Formulation of biogenic fluorescent pigmented PHB nanoparticles from Rhodanobacter sp. for drug delivery.

Biogenic nanoparticles (NPs) have emerged as promising therapeutic formulations in effective drug delivery. Despite of various positive attributes, these NPs are often conjugated with various cytotoxic organic fluorophores for bioimaging, thereby reducing its effectiveness as a potential carrier. Herein, we aim to formulate biogenic fluorescent pigmented polyhydroxybutyrate (PHB) NPs from Rhodanobacter sp. strain KT31 (OK001852) for drug delivery. The bacterial strain produced 0.5 g L-1 of polyhydroxyalkanoates (PHAs) from 2.04 g L-1 of dry cell weight (DCW) under optimised conditions via submerged fermentation. Further, structural, thermal, and morphological charactersiation of the extracted PHAs was conducted using advance analytical technologies. IR spectra at 1719.25 cm-1 confirmed presence of C = O functional group PHB. NMR and XRD analysis validated the chemical structure and crystallinity of PHB. TG-DTA revealed Tm (168 °C), Td (292 °C), and Xc (35%) of the PHB. FE-SEM imaging indicated rough surface of the PHB film and the biodegradability was confirmed from open windro composting. WST1 assay showed no significant cell death (> 50%) from 100 to 500 µg/mL, endorsing non-cytotoxic nature of PHB. PHB NPs were uniform, smooth and spherical with size distribution and mean zeta potential 44.73 nm and 0.5 mV. IR and XRD peaks obtained at 1721.75 cm-1 and 48.42 Å denoted C = O and crystalline nature of PHB. Cell proliferation rate of PHB NPs was quite significant at 50 µg/mL, establishing the non-cytotoxic nature of NPs. Further, in vitro efficacy of the PHB NPs needs to be evaluated prior to the biomedical applications.

FuncPEP v2.0: An Updated Database of Functional Short Peptides Translated from Non-Coding RNAs.

Over the past decade, there have been reports of short novel functional peptides (less than 100 aa in length) translated from so-called non-coding RNAs (ncRNAs) that have been characterized using mass spectrometry (MS) and large-scale proteomics studies. Therefore, understanding the bivalent functions of some ncRNAs as transcripts that encode both functional RNAs and short peptides, which we named ncPEPs, will deepen our understanding of biology and disease. In 2020, we published the first database of functional peptides translated from non-coding RNAs-FuncPEP. Herein, we have performed an update including the newly published ncPEPs from the last 3 years along with the categorization of host ncRNAs. FuncPEP v2.0 contains 152 functional ncPEPs, out of which 40 are novel entries. A PubMed search from August 2020 to July 2023 incorporating specific keywords was performed and screened for publications reporting validated functional peptides derived from ncRNAs. We did not observe a significant increase in newly discovered functional ncPEPs, but a steady increase. The novel identified ncPEPs included in the database were characterized by a wide array of molecular and physiological parameters (i.e., types of host ncRNA, species distribution, chromosomal density, distribution of ncRNA length, identification methods, molecular weight, and functional distribution across humans and other species). We consider that, despite the fact that MS can now easily identify ncPEPs, there still are important limitations in proving their functionality.

Reclamation of chromium-contaminated soil by native Cr(VI)-reducing and PHA-accumulating Bacillus aryabhattai CTSI-07.

Reclamation of chromium-contaminated soil by bacteria is a big confront concerning to soil health restoration, food safety, and environmental protection. Herein, the chromium-resistant Bacillus aryabhattai CTSI-07 (MG757377) showed resistance to 1000 and 300 ppm of Cr(VI) in nutrient rich Luria Bertani (LB) and nutrient-deficient sucrose low phosphate (SLP) medium, respectively. It reduced 96.7% of Cr(VI) from contaminated soil in the presence of 100 ppm of Mg within 96 h under optimized conditions. Furthermore, Cr(VI) reduction by the bacteria was validated by Fourier transform infrared spectroscopic (FTIR) and X-ray diffraction (XRD) analysis. Besides Cr(VI) reduction, the bacterial strain also showed plant growth promoting traits like N2 fixation and indole acetic acid (IAA) production. On the other hand, transmission electron microscopy (TEM) imaging confirmed polyhydroxyalkanoates' (PHAs) granule accumulation and 0.5 g/l of PHAs was extracted from bacterial cell using SLP medium. Infra-red (IR) spectra and proton nuclear magnetic resonance (1H NMR) chemical shift patterns established the PHAs as polyhydroxybutyrate (PHB). Melting (Tm) and thermal degradation (Td) temperature of the PHB were 169 °C and 275 °C, respectively, as evident from thermogravimetry differential thermal analysis (TG-DTA). Atomic force microscopic (AFM) imaging depicted that the PHB film surface was rough and regular. Furthermore, the multi-metal-resistant, plant growth-promoting, and PHB-producing bacteria could reduce 99.82% of Cr(VI) from contaminated soil within 120 days in pot culture. Thus, it can be used for long-term reclamation of chromium-contaminated soil to restore soil health, provide food safety, and environmental protection.

Anti-miR-93-5p therapy prolongs sepsis survival by restoring the peripheral immune response.

Sepsis remains a leading cause of death for humans and currently has no pathogenesis-specific therapy. Hampered progress is partly due to a lack of insight into deep mechanistic processes. In the past decade, deciphering the functions of small noncoding miRNAs in sepsis pathogenesis became a dynamic research topic. To screen for new miRNA targets for sepsis therapeutics, we used samples for miRNA array analysis of PBMCs from patients with sepsis and control individuals, blood samples from 2 cohorts of patients with sepsis, and multiple animal models: mouse cecum ligation puncture-induced (CLP-induced) sepsis, mouse viral miRNA challenge, and baboon Gram+ and Gram- sepsis models. miR-93-5p met the criteria for a therapeutic target, as it was overexpressed in baboons that died early after induction of sepsis, was downregulated in patients who survived after sepsis, and correlated with negative clinical prognosticators for sepsis. Therapeutically, inhibition of miR-93-5p prolonged the overall survival of mice with CLP-induced sepsis, with a stronger effect in older mice. Mechanistically, anti-miR-93-5p therapy reduced inflammatory monocytes and increased circulating effector memory T cells, especially the CD4+ subset. AGO2 IP in miR-93-KO T cells identified important regulatory receptors, such as CD28, as direct miR-93-5p target genes. In conclusion, miR-93-5p is a potential therapeutic target in sepsis through the regulation of both innate and adaptive immunity, with possibly a greater benefit for elderly patients than for young patients.

PHAs production by facultative anaerobic bacteria Bacillus cereus FM5 through submerged and solid-state fermentation under anoxic condition.

PHAs (polyhydroxyalkanoates) are the bio-polyester synthesized by different aerobic and anaerobic bacteria as energy storage granule. However, its synthesis by anaerobes or facultative anaerobes is an imperative part of their physiology via assimilating broad range of substrates than aerobes. Thus, three Gram positive facultative anaerobic PHAs producers viz., Enterococcus sp. FM3, Actinomyces sp. CM4 and Bacillus sp. FM5 were selected. Among them, Bacillus sp. FM5 showed higher cell biomass production in MSM (mineral salt medium) comprised of glucose & peptone as carbon & nitrogen source at pH 9, temperature 37 °C, inoculum 10% and incubation period 72 h. Under optimized condition, Bacillus sp. FM5 produced 0.89 and 1.5 g l-1 of PHAs through submerged and solid-state fermentation in anoxic condition. In-silico analysis confirmed the facultative anaerobic PHAs producing bacteria as Bacillus cereus FM5. IR spectra of PHAs illustrated a strong absorption peak at 1718.50 cm-1 representing carbonyl ester (C=O) functional group of PHB (polyhydroxybutyrate), belonging to the family PHAs. It is the first report demonstrating PHAs production by Bacillus cereus FM5 in anoxic condition through different bioprocess technology, which may pave the way in the arena of further biopolymer research.

The Role of Non-Coding RNAs in Chromosomal Instability in Cancer.

Chromosomal instability (CIN) is characterized by an increased frequency of changes in chromosome structure or number and is regarded as a hallmark of cancer. CIN plays a prevalent role in tumorigenesis and cancer progression by assisting the cancer cells' phenotypic adaptation to stress, which have been tightly linked to therapy resistance and metastasis. Both CIN-inducing and CIN-repressing agents are being clinically tested for the treatment of cancer to increase CIN levels to unsustainable levels leading to cell death or to decrease CIN levels to limit the development of drug resistance, respectively. Non-coding RNAs (ncRNAs) including microRNAs and long ncRNAs (lncRNAs) have been fundamentally implicated in CIN. The miR-22, miR-26a, miR-28, and miR-186 target important checkpoint proteins involved in mediating chromosomal stability and their expression modulation has been directly related to CIN occurrence. lncRNAs derived from telomeric, centrosomal, and enhancer regions play an important role in mediating genome stability, while specific lncRNA transcripts including genomic instability inducing RNA called Ginir, P53-responsive lncRNA termed as GUARDIN, colon cancer-associated transcript 2, PCAT2, and ncRNA activated by DNA damage called NORAD have been shown to act within CIN-associated pathways. In this review, we discuss how these ncRNAs either maintain or disrupt the stability of chromosomes and how these mechanisms could be exploited for novel therapeutic approaches targeting CIN in cancer patients. SIGNIFICANCE STATEMENT: Chromosomal instability increases tumor heterogeneity and thereby assists the phenotypic adaptation of cancer cells, causing therapy resistance and metastasis. Several microRNAs and long non-coding RNAs that have been causally linked to chromosomal instability could represent novel therapeutic targets. Understanding the role of non-coding RNAs in regulating different genes involved in driving chromosomal instability will give insights into how non-coding RNAs can be utilized toward modifying chemotherapeutic regimens in different cancers.

Climate change and vulnerability of agribusiness: Assessment of climate change impact on agricultural productivity.

The current study has mapped the impact of changes in different climatic parameters on the productivity of major crops cultivated in India like cereal, pulses, and oilseed crops. The vulnerability of crops to different climatic conditions like exposure, sensitivity, and adaptive indicators along with its different components and agribusiness has been studied. The study uses data collected over the past six decades from 1960 to 2020. Analytical tools such as the Tobit regression model and Principal Component Analysis were used for the investigation which has shown that among climatic parameters, an increase in temperature along with huge variations in rainfall and consistent increase in CO2 emissions have had a negative impact by reducing crop productivity, particularly cereals (26 percent) and oilseed (35 percent). Among various factors, adaptive factors such as cropping intensity, agricultural machinery, and livestock density in combination with sensitivity factors such as average operational land holding size and productivity of cereals, and exposure indicators like Kharif (June-September) temperature, heavy rainfall, and rate of change in maximum and minimum Rabi (October-February) temperature have contributed significantly in increasing crop vulnerability. The agribusiness model needs to be more inclusive. It should pay attention to small and remote farmers, and provide them with inclusive finance that can facilitate the adoption of climate-smart financial innovations, serve the underserved segments, and help them reach the target of a sustainable and inclusive agribusiness model. Though the social, technological, and economic initiatives can enhance the adaptive capacity of farmers, political measures still have a major role to play in providing a healthy climate for agriculture in India through tailored adaptive approaches like the adoption of craft climate adaptation program, dilating the irrigation coverage and location-centric management options. Hence, multidisciplinary and holistic approaches are worth emphasizing for evaluating the future impacts of change in climate on Indian agriculture.

Biochemical aspects of pathogenic variability in white rust infected Indian mustard.

White rust caused by Albugo candida, an oomycete pathogen, is a devastating disease of Brassica juncea (Indian mustard) worldwide. There is a need to screen virulent white rust isolates to challenge the developed white rust-resistant B. juncea cultivars to screen their resistance potential. The current study explores pathogenic and biochemical response of Indian mustard to white rust isolates collected from three different geographic locations of India. The observations refine our understanding of the disease severity in India. Disease progression and biochemical responses were studied in the cotyledonary as well as true leaf stage of the B. juncea cultivar Varuna at different time points. The biochemical findings highlight the fluctuation of significant biochemical parameters such as total proteins, sugars, and phenols, superoxide dismutase, and hydrogen peroxide during the A. candida infection in B. juncea.

"Update vision on COVID-19: Structure, immune pathogenesis, treatment and safety assessment".

The on-going SARS-CoV-2 causing COVID-19 discovered in December 2019, is responsible for a global pandemic. The virus belongs to the group of enveloped viruses containing linear, non-segmented, single stranded, positive sense strand RNA as genetic material. Already six different strains Coronaviruses are being reported to infect humans, however the seventh one is genetically similar to the SARS Coronavirus and termed as SARS-CoV-2. Specific crucial macromolecules such as membrane, nuclear, spike and enveloped proteins including HE esterase are present in the virus that interact with ACE2, APN, NEU-5, 9SC2 moiety of humans plays significant role in occurrence and transmission of the devastating disease. This review article summarizes the structure, histopathology, transmission of novel Coronavirus, its symptoms with preventive measures & currently prescribed drugs. Though various drugs and therapy have been administrated or implemented to restrict COVID-19, however it is imperative to develop an antidote against SARS-CoV-2 by the scientific or research community to save life.

APPLE and translation: When a small peptideproduced from a "non-coding RNA" matters!

Sun et al. (2021) identified a novel translation initiation mechanism mediated through a new type of regulator named APPLE, a small peptide produced from a non-coding RNA transcript in acute myeloid leukemia, providing unforeseen opportunities for targeting the translation machinery in cancer cells.

Non-coding RNAs regulation of macrophage polarization in cancer.

Noncoding RNA (ncRNA) transcripts that did not code proteins but regulate their functions were extensively studied for the last two decades and the plethora of discoveries have instigated scientists to investigate their dynamic roles in several diseases especially in cancer. However, there is much more to learn about the role of ncRNAs as drivers of malignant cell evolution in relation to macrophage polarization in the tumor microenvironment. At the initial stage of tumor development, macrophages have an important role in directing Go/No-go decisions to the promotion of tumor growth, immunosuppression, and angiogenesis. Tumor-associated macrophages behave differently as they are predominantly induced to be polarized into M2, a pro-tumorigenic type when recruited with the tumor tissue and thereby favoring the tumorigenesis. Polarization of macrophages into M1 or M2 subtypes plays a vital role in regulating tumor progression, metastasis, and clinical outcome, highlighting the importance of studying the factors driving this process. A substantial number of studies have demonstrated that ncRNAs are involved in the macrophage polarization based on their ability to drive M1 or M2 polarization and in this review we have described their functions and categorized them into oncogenes, tumor suppressors, Juggling tumor suppressors, and Juggling oncogenes.

N-terminal truncation of VC0395_0300 protein from Vibrio cholerae does not lead to loss of diguanylate cyclase activity.

The bacterial secondary messenger bis-(3',5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP) has been implicated in the pathogenesis of Vibrio cholerae, due to its significant role in regulating the virulence, biofilm formation and motility of the host organism. The VC0395_0300 protein from V. cholerae, possessing a GGEEF sequence has been established as a diguanylate cyclase (DGC) capable of catalyzing the conversion of two GTP molecules to form cyclic-di-GMP. This in turn, plays a crucial role in allowing the organism to adopt a dual lifestyle, thriving both in human and aquatic systems. The difficulty in procuring sufficient amounts of homogenous soluble protein for structural assessment of the GGDEF domain in VC0395_0300 and the lack of soluble protein yield, prompted the truncation into smaller constructs (Sebox31 and Sebox32) carrying the GGDEF domain. The truncates retained their diguanylate cyclase activity comparable to the wild type, and were able to form biofilms as well. Fluorescence and circular dichroism spectroscopy measurements revealed that the basic structural elements do not show significant changes in the truncated proteins as compared to the full-length. This has also been confirmed using homology modeling and molecular docking of the wild type and truncates. This led us to conclude that the truncated constructs retain their activity in spite of the deletions in the N terminal region. This is supportive of the fact that DGC activity in GGDEF proteins is predominantly dependent on the presence of the conserved GGD(/E)EF domain and its interaction with GTP.

Phytoplankton diversity in relation to physicochemical attributes and water quality of Mandakini River, Garhwal Himalaya.

Phytoplankton are important biological indicators of water quality. This current study assessed the physicochemical parameters and phytoplankton diversity of Mandakini River, an important tributary of the River Ganga. Water and phytoplankton samples were collected from three sampling sites located at three different altitudes for a period of twelve months (July 2018-June 2019). Water samples were analyzed for fourteen important physicochemical parameters along with the identification of phytoplankton by following the standard methodology. A total of 21 species of phytoplankton under three major groups Bacillariophyceae (Cymbella aequalis, Diatoma vulgaris, Fragilaria arcus, Frustulia rhomboids, Gomphonema geminatum, Navicula confervacea, Nitzchia diversa, and Synedra ulna); Chlorophyceae (Volvox sp., Cladophora glomerata, Closterium longissima, Hydrodictyon sp., Microspora amoena, Spirogyra sp., Oedogonium sp., Ulothrix zonata, and Zygnema cylindrospermum); and Cyanophyceae (Anabaena ambigua, Chlorococcum humicola, Nodularia sp., and Oscillatoria sancta) were observed and recorded during the study period. Site S3 (Rudraprayag) had the highest species diversity. From this study, the effect of physicochemical parameters on the diversity and density of phytoplankton was observed. It also includes the overall significance of phytoplankton and physicochemical parameters to the water quality of the Mandakini River along with the key factors that were responsible for the degradation of water quality. The current study also provides baseline information to future researchers working in a similar discipline.

Extremophile - An Adaptive Strategy for Extreme Conditions and Applications.

The concurrence of microorganisms in niches that are hostile like extremes of temperature, pH, salt concentration and high pressure depends upon novel molecular mechanisms to enhance the stability of their proteins, nucleic acids, lipids and cell membranes. The structural, physiological and genomic features of extremophiles that make them capable of withstanding extremely selective environmental conditions are particularly fascinating. Highly stable enzymes exhibiting several industrial and biotechnological properties are being isolated and purified from these extremophiles. Successful gene cloning of the purified extremozymes in the mesophilic hosts has already been done. Various extremozymes such as amylase, lipase, xylanase, cellulase and protease from thermophiles, halothermophiles and psychrophiles are of industrial interests due to their enhanced stability at forbidding conditions. In this review, we made an attempt to point out the unique features of extremophiles, particularly thermophiles and psychrophiles, at the structural, genomic and proteomic levels, which allow for functionality at harsh conditions focusing on the temperature tolerance by them.

Biocompatible PHB Production from Bacillus Species Under Submerged and Solid-State Fermentation and Extraction Through Different Downstream Processing.

Catastrophic global accumulation of non-biodegradable plastic has led to efforts for production of alternative eco-friendly biopolymer. Here, we attempted to produce a biodegradable, cytocompatible and eco-friendly polyhydroxy-butyrate (PHB) from a pigmented Bacillus sp. C1 (2013) (KF626477) through submerged (SmF) and solid-state fermentation (SSF). Under SmF and SSF, 0.60 g l-1 and 1.56 g l-1 of PHB with 0.497 g l-1 of yellow fluorescent pigment (YFP) was produced. Fourier transform infrared (FTIR) absorption bands at 1719-1720 cm-1 indicate the presence of C=O group of PHB. Nuclear magnetic resonance (NMR) exhibited the typical chemical shift patterns of PHB, and crystallinity was confirmed from X-ray diffraction (XRD). The melting temperature (Tm), degradation temperature (Td) and crystallinity (Xc) of extracted PHB were found to be 171 °C, 288 °C and 35%, respectively. FACS (Fluorescence-activated cell sorting) confirmed cytocompatibility of PHB at 400 µg ml-1 in mouse fibroblast line. Moreover, biodegradability and elevated cytocompatibility of the PHB produced through SSF make them highly potential biomaterials to be used as a drug delivery carrier in future.

Revisiting Plant-Microbe Interactions and Microbial Consortia Application for Enhancing Sustainable Agriculture: A Review.

The present scenario of agricultural sector is dependent hugely on the use of chemical-based fertilizers and pesticides that impact the nutritional quality, health status, and productivity of the crops. Moreover, continuous release of these chemical inputs causes toxic compounds such as metals to accumulate in the soil and move to the plants with prolonged exposure, which ultimately impact the human health. Hence, it becomes necessary to bring out the alternatives to chemical pesticides/fertilizers for improvement of agricultural outputs. The rhizosphere of plant is an important niche with abundant microorganisms residing in it. They possess the properties of plant growth promotion, disease suppression, removal of toxic compounds, and assimilating nutrients to plants. Utilizing such beneficial microbes for crop productivity presents an efficient way to modulate the crop yield and productivity by maintaining healthy status and quality of the plants through bioformulations. To understand these microbial formulation compositions, it becomes essential to understand the processes going on in the rhizosphere as well as their concrete identification for better utilization of the microbial diversity such as plant growth-promoting bacteria and arbuscular mycorrhizal fungi. Hence, with this background, the present review article highlights the plant microbiome aboveground and belowground, importance of microbial inoculants in various plant species, and their subsequent interactive mechanisms for sustainable agriculture.

Study and overview of the novel corona virus disease (COVID-19).

In December 2019, a new disease with pneumonia-like symptoms was spreading throughout Wuhan in China which was entitled as novel coronavirus disease or COVID -19 caused by the virus SARS CoV-2. Within a span of a few days, this disease became a global threat and was termed as a pandemic by the World Health Organization (WHO) on March 11, 2020, since then the disease has affected more than 1.5 crore people worldwide and around 6.9 lakh people in India as of July 5, 2020. The origin of the COVID-19 disease has been traced back to the bats, but the intermediary contact is unknown. The disease spreads by respiratory droplets and contaminated surfaces. In most cases, the virus shows mild symptoms like fever, fatigue, dyspnea, cough, etc. which may become severe if appropriate precautions are not adhered to. For people with comorbidities (usually elderly) the disease may turn deadly and cause pneumonia, Acute Respiratory Disease Syndrome (ARDS), and multi-organ failure, thereby affecting a person's ability to breathe leading to being put on the ventilator support. The reproduction number (Rℴ) of COVID-19 is much higher than its predecessors and genetically similar diseases like SARS-CoV and MERS-CoV. This paper discusses the epidemiological characteristics of the SARS-CoV-2 virus, its phylogenetic relationship with the previous pandemic causing viruses such as SARS-CoV-1 and MERS-CoV and analyzes the various responses to this global pandemic worldwide, focusing on the actions taken by India and their outcomes.

Improvement of rice plant productivity by native Cr(VI) reducing and plant growth promoting soil bacteria Enterobacter cloacae.

Rapid industrialization and anthropogenic activities have produced huge amount of noxious Cr(VI), which accumulate in the soil for longer period. As a consequence, that decreases rice plant productivity in contiguous agricultural field of Sukinda mining area, Odisha. Thus, the high Cr(VI) resistant native bacterial strain CTWI-06 was selected for the study, which depicted resistance to 3500 ppm of Cr(VI) and wide array of other metals. Under optimized condition, the multi-metal resistant bacteria reduced 94% Cr(VI) within 92 h and Cr(VI) reduction was confirmed by FTIR and XRD analysis. Plant growth promoting traits like N2 fixation; phosphate (146.87 ppm), potassium (12.55 ppm) and Zn solubilization; ammonification; IAA production (114 µg mL-1) and suppression of fungal phytopathogens such as Rhizoctonia solani (ITCC 2060) and Phytium debaryanum (ITCC 5488) were also recorded. The bacterial strain was identified as Enterobacter cloacae CTWI-06 by 16S rDNA sequence (Accession No. MG757378). It significantly improved growth traits as well as productivity of Mahalakshmi rice variety in pot culture. Thus, the potential Cr(VI) reducing and PGPB strain may be utilized for long term bioremediation of Cr(VI) in chromium contaminated soil and to maintain soil fertility.