Classification of e-waste using machine learning-assisted laser-induced breakdown spectroscopy.

Waste management and the economy are intertwined in various ways. Adopting sustainable waste management techniques can contribute to economic growth and resource conservation. Artificial intelligence (AI)-based classification is very crucial for rapid and contactless classification of metals in electronic waste (e-waste) management. In the present research work, five types of aluminium alloys, because of their extensive use in structural, electrical and thermotechnical functions in the electronics industry, were taken. Laser-induced breakdown spectroscopy (LIBS), a spectral identifier technique, was employed in conjunction with machine learning (ML) classification models of AI. Principal component analysis (PCA), an unsupervised ML classifier, was found incapable to differentiate LIBS data of alloys. Supervised ML classifier was then trained (for 10-fold cross-validation) on randomly selected 80% and tested on 20% spectral data of each alloy to assess classification capacity of each. In most of the tested variants of K nearest neighbour (kNN) the resulting accuracy was lower than 30% but kNN ensembled with random subspace method showed improved accuracy up to 98%. This study revealed that an AI-based LIBS system can classify e-waste alloys rather effectively in a non-contactless mode and could potentially be connected with robotic systems, hence, minimizing manual labour.

Anakinra treatment efficacy in reduction of inflammatory biomarkers in COVID-19 patients: A meta-analysis.

INTRODUCTION: Anakinra is being empirically considered for the treatment of COVID-19 patients. The aim is to assess the efficacy of anakinra treatment on inflammatory marker reduction, including c-reactive protein (CRP) concentrations, serum ferritin, and serum d-dimer levels. METHODS: Adhering to PRISMA 2020 statement guidelines, a systematic search was conducted across the following databases from December 2019 until January 10, 2022: PubMed/MEDLINE, Cochrane Central, Web of Science, Scopus, and EMBASE. The following keywords were employed: Anakinra, COVID*, SARS-CoV-2, inflammatory, CRP, D-dimer, Ferritin, hematological, laboratory, clinical, trials. The findings were collated and presented in a tabulated manner, and statistically analyzed using Review Manger 5.4 (Cochrane). RESULTS: In total, 2032 patients were included (881 in the anakinra and 1151 in the control/standard care group); 69.1% of them were males. Overall, the mean difference from admission until last follow-up in CRP values was -9.66, where notable reductions were seen in the anakinra group (SMD = -0.46, p < 0.00001, N = 655). Serum ferritin mean values were reduced by 1467.16 in the anakinra group (SMD = -0.31, p = 0.004, N = 537). D-dimer mean values were largely reduced by 4.04 in the anakinra group (SMD = -0.38, p = 0.0004, N = 375). CONCLUSION: This study finds that anakinra is potentially a strong candidate as an anti-inflammatory agent to reduce mortality in COVID-19 patients, specifically in patients with elevated inflammatory biomarkers.

Discovery of potent and selective reversible Bruton's tyrosine kinase inhibitors.

Bruton's tyrosine kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase member of the TEC family of tyrosine kinases. Pre-clinical and clinical data have shown that targeting BTK can be used for the treatment for B-cell disorders. Here we disclose the discovery of a novel imidazo[4,5-b]pyridine series of potent, selective reversible BTK inhibitors through a rational design approach. From a starting hit molecule 1, medicinal chemistry optimization led to the development of a lead compound 30, which exhibited 58 nM BTK inhibitory potency in human whole blood and high kinome selectivity. Additionally, the compound demonstrated favorable pharmacokinetics (PK), and showed potent dose-dependent efficacy in a rat CIA model.

Colchicine, COVID-19 and hematological parameters: A meta-analysis.

INTRODUCTION: Colchicine has the potential in reducing patient morbidity and mortality in COVID-19 infection owing to its anti-inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID-19 patients. METHODS: In accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS-CoV-2, anti-inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, and Google Scholar. The meta-analysis was conducted using Review Manager 5.4. RESULTS: In total, six studies were included, of which four reported c-reactive protein (CRP) standardized mean reductions in the colchicine group (N = 165) as opposed to the control (N = 252; SMD = -0.49, p < 0.001). On noting lactate dehydrogenase (LDH) values post treatment, the colchicine group (N = 204) showed significant reductions at the end of treatment compared to control (N = 290; SMD = -0.85, p < 0.001). Finally, the D-dimer values in colchicine groups (N = 129) compared to control (N = 216) also documented a negative effect size (SMD = -0.9, p < 0.001). CONCLUSION: Colchicine has efficacy in reducing inflammatory biomarkers observed in moderate-to-severe COVID-19 patients. It may be worthwhile to consider monitoring the clinical and laboratory parameters of patients in further trials to consider colchicine as a strong candidate for an adjunct to COVID-19 treatment.

The dawn of phage therapy.

Bacteriophages or phages, being the most abundant entities on earth, represent a potential solution to a diverse range of problems. Phages are successful antibacterial agents whose use in therapeutics was hindered by the discovery of antibiotics. Eventually, because of the development and spread of antibiotic resistance among most bacterial species, interest in phage as therapeutic entities has returned, because their noninfectious nature to humans should make them safe for human nanomedicine. This review highlights the most recent advances and progress in phage therapy and bacterial hosts against which phage research is currently being conducted with respect to food, human, and marine pathogens. Bacterial immunity against phages and tactics of phage revenge to defeat bacterial defense systems are also summarized. We have also discussed approved phage-based products (whole phage-based products and phage proteins) and shed light on their influence on the eukaryotic host with respect to host safety and induction of immune response against phage preparations. Moreover, creation of phages with desirable qualities and their uses in cancer treatment, vaccine production, and other therapies are also reviewed to bring together evidence from the scientific literature about the potentials and possible utility of phage and phage encoded proteins in the field of therapeutics and industrial biotechnology.

Prevalence of QTc interval prolongation and its associated risk factors among psychiatric patients: a prospective observational study.

BACKGROUND: QT interval prolongation is a growing concern worldwide, posing psychiatric patients to life-threatening fatal arrhythmias i.e., torsade de pointes. This study aimed to identify the prevalence of QT interval prolongation, its associated risk factors and prescribing patterns of QT prolonging drugs among psychiatric patients. METHOD: A prospective observational study was conducted that included psychiatric patients from a tertiary care hospital and a psychiatry clinic in Peshawar, Khyber Pakhtunkhwa, Pakistan. Electrocardiogram was recorded of those patients who were using psychotropic medications for ≥7 days, aged 18 years or more, and of either gender, male or female. The Fredericia correction formula was used for measuring QTc values (corrected QT). Chi-square test was applied to estimate differences between patients with or without prolonged QTc interval whereas, logistic regression analysis was performed to identify various predictors of QT interval prolongation. RESULTS: Out of 405 patients, the QTc interval was prolonged in 23 (5.7%) patients including 1 (0.2%) patient with highly abnormal prolonged QTc interval (> 500 ms). QT drugs (91.6%), female sex (38.7%) and hypertension (10.6%) were the most common QT prolonging risk factors. Prolonged QTc interval was significantly higher among male patients (p = 0.007). CONCLUSION: In the present study, QT interval prolongation was observed in a considerable number of psychiatric patients. While, the high prevalence of QT prolonging risk factors among these patients warrants the increased risk of fatal arrhythmias. Therefore, risk assessment and electrocardiographic monitoring, and prescription of safer alternatives are highly recommended.

Prevalence of the risk factors for QT prolongation and associated drug-drug interactions in a cohort of medical inpatients.

BACKGROUND/PURPOSE: Medical inpatients are at increased risk of QT interval prolongation due to multiple risk actors and QT prolonging drugs. This study aimed to identify the prevalence of risk factors for QT prolongation; QT prolonging medications; associated drug-drug interactions (QT-DDIs); their predictors; and TdP (torsades de pointes) risks of drugs. METHODS: This cohort study was carried out in medical wards of two tertiary hospitals in Khyber Pakhtunkhwa, Pakistan. The QT-DDIs were identified using Micromedex DrugReax® and AZCERT (Arizona Center for Education and Research on Therapeutics) QT drugs lists. AZCERT QT drugs lists were used to identify TdP risks. Logistic regression analysis was performed to identify predictors of QT-DDIs. RESULTS: Total 400 patients were included in this study. The most frequent QT prolonging risk factors included use of ≥1 QT prolonging drugs (74.5%), female gender (55%) and diabetes mellitus (36.3%). Total 487 QT prolonging drugs were identified. According to AZCERT classification, 33.8% of the interacting drugs were included in list-1 (known risk of TdP), 0.9% in list-2 (possible risk of TdP) and 58.8% in list-3 (conditional risk of TdP). The occurrence of QT-DDIs was significantly associated with ≥10 prescribed medications (p = 0.01), chronic liver disease (p = 0.05), chronic obstructive pulmonary disease (p = 0.03), gastroenteritis (p = 0.02), antimicrobials (p < 0.001), antiemetics (p < 0.001) and antinausea (p < 0.001). CONCLUSION: A substantial number of patients were exposed to risk factors for QT prolongation; and QT prolonging drugs such as proton pump inhibitors, antimicrobials and diuretics which may lead to serious outcomes.

Structure-activity relationships of strigolactones via a novel, quantitative in planta bioassay.

Strigolactones (SLs) are plant hormones with various functions in development, responses to stress, and interactions with (micro)organisms in the rhizosphere, including with seeds of parasitic plants. Their perception for hormonal functions requires an α,ß-hydrolase belonging to the D14 clade in higher plants; perception of host-produced SLs by parasitic seeds relies on similar but phylogenetically distinct proteins (D14-like). D14 and D14-like proteins are peculiar receptors, because they cleave SLs before undergoing a conformational change that elicits downstream events. Structure-activity relationship data show that the butenolide D-ring is crucial for bioactivity. We applied a bioisosteric approach to the structure of SLs by synthetizing analogues and mimics of natural SLs in which the D-ring was changed from a butenolide to a lactam and then evaluating their bioactivity. This was done by using a novel bioassay based on Arabidopsis transgenic lines expressing AtD14 fused to firefly luciferase, in parallel with the quantification of germination-inducing activity on parasitic seeds. The results obtained showed that the in planta bioassay is robust and quantitative, and thus can be confidently added to the SL-survey toolbox. The results also showed that modification of the butenolide ring into a lactam one significantly hampers the biological activity exhibited by SLs possessing a canonical lactonic D-ring.

Potential drug-drug interactions in outpatient department of a tertiary care hospital in Pakistan: a cross-sectional study.

BACKGROUND: Potential drug-drug interactions (pDDIs) are one of the preventable drug related problems having the risk of serious adverse events or therapeutic failure. In developing countries like Pakistan, this issue remains poorly addressed. The objective of this study was to explore prevalence of pDDIs in the Outpatient Department (OPD) of a tertiary care hospital in Pakistan. The secondary aim was to describe the levels of reported pDDIs and develop a list of widespread clinically relevant interactions. METHODS: Prescriptions of 2400 OPD patients were analyzed for pDDIs through Micromedex Drug-Reax®. Prevalence, severity- and documentation-levels and widespread clinically relevant interactions were reported. RESULTS: Of total 2400 prescriptions, pDDIs were present in 22.3%. Whereas, moderate- and major-pDDIs were found in 377 (15.7%) and 225 (9.4%), respectively. PDDIs were more prevalent in Medicine (9.2%) and Cardiology (2.6%) as compared with other OPD specialties. Total 942 pDDIs were identified, of which, the majority were either moderate- (61.9%) or major-pDDIs (32.1%). Some of the most common interactions were ibuprofen + levofloxacin (n = 50), ciprofloxacin + diclofenac (32), aspirin + atenolol (24), and diclofenac + levofloxacin (19). The potential adverse outcomes of widespread interactions were seizures, bleeding, QT-interval prolongation, arrhythmias, tendon rupture, hypoglycemia/hyperglycemia, serotonin syndrome, drug toxicity, and decreased therapeutic response. CONCLUSIONS: OPD patients were at risk to pDDIs, particularly to major- and moderate-pDDIs. Screening of prescriptions for pDDIs and monitoring of pharmacotherapy in terms of response and associated adverse drug events will contribute to patient safety.

Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile.

Inherited erythromelalgia, the first human pain syndrome linked to voltage-gated sodium channels, is widely regarded as a genetic model of human pain. Because inherited erythromelalgia was linked to gain-of-function changes of sodium channel Na(v)1.7 only a decade ago, the literature has mainly consisted of reports of genetic and/or clinical characterization of individual patients. This paper describes the pattern of pain, natural history, somatosensory profile, psychosocial status and olfactory testing of 13 subjects with primary inherited erythromelalgia with mutations of SCN9A, the gene encoding Na(v)1.7. Subjects were clinically profiled using questionnaires, quantitative sensory testing and olfaction testing during the in-clinic phase of the study. In addition, a detailed pain phenotype for each subject was obtained over a 3-month period at home using diaries, enabling subjects to self-report pain attacks, potential triggers, duration and severity of pain. All subjects reported pain and heat in the extremities (usually feet and/or hands), with pain attacks triggered by heat or exercise and relieved mainly by non-pharmacological manoeuvres such as cooling. A large proportion of pain attacks (355/1099; 32%) did not involve a specific trigger. There was considerable variability in the number, duration and severity of pain attacks between subjects, even those carrying the same mutation within a family, and within individuals over the 12-13 week observation period. Most subjects (11/13) had pain between attacks. For these subjects, mean pain severity between pain attacks was usually lower than that during an attack. Olfaction testing using the Sniffin'T test did not demonstrate hyperosmia. One subject had evidence of orthostatic hypotension. Overall, there was a statistically significant correlation between total Hospital Anxiety and Depression Scale scores (P= 0.005) and pain between attacks and for Hospital Anxiety and Depression Scale Depression scores and pain between attacks (P= 0.001). Hospital Anxiety and Depression Scale scores for five subjects were below the threshold for mild anxiety or depression and none of the 13 subjects were severely anxious and/or depressed. Quantitative sensory testing revealed significantly increased detection thresholds for cold and warm stimuli at affected, compared to unaffected sites. By contrast, significantly decreased cold and heat pain thresholds were found at unaffected sites. Sensory profiles varied considerably between affected and unaffected sites, suggesting the existence of small fibre neuropathy in symptomatic sites. This in-depth clinical characterization of a well-defined inherited erythromelalgia population indicates the importance of characterizing the pain phenotype in individuals before undertaking clinical trials, given the inherent variability of pain both between and within inherited erythromelalgia subjects, even those within a family who carry the same mutation.

Nickel adsorption onto polyurethane ethylene and vinyl acetate sorbents.

The present study was conducted to appraise the efficiencies of polyurethane ethylene sorbent (PES) and vinyl acetate sorbent (VAS) for nickel (Ni) adsorption. Process variables, i.e. Ni(II) ions initial concentration, pH, contact time and adsorbent dosage were optimized by response surface methodology (RSM) approach. The Ni(II) adsorption was fitted to the kinetic models (pseudo-first-order and pseudo-second-order) and adsorption isotherms (Freundlich and Langmuir). At optimum conditions of process variables, 171.99 mg/g (64.7%) and 388.08 mg/g (92.7%) Ni(II) was adsorbed onto PES and VAS, respectively. The RSM analysis revealed that maximum Ni(II) adsorption can be achieved at 299 mg/L Ni(II) ions initial concentration, 4.5 pH, 934 min contact time and 1.3 g adsorbent dosage levels for PES, whereas the optimum values for VAS were found to be 402 mg/L Ni(II) ions initial concentration, 4.6 pH, 881 min contact time and 1.2 g adsorbent dosage, respectively. The -OH and -C = O- were involved in the Ni(II) adsorption onto PES and VAS adsorbents. At optimum levels, up to 53.67% and 80.0% Ni(II) was removed from chemical industry wastewater using PES and VAS, respectively, which suggest that PES and VAS could possibly be used for Ni(II) adsorption from industrial wastewater.

RARE CASE OF IDIOPATHIC GINGIVAL FIBROMATOSIS AFFECTING PRIMARY DENTITION.

Gingival fibromatosis (GF) is a rare condition with an estimated incidence of 1750,000 in autosomal dominant cases and is supposedly genetic in origin. Gingival fibromatosis (GF) may occur as an isolated finding (Idiopathic gingival fibromatosis or IGF) or in combination with additional clinical problems that is, giving rise to syndromic forms of the disease. It usually is triggered when permanent dentition starts to erupt and can cover crowns of the teeth. Gingival fibromatosis occasionally manifests at birth or affect primary dentition. This enlargement may cause mal-position and diastema. Surgical excision of excessive fibrous tissue is the only treatment but it recurs. We are presenting here a case of 5 year old patient presenting with severe idiopathic gingival fibromatosis covering crowns of primary teeth and causing functional impairment.

Does institutional quality complement the relationship between ownership structure and corporate social responsibility?

The key purpose of the Study is to examine if institutional quality complements the relationship between Ownership Structure and Corporate Social Responsibility disclosure and performance in the light of legitimacy and agency theory. To the best of my knowledge, it is the first study in literature of finance. The sample comprises of 112 top-performing listed firms (based on market capitalization) at Pakistan Stock Exchange from 2010 to 2019. Institutional quality comprised of world governance indicators which is developed via principal component analysis, an instrumental variable approach and content analysis are used for CSR Disclosure Index to demonstrate the relationship between ownership structure and CSR. The resources complementary phenomenon is adopted to examine the institutional quality's role. Our results show significantly positive impact of Institutional and Foreign Ownerships on CSR while negative significant influence of CEO Duality and Family Ownership on CSR, suggesting that well governed firms will be more socially responsible. In addition, the findings suggest the institutional quality's positive moderating role on the relationship between ownership structure and CSR, signifying the institutional quality's complementary role for the weak corporate environment in Pakistan. Our findings are robust to a series of tests by using Generalized Method of Moment (GMM).

New 1,3,4-Thiadiazole Derivatives as α-Glucosidase Inhibitors: Design, Synthesis, DFT, ADME, and In Vitro Enzymatic Studies.

Diabetes is an emerging disorder in the world and is caused due to the imbalance of insulin production as well as serious effects on the body. In search of a better treatment for diabetes, we designed a novel class of 1,3,4-thiadiazole-bearing Schiff base analogues and assessed them for the α-glucosidase enzyme. In the series (1-12), compounds are synthesized and 3 analogues showed excellent inhibitory activity against α-glucosidase enzymes in the range of IC50 values of 18.10 ± 0.20 to 1.10 ± 0.10 µM. In this series, analogues 4, 8, and 9 show remarkable inhibition profile IC50 2.20 ± 0.10, 1.10 ± 0.10, and 1.30 ± 0.10 µM by using acarbose as a standard, whose IC50 is 11.50 ± 0.30 µM. The structure of the synthesized compounds was confirmed through various spectroscopic techniques, such as NMR and HREI-MS. Additionally, molecular docking, pharmacokinetics, cytotoxic evaluation, and density functional theory study were performed to investigate their behavior.

Effectiveness of digital tools for smoking cessation in Asian countries: a systematic review.

AIM: The use of tobacco is responsible for many preventable diseases and deaths worldwide. Digital interventions have greatly improved patient health and clinical care and have proven to be effective for quitting smoking in the general population due to their flexibility and potential for personalization. However, there is limited evidence on the effectiveness of digital interventions for smoking cessation in Asian countries. METHODS: Three major databases - Web of Science (WOS), Scopus, and PubMed - for relevant studies published between 1 January 2010 and 12 February 2023 were searched for studies evaluating the effectiveness of digital intervention for smoking cessation in Asian countries. RESULTS: A total of 25 studies of varying designs were eligible for this study collectively involving a total of n = 22,005 participants from 9 countries. Among different digital tools for smoking cessation, the highest abstinence rate (70%) was reported with cognitive behavioural theory (CBT)-based smoking cessation intervention via Facebook followed by smartphone app (60%), WhatsApp (59.9%), and Pharmacist counselling with Quit US smartphone app (58.4%). However, WhatsApp was preferred over Facebook intervention due to lower rates of relapse. WeChat was responsible for 15.6% and 41.8% 7-day point prevalence abstinence. For telephone/text messaging abstinence rate ranged from 8-44.3% and quit rates from 6.3% to 16.8%. Whereas, no significant impact of media/multimedia messages and web-based learning on smoking cessation was observed in this study. CONCLUSION: Based on the study findings the use of digital tools can be considered an alternative and cost-effective smoking cessation intervention as compared to traditional smoking cessation interventions.

Development and characterization of a biodegradable film based on guar gum-gelatin@sodium alginate for a sustainable environment.

A significant amount of plastic trash has been dumped into the environment across the world, contributing to the present white pollution crisis. Therefore, plastic manufacturing and disposal must be examined. Biodegradable plastics (BPs) have recently become the subject of study due to their beneficial biodegradability and harmlessness, and they have been the most efficient method for addressing the issue of plastic pollution. This study aims to enhance the synthesis of biodegradable polymers from sodium alginate (Na-Alg) with the addition of guar gum, corn starch, and gelatin using the solution-casting method, followed by mixing in suitable proportions and drying at a certain temperature, resulting in thin film formation. To enhance qualities of the already produced polymer, additional substances such as glycerol, PVA, and latex were added as plasticizers. Characterization techniques such as scanning electron microscopy (SEM), tensile strength, thermogravimetric analysis (TGA), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), differential scanning calorimetry (DSC), UV-vis spectroscopy, and Fourier transform infrared (FTIR) spectroscopy were used to study structural characteristics, surface morphology, polymeric linkages, water absorption capabilities, chemical conductivity, and light transmittance of the newly formed films. These characterization results depict a remarkable achievement in the sense of the high degradability and impressive tensile strength of the newly formed films. In addition, SEM images indicated a porous structure with interconnected pores. FT-IR confirms the occurrence of molecular interactions between separate components. Consequently, different films showed different behavior of degradability, and it is suggested from interpreting the results that the polymeric films may be a viable biodegradable option.

Pharmacokinetic and pharmacodynamic profiling of a P2X7 receptor allosteric modulator GSK1482160 in healthy human subjects.

AIMS: This paper describes findings from the first-in-human study for GSK1482160, an orally available allosteric P2X7 receptor modulator. The study aimed to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of the compound in healthy subjects. METHODS: Escalating single doses of up to 1 g were administered to healthy subjects in a single-blind and placebo-controlled fashion. Safety, tolerability, blood drug concentrations and ex vivo Il-1ß production in blood were evaluated. RESULTS: Drug concentration peaked within 3.5 h of dosing under fasting conditions and declined thereafter with a relatively short half-life of less than 4.5 h. Exposure was proportional to dose with between subject variability of less than 60%. A PK/PD model quantified Il-1ß as a function of drug exposure. The model allowed simulation of in vivo pharmacology for various untested dose levels and regimens. Furthermore, the mechanistic model supported the hypothesis that the compound reduces the efficacy of ATP at the P2X7 receptor without affecting its affinity. No major safety or tolerability concerns were identified in this small study (n = 29), except for one case of asymptomatic accelerated idioventricular rhythm at the top dose. CONCLUSION: The model-based approach maximized analysis power by integrating all biomarker data and revealed mechanistic insight into the pharmacology of P2X7 modulation by GSK1482160. Simulations by this model ultimately led to the discontinuation of the development of this compound. The therapeutic relevance of the P2X7 receptor remains to be tested in patients. The mechanistic-model-based approach can be applied widely to drug development.

Biochemical analysis, photosynthetic gene (psbA) down-regulation, and in silico receptor prediction in weeds in response to exogenous application of phenolic acids and their analogs.

Chemical herbicides are the primary weed management tool, although several incidences of herbicide resistance have emerged, causing serious threat to agricultural sustainability. Plant derived phenolic acids with herbicidal potential provide organic and eco-friendly substitute to such harmful chemicals. In present study, phytotoxicity of two phenolic compounds, ferulic acid (FA) and gallic acid (GA), was evaluated in vitro and in vivo against three prevalent herbicide-resistant weed species (Sinapis arvensis, Lolium multiflorum and Parthenium hysterophorus). FA and GA not only suppressed the weed germination (80 to 60% respectively), but also negatively affected biochemical and photosynthetic pathway of weeds. In addition to significantly lowering the total protein and chlorophyll contents of the targeted weed species, the application of FA and GA treatments increased levels of antioxidant enzymes and lipid peroxidation. Photosynthetic gene (psbA) expression was downregulated (10 to 30 folds) post 48 h of phenolic application. In silico analysis for receptor identification of FA and GA in psbA protein (D1) showed histidine (his-198) and threonine (thr-286) as novel receptors of FA and GA. These two receptors differ from the D1 amino acid receptors which have previously been identified (serine-264 and histidine-215) in response to PSII inhibitor herbicides. Based on its toxicity responses, structural analogs of FA were also designed. Four out of twelve analogs (0.25 mM) significantly inhibited weed germination (30 to 40%) while enhancing their oxidative stress. These results are unique which provide fundamental evidence of phytotoxicity of FA and GA and their analogs to develop cutting-edge plant based bio-herbicides formulation in future.

Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent ß-thalassemia: results from Thal-Thalido study.

Regular blood transfusion is the mainstay of treatment in transfusion-dependent ß-thalassemia (TDT); however, transfusions culminate in an array of serious complications. Therefore, a single-arm, non-randomized clinical trial was conducted in hydroxyurea refractory TDT patients to explore the long-term safety and efficacy of thalidomide. The primary outcomes for efficacy were rise in hemoglobin (Hb) level and changes in transfusion frequency. Whereas, several clinical and laboratory parameters were assessed for safety of thalidomide. Secondary outcomes included changes in serum ferritin, serum lactate dehydrogenase (LDH), serum uric acid, red blood cell indices, and size of liver and spleen. A total of 532 patients were followed for a period of 30 months. Significant increase in mean Hb level was identified at 6 months (1.4 g/dL, p ≤ 0.001) and 30 months (2 g/dL, p ≤ 0.001) in comparison with baseline. A total of 408 (76.7%) patients responded to thalidomide therapy (excellent responders 25.8%, good responders 31%, and partial responders 19.9%) and attained transfusion independence within 6 months of therapy. A significant decline in mean ferritin, LDH level, liver size, and spleen size was observed. No unfavorable effects were observed on kidney and liver functions. Mild adverse events were reported in 48 (9%) patients and serious adverse events, including cerebral vascular accident and portal vein thrombosis were reported in two patients each. This study concludes that thalidomide is an effective and well-tolerated drug that can improve Hb levels and reduce transfusion burden in hydroxyurea refractory TDT patients.Trial registration: This trial is registered at http://www.clinicaltrial.gov as # NCT03651102.