MARS and RNAcmap3: The Master Database of All Possible RNA Sequences Integrated with RNAcmap for RNA Homology Search.

Recent success of AlphaFold2 in protein structure prediction relied heavily on co-evolutionary information derived from homologous protein sequences found in the huge, integrated database of protein sequences (Big Fantastic Database). In contrast, the existing nucleotide databases were not consolidated to facilitate wider and deeper homology search. Here, we built a comprehensive database by incorporating the non-coding RNA (ncRNA) sequences from RNAcentral, the transcriptome assembly and metagenome assembly from metagenomics RAST (MG-RAST), the genomic sequences from Genome Warehouse (GWH), and the genomic sequences from MGnify, in addition to the nucleotide (nt) database and its subsets in National Center of Biotechnology Information (NCBI). The resulting Master database of All possible RNA sequences (MARS) is 20-fold larger than NCBI's nt database or 60-fold larger than RNAcentral. The new dataset along with a new split-search strategy allows a substantial improvement in homology search over existing state-of-the-art techniques. It also yields more accurate and more sensitive multiple sequence alignments (MSAs) than manually curated MSAs from Rfam for the majority of structured RNAs mapped to Rfam. The results indicate that MARS coupled with the fully automatic homology search tool RNAcmap will be useful for improved structural and functional inference of ncRNAs and RNA language models based on MSAs. MARS is accessible at https://ngdc.cncb.ac.cn/omix/release/OMIX003037, and RNAcmap3 is accessible at http://zhouyq-lab.szbl.ac.cn/download/.

Differential expression and global analysis of miR156/SQUAMOSA promoter binding-like proteins (SPL) module in oat.

SQUAMOSA promoter binding-like proteins (SPLs) are important transcription factors that influence growth phase transition and reproduction in plants. SPLs are targeted by miR156 but the SPL/miR156 module is completely unknown in oat. We identified 28 oat SPL genes (AsSPLs) distributed across all 21 oat chromosomes except for 4C and 6D. The oat- SPL gene family represented six of eight SPL phylogenetic groups, with no AsSPLs in groups 3 and 7. A novel oat miR156 (AsmiR156) family with 21 precursors divided into 7 groups was characterized. A total of 16 AsSPLs were found to be targeted by AsmiR156. Intriguingly, AsSPL3s showed high transcript abundance during early inflorescence (GS-54), as compared to the lower abundance of AsmiR156, indicating their role in reproductive development. Unravelling the SPL/miR156 regulatory hub and alterations in expression patterns of AsSPLs could provide an essential toolbox for genetic improvement in the cultivated oat.

Multiple sequence alignment-based RNA language model and its application to structural inference.

Compared with proteins, DNA and RNA are more difficult languages to interpret because four-letter coded DNA/RNA sequences have less information content than 20-letter coded protein sequences. While BERT (Bidirectional Encoder Representations from Transformers)-like language models have been developed for RNA, they are ineffective at capturing the evolutionary information from homologous sequences because unlike proteins, RNA sequences are less conserved. Here, we have developed an unsupervised multiple sequence alignment-based RNA language model (RNA-MSM) by utilizing homologous sequences from an automatic pipeline, RNAcmap, as it can provide significantly more homologous sequences than manually annotated Rfam. We demonstrate that the resulting unsupervised, two-dimensional attention maps and one-dimensional embeddings from RNA-MSM contain structural information. In fact, they can be directly mapped with high accuracy to 2D base pairing probabilities and 1D solvent accessibilities, respectively. Further fine-tuning led to significantly improved performance on these two downstream tasks compared with existing state-of-the-art techniques including SPOT-RNA2 and RNAsnap2. By comparison, RNA-FM, a BERT-based RNA language model, performs worse than one-hot encoding with its embedding in base pair and solvent-accessible surface area prediction. We anticipate that the pre-trained RNA-MSM model can be fine-tuned on many other tasks related to RNA structure and function.

Physiological and behavioral assessment of Metaphire posthuma in response to clothianidin insecticide: Insights from molecular and biochemical analysis.

In the present study, Clothianidin [(E) - 1-(2 - chloro-1,3 - thiazol - 5-ylmethyl) - 3-methyl - 2- nitroguanidine] (CLO) was selected as a soil pollutant and earthworm was employed as a test organism. The various responses like biochemical and detoxification process of earthworm Metaphire posthuma towards Clothianidin at lethal and sublethal doses were studied using OECD-standardized toxicological guidelines. The present study examined the toxicity of CLO to earthworms after 28 days of exposure at conc. 0, 1.5, 3, 6, 12 and 24 mg kg-1 in a soil mixture. Biochemical markers including Guaiacol peroxidase (POD), Superoxide dismutase (SOD), Catalase (CAT), Glutathione S-transferase (GST) and content of Malondialdehyde (MDA) in earthworms were measured. Acute toxicity tests revealed that CLO caused a concentration-dependent increase in mortality with LC50 (Lethal concentration) values of 10.960 and 8.201 mg kg-1 for 7th and 14th day respectively. The earthworms were exposed to CLO contaminated soil for 56 days and reflecting the significant decrease in earthworm growth, cocoon and hatchling production. Moreover, enzyme activities such as CAT, SOD, POD and MDA content were significantly enhanced with the increased concentration and exposure period of CLO. Molecular docking studies indicated that CLO primarily interacts to the junction site of SOD and in active centres of CAT, POD and GST. As a result, the current findings imply that the sub chronic CLO exposure can induce variations in physiology and avoidance behaviour of earthworms, oxidative stress as well as alterations in enzyme activities.

Efficacy and safety of abemaciclib alone and with PI3K/mTOR inhibitor LY3023414 or galunisertib versus chemotherapy in previously treated metastatic pancreatic adenocarcinoma: A randomized controlled trial.

BACKGROUND: Pancreatic ductal adenocarcinomas (PDAC) are characterized by frequent cell cycle pathways aberrations. This study evaluated safety and efficacy of abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, as monotherapy or in combination with PI3K/mTOR dual inhibitor LY3023414 or TGFß inhibitor galunisertib versus standard of care (SOC) chemotherapy in patients with pretreated metastatic PDAC. METHODS: This Phase 2 open-label study enrolled patients with metastatic PDAC who progressed after 1-2 prior therapies. Patients were enrolled in a safety lead-in (abemaciclib plus galunisertib) followed by a 2-stage randomized design. Stage 1 randomization was planned 1:1:1:1 for abemaciclib, abemaciclib plus LY3023414, abemaciclib plus galunisertib, or SOC gemcitabine or capecitabine. Advancing to Stage 2 required a disease control rate (DCR) difference ≥0 in abemaciclib-containing arms versus SOC. Primary objectives for Stages 1 and 2 were DCR and progression-free survival (PFS), respectively. Secondary objectives included response rate, overall survival, safety, and pharmacokinetics. RESULTS: One hundred and six patients were enrolled. Abemaciclib plus galunisertib did not advance to Stage 1 for reasons unrelated to safety or efficacy. Stage 1 DCR was 15.2% with abemaciclib monotherapy, 12.1% with abemaciclib plus LY3023414, and 36.4% with SOC. Median PFS was 1.7 months (95% CI: 1.4-1.8), 1.8 months (95% CI: 1.3-1.9), and 3.3 months (95% CI: 1.1-5.7), respectively. No arms advanced to Stage 2. No new safety signals were identified. CONCLUSION: In patients with pretreated metastatic PDAC, abemaciclib-based therapy did not improve DCRs or PFS compared with SOC chemotherapy. No treatment arms advanced to Stage 2. Abemaciclib remains investigational in patients with PDAC.

Unusual Clinical Presentation of Nephrotic Syndrome With Significant Renal Vein Thrombosis in a Young Male: A Case Report and Literature Review.

Primary membranous glomerulopathy is the most common cause of idiopathic nephrotic syndrome, with increasing recognition as an autoimmune-mediated disease. We present the case of a 31-year-old Hispanic male with no prior medical or family history, presenting with one month of dyspnea on exertion, lower extremity, and periorbital edema with a recent diagnosis of pulmonary embolism. Upon further imaging, renal vein thrombosis was discovered with significant lab dysfunction concerning nephrotic syndrome. Further, a workup of kidney biopsy and serum antibody levels revealed the cause to be anti-phospholipase A2 receptor (PLA2R)-mediated.

Efficient Turn-On Zr Based Metal Organic Framework Fluorescent Sensor for Ultrafast Detection of Danofloxacin in Milk Samples.

Metal organic framework, UiO-67 was synthesized by coordinating Zr(IV) with 4,4'-biphenyldicarboxylic acid (BPDC) ligand. Morphology and crystallinity of MOF was confirmed with FE-SEM and PXRD procedure. Danofloxacin (DANO), a veterinary fluoroquinolone antibiotic, was detected in milk by employing UiO-67 as "turn-on" fluorescent sensor. Original photoluminescent (PL) efficiency of UiO-67 sensor was enhanced on its electronic interaction with DANO molecule. Significant PL efficiency enhancement, lower detection limit 0.49 ng/mL (1.37 nM), swift detection (time < 1 min), and excellent linear correlation (R2 = 0.9988) indicated extraordinary sensitivity of developed UiO-67 sensor for DANO. Selectivity and performance of sensor was unaltered in presence of interfering species and detection results were obtained under permissible variation limits. Method applied successfully for ultra-trace detection of DANO residues in milk samples.

Monitoring of antimicrobial usage among adult bovines in dairy herds of Punjab, India: A quantitative analysis of pattern and frequency.

The present study aimed to evaluate the antimicrobial usage (AMU) pattern in dairy herds of Punjab, India. The on-farm quantification of AMU in adult bovine animals by the manual collection of empty drug containers ("bin method") along with the records of the treatment was carried out in 38 dairy farms involving 1010 adult bovines for 1 year from July 2020 to June 2021. The farm owners were asked to record the antibiotic treatments as well as to deposit empty antibiotic packaging/vials into the provided bins placed at the farms. A total of 14 different antibiotic agents in 265 commercial antibiotic products were administered to the dairy herds during the study. A total of 179 (67.55%) administered products contained antimicrobials of "critical importance" as per the World Health Organization (WHO). Mastitis (54.72%), followed by the treatment of fever (19.62%), reproductive problems (15.47%), and diarrhea (3.40%) accounted for the majority of drugs administered in the herds during the study period. The most commonly used antibiotics were enrofloxacin (89.47% herds; 21.51% products), followed by ceftriaxone (50% herds; 12.83% products), amoxicillin (50% herds; 12.83% products), oxytetracycline (55.26% herds; 11.70% products), and procaine penicillin (47.37% herds; 12.83% products). The highest quantity of AMU [in terms of antimicrobial drug use rate (ADUR)] was observed for ceftiofur, followed by ceftriaxone, procaine benzyl penicillin ceftizoxime, enrofloxacin, cefoperazone, amoxicillin and ampicillin. A total of 125 (47.17%) products contained "highest priority critically important antimicrobials" (HPCIA) and 54 (20.37%) products contained "high priority critically important antimicrobials". In terms of overall number of animal daily doses (nADD), the highest priority critically important antimicrobials (HPCIA) of the WHO such as third-generation cephalosporins and quinolones, respectively accounted for 44.64 and 22.35% of the total antibiotic use in the herds. The bin method offers an alternative to monitoring AMU as a more accessible approach for recording the actual consumption of antimicrobials. The present study, to the best of our knowledge, is the first of its kind to provide an overview of the qualitative and quantitative estimate of AMU among adult bovines from India.

Interaction and association analysis of malting related traits in barley.

Barley is considered as a foundation of the brewing and malting industry. Varieties with superior malt quality traits are required for efficient brewing and distillation processes. Among these, the Diastatic Power (DP), wort-Viscosity (VIS), ß-glucan content (BG), Malt Extract (ME) and Alpha-Amylase (AA) are controlled by several genes linked to numerous quantitative trait loci (QTL), identified for barley malting quality. One of the well-known QTL, QTL2, associated with barley malting trait present on chromosome 4H harbours a key gene, called as HvTLP8 that has been identified for influencing the barley malting quality through its interaction with ß-glucan in a redox-dependent manner. In this study, we examined to develop a functional molecular marker for HvTLP8 in the selection of superior malting cultivars. We first examined the expression of HvTLP8 and HvTLP17 containing carbohydrate binding domains in barley malt and feed varieties. The higher expression of HvTLP8 prompted us to further investigate its role as a marker for malting trait. By exploring the 1000 bp downstream 3' UTR region of HvTLP8, we found single nucleotide polymorphism (SNP) in between Steptoe (feed variety) and Morex (malt variety), which was further validated by Cleaved Amplified Polymorphic Sequence (CAPS) marker assay. Analysis of 91 individuals from the Steptoe x Morex doubled haploid (DH) mapping population revealed CAPS polymorphism in HvTLP8. Highly significant (p<0.001) correlations among ME, AA and DP malting traits were observed. The correlation coefficient (r) between these traits ranged from 0.53 to 0.65. However, the polymorphism in HvTLP8 did not correlate effectively with ME, AA, and DP. Altogether, these findings will help us to further design the experiment regarding the HvTLP8 variation and its association with other desirable traits.

One Health activities to reinforce intersectoral coordination at local levels in India.

India's dense human and animal populations, agricultural economy, changing environment, and social dynamics support conditions for emergence/re-emergence of zoonotic diseases that necessitate a One Health (OH) approach for control. In addition to OH national level frameworks, effective OH driven strategies that promote local intersectoral coordination and collaboration are needed to truly address zoonotic diseases in India. We conducted a literature review to assess the landscape of OH activities at local levels in India that featured intersectoral coordination and collaboration and supplemented it with our own experience conducting OH related activities with local partners. We identified key themes and examples in local OH activities. Our landscape assessment demonstrated that intersectoral collaboration primarily occurs through specific research activities and during outbreaks, however, there is limited formal coordination among veterinary, medical, and environmental professionals on the day-to-day prevention and detection of zoonotic diseases at district/sub-district levels in India. Examples of local OH driven intersectoral coordination include the essential role of veterinarians in COVID-19 diagnostics, testing of human samples in veterinary labs for Brucella and leptospirosis in Punjab and Tamil Nadu, respectively, and implementation of OH education targeted to school children and farmers in rural communities. There is an opportunity to strengthen local intersectoral coordination between animal, human and environmental health sectors by building on these activities and formalizing the existing collaborative networks. As India moves forward with broad OH initiatives, OH networks and experience at the local level from previous or ongoing activities can support implementation from the ground up.

Biodegradation of different types of microplastics: Molecular mechanism and degradation efficiency.

Microplastics are widely distributed and a major pollutant in our ecosystem. Microplastics (MPs) are very small size plastic (<5 mm) present in environment, which comes from industrial, agricultural and household wastes. Plastic particles are more durable due to the presence of plasticizers and chemicals or additives. These plastics pollutants are more resistant to degradation. Inadequate recycling and excessive use of plastics lead to a large amount of waste accumulating in the terrestrial ecosystem, causing a risk to humans and animals. Thus, there is an urgent need to control microplastic pollution by employing different microorganisms to overcome this hazardous issue for the environment. Biological degradation depends upon different aspects, including chemical structure, functional group, molecular weight, crystallinity and additives. Molecular mechanisms for degradation of MPs through various enzymes have not extremely studied. It is necessary to degrade the MPs and overcome this problem. This review approaches different molecular mechanisms to degrade different types of microplastics and summarize the degradation efficiency of different types of bacteria, algae and fungal strains. The present study also summarizes the potential of microorganisms to degrade different polymers and the role of different enzymes in degradation of microplastics. To the outstanding of our awareness, this is the first article devoted to the role of microorganisms with their degradation efficiency. Furthermore, it also summarizes the role of intracellular and extracellular enzymes in biological degradation mechanism of microplastics.

Synergistic effect of biochar amendment in milk processing industry sludge and cattle dung during the vermiremediation.

The effective and sustainable management of fast growing and large quantities of industrial waste is a serious issue. The purpose of the present study was to assess the synergistic effect of biochar (BC) amended in milk processing industry sludge (MS) mixed with cattle dung (CD) in different ratios through vermiremediation. The MS25 and MS25BC10 (25:75 + 10 % BC) showed the least mortality and greatest earthworm growth and development. The final product from all feed mixtures recorded a decrease in pH, total organic carbon and C/N ratio. Other parameters viz., electrical conductivity, total available phosphorus, total Kjeldahl nitrogen, total sodium, total potassium and ash content was observed to be increased after vermicomposting. Significantly lower heavy metal content was found in all biochar amended feed mixtures than in mixtures without biochar. The germination index of Trigonella foenum-graecum showed a value ranging from 89.14 to 131.46 % for mixtures without BC and 115.18-153.47 % for biochar amended mixtures.

Agronomic biofortification of forage crops with zinc and copper for enhancing nutritive potential: a systematic review.

Many developing countries are facing a silent increase in deficiency of micronutrients in forage crops that results in decreased levels of essential nutrients in animals. Micronutrients are essential not only for basic metabolic processes of forage crops but also for sustaining animal health. Forage productivity and quality are severely affected by soil micronutrients deficiencies, especially zinc and copper. This review summarizes the literature highlighting the significance of different methodologies used to increase the biomass and quality of forage so as to enhance the micronutrient content of the forage crops through biofortification. Biofortification is a promising and sustainable agriculture-based strategy to reduce micronutrient deficiency in crops. The experiments and trials conducted at different locations of the world showed that copper and zinc concentrations in animal fodders can be enhanced through the process of foliar application. Additionally, agronomic biofortification showed more promising results, and thus is an outstanding, fast, and cost-effective technique for the immediate enrichment of forage in order to overcome malnutrition in animals. © 2022 Society of Chemical Industry.

Artificial intelligence inspired multilanguage framework for note-taking and qualitative content-based analysis of lectures.

With the advent of technology and digitization, the use of Information and Communication Technology (ICT) and its tools for the imperative dissemination of information to learners are gaining more ground. During the process of the conveyance of lectures, it is mostly observed that students (learners) are supposed to take notes (minutes) of the subject matter being delivered to them. The existence of different factors like disturbance (noise) from the environment, learner's lack of interest, problems with the tutor's voice, and pronunciation, or others, may hinder the practice of preparing (or taking) lecture notes effectively. To tackle such an issue, we propose an artificial intelligence-inspired multilanguage framework for the generation of the lecture script (of complete) and minutes (only important contents) of the lecture (or speech). We also aimed to perform a qualitative content-based analysis of the lecture's content. Furthermore, we have validated the performance(accuracy) of the proposed framework with that of the manual note-taking method. The proposed framework outperforms its counterpart in terms of note-taking and performing the qualitative content-based analysis. In particular, this framework will assist the tutors in getting insights into their lecture delivery methods and materials. It will also help them improvise to a better approach in the future. The students will be benefited from the outcomes as they do not have to invest valuable time in note-taking/preparation.

Sustainable Development Goal for Quality Education (SDG 4): A study on SDG 4 to extract the pattern of association among the indicators of SDG 4 employing a genetic algorithm.

Sustainable Development Goals (SDG) are at the forefront of government initiatives across the world. The SDGs are primarily concerned with promoting sustainable growth via ensuring wellbeing, economic growth, environmental legislation, and academic advancement. One of the most prominent goals of the SDG is to provide learners with high-quality education (SDG 4). This paper aims to look at the perspectives of the Sustainable Development Goals improvised to provide quality education. We also analyze the existing state of multiple initiatives implemented by the Indian government in the pathway to achieving objectives of quality education (SDG 4). Additionally, a case study is considered for understanding the association among the observed indicators of SDG4. For this purpose, exploratory data analysis, and numerical association rule mining in combination with QuantMiner genetic algorithm approaches have been applied. The outcomes reveal the presence of a significant degree of association among these parameters pointing out the fact that understanding the impact of one (or more) indicator on other related indicators is critical for achieving SDG 4 goals (or factors). These findings will assist governing bodies in taking preventive measures while modifying existing policies and ensuring the effective enactment of SDG 4 goals, which also will subsequently aid in the resolution of issues related to other SDGs.

Metsulfuron-methyl induced physiological, behavioural and biochemical changes in exotic (Eisenia fetida) and indigenous (Metaphire posthuma) earthworm species: Toxicity and molecular docking studies.

In modern agricultural practices, Metsulfuron-methyl (sulfonylurea herbicide) is widely employed to inhibit the weeds and grasses. The current study revealed that Metaphire posthuma was more sensitive than Eisenia fetida against Metsulfuron-methyl (MSM). The LC50 values for Eisenia fetida were 2884.08 mgkg-1 and 1871.18 mgkg-1after 7 and 14 days, respectively. Similarly, the LC50 values for Metaphire posthuma were 2449.34 mgkg-1 and 1673.10 mgkg-1for 7 and 14 days, respectively. Reproduction parameters were significantly decreased at 400 (T3), 800 (T4) and 1600 (T5) mgkg-1 MSM in E. fetida whereas at 200 (T2), 400 (T3), 800 (T4), 1600 (T5) mgkg-1 MSM in M. posthuma. EC50 of avoidance response for 20% MSM by E. fetida and M. posthuma was recorded 901.76 mgkg-1and 544.21 mgkg-1 respectively. Malondialdehyde (MDA) content along with guaiacol peroxidase (POD), catalase (CAT) and superoxide dismutase (SOD) activities were initially increased up to 21st day by MSM, inducing a slight oxidative stress in earthworms and recovered to control level on 28th day. The GST activities were continuously stimulated throughout the exposure period and enhance the detoxification effect thereby preventing the earthworms from toxins. Molecular docking studies indicated that hydrogen bonding and hydrophobic interactions are key forces in binding between MSM and SOD/CAT/POD/GST. As a result, this is the first study to be reported on physiological, behavioural and biochemical changes in two different earthworm species under the exposure of sulfonyl urea herbicide.

Correlation of the combined symptom and medication score with quality of life, symptom severity and symptom control in allergic rhinoconjunctivitis.

Background: The European Academy of Allergy and Clinical Immunology recommended the Combined Symptom and Medication Score (CSMS) as primary endpoint in clinical trials on allergen-specific immunotherapy (AIT) in allergic rhinoconjunctivitis. Here, the correlation between the CSMS and the validated standardised Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)), Rhinitis Control Assessment Test (RCAT) and Visual Analogue Scale (VAS) was analysed. Methods: Two prospective, multicentre, non-interventional studies on tree pollen, grass pollen and house dust mite allergic patients were performed. The first study comprised 167 patients receiving AIT (AIT population), and the second included 56 patients treated with symptomatic medication only (control population). For up to two seasons (pollen)/exposure periods (house dust mites), participants documented their symptoms and medication intake in a CSMS diary, including VAS. In addition, the standardised RQLQ(S) and the RCAT were completed during study visits. Results: Comparison between CSMS and RQLQ(S) revealed a positive correlation in the AIT population (r = 0.426) and in the control population (r = 0.569). For CSMS and RCAT, a negative correlation with r = -0.409 (AIT) and r = -0.547 (control) was shown. Positive correlation between CSMS and VAS was also demonstrated with r = 0.585 (AIT) and r = 0.563 (control). Conclusion: These results support the assumption that the CSMS correlates with quality of life, symptom severity and symptom control on the one hand, while the moderate strength of correlations on the other hand mirrors distinctions of the CSMS compared to the assessments used here.

A 7-Year Retrospective Analysis of Titanium Plates Removal Following Orthognathic Surgery.

Objective: The aim of this study was to investigate the incidence of plate removal in orthognathic surgery patients and the reasons for their removal and to potentially identify the factors that may contribute to it. Methods: A retrospective study included all patients who underwent orthognathic surgery at Selayang Hospital from January 2011 to December 2017. The variables of interest recorded included patient age, gender, the existing skeletal deformity, type of surgery undertaken and number and location of plates inserted and removed. In addition, the reasons for plate removal and duration between plate insertion and removal were also recorded. Results: Ninety-seven patients with a mean age of 21.33 were included in the study. Nine patients with total of 33 plates had their miniplate fixation removed. Three patients underwent bi-maxillary surgery, and six patients underwent BSSO. The average time from insertion to removal was 22.33 months. The reasons for removal included pain, palpable and exposed plates, infection and on patient request. Conclusion: We report a 9.28% incidence of plate removal in patients who undergo orthognathic surgery which is comparable to the existing literature.