordinates, because it is then possible to write all transformations of such a group in a manifestly linear way. The 2-sphere metric, Bondi-Metzner-Sachs metric, asymptotic Killing vectors, generators of supertranslations, as well as boosts and rotations of Minkowski spacetime, are all re-expressed in homogeneous projective coordinates. Last, the integral curves of vector fields which generate supertranslations are evaluated in detail. This work prepares the ground for more advanced applications of the differential geometry of asymptotically flat spacetimes in projective coordinates.

The Solvency II regulatory framework specifies procedures and parameters for determining solvency capital requirements (SCRs) for insurance companies. The proposed standard SCR calculations involve two steps. The Value–at–Risk (VaR) of each risk driver is measured and, in a second step, all components are aggregated to the company’s overall SCR, using the Standard Formula. This formula has two inputs: the VaRs of the individual risk drivers and their correlations. The appropriate calibration of these input parameters has been the purpose of various Quantitative Impact Studies that have been conducted during recent years. This paper demonstrates that the parameter calibration for the equity–risk module—overall, with about 25%, the most significant risk component—is seriously flawed, giving rise to spurious and highly erratic parameter values. As a consequence, an implementation of the Standard Formula with the currently proposed calibration settings for equity–risk is likely to produce inaccurate, biased and, over time, highly erratic capital requirements.

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether ARA metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and arachidonic acid (ARA) metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2, prostaglandin F2α, lipoxin A4, ±8(9)-EET, ±11(12)-EET, and ±8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (PLA2 and COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including IFN-γ, TGF-β1, IL-4, and IL-6. In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. In this study, we revealed the structure of the cecal flora of Wenchang chickens infected with S. Typhimurium and demonstrated that S. Typhimurium can mediate the onset and development of intestinal inflammation through the activation of the metabolic pathway of ARA cyclooxygenase in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

The classification of kidney tumors has undergone a remarkable evolution since the early 19th century, reflecting advances in medical science and technology. This historical overview traces the development of renal tumor classification, beginning with early clinical observations and macroscopic descriptions to the integration of molecular diagnostics in contemporary classifications. The establishment of international organizations like the World Health Organization (WHO) facilitated collaboration and standardization in tumor classification, leading to refined classifications and standardized nomenclature. Advancements in histological and molecular studies, particularly genetic analyses, revolutionized the understanding of renal cell carcinomas, enabling precise categorization based on molecular characteristics. The journey from rudimentary classifications to sophisticated systems based on detailed histological, immunohistochemical, and molecular criteria underscores the continuous evolution of kidney tumor classification. This article provides a comprehensive overview of this evolution, highlighting the contributions of scholars and the impact of technological advancements on our understanding and management of kidney tumors.

Pseudomonas donghuensis P482 exhibits broad antibacterial and antifungal activity, primarily related to the production of 7-hydroxytropolone (7-HT). However, the restricted nutritional conditions (viz. mineral medium with single carbon source) diminished the antagonistic activity of P482. In this study, we unveil profiles of the secondary metabolites from P482 and its selected mutants, using nutrient-diluted (10% tryptone soy broth, TSB) and nutrient-restricted (M9 with either 0.4% glucose or 0.4% glycerol as a sole carbon source) media to explore differences in the quantity and quality of the secondary metabolites produced. No 7-HT was found to be synthetized by P482 under restricted nutritional conditions. However, both the wild-type and the tested mutants of P482 still did express some antagonistic activity towards the plant pathogenic bacteria tested. Based on these results, we postulate that 7-HT is not the sole antimicrobial compound produced by P. donghuensis P482 and that other antimicrobials may be involved in P482 antagonistic activity under limiting-nutrient conditions.

In this study, we present data on the effects of condensed (CTs) and hydrolysable (HTs) tannins, polyphenols extracted from plants, at different concentrations on zebrafish development to identify the range of concentrations with toxic effects. Zebrafish embryos were exposed to CTs and HTs at two different concentration ranges (5.0, 10.0, 20.0 μgL-1 and 5.0, 10.0, 20.0 mgL-1) for 72 h. The toxicity parameters were observed up to 72 h of treatment. The uptake of CTs and HTs by zebrafish larvae was assessed by HPLC analysis. The qRT-PCR analysis was performed to evaluate gene expression of cd63, zhe1 and klf4, involved in the hatching process of zebrafish. CTs and HTs at 5.0, 10.0, and 20.0 μgL-1 were not toxic. On the contrary, at 5.0, 10.0, and 20.0 mgL-1 HTs induced a delayed in hatching starting from 48 h of treatment, while CTs showed a delayed in hatching mainly at 48h. The analysis of gene expression showed a down-regulation in the group exposed to HTs confirming the hatching data. We believe that this study is important to define the optimal doses of CTs and HTs, to be employed in different application fields such as chemical and animal feed industry, and medical science.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

.Background: Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising results in patients with colorectal carcinoma at high risk of recurrence but still without clinically and radiologically evident signs of peritoneal spread. This study aims to analyze the feasibility of this proactive, early phase, multimodality approach. Methods: A mono-institutional, prospective, parallel, two-stage phase II trial enrolled 49 patients to standard surgery or surgery plus intraoperative HIPEC. Before the procedure and during surgery, patients received intravenous fluorouracil (and leucovorin to potentiate oxaliplatin activity. Data analysis included length of hospital stay, surgery duration, type of surgery and chemotherapy-related complications risk score. Results: No significant difference was seen in the median time spent in the hospital with a median stay of 7 days in both groups (p=0.5720). The surgical procedure's median duration was longer in the HIPEC group than in the control one. Side-effects and surgical complications did not cross at any time the Pocock-type boundary for side/effect monitoring (p=0.80, N.S.). Conclusions: The present prospective study results demonstrate the feasibility and safety of the colorectal surgery plus HIPEC treatment in patients with colorectal cancer patients at high-risk for peritoneal invasion, although clinically and radiologically undetectable.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Previous research has already examined the relationship between Future Anxiety, a construct recently introduced in Italy, and mental health in young adults, although possible mediating variables in this relationship have so far never been investigated. The present study attempts to fill this gap by exploring the incidence of Future Anxiety on psychological distress in a group of 302 young Italian adults (18 - 30 years; M = 21.9; SD = 2.6), presenting and evaluating the simultaneous mediating effect of Intolerance of Uncertainty and Non-Pathological Worry.Findings highlighted how Future Anxiety had a positive and significant direct effect on Stress and Depression, but not on Anxiety. In the three serial mediation models proposed, Intolerance of Uncertainty and Non-Pathological Worry mediated the relationship between Future Anxiety and mental health outcomes. The results also confirmed the hypothesized serial mediation effect by highlighting how young adults with greater Future Anxiety experienced more Intolerance of Uncertainty, which positively affected Non-Pathological Worry levels and, in turn, exacerbated psychological distress. Finally, results indicated that female participants experienced more Stress, Anxiety, and Depression in relation to Future Anxiety compared to males. Starting from the review of main references on this subject, the results discussed provide new insights for understanding youth psychological distress. Finally, practical implications for the design of supportive interventions for this study’s target group are proposed.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-i in T1D HF management, alongside the emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk, through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests SGLT2-i significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-i into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-i and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim at clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.

Carbohydrates and lipids integrate into a complex metabolic network that is essential to maintain homeostasis. In insects, as in most metazoans, dietary carbohydrates are taken up as monosaccharides whose excess is toxic, even at relatively low concentrations. To cope with this toxicity, monosaccharides are stored either as glycogen or neutral lipids, the latter constituting a quasi-unlimited energy store. Breakdown of these stores in response to energy demand depends on insect species and on several physiological parameters. In this chapter, we review the multiple metabolic pathways and strategies linking carbohydrates and lipids that insects utilize to respond to nutrient availability, food scarcity or physiological activities.

Tryptophan, an essential amino acid in mammals obtained from the diet, is influenced by maternal diet, which impacts early life and development of offspring. This is studied under the Developmental Origins of Diseases and Health (DOHaD) concept, so factors from conception to early childhood affect health and disease susceptibility. Tryptophan is metabolized mainly through two pathways: serotonin (5-HT) and kynurenine. The kynurenine pathway, active in the brain, gut, liver, and placenta, breaks down over 95% of tryptophan and plays roles in inflammation, neurotransmission, immune responses, and immune modulation during pregnancy. The serotonin pathway uses up to 5% of Tryptophan, mainly in the gut, adipose tissues, pancreatic cells, and central nervous system, and regulates responses to environmental changes, including sleep, cognition, and feeding behavior. Key enzymes in these pathways include Trp-2,3-dioxygenase (TDO), indoleamine-2,3-dioxygenase (IDO) type1 (IDO1), and type 2 (IDO2) (kynurenine pathway), and tryptophan hydroxylase type 1 (TPH1) and type 2 (TPH2), serotonin pathway. The fetus-placental unit manages tryptophan metabolism. Serotonin and kynurenine are crucial for placental health and fetal development. Serotonin adjusts placental blood volume and aids neurodevelopment. Kynurenine metabolites protect the fetus from maternal immunity and offer initial neuroprotection. At birth, infants switch from placental nutrients to breast milk, rich in tryptophan and protective bioactive molecules. Tryptophan, solely from breast milk, is crucial for infants. Its levels are high in newborns (first three weeks, 2-4 times higher than in adults), gradually declining to adult levels by the fourth week. The highlights the importance of tryptophan for the serotonin and kynurenine pathways in fetuses, newborns and babies applied to the DOHaD concept.

Anaemia is the most prevalent nutritional deficiency in the World and is associated with long-lasting developmental effects in children. Anaemia weakens the immune system and im-pairs cognitive development of children. Anaemia is multifactorial; therefore, anaemia’s pre-ventive/control measures should be evidence-based. This paper aimed to investigate the preva-lence and correlates of anaemia in preschool aged children at individual, maternal/household and community level in the Democratic Republic of Congo (DRC). Retrospective, nationally representative cross-sectional data, the 2013-2014 DRC Demographic and Health Survey (DHS) was used. Three -levels random intercept logistics regression models were fitted to the data using the outcome anaemia in children, defined as a haemoglobin concentration below 11dl with potential risk factors grouped at individual, maternal/household and community levels. Anaemia in children is a severe public health issue in the DRC, 63% of school-aged children are anaemic. Anaemia is highly prevalent amongst males, children with infections (fever/malaria and intestinal parasites), whose mothers are anaemic, from the poorest household, and whose drinking source of water is unclean, and who reside in provinces with recent/previous armed forces attacks. Results from this paper highlight the need for a clean and safe environment for children’s growth.

Background Glioblastoma (GBM) is a poor prognosis malignant grade 4 glioma. After surgical resection, standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. The DC vaccination increased the amount of intratumoral-activated cytotoxic T lymphocytes and decreased the number of FoxP3-positive regulatory T cells. Based on these da-ta, we have developed a phase II protocol with the DC vaccine concomitant to standard RT-CT in patients undergoing surgery for GBM. Methods This is a single-arm, monocentric, phase II trial evaluating progression-free survival (PFS) and the safety of a DC vaccination integrated with standard therapy in resected GBM patients. The vaccine administration begins at the end of the RT-CT (Induction Phase) and is subsequently al-ternated with TMZ cycles (Maintenance Phase). The primary endpoints are PFS and safety. Among the secondary endpoints, are the in vitro and in vivo Immune response evaluations. Results By December 2022 , nine patients had been enrolled in the first step. Two patients progressed within three months after leukapheresis and none had experienced DC vaccine-related G3-4 tox-icity. Five patients had a positive DTH test against KLH. By June 2023. The median OS from leu-kapheresis was 23.1 months and 24.7 from surgery. Conclusions This combination therapy is well-tolerated, and we have achieved the two endpoints required for the first step. Therefore, the study will proceed to enroll the remaining 19 patients.

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological center of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of the relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the key words: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its etiology. The angular cephalometric measurements differ from the average height normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusion: The greater part of the existing literature regarding cephalometric measurements in short statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature, should be the focus of future studies. These quantitative data are required to potentially establish cut-off values to refer for genetic testing based on craniofacial phenotypes.

(1) Background: a study was undertaken to determine the prevalence of chronic diseases and health conditions that affect oral health and oral health self-care among independent living older adults in rural areas of Victoria, Australia; (2) Methods: The study analysed data from the Crossroads-II project, with a total of 1407 participants aged 55 years and older. Participants self-completed questionnaires about health conditions, service use, and demographics. 572 attended a 2-hour health screening that included an assessment of prescribed medications; (3) Results: Most participants were female (55.3%), with a mean age of 69.1 (SD=9.2) years. Participants had a high prevalence of medical conditions, the most common were high blood pressure, arthritis, high lipids, hearing loss, and chronic pain. Almost all participants reported taking medications, with an average of 4.3 medications per person. Among those who attended the health screening, 78.1% were taking medications that could cause xerostomia (dry mouth); (4) Conclusions: This study provides initial information on the prevalence of medical conditions, medication usage, with potential impact on oral health of older adults living in rural Victoria. This information would be valuable for healthcare and dental workforce planning, policy development, and improving the overall well-being of this population.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol-gel transition. We started with the synthesis of three cationic azobenzenes (AZO A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV-Vis and ¹H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel-sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels.

Iron metabolism plays a crucial role in the management of hemoglobinopathies, particularly in conditions such as β-thalassemia and sickle cell anemia (SCA). This paper describes the mechanisms of iron overload in patients with transfusion-dependent thalassemia (TDT), non-transfusion-dependent thalassemia (NTDT), and SCA, highlighting the distinct paths leading to iron accumulation in each condition. The primary focus of this review article is on the role of genetic modifiers influencing iron metabolism and the variability in iron overload presentation among patients. Genetic mutations in genes such as HFE, HAMP, TFR2, SLC40A1, and others significantly impact iron regulation. These modifiers can exacerbate or ameliorate iron overload, and understanding these genetic factors is important for explaining the diverse disease severity and differences in the mechanism and clinical presentation of iron overload in these patients. The ongoing INHERENT study aims to further elucidate the influence of these genetic modifiers through a comprehensive genome-wide association study, potentially leading to novel therapeutic interventions for managing iron homeostasis in hemoglobinopathy patients.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR&gt;MTYR&gt;&gt;TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol® modified citrus pectin (P-MCP) is a food supplement generally recognized as safe (GRAS) by the Food and Drug Administration (FDA) and is a competitive inhibitor of galectin-3 protein, involved in cancer pathogenesis. P-MCP treatment of BRPC-M0 patients for 6 months led to a 75% prostate-specific antigen doubling time (PSADT) improvement. To determine the longer-term effects of P-MCP we investigated an additional 12 months of treatment (phase II) with oral P-MCP at 4.8 grams X 3/day in patients with no disease progression in the previous 6 months. Of the 46 patients that entered the second phase, 7 patients withdrew consent and continued therapy independently, and 39 received another 12 months of therapy. After a total of 18 months P-MCP treatment, 62% (n=24) had a decreased/stable PSA, 90% (n=35) had improved PSADT, and 85% (n=33) had a durable long-term response, with a decreased/stable PSA, and/or improvement of PSADT, and negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long term durable efficacy, and is safe, in BRPC-M0.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

In these last years, self-healing polymers have emerged as a topic of considerable interest owing to their capability to partially restore material properties and thereby extend the product's lifespan. The main purpose of this study is to investigate the nano-indentation response in terms of hardness, reduced modulus, contact depth and coefficient of friction of a self-healing resin developed for use in aeronautical and aerospace contexts. To achieve this, the bifunctional epoxy precursor underwent tailored functionalization to improve its toughness, facilitating effective compatibilization with a rubber phase dispersed within the host epoxy resin. This approach aimed to highlight the significant impact of the quantity and distribution of rubber domains within the resin on enhancing its mechanical properties. The main results are that pure resin exhibits a higher hardness (about 36.7% more) and reduced modulus (about 7% more), consequently leading to a lower contact depth and coefficient of friction (11.4% less) compared to other formulations that, conversely, are well-suited for preserving damage from mechanical stresses due to their capabilities in absorbing mechanical energy. Furthermore, finite element method (FEM) simulations of the nanoindentation process were conducted. The numerical results were meticulously compared with experimental data, demonstrating a good agreement. This validation of the FEM model underscores its efficacy in predicting the mechanical behavior of nanocomposite materials under nanoindentation. The proposed investigation aims to contribute knowledge and optimization tips about self-healing resins.

The aim of this article is to present the course of the COVID-19 pandemic in Poland in 2020-2022, the formation of ad hoc health and anti-crisis policies, an assessment of crisis management and the perceived impact of the pandemic and anti-crisis measures.The paper draws on literature, official reports on the pandemic, data from Eurostat and other information from state institutions and public organisations.Particular attention was paid to the analysis and evaluation of the objectives, instruments and effects of the policies pursued by the state in a coordinated manner, i.e. the anti-pandemic policy and the anti-crisis policy. The anti-pandemic policy in Poland has failed to protect the country from significant personal losses and negative impacts on the health of the population and demographic processes.The anti-crisis policy of the state carried out with the mobilisation of businesses and disciplined society, in the form of anti-crisis shields supplemented and adjusted on an ongoing basis, allowed Poland to avoid a deep crisis and economic recession. Attention was drawn to the need to coordinate the management of health and economic crises nationally and internationally, and to the need to have a medium-term anti-crisis state strategy and a system for the early detection of crisis symptoms.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

Chenodeoxycholic acid (CA) is a naturally occurring bile acid that is produced in the liver from cholesterol. Three CA complexes using Zn(II), Mg(II), and Ca(II) ions were synthesized to examine the chelation tendencies of CA towards these metal ions. The complexation reaction of CA with the metal ions under investigation was conducted with a 1:1 molar ratio (CA to metal) at 60-70°C in natural media (pH 7-8), which consisted of a binary solvent of MeOH and H2O (1:1). The resulting CA complexes were characterized using analytical data (metal, H, C, and Cl, analysis) and spectral data (UV-visible, FT-IR, and 1H NMR) to elucidate the complexes’ structures. The results suggested that CA in anion form utilized oxygen atoms of the carboxylate group (-COO−) to capture Zn(II), Mg(II), and Ca(II) ions. This produced complexes with the general compositions of [Zn(CA)(H2O)Cl], [Mg(CA)(H2O)Cl]H2O, and [Ca(CA)(H2O)Cl]2H2O, respectively. The Kirby-Bauer disc diffusion assay was then used to explore the bioactivity of the CA complexes toward three fungal species, three Gram-positive bacteria, and two Gram-negative bacteria. The Ca(II) and Mg(II) complexes exhibited marked inhibitory effects on the cell growth of the fungal species Aspergillus niger with potency equal to 127% and 116% of the activity of the positive control, respectively. The Zn(II) and Ca(II) complexes strongly inhibited the growth of Penicillium sp., while the Zn(II) and Mg(II) complexes showed strong growth inhibition towards the Gram-negative species Pseudomonas aeruginosa.

[Co(AMPY)(DAPY)Cl2(H2O)].H2O (1) [Cu(AMPY)(DAPY)Cl2(H2O)].H2O (2) [Zn(AMPY)(DAPY)Cl2(H2O)] (3) were prepared from the ligands; AMPY = 2-amino-4-methylpyrimidine (L1), DAPY = 2,3-diaminopyridine (L2) and CoCl2.6H2O, CuCl2.2H2O and ZnCl2 in water/ethanol solutions and the three products characterized by elemental analysis, ultraviolet-visible spectroscopy (UV–Vis), Fourier-transform infrared spectroscopy (FT-IR), magnetic susceptibility, molar conductivity methods, and TGA analysis. The X-ray powder diffraction of the Co(II), Cu(II), and Zn(II) compounds showed that the geometry of monoclinic and SEM analysis revealed their morphology with a smooth surface. Molecular modeling was performed for all compounds using the density functional method DFT/B3LYP to study the structures and the frontier molecular orbitals (HOMO and LUMO). We have used Gaussian09 software for the calculations. In this study, different complexes were tested against Gram negative and Gram positive bacterial species to give insight into their broad-spectrum effects. The used pathogenic strains were two Gram positive species "Staphylococcus aureus and Micrococcus luteus" and two Gram negative species "Salmonella thyphimurium and Escherichia coli. The antifungal activity was evaluated against a pathogenic reference strain of the yeast Candida albicans. The antimicrobial and antioxidant assay results demonstrate that the tested compounds are effective against Gram positive and negative bacteria. Additionally, the compounds have an antifungal effect against Candida albicans with a maximum inhibitory zone of 2.5cm. The results demonstrated high antioxidant potential for the Zn(II) complex with a DPPH scavenging of 91.5%, however, the Cu(II) complex was low (16.5%). The data of docking with tyrosyl-tRNA synthetase presented that all compounds fit very well in the catalytic pockets of the proteins of the receptor.

The aim was to identify if surface electromyography (sEMG) parameters are indicative of post-activation potentiation (PAP)/post-activation performance enhancement (PAPE), in terms of twitch potentiation and voluntary performance. Three databases were used in March 2024, with the following inclusion criteria: (a) original research, assessed in healthy human adults, (b) sEMG parameters were measured. The exclusion criteria were: (a) studies with no PAP/PAPE-protocol, (b) non-randomized control trials. The following data were extracted: study characteristics/demographics, PAP/PAPE-protocols, sEMG parameters, twitch/performance outcomes, and study findings. A modified physiotherapy evidence database (PEDro) scale was used for quality assessment. Fifteen randomized controlled trials (RCTs), with a total of 199 subjects were included. The M-wave amplitude (combined with a twitch torque outcome) was shown to generally be indicative of PAP. The sEMG amplitude (in some muscles) were found to be indicative of PAPE during ballistic movements, while a small decrease in the MdF (in certain muscles) were shown to reflect PAPE. Changes in the Hmax/Mmax ratio were found to contribute (temporally) to PAP, while the H-reflex amplitude was shown to be neither indicative of PAP nor PAPE. This review provides preliminarily findings suggesting that certain sEMG parameters could be indicative of PAP/PAPE. However, future research is warranted.

In a recent paper, we have shown how gravity and information can be related. The relation is based on the thermodynamic extension of the gravitational system under consideration using the holographic principle. Using this idea, we were able to derive the Gullstrand-Painlevé (GP) metric. In this short paper, we re-derive the GP metric using information. However, we now extend the spacetime to 5D with the fifth dimension being time, that is, the (3+1)D spacetime is now promoted to (3+1+1)D spacetime. We also comment on the possible Braneworld interpretation of this model.

Small and micro hydropower represents an attractive solution for electricity generation, with low cost and low environmental impact. The pump-as-turbine (PAT) approach has promise in this application owing to its low purchase and maintenance costs. In this paper, a new method to predict the inverse characteristic of industrial centrifugal pumps is presented. This method is based on results of simulations performed with commercial three-dimensional CFD software. Model results have been first validated in pumping mode using data supplied by pump manufacturers. Then, results have been compared to experimental data for a pump running in reverse condition. Experimentation has been performed on a dedicated test bench installed in the Department of Civil Construction and Environmental Engineering of the University of Naples Federico II. Three different pumps, with different specific speeds, have been analyzed. Using the model results, the inverse characteristic and the best efficiency point have been evaluated. Finally, results of this methodology have been compared to prediction methods available in the literature.

Recently, polyacetylene (PA) is receiving a renewed scientific attention due to its electrical properties potentially useful for energy applications (e.g., fabrication of electrodes for batteries and supercapacitors) and unique functional characteristics (e.g., flame retardant, oxygen scavenger, EMI-shielding, etc.). This chemical compound can be obtained in form of a polyacetylene-PVOH copolymers simply by chemical dehydration of poly(vinyl alcohol) (PVOH), which is a very common type of polymer, widely used in packaging and other technological areas. This very inexpensive chemical reaction for the large-scale synthesis of PA/polyvinylenes has been investigated by reacting PVOH with fuming sulfuric acid at room temperature. In this process, PVOH, shaped in form of film, is dipped in fuming sulfuric acid (i.e., H₂SO₄ at 95-97%) and, after complete chemical-dehydration, it has been mechanically removed from the liquid phase by using a nylon sieve. The reduction process leads to a substantial PVOH film conversion to PA as it has been proved by infrared spectroscopy (ATR-mode). Indeed, the ATR spectrum of the reaction product included all characteristic absorption bands of PA. The reaction product has been also characterized by UV-Vis spectroscopy in order to evidence the presence in the structure of conjugated carbon-carbon double bonds of various lengths. Differential scanning calorimetry (DSC) and thermogravimetric analysis have been used respectively to investigate the PA solid-state cis-trans isomerization and thermal stability in air and nitrogen, respectively.

Underwater Sensor Networks (UWSNs) can enable a broad range of applications such as resource monitoring, disaster prevention, and navigation-assisted. It is especially relevant for sensor nodes location in UWSNs. Global Positioning System (GPS) is not suitable for using in UWSNs because of the underwater propagation problems. Hence some localization algorithms based on the precise time synchronization between sensor nodes have been proposed which are not feasible for UWSNs. In this paper, we propose a localization algorithm called Two-Phase Time Synchronization-Free Localization Algorithm (TP-TSFLA). TP-TSFLA contains two phases, namely, range-based estimation phase and range-free evaluation phase. In the first phase, we address a time synchronization-free localization scheme base on the Particle Swarm Optimization (PSO) algorithm to decrease the localization error. In the second phase, we propose a Circle-based Range-Free Localization Algorithm (CRFLA) to locate the unlocalized sensor nodes which cannot obtain the location information through the first phase. In the second phase, sensor nodes which are localized in the first phase act as the new anchor nodes to help realize localization. Hence in this algorithm, we use a small number of mobile beacons to help achieve location without any other anchor nodes. Besides, to improve the precision of the range-free method, an extension of CRFLA by designing a coordinate adjustment scheme is updated. The simulation results show that TP-TSFLA can achieve a relative high localization ratio without time synchronization.

Nowadays, the growing concern about improving thermal comfort in textiles, asphalt pavements and buildings has stimulated research into phase change materials (PCMs). However, the incorporation of PCMs directly causes mechanical impacts. Therefore, this study herein reported focuses on designing coaxial phase change fibres using commercial cellulose acetate (CA) or recycled CA obtained from cotton fabrics (CAt) as a coating and polyethylene glycol (PEG) 2000 as a core. The phase change fibres (PCF) were produced by wet spinning, varying the parameters: (i) CA concentration, molecular weight and source (virgin versus recycled); and (ii) PEG concentration and ejection. For phase change recycled fibres (PCFt), PEG concentration and ejection were varied. The fibres were assessed for their optical, chemical, thermal and mechanical properties. Bright-field microscopy images and Scanning Electron Microscopy (SEM) micrographs proved the coaxial structure. Fourier Transform Infrared spectroscopy (FTIR) confirmed the presence of PEG in the core. Thermogravimetric Analysis (TGA) proved the ability of PCFs to tolerate high temperatures. Differential Scanning Calorimetry (DSC) attested to the presence of PEG2000 peaks, since their melting points were close to those of virgin PEG2000, with a slight change in the PCFs and PCFts caused by the protective sheath of CA and CAt.

Epilepsy is a common neurological condition, typically diagnosed using Electroencephalogram (EEG). Large scale EEG datasets have recently been made publicly available, allowing the use of advanced Machine Learning (ML) algorithms to analyze EEG patterns associated with epilepsy. While most existing studies focus on identifying seizures in the EEG, few have tried to identify preictal EEG segments. Identifying preictal EEG segments are not only useful in developing early warning systems but also helps inform the course of treatment for the patient. In this study, we propose to represent EEG segments as images, instead of time-series data, and identify preictal EEG segments using a preexisting ML algorithm (YOLOv8) designed for image processing. Multiplexed images (containing the original EEG signal represented on a 2D grid, kurtosis, and spectral entropy) achieve the best accuracy of 95.75% on the dataset while images just containing the EEG signal result in an accuracy of 91.25%. Using only spectrograms, generated from the original EEG signal, results in an accuracy of 90.15%.

The incidence of diabetes mellitus (DM) continues to rise worldwide and one of the most serious microvascular complications is diabetic kidney disease (DKD), which is the leading cause of end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection of DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques to quantify previously analyzed metabolites, such as tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. We performed the targeted analy-sis of metabolites from urine and serum samples, collected from 110 subjects. Of these, 90 patients with type 2 DM (T2DM) were divided according to the urinary albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects were rep-resented by healthy controls. Through various validation methods, we identified several metabolites as potential biomarkers, such as kynurenic acid, glycine, and l-tryptophan in serum and l-acetylcarnitine, tiglylglycine, and tau-rine in urine.

Pyrethroid pesticides (PYRs) as the third most widely used pesticides, following organophosphorus and carbamate pesticides, which are of significant importance in the analysis and detection of vegetables. However, the current pretreatment technology for PYRs confronts challenges of difficult separation and low enrichment efficiency, resulting in a cumbersome and time-consuming pretreatment process with poor selectivity. Here, a simple and efficient magnetic solid-phase extraction (MSPE) strategy was developed to simultaneously purify and enrich five PYRs in vegetables, with the magnetic covalent organic framework nanomaterial COF-SiO2@Fe3O4 as an adsorbent. The COF-SiO2@Fe3O4 was prepared by a simple solvothermal conditions method, using Fe3O4 as magnetic core, benzidine and 3,3,5,5-tetraaldehyde biphenyl as two building units. COF-SiO2@Fe3O4 could effectively capture the targeted PYRs by virtue of its abundant π-electron system and hydroxyl groups. The impact of various experimental parameters on extraction efficiency was investigated to optimize the MSPE conditions, including adsorbent amount, extraction time, elution solvent type and elution time. Subsequently, method validation was conducted under the optimal conditions in conjunction with gas chromatography-mass spectrometry (GC-MS). Within the range of 5.00–100 μg·kg-1 (1.00–100 μg·kg-1 for bifenthrin and 2.5–100 μg·kg-1 for fenpropathrin), the five PYRs exhibited a strong linear relationship, with determination coefficients ranging from 0.9990 to 0.9997. The limits of detection (LODs) were 0.3–1.5 μg·kg-1, and the limits of quantification (LOQs) were 0.9–4.5 μg·kg-1. The recoveries were 80.2–116.7% with relative standard deviations (RSDs) below 7.0%. Finally, COF-SiO2@Fe3O4, NH2-SiO2@Fe3O4 and Fe3O4 were compared as MSPE adsorbents for PYRs. The results indicated that COF-SiO2@Fe3O4 was an efficient and rapid selective adsorbent for PYRs. This method holds promising prospects for the determination of PYRs in real samples.