Chemical Linkage Research Articles

Influence of Building Block Symmetry on the Band Structure of Stacked 2D Polyimide Covalent Organic Frameworks.

Covalent organic frameworks (COFs) are a class of crystalline porous materials distinctively built solely from organic elements, carbon, oxygen, hydrogen, and often nitrogen or boron. They form light, mechanically rigid, and chemically stable networks that have many advantages, but their low solubility and poor processability create issues with developing large-scale films or membranes. Two-dimensional (2D) COFs possess periodic porous crystallinity, functionality, modularity, and layered one-dimensional (1D) transport channels. All of these traits, along with the semiconducting properties of selected COFs, make them interesting candidates for integration in optoelectronic devices. Therefore, it is still a challenge to explore computationally and structurally the semiconductivity of COFs and to determine their final potential. Herein, we report on the possible semiconducting properties and results of polyimide-COF materials using density functional theory calculations. Our analysis includes monolayers and multilayers (AA- and AB-stacked modes) of mellitic triimide frameworks designed from mellitic trianhydride (MTA) as the main building knot, including MTI-TAPB-COF, which was previously synthesized from the condensation reaction of MTA and 1,3,5-tris(4-aminophenyl)benzene (TAPB), and other previously unreported structures based on MTA. Respective frameworks have been selected due to the difference in building block symmetry (C3 + C2 and C3 + C3) and different chemical linkages, either by benzene or by pyridine rings. We find the polyimide multilayers to be stable and with varying electronic properties. The finite band gap exhibited by every structure (monolayer and stacked) was sensitive to atomic arrangement. Stacking introduces dispersion to an otherwise flat band structure of the materials, which appeared to be highly sensitive to stacking direction. The effect of stacking was similar for each COF, but the magnitude of band structure change was different and dependent on the symmetry of the building blocks.

Selective RNA‐targeting of mTORC1 and 2 to ameliorate Alzheimer’s Disease pathogenesis

AbstractBackgroundIt has been well described that inhibition of the kinase, mechanistic target of rapamycin (mTOR), improves age‐related pathologies including Alzheimer’s Disease (AD). However, mTOR exists as a complex and exerts differential functions depending on its binding partners. Suppression of mTORC1 has yielded positive outcomes for AD‐related measures (decreased amyloid beta/tau pathologies and improved cognition)1. In contrast, increased mTORC2 activity also resulted in positive outcomes in AD models (improved brain insulin sensitivity and neuronal survival)2, suggesting that a therapeutic which inhibits mTORC1 while upregulating mTORC2 may be desirable for AD. However, no such therapeutic exists.MethodTo inhibit mTORC1, we used a raptor siRNA which has been chemically modified to be stable for in vivo purposes. To upregulate mTORC2, we bioinformatically identified natural antisense transcripts (NATs) of rictor and designed custom siRNAs to target the various transcripts. Following an in vitro screen of the custom siRNAs, we determined which NATs yield upregulation of rictor when targeted and designed more siRNAs targeting the same transcript to optimize our mTORC2‐upregulating siRNA. Cellular RNA and protein were quantified using RT‐qPCR and western blot, respectively.ResultWe demonstrate efficient knockdown of raptor in all transfected cell lines, as well as in mouse brain. Raptor knockdown has been confirmed at both the RNA and protein level. Furthermore, we successfully upregulated expression of rictor using rictor NAT‐targeting siRNAs (AntagoNATs) in multiple cell lines. Downstream analyses suggest a therapeutic effect for both raptor knockdown and rictor upregulation in the context of AD.ConclusionNucleic acid‐based therapeutics which target RNA have been outcompeting and replacing small molecule protein‐targeting drugs in recent years. However, RNA‐targeted therapeutics have been largely unexplored for AD. Chemical linkage of raptor siRNA to rictor AntagoNAT siRNA yields the first therapeutic to selectively inhibit mTORC1 and upregulate mTORC2, providing a modern RNA‐targeting therapeutic for AD.

Satellite-Type Sulfur Atom Distribution in Trithiocarbonate Bond-Bridged Dimeric Prodrug Nanoassemblies: Achieving Both Stability and Activatability.

Homodimeric prodrug nanoassemblies (HDPNs) hold promise for improving the delivery efficiency of chemo-drugs. However, the key challenge lies in designing rational chemical linkers that can simultaneously ensure the chemical stability, self-assembly stability, and site-specific activation of prodrugs. The "in series" increase in sulfur atoms, such as trisulfide bond, can improve the assembly stability of HDPNs to a certain extent, but limits the chemical stability of prodrugs. Herein, trithiocarbonate bond (─SC(S)S─), with a stable "satellite-type" distribution of sulfur atoms, is developed via the insertion of a central carbon atom in trisulfide bonds. ─SC(S)S─ bond effectively addresses the existing predicament of HDPNs by improving the chemical and self-assembly stability of homodimeric prodrugs while maintaining the on-demand bioactivation. Furthermore, ─SC(S)S─ bond inhibits antioxidant defense system, leading to up-regulation of the cellular ROS and apoptosis of tumor cells. These improvements of ─SC(S)S─ bond endow the HDPNs with in vivo longevity and tumor specificity, ultimately enhancing the therapeutic outcomes. ─SC(S)S─ bond is, therefore, promising for overcoming the bottleneck of HDPNs for efficient oncological therapy.

Amination of N-(Organodithio)phthalimides for the Modular Synthesis of Aminodisulfides.

Synthetic methods for unsymmetrical aminodisulfides are greatly needed due to their applications in drug discovery, linker chemistry, and materials sciences. In this study, an amination reaction of N-dithiophthalimides has been developed for the divergent synthesis of unsymmetrical aminodisulfides. The reaction proceeds under mild conditions and provides the aminodisulfides in excellent yields without cleavage of the disulfide bond. The N-dithiophthalimides are readily available from several bilateral disulfurating reagents, and the broad substrate scope of this reaction allows for the modular synthesis of a variety of unsymmetrical aminodisulfides in two-step operations.

Plasmon-induced immobilization of xanthene chemosensors toward repurposing as SERS nanotags

Surface-enhanced Raman spectroscopy (SERS) has emerged as a powerful tool in biophysics, bioanalytical chemistry, and biomedicine due to its unique ability to monitor extracellular chemical activity using fiber optics and multiplexed detection, which are essential for the study of complex biological systems. However, the exceptionally limited choice of SERS nanotags has hindered the practical application of SERS sensing in the fields. Enormous efforts and time are needed to develop new nanotag lines from ab initio for different targeted analytes. This study is inspired by the extensive range of fluorescent chemosensors already in use for various applications and takes a pioneering step toward repurposing them as the SERS nanotags. More specifically, this study explores the potential of plasmon-induced aromatic radical substitution reaction to immobilize xanthene-based chemosensors onto plasmonic nanostructures using a chemical linker without pre-modifying the chemical structures of the chemosensors or compromising the functionality of their binding groups towards specific analytes. Using this proposed method, we immobilize two primary xanthene-based chemosensors and demonstrate their functionality as SERS chemosensors.

Revealing Novel-Strain-Specific and Shared Epitopes of Infectious Bronchitis Virus Spike Glycoprotein Using Chemical Linkage of Peptides onto Scaffolds Precision Epitope Mapping.

The avian coronavirus, infectious bronchitis virus (IBV), is an economically important infectious disease affecting chickens, with a diverse range of serotypes found globally. The major surface protein, spike (S), has high diversity between serotypes, and amino acid differences in the S1 sub-unit are thought to be responsible for poor cross-protection afforded by vaccination. Here, we attempt to address this, by using epitope mapping technology to identify shared and serotype-specific immunogenic epitopes of the S glycoprotein of three major circulating strains of IBV, M41, QX, and 4/91, via CLIPS peptide arrays based on peptides from the S1 sub-units. The arrays were screened with sera from chickens immunised with recombinant IBV, based on Beau-R backbone expressing heterologous S, generated in two independent vaccination/challenge trials. The screening of sera from rIBV vaccination experiments led to the identification of 52 immunogenic epitopes on the S1 of M41, QX, and 4/91. The epitopes were assigned into six overlapping epitope binding regions. Based on accessibility and location in the hypervariable regions of S, three sequences, 25YVYYYQSAFRPPNGWHLQGGAYAVVNSTN54, 67TVGVIKDVYNQSVASI82, and 83AMTVPPAGMSWSVS96, were selected for further investigation, and synthetic peptide mimics were recognised by polyclonal sera. These epitopes may have the potential to contribute towards a broader cross-protective IBV vaccine.

Antibody-Drug Conjugates (ADC) in HER2/neu-Positive Gynecologic Tumors.

Antibody-drug conjugates (ADCs) are a new class of targeted anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a highly cytotoxic molecule payload bonded through specifically designed cleavable or non-cleavable chemical linkers. One such tumor surface receptor is human epidermal growth factor 2 (HER2), which is of interest for the treatment of many gynecologic tumors. ADCs enable the targeted delivery of a variety of cytotoxic therapies to tumor cells while minimizing delivery to healthy tissues. This review summarizes the existing literature about HER2-targeting ADC therapies approved for use in gynecologic malignancies, relevant preclinical studies, strategies to address ADC resistance, and ongoing clinical trials.

Ion recognition enables fast Mg–Cl bond dissociation kinetics and better Mg plating/stripping reversibility

Rechargeable Mg-metal batteries hold considerable promise for renewable energy storage and utilization. However, the Mg stripping/plating processes suffer from sluggish ion pairs dissociation kinetics, resulting in poor rate and cycle properties. In this work, an efficient skeleton host containing dissimilar coupling elements with varied electronegativity has been designed to promote interfacial reaction kinetics by accelerating the Mg–Cl bond dissociation process. As a proof-of-concept prototype, the N/O-doped cobalt nanoparticles embedded in carbonaceous polyhedrons has been synthesized via facile high temperature annealing of zeolitic imidazolate framework-67 (ZIF-67). The exposed electron-rich N/O sites and electron-deficient Co sites can regulate the adsorbing structure configuration of [Mg-Cl]+ complex ions by selectively bonding with the Mg2+ and Cl– through chemical coordination linkage, respectively. The elongated bond length from 2.596 Å to 2.679 Å and the weakened bond strength are beneficial for the complex ions dissociation, leading to better charge transfer kinetics. In addition, the better magnesiophilic property accompanied by the conductive and porous permeable three-dimensional architecture realizes the homogeneous electrodeposition of Mg and improved electrode kinetics. The decreased overpotential has been verified in both magnesium organohaloaluminates electrolyte (from 290 mV to 189 mV) and conventional Mg(TFSI)2-based electrolyte (from 600 mV to 200 mV). The designed skeleton host also exhibits excellent long cycle lifespan above 2300 h and extra-high average Coulombic efficiency of 99.65 % within 700 cycles. The accelerated bond splitting strategy enables improved metal-anode reversibility, which is also insightful to high concentrated or other electrolyte systems that contain abundant ion pairs or aggregates.

Ultra-high temperature suspending stabilizer and cement slurry interface interaction law and mechanism study for ultra-deep well cementing

The high temperature issue that cementing is facing is getting more and more significant as oil and gas extraction is being expanded to deep stratum. In order to increase the sedimentation stability of cement slurry under ultra-high temperature conditions, a suspension stability of cement slurry was created in the study. On the basis of previous research, its mechanism of action was examined from the perspective of interface interaction. The suspension stabilizer's low temperature adsorption behavior was investigated using the Zeta potential test and the total organic carbon (TOC) test. The findings indicate that the suspension stabilizer's apparent adsorption activation energy is 44.667 kJ/mol, which is in the range of chemical adsorption. The XRD test, infrared spectrum test, and Raman spectrum test were used to examine the cement's hydration byproducts. The findings demonstrate that hydrated calcium silicate (C-S-H) is the predominant component of the cement paste's short-term hydration products during ultra-high temperature curing. Ion concentration testing and molecular dynamics modeling were used to examine the interface interaction mechanism between the suspension stabilizer and the hydration products. The findings indicated that a network of chemical interactions, including hydrogen and ionic bonds, interacted between suspension stabilizer and C-S-H. The sedimentation stability of cement slurry is maintained by the persistence of these chemical linkages at extremely high temperatures.

A Self-Immolative DNA Nanogel Vaccine toward Cancer Immunotherapy.

The development of precisely engineered vehicles for intracellular delivery and the controlled release of payloads remains a challenge. DNA-based nanomaterials offer a promising solution based on the A-T-G-C alphabet-dictated predictable assembly and high programmability. Herein, we present a self-immolative DNA nanogel vaccine, which can be tracelessly released in the intracellular compartments and activate the immune response. Three building blocks with cytosine-rich overhang domains are designed to self-assemble into a DNA nanogel framework with a controlled size. Two oligo agonists and one antigen peptide are conjugated to the building blocks via an acid-labile chemical linker. Upon internalization into acidic endosomes, the formation of i-motif configurations leads to dissociation of the DNA nanogel vaccine. The acid-labile chemical linker is cleaved, releasing the agonists and antigen in their traceless original form to activate antigen-presenting cells and an immune response. This study presents a novel strategy for constructing delivery platforms for intracellularly stimuli-triggered traceless release of therapeutics.

Nanoscale celecoxib prodrugs: As efficient anti-inflammatory principles

We have synthesized lipidic prodrugs of celecoxib by grafting aliphatic chains to celecoxib through acyl sulfonamide (1), aryl sulfonyl carbamate (2) and aryl sulfonyl urea (3) chemical linkages. Their molecular formulas were confirmed through HR-MS and the formation of ester bond by FTIR and NMR spectroscopy. Nanoparticles of the different prodrugs 1-3 were successfully formulated using emulsion evaporation method and DSPE-PEG2000 as the only excipient. All nanoparticles depicted size between 130 and 160 nm, PdI ≤0.2 and negative zeta potential values from −25 to −35 mV. In addition, they were stable upon storage at 4 °C and/or at room temperature for about a month (in shelf). Morphology of all nanoparticles were spherical-type as observed in transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The encapsulation efficiency of the prodrug was as high as 99% for all three corresponding prodrugs NPs. The nanoscale prodrugs 1–3, are reported for the first time. Moreover, all the characterization data (physicochemical and biological) regarding NPs are also unique. In addition, all prodrug nanoparticles have preserved in vitro anti-inflammatory activity when incubated with the THP-1 cell line activated with lipopolysaccharide (LPS). In vivo studies on a collagen induced arthritis murine model showed results: Prodrug 3 NPs showed activity but were not as efficient as celecoxib in its free form, this might be due to no or very slow release of celecoxib from the prodrug 3 NPs. To promote the reduction of inflammation using NPs would require to explore the possible administration (in vivo) of other prodrugs 1 and 2 NPs in the future.

Reversible, Covalent DNA Condensation Approach Using Chemical Linkers for Enhanced Gene Delivery.

Nonviral gene delivery has emerged as a promising technology for gene therapy. Nonetheless, these approaches often face challenges, primarily associated with lower efficiency, which can be attributed to the inefficient transportation of DNA into the nucleus. Here, we report a two-stage condensation approach to achieve efficient nuclear transport of DNA. First, we utilize chemical linkers to cross-link DNA plasmids via a reversible covalent bond to form smaller-sized bundled DNA (b-DNA). Then, we package the b-DNA into cationic vectors to further condense b-DNA and enable efficient gene delivery to the nucleus. We demonstrate clear improvements in the gene transfection efficiency in vitro, including with 11.6 kbp plasmids and in primary cultured neurons. Moreover, we also observed a remarkable improvement in lung-selective gene transfection efficiency in vivo by this two-stage condensation approach following intravenous administration. This reversible covalent assembly strategy demonstrates substantial value of nonviral gene delivery for clinical therapeutic applications.

Rational Design of a Chemical Bath Deposition Based Tin Oxide Electron-Transport Layer for Perovskite Photovoltaics.

Chemical bath deposition (CBD) is widely used to deposit tin oxide (SnOx ) as an electron-transport layer in perovskite solar cells (PSCs). The conventional recipe uses thioglycolic acid (TGA) to facilitate attachments of SnOx particles onto the substrate. However, nonvolatile TGA is reported to harm the operational stability of PSCs. In this work, a volatile oxalic acid (OA) is introduced as an alternative to TGA. OA, a dicarboxylic acid, functions as a chemical linker for the nucleation and attachment of particles to the substrate in the chemical bath. Moreover, OA can be readily removed through thermal annealing followed by a mild H2 O2 treatment, as shown by FTIR measurements. Synergistically, the mild H2 O2 treatment selectively oxidizes the surface of the SnOx layer, minimizing nonradiative interface carrier recombination. EELS (electron-energy-loss spectroscopy) confirms that the SnOx surface is dominated by Sn4+ , while the bulk is a mixture of Sn2+ and Sn4+ . This rational design of a CBD SnOx layer leads to devices with T85 ≈1500h, a significant improvement over the TGA-based device with T80 ≈250h. The champion device reached a power conversion efficiency of 24.6%. This work offers a rationale for optimizing the complex parameter space of CBD SnOx to achieve efficient and stable PSCs.

Radiation-Induced Surface Modification of MXene with Ionic Liquid to Improve Electrochemical Properties and Chemical Stability.

For the first time, an ionic liquid was grafted onto Ti3C2Tx MXene interlayers (MXene-g-IL) using a radiation technique. The IL was tightly immobilized on the surface of MXene nanosheets via chemical linkage, which exhibited excellent specific capacitance (160 F g-1 at 5 mV s-1) and improved structural stability (maintaining the sheet-like structure for 180 days). The facile, efficient, and scalable synthetic strategy derived from the radiation technique can open a new avenue for covalent functionalization of MXene-based materials and promote their further application.

A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy.

Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment of hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, that are mainly associated with modest specificity and therapeutic benefit, the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tumor toxicity. Based on their beneficial mechanism of action, 15 ADCs have been approved to date by the market approval by the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and/or other international governmental agencies for use in clinical oncology, and hundreds are undergoing evaluation in the preclinical and clinical phases. Here, our aim is to provide a comprehensive overview of the key features revolving around ADC therapeutic strategy including their structural and targeting properties, mechanism of action, the role of the tumor microenvironment and review the approved ADCs in clinical oncology, providing discussion regarding their toxicity profile, clinical manifestations and use in novel combination therapies. Finally, we briefly review ADCs in other pathological contexts and provide key information regarding ADC manufacturing and analytical characterization.

Development of potent antibody drug conjugates against ICAM1+ cancer cells in preclinical models of cholangiocarcinoma

As a highly lethal adenocarcinoma of the hepatobiliary system, outcomes for cholangiocarcinoma (CCA) patients remain prominently poor with a 5-year survival of <10% due to the lack of effective treatment modalities. Targeted therapeutics for CCA are limited and surgical resection of CCA frequently suffers from a high recurrence rate. Here we report two effective targeted therapeutics in this preclinical study for CCA. We first performed a quantitative and unbiased screening of cancer-related antigens using comparative flow cytometry in a panel of human CCA cell lines, and identified intercellular adhesion molecule-1 (ICAM1) as a therapeutic target for CCA. After determining that ICAM1 has the ability to efficiently mediate antibody internalization, we constructed two ICAM1 antibody-drug conjugates (ADCs) by conjugating ICAM1 antibodies to different cytotoxic payloads through cleavable chemical linkers. The efficacies of two ICAM1 ADCs have been evaluated in comparison with the first-line chemodrug Gemcitabine in vitro and in vivo, and ICAM1 antibodies coupled with warhead DX-8951 derivative (DXd) or monomethyl auristatin E (MMAE) elicit a potent and consistent tumor attenuation. In summary, this study paves the road for developing a promising targeted therapeutic candidate for clinical treatment of CCA.

Expert consensus on the management of breast cancer antibody-drug conjugates infusion

Antibody-drug conjugates (ADC) are a new class of antineoplastic agents whose structure is composed of a monoclonal antibody covalently attached to a cytotoxic drug via a chemical linker. The introduction and clinical application of ADC change the treatment pattern of human epidermal growth factor receptor 2 (HER2) and triple-negative breast cancer, which is put forward new requirements for the standardized use and management of ADC drugs for medical staff. ADC drugs infusion norms and the prevention and management of adverse reactions are important prerequisites for ensuring drug efficacy and safety. Therefore, the Breast Cancer Case Manager Branch of the Chinese Medical Education Association and the consensus formulation group on targeted drug infusion norms jointly formulated an expert consensus on management of breast cancer antibody-drug conjugates infusion norms. The aim is to provide practical guidance and the early prevention and timely management of related adverse reactions of ADC drugs such as Trastuzumab Emtansine, Trastuzumab Deruxtecan, and Sacituzumab Govitecan for clinical staff.

Investigation on the impact of elevated temperature on sustainable geopolymer composite

Geopolymer concrete (GPC) is an eco-friendly, sustainable, cementless and green concrete. It could be an alternative to the conventional concrete. In alkaline circumstances, the alumina and silica concentration in geopolymer concrete creates the geopolymer bond, while regular concrete creates C-S-H (calcium silicate hydrate bond). The final result of the geopolymer bond does not include any water. At elevated temperatures, geopolymer concrete would thus be more stable. Due to its greater strength and durability quality, geopolymer concrete may be the ideal replacement for ordinary portland cement (OPC) concrete. This research intends to examine how specimens of geopolymer concrete and regular concrete respond to exposure to increased temperatures between 100°C and 800°C. Mass loss, ultrasonic pulse velocity, compressive strength, X-ray diffraction, thermogravimetric analysis and derivative thermogravimetric analysis were all examined throughout the experimental examination. Both concrete specimens lose mass or weight as the exposure temperature rises; OPC concrete samples spalls at 600°C, while GPC sample fail at 800°C. GPC specimens lose around 12% of their original mass after being exposed to temperatures of 800°C, while OPC specimens lose about 7%. The GPC specimens maintained 60% of their initial compressive strength after being exposed to a temperature of 700°C, but the OPC concrete specimens only kept 52%. With each increase in exposure to extreme temperatures, the peaks of quartz and cristobalite are lowered. Only the form or structure of the mineral oxide would change; the chemical linkages would remain. The GPC samples subjected to temperatures of 100°C exhibit effective thermal stability than all other specimens exposed to extreme temperatures. As the exposure temperature rises, the GPC specimens become more thermally stable. According to the experimental findings, the GPC specimens’ bonding structure makes them more resistant to high temperatures than regular concrete specimens. Micropores are present in the voids of the geopolymer matrix, while mesopores and micropores are present in the voids of the OPC matrix. While OPC bonding is C-S-H formed by the hydration of lime and silica contained in the cement, the geopolymer bonding did not include the water content in the final or end result of geopolymerisation for strengthening.

Plant-based synthesis of TiO2 – rGO nanocomposite for the efficient photocatalytic degradation of an emerging contaminant: Experimental and theoretical investigations

The need to develop sustainable and efficient photocatalysts for the degradation of contaminants of emerging concern has gained considerable attention. In this study, plant-based titanium dioxide-reduced graphene oxide (TiO2-rGO) photocatalyst was synthesized by a hydrothermal method using Azadirachta indica (AI) leaf extract. Morphological and chemical properties of the AI-TiO2-rGO photocatalyst were evaluated in detail. The clusters of AI-TiO2 wrapped in AI-rGO were identified with TEM analysis, and from the XRD, the purity of AI-TiO2-rGO was confirmed. The low band gap (2.80 eV) of AI-TiO2-rGO made it a suitable photocatalyst under visible light. The X-ray photoelectron spectroscopy (XPS) results indicated the establishment of strong Ti-O-C chemical linkage within the AI-TiO2-rGO photocatalyst. The efficiency of AI-TiO2-rGO was assessed for the degradation of carbamazepine (CBZ) under UV-A irradiation (94.28%) and visible light (59.97%) in a batch photocatalytic reactor for 60 min. The optimized conditions such as AI-TiO2-rGO dosage (50 mg/L), initial CBZ concentration (4.5 mg/L), and light source (UV-A (60 W)), were validated with response surface methodology (RSM). The mechanism of degradation of CBZ by AI-TiO2-rGO was explained with the identification of intermediate compounds, and three plausible CBZ degradation pathways were proposed. The reusability study suggested that the AI-TiO2-rGO photocatalyst could be effectively used for 8 cycles. The evaluation of toxicity of treated water with E.Coli growth curve (reduction in Iind to 30.12% (UV) and 27.65% (visible)) signified that the treated water was less toxic. The comparison of AI-TiO2-rGO with chemically synthesized TiO2-rGO indicated that even though AI-TiO2-rGO exhibited a slightly higher band gap (2.80 eV), it can be the better alternative for the photocatalysts synthesized by chemical route. The economic analysis of the overall process proved that the application of AI-TiO2-rGO was more cost-effective and sustainable than the conventional TiO2 photocatalyst. Overall, the study provides valuable insight into synthesizing recyclable plant-based photocatalysts to degrade recalcitrant emerging contaminants in the water.

Antibody-Drug Conjugates for the Treatment of Renal Cancer: A Scoping Review on Current Evidence and Clinical Perspectives.

Antibody-drug conjugates (ADCs) are complex chemical structures composed of a monoclonal antibody, serving as a link to target cells, which is conjugated with a potent cytotoxic drug (i.e., payload) through a chemical linker. Inspired by Paul Ehrlich's concept of the ideal anticancer drug as a "magic bullet", ADCs are also highly specific anticancer agents, as they have been demonstrated to recognize, bind, and neutralize cancer cells, limiting injuries to normal cells. ADCs are among the newest pharmacologic breakthroughs in treating solid and hematologic malignancies. Indeed, in recent years, various ADCs have been approved by the Food and Drug Administration and European Medicines Agency for the treatment of several cancers, resulting in a "practice-changing" approach. However, despite these successes, no ADC is approved for treating patients affected by renal cell carcinoma (RCC). In the present paper, we thoroughly reviewed the current literature and summarized preclinical studies and clinical trials that evaluated the activity and toxicity profile of ADCs in RCC patients. Moreover, we scrutinized the potential causes that, until now, hampered the therapeutical success of ADCs in those patients. Finally, we discussed novel strategies that would improve the development of ADCs and their efficacy in treating RCC patients.