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Biotherapeutics hold great promise for the treatment of several diseases and offer innovative possibilities for new treatments that target previously unaddressed medical needs. ...Despite successful transitions from preclinical to clinical stages and regulatory approval, there are instances where adverse reactions arise, resulting in product withdrawals. As a result, it is essential to conduct thorough evaluations of safety and effectiveness on an individual basis. This article explores current practices, challenges, and future approaches in conducting comprehensive preclinical assessments to ensure the safety and efficacy of biotherapeutics including monoclonal antibodies, toxin-conjugates, bispecific antibodies, single-chain antibodies, Fc-engineered antibodies, antibody mimetics, and siRNA-antibody/peptide conjugates.
Glycosyl triazoles are conveniently accessible and contain multiple metal-binding units that may assist in metal-mediated catalysis. Azide derivatives of d-glucose have been converted to their ...respective aryltriazoles and screened as ligands for the synthesis of 2-substituted benz-fused azoles and benzimidazoquinazolinones by Cu-catalyzed intramolecular Ullmann type C-heteroatom coupling. Good to excellent yields for a variety of benz-fused heterocyles were obtained for this readily accessible catalytic system.
The development of drug delivery systems using nanoparticles as carriers for small and large therapeutic molecules remains a rapidly growing area of research. The advantages of using proteins to ...prepare nanoparticles for drug delivery applications include their abundance in natural sources, biocompatibility, biodegradability, easy synthesis process, and cost-effectiveness. In contrast to several particulate systems like nanoparticles from metallic and inorganic/synthetic sources, the protein nanoparticles do not have limitations such as potential toxicity, large size, accumulation, or rapid clearance from the body. In addition, protein-based nanoparticles offer the opportunity for surface modification by conjugation of other protein and carbohydrate ligands. This enables targeted delivery to the desired tissue and organ, which further reduces systemic toxicity. The use of protein nanoparticles for such applications could therefore prove to be a better alternative to maneuver and improve the pharmacokinetic and pharmacodynamic properties of the various types of drug molecules. In this review, while focusing on the properties of a few proteins such as the silk protein fibroin, we attempt to provide an overview of the existing protein-based nanoparticles. We discuss various methods for the synthesis of this class of nanoparticles. The review brings forth some of the factors that are important for the design of this class of nanoparticles and highlights the applications of the nanoparticles obtained from these proteins.
One of the major issues that manufacturers and suppliers of styrene-butadiene-styrene (SBS) modified bitumen face is erosion in its properties during storage and transportation. If appropriate ...controls are not in place, properties of SBS modified bitumen can erode significantly during storage and transportation, resulting in substandard quality of roads when constructed using such products. We report a comprehensive study of the effect of storage temperature, SBS concentration, polymer type and base bitumen on the properties of polymer modified bitumen during storage at elevated temperatures in sealed aluminium tubes. Our results show that storage temperature, SBS concentration and polymer type play a major role in the observed property erosion, while type of base bitumen has a lesser effect. The samples were stored in sealed aluminium tubes at temperatures of 150 °C, 180 °C and 210 °C for up to 21 days. At 150 °C, the properties of PMB's remained intact even after storing for 21 days. But, significant erosion in conventional and rheological properties of SBS modified bitumen takes place within the first 3 days of storage at temperatures ≥ 180 °C. At 210 °C, the PMB properties degrade to the base bitumen values within 1 day. Gel permeation chromatography and rheological results clearly show degradation of SBS molecules. The property loss is most significant when the SBS concentration is between 3% and 6%, in the steep middle region of the S-curve (softening point vs. polymer concentration). 3% SBS content is close to the network formation threshold of the polymer molecules in bitumen. Conventional polymer grades such as D1101, D1184, LG411 and Elvaloy 4170 showed maximum erosion in properties, while D1192 grade (with higher vinyl content > 35%) showed significantly lower drop. The newer polymer grade introduced by Kraton, MD0243, remained completely stable at 180 °C even after 21 days. Among PMBs with different base bitumens, noticeable differences were observed only when the SBS concentration was in the steep middle region of the S-curve (3–6%). We have discussed all the results in the background of the S-curve, there by highlighting the major role played by SBS concentration in property erosion during storage. Our results have important implications for storage and handling guidelines for polymer modified bitumens.
•Significant property erosion is observed in SBS modified bitumen within the first 3 days of storage at temperatures ≥ 180 °C, even in sealed containers. Gel permeation chromatography and rheological results clearly show degradation of SBS molecules.•Storage temperature, SBS concentration and polymer type play a significant role in the observed property erosion, while base bitumen type have a lesser effect.•Maximum erosion is observed when the SBS concentration is between 3% and 6%.•Polymer grades such as D1101, D1184, LG411 and Elvaloy 4170 showed maximum erosion. Performance of D1192 grade was significantly better. The newer grade, MD0243, remained stable throughout.•Our results have important implications for storage and handling guidelines for PMBs.
Immune checkpoint therapy (ICT) has dramatically altered clinical outcomes for cancer patients and conferred durable clinical benefits, including cure in a subset of patients. Varying response rates ...across tumor types and the need for predictive biomarkers to optimize patient selection to maximize efficacy and minimize toxicities prompted efforts to unravel immune and non-immune factors regulating the responses to ICT. This review highlights the biology of anti-tumor immunity underlying response and resistance to ICT, discusses efforts to address the current challenges with ICT, and outlines strategies to guide the development of subsequent clinical trials and combinatorial efforts with ICT.
Immune checkpoint therapy provides clinical benefits to many patients across different tumor types. Sharma, Goswami, and colleagues review the mechanisms of and clinical advances in immune checkpoint therapy and outline the challenges and approaches to broaden the clinical utility of immune checkpoint therapy.
An integrated approach involving vermicompost, chromate reducing bacteria and AMF was tested to manage the toxic impacts of Cr(VI) on
Ocimum basilicum
as a model plant. Pot experiments were conducted ...on
O. basilicum
plants in an artificially Cr(VI)-contaminated soil in two phases of experiment as bioinoculants experiment and vermicompost experiment. In the first phase of the bioinoculants experiment the series of gradient concentrations of Cr(VI) (0, 25, 50 and 100 mg kg
–1
in soil) were evaluated with previously isolated four efficient Cr(VI)-reducing rhizo-bacterial strains (
Bacillus Cereus
strain SUCR 44
,
BC;
Microbacterium
sp. strain SUCR 140, MB;
Bacillus thuringiensis
strain SUCR186, BT; and
Bacillus subtilis
strain SUCR188; BS) along with Arbuscular Mycorrhizal Fungus—
Glomus fasciculatum
(GF) in alone and in co-inoculation form. In the second experiment (vermicompost) the best performing strain (MB) was tested alone or in combination with GF along with different doses of vermicompost. It was observed that vermicompost by itself could be useful in decreasing the bioavailable Cr(VI), uptake of Cr besides improving the nutritional status of plants. The vermicompost also played an important and indirect role and improved herb yield by supporting the multiplication of MB (
Microbacterium
sp.), an efficient chromate reducing rhizobacteria, that further decreased the bioavailable and toxic form of Cr and improved population and colonization of GF too. The translocation of Cr(VI) was averted through improved colonization of GF, also prevented higher accumulation of Cr in aerial parts (leafy herb) of
O. basilicum
.
Anthropogenic disturbances are detrimental to the functioning and stability of natural ecosystems. Critical ecosystem processes driven by microbial communities are subjected to these disturbances. ...Here, we examine the stabilizing role of bacterial diversity on community biomass in the presence of abiotic perturbations such as addition of heavy metals, NaCl and warming. Bacterial communities with a diversity gradient of 1-12 species were subjected to the different treatments, and community biomass (OD600) was measured after 24 h. We found that initial species richness and phylogenetic structure impact the biomass of communities. Under abiotic perturbations, the presence of tolerant species in community largely contributed in community biomass production. Bacterial diversity stabilized the biomass across the treatments, and differential response of bacterial species to different perturbations was the key reason behind these effects. The results suggest that biodiversity is crucial for maintaining the stability of ecosystem functioning and acts as ecological insurance under abiotic perturbations. Biodiversity in natural ecosystems may also uphold the ecosystem functioning under anthropogenic disturbance.
Glycosyl triazoles have been introduced as efficient ligands for the Cu-catalyzed Sonogashira reaction to overcome the challenges of sideways homocoupling reactions in Cu catalysis in this reaction. ...The atmospheric oxygen in a sealed tube did not affect the coupling, and no need of complete exclusion of oxygen was experienced in the presence of glycohybrid triazole ligand L3. High product yields were obtained at 130 °C for a variety of substrates including aliphatic and aromatic terminal alkynes and differently substituted aromatic halides including 9-bromo noscapine. In contrast, at room temperature, a very low loading of the L3-Cu catalytic system could produce excellent yields in Glaser coupling including homocoupling and heterocoupling of a variety of aliphatic and aromatic alkynes.
The glycosyl 1,2,3-triazoles are expediently accessible from readily available sugar-derived glycosyl azide by utilizing modular CuAAC “Click Chemistry”, and the resulting glycohybrid skeleton ...possesses efficient metal-coordinating centers that support a wide range of metal-mediated efficient catalysis in various imperative organic transformations. Here, we designed and developed pyridyl glycosyl triazoles by employing the CuAAC reaction of d-glucose-derived glycosyl azides and alkynyl pyridines. These pyridyl glycosyl triazoles with Cu(I) salt were explored as an efficient catalyst to successfully assemble 2-amino-3-substituted and 3-substituted quinazolinones by the domino/tandem cross-coupling reaction of various N-substituted o-halobenzamides with cyanamide and formamide, respectively. The devised protocol has some notable features, including biocompatibility, low cost, easily accessible starting materials for the glycosyl ligands, high yield, broad spectrum, low catalytic loading, and mild reaction conditions.
The concept of DNA barcoding for species identification has gained considerable momentum in animals because of fairly successful species identification using cytochrome oxidase I (COI). In plants, ...matK and rbcL have been proposed as standard barcodes. However, barcoding in complex genera is a challenging task.
We investigated the species discriminatory power of four reportedly most promising plant DNA barcoding loci (one from nuclear genome--ITS, and three from plastid genome--trnH-psbA, rbcL and matK) in species of Indian Berberis L. (Berberidaceae) and two other genera, Ficus L. (Moraceae) and Gossypium L. (Malvaceae). Berberis species were delineated using morphological characters. These characters resulted in a well resolved species tree. Applying both nucleotide distance and nucleotide character-based approaches, we found that none of the loci, either singly or in combinations, could discriminate the species of Berberis. ITS resolved all the tested species of Ficus and Gossypium and trnH-psbA resolved 82% of the tested species in Ficus. The highly regarded matK and rbcL could not resolve all the species. Finally, we employed amplified fragment length polymorphism test in species of Berberis to determine their relationships. Using ten primer pair combinations in AFLP, the data demonstrated incomplete species resolution. Further, AFLP analysis showed that there was a tendency of the Berberis accessions to cluster according to their geographic origin rather than species affiliation.
We reconfirm the earlier reports that the concept of universal barcode in plants may not work in a number of genera. Our results also suggest that the matK and rbcL, recommended as universal barcode loci for plants, may not work in all the genera of land plants. Morphological, geographical and molecular data analyses of Indian species of Berberis suggest probable reticulate evolution and thus barcode markers may not work in this case.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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