Design, synthesis and evaluation of 177Lu-labeled inverso and retro-inverso A9 peptide variants targeting HER2-overexpression.

Several HER2-specific peptides are being continuously explored to find a candidate with suitable pharmacokinetic properties for development of effective radiopharmaceutical that can find applications for clinical screening of breast cancer patients. In the present work with an aim of preparing a radiopeptide with improved metabolic stability and in vivo pharmacokinetic performance we modified our previously reported [177Lu]DOTA-L-A9 peptide. Here we designed an 'inverso' peptide with all d-amino acids and a 'retro-inverso' peptide where sequence of d-amino acids was reversed. Higher secondary structure stabilization of retro- inverso A9 variant compared to inverso A9 peptide was evident by circular dichroism studies. The two radiopeptides [177Lu]DOTA-D-A9 and [177Lu]DOTA-rD-A9 exhibited significantly improved in vivo metabolic stability over the original l-peptide. The retro-inverso variant, [177Lu]DOTA-rD-A9 demonstrated better pharmacokinetic behavior with significantly higher tumor uptake than the inverso peptide, [177Lu]DOTA-D-A9 and the original peptide, [177Lu]DOTA-L-A9. In the present case of A9 peptide, reversal of the peptide sequence of d-amino acids boosted the uptake and retention of radioactivity in HER2-positive tumor. The present study can thus guide the design and development of newer and improved versions of peptides.

Targeting HER2-receptors with 177Lu-labeled triazole stapled cyclic peptidomimetic.

In this study on-resin Cu(I)-catalyzed click reaction was performed to synthesize triazole-stapled cyclic peptidomimetic, DOTA-c[TZ]A9 targeting HER2 receptor expression in breast cancers. Spectroscopic (circular dichroism) and docking analysis provided evidence of enhanced helicity and secondary structure stabilization along with improved HER2 affinity in comparison to the corresponding linear peptide, DOTA-[Pra1, Aza7]A9. 177Lu-labeled cyclic peptide, 177Lu-DOTA-c[TZ]A9 displayed higher in vitro serum stability and in vivo metabolic stability and better HER2 binding affinity {Kd of 16.93 ± 3.02 nM} than the linear counterpart, [177Lu]DOTA-[Pra1, Aza7]A9 {Kd of 26.28 ± 2.87 nM}. Biodistribution profile in SKBR3 tumor bearing SCID mice demonstrated elevated radioactivity levels and prolonged retention of cyclic peptide in the tumor compared to the linear peptide. Thus, solid phase click cyclization technique can be extended towards preparation of triazole-stapled peptides targeting different receptors with improved stability and efficacy.

The Myb-like transcription factor phosphorus starvation response (PtPSR) controls conditional P acquisition and remodelling in marine microalgae.

Phosphorus (P) is one of the limiting macronutrients for algal growth in marine environments. Microalgae have developed adaptation mechanisms to P limitation that involve remodelling of internal phosphate resources and accumulation of lipids. Here, we used in silico analyses to identify the P-stress regulator PtPSR (Phaeodactylum tricornutum phosphorus starvation response) in the diatom P. tricornutum. ptpsr mutant lines were generated using gene editing and characterised by various molecular, genetics and biochemical tools. PtPSR belongs to a clade of Myb transcription factors that are conserved in stramenopiles and distantly related to plant P-stress regulators. PtPSR bound specifically to a conserved cis-regulatory element found in the regulatory region of P-stress-induced genes. ptpsr knockout mutants showed reduction in cell growth under P limitation. P-stress responses were impaired in ptpsr mutants compared with wild-type, including reduced induction of P-stress response genes, near to complete loss of alkaline phosphatase activity and reduced phospholipid degradation. We conclude that PtPSR is a key transcription factor influencing P scavenging, phospholipid remodelling and cell growth in adaptation to P stress in diatoms.

Machine learning technology in biohydrogen production from agriculture waste: Recent advances and future perspectives.

Agricultural waste biomass has shown great potential to deliver green energy produced by biochemical and thermochemical conversion processes to mitigate future energy crises. Biohydrogen has become more interested in carbon-free and high-energy dense fuels among different biofuels. However, it is challenging to develop models based on experience or theory for precise predictions due to the complexity of biohydrogen production systems and the limitations of human perception. Recent advancements in machine learning (ML) may open up new possibilities. For this reason, this critical study offers a thorough understanding of ML's use in biohydrogen production. The most recent developments in ML-assisted biohydrogen technologies, including biochemical and thermochemical processes, are examined in depth. This review paper also discusses the prediction of biohydrogen production from agricultural waste. Finally, the techno-economic and scientific obstacles to ML application in agriculture waste biomass-based biohydrogen production are summarized.

Emerging technologies for sustainable production of biohydrogen production from microalgae: A state-of-the-art review of upstream and downstream processes.

Biohydrogen (BioH2) is considered as one of the most environmentally friendly fuels and a strong candidate to meet the future demand for a sustainable source of energy. Presently, the production of BioH2 from photosynthetic organisms has raised a lot of hopes in the fuel industry. Moreover, microalgal-based BioH2 synthesis not only helps to combat current global warming by capturing greenhouse gases but also plays a key role in wastewater treatment. Hence, this manuscript provides a state-of-the-art review of the upstream and downstream BioH2 production processes. Different metabolic routes such as direct and indirect photolysis, dark fermentation, photofermentation, and microbial electrolysis are covered in detail. Upstream processes (e.g. growth techniques, growth media) also have a great impact on BioH2 productivity and economics, which is also explored. Technical and scientific obstacles of microalgae BioH2 systems are finally addressed, allowing the technology to become more innovative and commercial.

Impact of UDST: A step forward to end TB.

BACKGROUND: India is determined to eliminate TB by 2025 despite being a high burden country. Revised National Tuberculosis Control Programme (RNTCP) is being strengthened with introduction of Universal Drug Susceptibility Testing (UDST) for Rifampicin to achieve the elimination status. METHODOLOGY: We used a before-after comparison of baseline and intervention periods (12 months each) and analyzed data viz CBNAAT performed and case detection for both drug sensitive and drug resistant TB cases. RESULTS: After implementation of Universal DST, CBNAAT performed raised from 1252 to 3137 (increased by 2.5 times); Rif sensitive cases detected raised from 458 to 1241 (increased by 2.7 times) and Rif resistant cases detected raised from 54 to 82 (increased by 1.5 times) during baseline period (2017) and intervention period (2018). CONCLUSION: We conclude that introduction of UDST for Rifampicin in RNTCP has given a significant impact with increased case detection in our study.

Efficient capture of eosin yellow and crystal violet with high performance xanthan-acacia hybrid super-adsorbent optimized using response surface methodology.

Blending of xanthan and acacia gives a unique hybrid that was used for the synthesis of semi-interpenetrating network (semi-IPN) in which poly(acrylamide) chains were grafted onto hybrid of xanthan-acacia followed by their cross-linking (Xan-Aca-cl-poly(AAm)). Optimization was carried out under response surface methodology-central composite design (RSM-CCD). Maximum percentage swelling of semi-IPN obtained was 496.57%. The concentrations of acrylamide, citric acid and ammonium persulphate used as monomer, cross-linker and initiator, respectively were found to be significant parameters. The blend was highly effective in removal of both cationic (crystal violet) and anionic dyes (eosin yellow) showing maximum dye removal capacity of 97.58% and 95.42%, respectively under optimized parameters - 0.4 g semi-IPN dose in 15 ml dye solution of 10 mg L-1 concentration within 16 h. Adsorption mechanism of both the dyes followed three steps in accordance with intraparticle diffusion model along with mono layer langmuir adsorption criteria. Second order kinetics was followed in case of both dyes. Thermodynamic studies gave idea about the exothermic nature of adsorption. Semi-IPN could be recycled up to eight consecutive cycles and hence, can be utilized for industrial purpose for removal of dyes.

Evaluation of antimicrobial activity and bronchodialator effect of a polyherbal drug-Shrishadi.

OBJECTIVE: To investigate antimicrobial and bronchodialator effect of hydroalcholic extract of polyherbal drug Shirishadi containing Shirisha (Albezzia lebbeck), Nagarmotha (Cyprus rotandus) & Kantakari (Solanum xanthocarpum). METHODS: Antimicrobial activity was evaluated by disc diffusion method and MIC, MBC, MFC were calculated by micro dilution method. Hydroalcholic extract of this preparation was investigated for its phytochemical analysis, phenol and flavonoid were determined by spectrophotometric method and in vivo bronchodilator effect was analysed by convulsion time. RESULTS: The phytochemical tests revealed presence of alkaloids, anthraquinones, carbohydrates, flavonoids, saponins and tannins. The antimicrobial result showed the MIC of 6.25 mg/mL against Staphylococcus aureus and 12.5 mg/mL for Escherichia coli and 12.5 mg/mL against remaining bacteria tested, with strong antifungal activity. The maximum inhibition zone is found against Pseudomonas aeruginosa with MIC 16 mg/mL. Drug showed significant bronchodilator effect with 27.86% & 36.13% increase in preconvulsion time of guinea pigs pretreated with 100 & 200 mg/kg body weight of extract. CONCLUSIONS: The study reveals that the extracts possess antibacterial activity and antifungal activity in a dose dependent manner. This antimicrobial property may be due to presence of several saponins, further studies are highly needed for the drug development.