Gastrointestinal cancers, a major global cause of cancer-related mortality and disease burden, are a heterogeneous group of malignant aliments involving different organs of the digestive system. The late clinical diagnosis, genomic tumor heterogeneity, high complexity of the gastrointestinal tumor microenvironment, along with increasing treatment resistance have been recognized as the main contributing factors to the current inadequacy of the clinical interventions and poor prognosis of the gastrointestinal cancer patients. In the coming years, gastrointestinal cancer-related global mortality is unfortunately predicted to increase due to the absence of early detection and effective therapeutic options. Biomembrane-coated biomimetic nanoparticles (NPs) have recently been appointed as advanced nanotechnological tools for the clinical management of gastrointestinal cancers. These comprise not only cell-mimicking nanodevices (the pioneers of this top-down coating technology), but also exosome and bacterial mimetics. Due to their enhanced bio-interfacing features, biocompatibility, immune evasion, and specific targetability to tumorous tissues, these biomimetic nanostructures have been successfully exploited to provide safer, effective, and targeted gastrointestinal cancer applications. This review highlights the latest research on biomembrane-coated nanosystems for the clinical therapy and diagnosis of the most common and deadliest subtypes of gastrointestinal cancers, namely colorectal cancer, gastric cancer, liver cancer, esophageal cancer, and pancreatic cancer. The current challenges toward their clinical translation are also mentioned.

Nanovesicles (NVs) derived from biological membranes offer promising opportunities in the realm of ultra-precise cancer therapy, with proven therapeutic efficacy and safety profiles. These biomimetic NVs possess a versatile liposome-like structure capable of accommodating hydrophilic and hydrophobic agents. NVs derived from a plethora of biological sources, including eukaryotic cells [erythrocytes, platelets, immune cells, cancer cells and mesenchymal stem cells (MSCs)], extracellular vesicles (EVs), and bacteria, successfully proved to enable the tumor-targeted delivery of a wide panoply of therapeutic molecules. These include chemotherapeutics, imaging agents, nucleic acids and immunoadjuvants, highlighting their potential as natural lipid-based drug delivery systems (DDSs) in cancer-oriented therapies. Clinical translation, however, encounters challenging issues that require further research and refinement. Safety, immunogenicity, scalability, stability, production protocols, quality control, and understanding biological processes remain crucial aspects for clinical implementation. This review offers a critical and comparative analysis of different membrane sources, underlines several NV applications in tumor-targeted therapies, and outlines future research directions and current limitations. Addressing these challenges is pivotal to harnessing the full potential of NVs derived from biological membranes for safe and effective clinical use.

In the present study, industrial biomass fly ash (BFA)-based materials were successfully used as in-situ low-cost catalysts during biomass steam gasification in a bench-scale bubbling fluidised bed reactor, aiming to improve producer gas quality. BFA was used in three forms: (i) granulated (GBFA fresh), (ii) granulated and thermally treated (GBFA treated) and (iii) thermally treated in its original powder form (PBFA treated). CaCO3 and SiO2 were the main compounds in the GBFA fresh. Thermal treatment successfully converted CaCO3 to CaO in GBFA treated and PBFA treated samples. All BFA-based catalysts substantially increased the H2 concentration in the producer gas from pine gasification, in the order GBFA treated > PBFA treated > GBFA fresh > reference condition (inert material - granulated alumina). H2 concentration increased from 40.53 %vol.dry and inert (N2, Ar) free gas in the reference condition up to 54.12 %vol.dry and inert (N2, Ar) free gas using GBFA treated. The richness in CaO on treated samples enhanced the water gas shift reaction. All catalysts had a major effect on the H2:CO molar ratio (up to 140 % increase with GBFA treated). BFA-based materials also positively impacted the performance parameters, indicating their catalytic activity towards reforming and cracking reactions.

The presence of impurities in the iron oxides feedstock introduces significant challenges during the electrowinning process for green steelmaking, leading to unpredictable effects. In the present study, the impact of metallic iron content on the Faradaic efficiency and microstructure of iron deposits obtained through the electroreduction of iron-magnetite powders in alkaline suspensions (10 M NaOH) at low temperature (80 degrees C) was evaluated. The findings reveal that the presence of metallic iron may negatively impact the reduction process. A comparative analysis of suspensions with and without iron content showed that the Faradaic efficiency for iron-free samples (63%-76%) significantly exceeds that of iron-containing suspensions (37%-57%). This demonstrates that the presence of metallic iron in the suspension can hinder the electroreduction of magnetite to Fe, with the effect becoming more pronounced at higher Fe concentration. Changes were observed in the microstructure of iron deposits, with the dendrites becoming less sharp and more disordered in iron-containing suspensions. Particle size distribution analysis further revealed that larger metallic iron particles may contribute to the sedimentation and entrapment of magnetite particles, which negatively affect the current density and Faradaic efficiency.

Despite current medicine's fast-paced advances, many acute and chronic illnesses still lack truly effective and safe therapies. Cancer treatments often lead to off-target healthy tissue damage and poor therapeutic outcomes, wound standard treatments generally demonstrate poor healing efficacy and increased susceptibility to infection, and bone tissue engineering and myocardial tissue engineering can result in immunological rejection and limited availability. To tackle these issues, injectable hydrogels have emerged, and through the incorporation of nanoparticles, nanocomposite hydrogels have appeared as versatile platforms, offering improved biocompatibility, mechanical strength, stability, and precise controlled drug release, as well as targeted delivery with increased drug retention at the site of action, reducing systemic drug distribution to non-target sites. With the ability to deliver a diverse range of therapeutic entities, including low molecular weight drugs, proteins, antibodies, and even isolated cells, injectable nanocomposite hydrogels have revolutionized current therapies, working as multifunctional platforms capable of improving efficacy and safety in cancer treatment, including in chemotherapy, immunotherapy, photothermal therapy, magnetic hyperthermia, photodynamic therapy, chemodynamic therapy, radiotherapy, molecularly targeted therapy, and after tumor surgical removal, and in general, chronic diabetic or tumor-induced wound healing, as well as in bone tissue engineering and myocardial tissue engineering. This review provides a thorough summary and critical insight of current advances on injectable nanocomposite hydrogels as an innovative approach that could bring substantial contributions to biomedical research and clinical practice, with a focus on their applications in cancer therapy, wound healing management, and tissue engineering.

In the intricate tapestry of life, subcellular structures stand out as the fundamental building blocks that orchestrate the complexities of cellular function. Collectively, they govern the course of events at the subcellular level and cooperate to maintain cellular physiological functions and homeostasis and they are present in all eukaryotic cells, from the unicellular organisms to the more complex ones. Herein, we aim to explore the cutting-edge, bioinspired brunch of nanotechnology focused on the fabrication of biomimetic nanoparticles consisting of a synthetic core coated with the natural membranes deriving from membrane-bound subcellular organelles. Beyond the well-grounded biomedical evidence on the use of membranes derived from cells, exosomes and bacteria, recent insights have unlocked the potential of the nanosystems mimicking the subcellular intricacy for subcellular-oriented medicine. Despite the recent promising results, several challenges remain in the translation of this technology to the clinical settings. The current lack of standardization, challenging industrial scale-up, immunological concerns, as well as demanding regulatory considerations still remains aspects to be analyzed and discussed, in order to fill the current gap between the research and the clinical application.

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is a common form of hereditary kidney disease, with an estimated prevalence of 1 out of 1000 individuals worldwide. Although its key clinical manifestation is progressive formation and growth of renal cysts, extra-renal manifestations such as hypertension, cysts in other organs, cardiac valve disease and cerebral aneurysms reflect that it is a systemic disorder. Classical ADPKD is associated with heterozygous PKD1 and PKD2 pathogenic gene variants. Less common involved genes that may present as atypical cystic disease include GNAB, DNAJB11 and more recently ALG5/9. Genes associated to syndromic ciliopathies such IFT140 and OFD1 have also been related to atypical ADPKD. Literature reports that 10% patients with ADPKD phenotype will have de novo pathogenic variant. Around 7% of families have negative genetic testing despite clinical phenotype. Failure to consider broader genetic panels or exome sequencing if available may lessen diagnostic yield. Method We performed descriptive analysis on patients with no family history cystic disease and negative PKD1/PKD2 gene testing in our hereditary nephropathy clinic. Atypical cystic disease was defined as non-enlarged kidneys despite multiple cysts and asymmetrical kidney cyst affection in terms of size and quantity, determined through imaging studies. Results From January 2019 until December 2023, n = 39 genetic tests were performed in patients with cystic disease phenotype, n = 28 (13%) without family history. Twelve patients (31%) had positive PKD1/PKD2 variants analysed by PCR long range multiplex. Fig. 1 represents the genetic test results in the remaining patients (n = 16) with cystic disease phenotype and no family history. Positive genetic testing was obtained in n = 7 (43%). Ten patients (63%) presented features of atypical cystic disease. These had a median referral age of 48 years (IQR 34-58), n = 3 (30%) male. Three causal genetic variants were identified (1 with variants in IFT140 and 2 in OFD1 gene), the remaining with negative genetic test result. Patients without atypical features had a median age of referral 55 years (IQR 38-58), n = 4 (60%) were male. Variants in GANAB, LRP5 and PKHD1 genes were identified in this subgroup. Extra-renal manifestations were seen in in 70% and 50% of patients with and without atypical cystic disease, respectively. The main extra-renal manifestation encountered was hepatic cysts. One patient with a pathogenic OFD1 variant presented syndactyly. Conclusion In recent years, growing knowledge in the field and identification of genes involved in ciliopathies associated with atypical forms polycystic kidney disease have allowed for genetic diagnosis of non-PKD1/PKD2 forms. The identification of new genes associated with atypical forms of polycystic kidney disease has called attention to a potential overlap between polycystic and tubulointerstitial phenotypes. With growing knowledge in genetics leading to improvement of cystic kidney disease panels and increased experience in exome sequencing, diagnostic yield is likely to increase in the coming years. Genetic basis of disease is important considering possibility of avoiding primary transmission through pre-implantatory genetic diagnosis but also in the management and diagnosis of gene-specific systemic manifestations.

Abstract Background and Aims Alport syndrome (AS) is the most common cause of inherited chronic kidney disease. This disorder is caused by deleterious variants on COL4A3, COL4A4 or COL4A5 genes. These genes codify the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). Importantly, AS patients can develop chronic kidney disease (CKD) kidney disease that can be delayed or possibly prevented by timely initiation of therapy. The identification of at-risk relatives and their genetic testing allow to identify AS patients and initiate appropriate renal care and avoid unnecessary vigilance if the test is negative. Our aim was to assess the outcomes of Alport Syndrome cascade family screening in a tertiary hospital. Method In this study, we retrospectively assessed familial relatives at risk of AS index cases in our Nephrogenetics consult, from January 2018 to November 2023. After referral, routine tests to detect renal disease were done and AS gene panel was performed. Demographic and clinical data were also compiled. Results A total of 75 at-risk relatives were assessed, belonging to 26 families with a COL4A variant identified in the index case. Relatives at risk were mostly referred by primary care doctors (n = 52, 69.3%), with other 15 patients (20%) directly scheduled for consultation, and 8 (10.7%) referred by a nephrology clinic. In this cohort, an AS diagnosis was confirmed in 43 relatives (57.3%), with an additional 13 (17.3%) of the at-risk relatives with ongoing biochemical or molecular analyses. In 19 (25.4%) relatives the molecular study allowed the exclusion of AS. In the subgroup of patients diagnosed with AS (n = 43): median age at molecular diagnosis was 40.5 years (IQR 20.2-56.5years) and 26 (60.5%) were female. Thirty-five patients (81.4%) patients had autosomal dominant AS: 32 had a variant in COL4A3 (6 different variants were found: 4 were pathogenic or likely pathogenic and 2 were of uncertain significance) and 3 patients on COL4A4. COL4A5 variants were identified in 8 patients, 5 of them were female. Three (7%) patients presented with intermittent hematuria, 14 (32.6%) patients presented isolated hematuria, 10 (23.2%) patients had urinary protein/creatine (Up/cr) <0,3g/g, 7 (16.2%) presented Up/cr between 0.3g/g and 1g/g, 3 (7%) patients had Up/cr >1g/g; Six (14%) had CKD. Twenty-two (51.2%) patients were started on a renin angiotensin system inhibitor (RASi) and 5 (11.6%) were already under a RASi. At the last visit in this group of AS patients, the mean epiTFG was 104.2 ml/min (IQ 85.6-120-5 ml/min) and 6 (14%%) patients had epiTFG below 60 ml/min; mean Uprot/creat was 0.11g/g (IQR 0.06-0.32), 12 (28%) patients had no proteinuria. In the subgroup of relatives at risk were AS excluded (n = 19): median age was 38.5 years (IQR 20.2-56.0) and 11 (58%) were female. One patient had CKD, 7 (36.8%) had no signs of renal disease and 8 (42%) patients had intermittent hematuria. Conclusion Our retrospective review showed that the systematic screening of relatives at risk in our hospital was met with a high discovery rate of AS patients. Since there is clinical benefit in an early AS diagnosis, namely through improved renal care and prevention of disease progression, timely genetic/biochemical screening of at-risk relatives is advisable. Additionally, by discharging the relatives with a negative test, this is a more cost-effective approach than providing continuous vigilance to all.

The MAX phase/MXene/Ni composite with 3D porous structure prepared was assessed for energy conversion and storage application, using the hydrogen evolution reaction under alkaline conditions as a model system.

Phosphorus (P) removal from urban wastewater is increasingly relevant in the wastewater treatment sector. The present work aims to contribute to the study of the adsorption process as a P removal technology. Biogenic calcium carbonate from industrial eggshell waste prepared by milling and calcination was used as an adsorbent. Batch adsorption experiments were conducted using real wastewater with 40 mg P/L (orthophosphate), original pH 7.33, under stirring conditions (100 rpm). The adsorbent was characterized using SEM-EDS, XRD, and FTIR-ATR before and after adsorption. From an initial screening of calcination times (15, 30, 60, and 120 min) and considering a balance between P removal and energy saving, the adsorbent selected was eggshell calcined at 700 degrees C for 60 min. The Langmuir isotherms describe the experimental data with a maximum adsorption capacity of 4.57 mg P/g at 25 degrees C. The adsorption process reached equilibrium within 120 min for different dosages (5, 10, and 20 g/L at 25 degrees C). Batch experiments showed that SO42-, at a concentration of 2689 mg/L reduced the P adsorption selectivity for dosages <= 10 g/L at 25 degrees C. Characterization of the loaded adsorbent shows that P adsorption from real wastewater is mostly electrostatic attraction, with the contribution of ligand exchange and microprecipitation. The adsorption capacity and behavior of the selected adsorbent seem promising for P removal from urban wastewater compared with other low-cost adsorbents.

Lung cancer remains a major global health concern with high mortality rates and poor prognosis. Bridging the gap between the chemical and cellular understanding of cell-decorated biomimetic nanocomposites and their clinical translation is crucial for developing effective therapies. Nanocomposites show promise in targeted drug delivery and diagnostics, but their clinical application is hindered by biocompatibility and clearance issues. To overcome these challenges, biomimetic approaches utilizing cell membrane-coated nanomaterials emerge. By camouflaging nanomaterials with cell membranes, the biointerfaces are enhanced, and the inherent properties of the donor cell membranes are acquired. This review provides an overview of recent advancements on cell membrane-coated nanocomposites for lung cancer diagnosis and treatment. It discusses fabrication techniques, biomedical applications, challenges, and future prospects. The incorporation of cell membranes into nanocomposites holds potential for improved lung cancer therapy, but further development and refinement are needed for precise tumor targeting. Addressing the identified challenges will pave the way for clinical translation of these biomimetic nanoplatforms and advance lung cancer diagnosis and treatment.

Abstract Background and Aims Alport syndrome (AS) is the most common cause of inherited chronic kidney disease. This disorder is caused by deleterious variants on COL4A3, COL4A4 or COL4A5 genes. These genes codify the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). Alterations in any of collagen type IV constituents cause disruption of the GMB structure, allowing the leakage of red blood cells and proteins, mainly albumin, into the urine resulting in kidney damage and loss of renal function. In AS progressive kidney impairment can be delayed or possibly prevented by timely initiation of renin angiotensin aldosterone inhibitors (RAAi): in males with X-linked AS and in autosomal recessive AS ARAS at diagnosis and in females with XLAS and autosomal dominant AS at the onset of microalbuminuria. Recently, it was showed that sodium-cotransporter-2 inhibitors (SGLT2i) reduce proteinuria and slow the progression of kidney disease in many glomerular diseases. Thus, also in AS, SGLT2i could be promising in renal disease progression control. The aim of this study was to determine the proteinuria reduction and the effect on the glomerular filtration rate (GFR) in a group of AS patients with persistent proteinuria besides the use of RAAi in maximum tolerated doses after adding SGLT2i to the treatment. Method This study was single-center, observational and prospective study evolving 8 AS adult patients, without a diagnosis of diabetes, with persistent proteinuria besides the use of RAAi in maximum tolerated doses. All patients were prescribed wit dapagliflozin 10 mg daily. We determine the changes from baseline of urinary protein/creatine (Up/cr) and glomerular filtration rate (based on epiGFR formula). Results Eight AS patients were included in this study. All were male patients. One patient has XLAS and the other 7 patients have ADAS. No patient was diabetic, and all were under RAAi in maximum tolerated doses. We determine de Up/cr and epiGFR at baseline and median time of 213.5 days (IQR 208.3-259) after SGLT2i initiation. At baseline, the median of Up/cr was 1.4 (IQR 0.8-2.1) and after SGLT2i Up/cr was 1.5 (0.8-2.6), p = 0.727. Up/cr, after SGLT2i treatment, reduced in 3 patients and worsened in 5. Median epiGFR at baseline was 80.3 ml/min (IQR 40.9-109.5) and after SGLT2i initiation was 74.7 ml/min (40.4-112.0), p = 0.727. Conclusion In this study, we did not observe an improvement in Up/cr of AS patients with SGLT2i treatment. A slight decrease in GFR was observed that may be due to the well know hemodynamic effects of SGLT2i. The small cohort and short time of the study are factors that can interfere in these results and should not discourage the treatment of AS patients with SGLT2i.

Iron electrowinning offers a greener path for steel production. While alkaline media has received the most significant attention, the acidic media declined due to low Faradaic efficiency and difficulties imposed by fragile deposits. This study proposes, for the first time, prospects for acidic Fe electrowinning using a mixed-acid electrolyte (H 2 SO 4 +C 2 H 2 O 4 ), comparing the deposition from hematite suspensions and soluble Fe 2+ salts (FeSO 4 .7H 2 O). Oxalic acid emerges as a key factor, facilitating Fe electrodeposition by forming iron complexes in solution, addressing the challenge associated with slow Fe 2 O 3 dissolution in H 2 SO 4 .

Transdermal drug delivery systems (TDDSs) have provided many priorities over other administration routes, especially the oral route. Despite their advantages, there are some limitations regarding TDDSs, including those dedicated to the use of hydrophobic drugs. The emergence of novel nanostructures has presented various opportunities to develop advanced TDDSs to overcome the challenges on using these systems. Polymeric nanofibers present a unique structure for drug delivery applications due to their large loading capacity and ease of manipulation and functionalization. Natural-based polymeric nanofibers and synthetic polymeric nanofibers can both be used for transdermal drug delivery. Due to their favourable features, namely good biocompatibility, biodegradability, and low toxicity, natural polymeric nanofibers have attracted considerable interest over synthetic-based nanofibers. However, due to biosphere sources' scarcity and low flexibility, they are only used sparingly. Hence, the co-use of natural and synthetic polymers has been suggested to develop efficient TDDSs. So far, different methods have been proposed for polymeric nanofibers fabrication, in which electrospinning has been shown to be the most robust and flexible technique, particularly for natural polymers. This paper reviews the state-of-the art of the field of polymeric nanofibers, particularly covering TDDSs based on natural-based nanofibers.

Almeida, Catarina; de Faria, Vitória V. Paes; Dias, Joana P.; Lopes, Daniela; Carmo, Rute; Fernandes, João C.; Almeida, Clara; Gomes, Ana Marta Author Information

Abstract Background and Aims Cardiovascular (CV) disease remains the leading cause of death in peritoneal dialysis (PD) patients and traditional CV risk factors are unable to fully account for this high incidence. The aim of our study was to establish the incidence of CV events such as acute myocardial infarction (AMI) in the PD population and assess possible risk factors for its occurrence. Method We retrospectively studied patients on PD in our unit with a minimum 3-years dialysis vintage, between January 1st 2015 and April 30th 2022. Patients with previous CV disease were excluded. Demographic and clinical data were collected, such as traditional CV risk factors, AMI, peripheral artery disease, cerebrovascular events, as well as dialysis efficiency, hydration status obtained by Body Composition Monitor (Fresenius Medical Care) and PD-related infections before AMI or end of follow-up. Univariate analysis was performed and logistic regression was applied to access predictors of AMI. Results Of the 43 patients recruited, 53.5% were male, with a mean age of 56.4 ± 11.8 years. About 98% of patients were hypertensive, 21% were diabetic, 19% were obese, and 54% had dyslipidemia. Five (11.6%) patients had a CV event while on PD, 4 suffered AMI and 1 patient had an ischemic stroke. Patients’ characteristics are presented in Table 1. In the follow-up, peripheral arterial disease (p = 0.037), hyperphosphatemia (p = 0.035) and the cumulative number of peritonitis (p = 0.018) were associated with the occurrence of AMI. In our population we found a higher frequency of peritonitis in the year prior to the AMI (p = 0.024). In logistic regression, the cumulative number of peritonitis was a predictor of AMI (OR 4.918, CI 95%:1.093-22.132). In the mean follow-up time of 4.7 ± 1.4 years, the overall mortality was 21,7%, with CV disease accounting for 60% of the observed deaths. AMI and peritonitis were associated with higher mortality in PD patients (p = 0.016 and p = 0.009, respectively). Conclusion PD-related peritonitis was a predictor of AMI in these population. The risk is higher in the year following a peritonitis episode. This may be due to a chronic inflammatory state that persists after successful treatment of peritonitis which may predispose to enhanced CV risk. Similar to previous studies, we found that cumulative episodes of peritonitis were associated with increased mortality in PD population.

A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This strategy endows cloaked nanomaterials with improved interfacial properties, superior cell targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials. The structure, properties, and manner in which exosomes communicate with cells are first reviewed. This is followed by a discussion of the types of exosomes and their fabrication methods. We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering, regenerative medicine, imaging, and the treatment of neurodegenerative diseases. Finally, we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.