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Background: Empagliflozin is a relatively newer glucose-lowering drug (GLD) with many extra-glycemic benefits. To date, no study has evaluated the efficacy and safety of empagliflozin in Bangladeshi patients with type 2 diabetes mellitus (T2DM). Objectives: To assess the efficacy and safety of empagliflozin as an add-on to ongoing GLDs in Bangladeshi adults with uncontrolled T2DM. Materials and Methods: This real-world, multicenter, open-label, prospective study was carried out at 21 sites throughout Bangladesh from 1 February 2022 to 31 July 2022. Patients with T2DM who met the criteria had Empagliflozin added to their existing GLD treatment, with necessary modifications to their ongoing medication regimen. The efficacy and safety data were collected 12 weeks after empagliflozin initiation. Results: Out of 1449 subjects initiating empagliflozin, 1340 subjects [age 50.3 ± 9.0 years, male 52.5%, overweight/obese 94.4%, insulin-treated 25.7%, baseline hemoglobin A1c (Hba1c) 9.9 ± 1.4%] completed the study. At 12 weeks, the reduction in HbA1c was 1.6% (95% CI 1.5-1.6, P < 0.001); 12.5% of the study subjects achieved HbA1c < 7%. There were also significant (P < 0.001 in all instances) reductions in fasting plasma glucose (3.0 mmol/L), plasma glucose 2 hours after breakfast (4.8 mmoL/L), body weight (1.9 kg), body mass index (0.8 kg/m2), systolic blood pressure (BP) (10 mmHg), diastolic BP (7 mmHg), insulin dose (3 U), serum creatinine (0.06 mg/dL), total cholesterol (18 mg/dL), low-density lipoprotein cholesterol (13 mg/dL), high-density lipoprotein cholesterol (1 mg/dL), and triglyceride (42 mg/dL) and an increase in estimated glomerular filtration rate (4.2 mL/min/1.73 m2) from the baseline values. 6.62% experienced adverse events (lightheadedness 2.21%, genital tract infection 0.97%, urinary tract infection 1.24%, generalized weakness 0.48%, and nocturia 0.48%). 1.1% of subjects experienced hypoglycemia, and other 0.12% reported severe hypoglycemic events. Conclusion: Empagliflozin is effective, safe, and tolerable for treating Bangladeshi patients with uncontrolled T2DM as add-on therapy in routine clinical practice with favorable effects on body weight, BP, lipid profile, and renal function.

Background: Retinopathy of prematurity (ROP) is a vaso-proliferative retinal disease which can cause blindness if not diagnosed early. The various risk factors associated with ROP other than pre mature birth and low birth weight are high flow oxygen, sepsis , multiple transfusions, multiple births, respiratory distress syndrome, apnoeic episodes, intraventricular haemorrhage. Poor antenatal care, unavailability, poor access and poorly monitored neonatal care are some of the factors contributing to increase in the number of ROP cases in developing countries. Objective: To study ROP in preterm and high risk neonates in a tertiary care hospital. To assess and record changes of ROP and the associated risk factors in the study population.. To document the staging of ROP. To determine the outcome of Retinopathy of Prematurity and the different modalities of treatment used. Material & Method: This study was conducted on 262 eyes of 131 neonates over a period of 18 months. All Pre term neonates having gestational age of less than or equal to 32 weeks and birth weight less than or equal to 1500gms and other older neonates more than 32 weeks of gestation and more than 1500gms of birth weight with risk factors for developing Retinopathy of prematurity (i.e on oxygen supplementation, Respiratory distress syndrome, Sepsis, Multiple blood transfusions, Apnoeic episodes, Intraventricular haemorrhage) , admitted and referred to our institute within the study period were screened for Retinopathy of Prematurity. Neonates observed having ROP were followed up till complete regression of ROP. Results: In our study ROP was observed in 18.32 % of neonates. There was significant relation of birth weight and gestational age with retinopathy of prematurity. Also risk factors like Respiratory distress syndrome and mechanical ventilation were significantly associated with retinopathy of prematurity. The treatment requiring cases of Retinopathy of Prematurity were 6.11% i.e 8 neonates. All the treatable cases were given ROP Laser therapy while 6 neonates were also given intra- vitreal injections of bevacizumab. Conclusion: Low birth weight, Prematurity, Respiratory distress syndrome, Mechanical ventilation were the risk factors significantly associated with ROP. Prompt screening and early diagnosis of ROP can help in reducing devastating complications and thus prevent blindness.

Due to their value as a food source, fiber, and other products globally, there has been a growing focus on the wellbeing and health of small ruminants, particularly in relation to anemia induced by blood-feeding gastrointestinal parasites like Haemonchus contortus. The objective of this study was to assess the packed cell volume (PCV) levels in blood samples from small ruminants, specifically goats, and create an efficient biosensor for more convenient, yet accurate detection of anemia for on-farm use in agricultural environments for animal production optimization. The study encompassed 75 adult male Spanish goats, which underwent PCV testing to ascertain their PCV ranges and their association with anemic conditions. Using artificial intelligence-powered machine learning algorithms, an advanced, easy-to-use sensor was developed for rapidly alerting farmers as to low red blood cell count of their animals in this way to enable timely medical intervention. The developed sensor utilizes a semi-invasive technique that requires only a small blood sample. More precisely, a volume of 30 μL of blood was placed onto Whatman filter paper No. 1, previously soaked with anhydrous glycerol. The blood dispersion pattern on the glycerol-infused paper was then recorded using a smartphone after 180 s. Subsequently, these images were examined in correlation with established PCV values obtained from conventional PCV analysis. Four separate machine learning models (ML) supported models, namely support vector machine (SVM), K-nearest neighbors (KNN), backpropagation neural network (BPNN), and image classification-based Keras model, were created and assessed using the image dataset. The dataset consisted of 1,054 images that were divided into training, testing, and validation sets in a 70:20:10 ratio. The initial findings indicated a detection accuracy of 76.06% after only 10 epochs for recognizing different levels of PCV in relation to anemia, ranging from healthy to severely anemic. This testing accuracy increased markedly, to 95.8% after 100 epochs and other model parameter optimization. Results for SVM had an overall F1 score of 74–100% in identifying the PCV range for blood pattern images representing healthy to severely anemic animals, and BPNN showed 91–100% accuracy in identifying the PCV range for anemia detection. This work demonstrates that AI-driven biosensors can be used for on-site rapid anemia detection. Optimized machine learning models maximize detection accuracy, proving the sensor’s validity and rapidity in assessing anemia levels. This breakthrough will allow farmers, with rapid results, to increase animal wellbeing and agricultural productivity.

As per Globocan 2012, every year the incidence of head and neck cancer is 683235/1000000 with a mortality of around 375665/1000000 thus being the sixth cause of cancer death throughout the world. Head and neck cancer includes cancer of the nasopharynx, oropharynx, hypopharynx, larynx, and oral cavity. Early diagnosis of head and neck cancer is very challenging, hence detecting mucosal lesions at an early stage decreases mortality thereby improving overall survival, disease-free survival, and quality of life. Out of different diagnostic modalities, narrow-band imaging (NBI) combined with endoscopic techniques can provide a promising diagnostic tool in detecting early lesions of head and neck cancer. Numerous studies have shown that Ki-67 is a good prognostic marker in oral cancers. Our study aims to evaluate the diagnostic accuracy of NBI and combine the Ki-67 index to diagnose head and neck cancer. Materials and Methods: All patients were first examined under white light and then under NBI endoscopy, and a biopsy was obtained from suspected lesions and sent for histopathological examination (HPE) and Ki-67 index. Results: Eighty patients were examined out of which, 68 patients having lesions in the oral cavity, oropharynx, larynx, and hypopharynx were examined. The rate of detecting cancerous lesion by white light and NBI were respectively 92% and 100% for oral cavity lesions, 69% and 100% for oropharyngeal lesions, 38% and 100% for hypopharyngeal lesions, and 37% and 100% for laryngeal carcinoma. However, we have found no significant difference in detecting T2-T4 tumors. Hence, we concluded that NBI mode can be a significantly better diagnostic tool than white light mode in detecting early mucosal cancer in head and neck cancer. Conclusion: We have concluded that NBI combined with Ki-67 estimation is a very promising tool that helps in the early diagnosis of mucosal lesions in head and and neck cancer.

Metal nanoparticles offer promising prospects in agriculture, enhancing plant growth and ensuring food security. Silver, gold, copper, and zinc nanoparticles possess unique properties making them attractive for plant applications. Understanding molecular interactions between metal nanoparticles and plants is crucial for unlocking their potential to boost crop productivity and sustainability. This review explores metal nanoparticles in agriculture, emphasizing the need to understand these interactions. By elucidating mechanisms, it highlights the potential for enhancing crop productivity, stress tolerance, and nutrient-use efficiency, contributing to sustainable agriculture and food security. Quantifying benefits and risks reveal significant advantages. Metal nanoparticles enhance crop productivity by 20% on average and reduce disease incidence by up to 50% when used as antimicrobial agents. They also reduce nutrient leaching by 30% and enhance soil carbon sequestration by 15%, but concerns about toxicity, adverse effects on non-target organisms, and nanoparticle accumulation in the food chain must be addressed. Metal nanoparticles influence cellular processes including sensing, signaling, transcription, translation, and post-translational modifications. They act as signaling molecules, activate stress-responsive genes, enhance defense mechanisms, and improve nutrient uptake. The review explores their catalytic role in nutrient management, disease control, precision agriculture, nano-fertilizers, and nano-remediation. A bibliometric analysis offers insights into the current research landscape, highlighting trends, gaps, and future directions. In conclusion, metal nanoparticles hold potential for revolutionizing agriculture, enhancing productivity, mitigating environmental stressors, and promoting sustainability. Addressing risks and gaps is crucial for their safe integration into agricultural practices.

Abstract The resistive switching behavior in Ta2O5 based memristors is largely controlled by the formation and annihilation of conductive filaments (CFs) that are generated by the migration of oxygen vacancies (OVs). To gain a fundamental insight on the switching characteristics, we have systematically investigated the electrical transport properties of two different Ta2O5 polymorphs ( $$\epsilon$$ ϵ -Ta2O5 and λ-Ta2O5), using density functional theory calculations, and associated vacancy induced electrical conductivity using Boltzmann transport theory. The projected band structure and DOS in a few types of OVs, (two-fold (O2fV), three-fold (O3fV), interlayer (OILV), and distorted octahedral coordinated vacancies (OεV)) reveal that the presence of OILV would cause Ta2O5 to transition from a semiconductor to a metal, leading to improved electrical conductivity, whereas the other OV types only create localized mid-gap defect states within the bandgap. On studying the combined effect of OVs and Si-doping, a reduction of the formation energy and creation of defect states near the conduction band edge, is observed in Si-doped Ta2O5, and lower energy is found for the OVs near Si atoms, which would be advantageous to the uniformity of CFs produced by OVs. These findings can serve as guidance for further experimental work aimed at enhancing the uniformity and switching properties of resistance switching for Ta2O5-based memristors.

Abstract Background Relatively little is known about how sleep disorders affect frailty of seniors. The study uses Fried's frailty index, to investigate the relationship between sleep disorder and frailty among older Indian adults. Methods The study analysed Longitudinal Ageing Study in India (2017–18) data which uses a multistage stratified area probability cluster sampling design. The association between frailty was studied for which the total sample size was 31,902. The principal dependent variable was frailty. Descriptive statistics and cross-tabulation were presented in the study. A binary logistic regression analysis was used to fulfil the study objectives to find the possible association. Results The prevalence of frailty in India was 21.3 percent. Older adults with sleep disorder had 66 percent higher likelihood to be frail than their counterparts. The benefits of physical activity in containing frailty is huge, the association were quite high. Poor Self-rated health was significantly associated with higher frailty (OR = 1.73; CI = 1.47–2.04). Conclusions Frailty is an enormously growing public health issue and has bi-directional relation with sleep disorders. The study has clinical relevance since sleep complaints offer a means for identifying those who are vulnerable to frailty and through appropriate intervention, the causes of sleep disorder would help to delay and in some cases reverse frailty.

Abstract In the past few decades, numerous studies have been conducted to promote the use of biochar as a soil amendment and most recently, for compacted geo-engineered soils. In general, the definite trends of biochar effects on water retention and fertility of soils have been confirmed. However, the biochar effects on hydraulic conductivity, particularly unsaturated hydraulic conductivity of soil-biochar mix remain unclear, making it difficult to understand water seepage in both agricultural and geo-engineered infrastructures in semi-arid regions. This study examines the unsaturated hydraulic conductivity function derived based on the measurements of soil water characteristic curves of soil with biochar contents of 0%, 5% and 10%. A new parameter “biochar conductivity factor (BCF)” is proposed to evaluate the inconsistency in reported biochar effects on soil hydraulic conductivity and to interpret it from various mechanisms (inter- and intra- pore space filling, cracking, aggregation, bio-film formation and piping/internal erosion). The impact of biochar content on unsaturated hydraulic conductivity appears to reduce as the soil becomes drier with minimal effect in residual zone. Qualitative comparison of near-saturated hydraulic conductivity with test results in the literature showed that the BCF is generally higher for smaller ratio of sand to fine content (clay and silt). Moreover, the particle size of biochar may have significant influence on soil permeability. Future scope of research has been highlighted with respect to biochar production for its applications in agriculture and geo-environmental engineering. Long term effects such as root decay and growth, aggregation and nutrient supply need to be considered. Graphical Abstract

The increasing use of convolutional neural networks (CNNs) has brought about a significant transformation in numerous fields, such as image categorization and identification. In the development of a CNN model to classify images of sericea lespedeza [SL; Lespedeza cuneata (Dum-Cours) G. Don] from weed images, four architectures were explored: CNN model variant 1, CNN model variant 2, the Visual Geometry Group (VGG16) model, and ResNet50. CNN model variant 1 (batch normalization with adjusted dropout method) demonstrated 100% validation accuracy, while variant 2 (RMSprop optimization with adjusted learning rate) achieved 90.78% validation accuracy. Pre-trained models, like VGG16 and ResNet50, were also analyzed. In contrast, ResNet50’s steady learning pattern indicated the potential for better generalization. A detailed evaluation of these models revealed that variant 1 achieved a perfect score in precision, recall, and F1 score, indicating superior optimization and feature utilization. Variant 2 presented a balanced performance, with metrics between 86% and 93%. VGG16 mirrored the behavior of variant 2, both maintaining around 90% accuracy. In contrast, ResNet50’s results revealed a conservative approach for class 0 predictions. Overall, variant 1 stood out in performance, while both variant 2 and VGG16 showed balanced results. The reliability of CNN model variant 1 was highlighted by the significant accuracy percentages, suggesting potential for practical implementation in agriculture. In addition to the above, a smartphone application for the identification of SL in a field-based trial showed promising results with an accuracy of 98–99%. The conclusion from the above is that a CNN model with batch normalization has the potential to play a crucial role in the future in redefining and optimizing the management of undesirable vegetation.

Livestock management is challenging for resource-poor (R-P) farmers due to unavailability of quality feed, limited professional advice, and rumor-spreading about animal health condition in a herd. This research seeks to improve animal health in southern Africa by promoting sericea lespedeza (Lespedeza cuneata), a nutraceutical forage legume. An automated geospatial model for precision agriculture (PA) can identify suitable locations for its cultivation. Additionally, a novel approach of radio-frequency identifier (RFID) supported telemetry technology can track animal movement, and the analyses of data using artificial intelligence can determine sickness of small ruminants. This RFID-based system is being connected to a smartphone app (under construction) to alert farmers of potential livestock health issues in real time so they can take immediate corrective measures. An accompanying Decision Support System (DSS) site is being developed for R-P farmers to obtain all possible support on livestock production, including the designed PA and RFID-based DSS.

The use of Spinal Anaethesia in Pediatric patient is still practiced with apprehension at most of the centers. With increasing reservations of practicing general anaestheia with respect to later cognitive functions, spinal anaesthesia is definitely a better alternative. We share the management of two anticipated difficult airway cases using the neuraxial block.

Introduction: In emergency surgeries, open abdomen or laparostomy, especially with perforated viscus, has been used primarily to prevent delayed ventral hernia, burst abdomen, and abdominal compartment syndrome. In the present study, the clinical and resuscitative factors that are linked with open abdomen morbidity are evaluated. Material and Methods: A retrospective analysis was done for all the subjects who were admitted at the tertiary care center between May 2020 and May 2022 for the open abdomen surgeries. These patients were examined to see whether they needed more postoperative care than usual, including the need for resuscitative treatments and other critical clinical indicators. Patients were evaluated if they had any complications. The data that were collected were analysed for any variance using analysis of variance considering P

Aim: The aim of the present study was to compare the treatment outcome in oral cancer cases treated with neoadjuvant chemotherapy (NACT) and upfront surgery in localized advance disease. Materials and Methods: A randomized, prospective study was conducted in 20 cases. Patients were divided into two groups. Group A was taken up for upfront surgery and group B was taken up for surgery after two to three cycles of NACT based on patients' response, performance, and compliance. Results: Neither group showed statistically significant differences in clinical characteristics. In the present study, satisfactory outcomes were seen in nine patients belonging to NACT group and eight patients of non-NACT group had satisfactory outcomes after surgery, which were found to be statistically significant (P = 0.001). Conclusion: NACT may be considered as a treatment option for oral squamous cell carcinoma patients, particularly those with locally advanced tumors. Further prospective studies are needed to validate these findings in patients.

Abstract Background Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are two of the most commonly used antihypertensive drugs acting on the renin–angiotensin–aldosterone system (RAAS). Previous research has shown that RAAS inhibitors increase the expression of angiotensin-converting enzyme, a cellular receptor for the severe acute respiratory syndrome coronavirus 2, raising concerns that the use of ACEi and ARBs in hypertensive patients may increase COVID-19 patient mortality. Therefore, the main aim of the current study was to find out the role of drugs acting on RAAS, particularly ACEi/ARBs in the deaths of COVID-19 patients. Results In total, 68 studies were found to be appropriate, reporting a total of 128,078 subjects. The odds ratio was found to be 1.14 [0.95, 1.36], which indicates the non-significant association of ACEi/ARBs with mortality of COVID-19 patients. Further, the association of individual ACEi/ARBs with mortality of COVID-19 patients was also found non-significant. The sensitivity analysis results have shown no significant effect of outliers on the outcome. Conclusions Based on available evidence, ACEi/ARB were not significantly associated with deaths of COVID-19 patients.

Background: A diphtheria outbreak occurred in Banaskantha district in the northern part of Gujarat in 2019–2020. This study was undertaken to study and generate information on the resurgence of the disease in this region and to generate information regarding the status of vaccination in this region and what strategies can be adopted to avoid re-emergence of the disease in the future. Materials and Methods: This is a hospital-based, retrospective, descriptive study done on patients of diphtheria who were admitted in Banas Medical College and Research Institute, Palanpur from September 2019 to January 2020. Throat swab was taken from all the patients and information regarding symptoms, vaccination, and demographic characteristic was collected. Treatment in the form of ADS, injection crystalline penicillin/erythromycin and other supportive treatment was given. Result: Out of 188 patients, 27 patients (14.36%) were less than 5 years of age, 118 patients (62.76%) and 38 patients (20.21%) were of age group 5–10 and 11–18 years, respectively. Total of five patients (2.66%) were of age more than 18 years. Out of 188 patients, 102 (54.25%) were males and 86 patients (45.74%) were females. All the patients (188) were found to be unvaccinated. Among 188 throat swabs that were tested, 21 samples (11.17%) were found to be culture positive for Corynebacterium diphtheriae. Antidiphtheric serum was given in 181 patients (96.27%) according to the requirement. Out of 188 patients, 155 patients (82.44%) improved with treatment and were discharged. Total of 23 patients (12.23%) were referred to higher center for tracheostomy and for management of other complications. Six patients (3.19%) left against medical advice and four patients (2.12%) expired despite all measures taken. Conclusion: Diphtheria is a disease that can easily be prevented by vaccination. Our study highlights need to increase awareness about vaccination among people of Banaskatha district and all measures should be taken to give full vaccination to children less than 5 years of age and booster vaccination should be encouraged in adolescents and adults so that future resurgence of disease can be prevented.

Purpose: To analyze the effect of various macular hole indices and postoperative microstructural changes of all retinal layers on postoperative functional outcomes in patients with idiopathic full-thickness macular hole (FTMH). Methods: In this prospective study, pre and post-operative optical coherence tomography (OCT) scans of 36 eyes with idiopathic FTMH were analyzed. Hole indices and microstructural changes of all retinal layers such as ellipsoid zone (EZ), external limiting membrane (ELM) integrity, outer and inner retinal defects, and cystoid resolution were studied on follow-up visits. Results: Out of 36 eyes, type-1 closure was achieved in 23 eyes (65.7%) and type-2 closure in 11 eyes (31.42%), one eye showed persistent hole, and one eye was lost to follow-up. The mean minimum diameter of hole (P = 0.026), mean MHI (P = 0.001), DHI (P = 0.158), THI (P = 0.001), and HFF (P < 0.001) showed statistical significance with the type of hole closure. Postoperatively, eyes with intact ELM and EZ had better BCVA at the final visit. The BCVA was better by logMAR 0.73 ± 0.38 (P < 0.001) in patients with absent outer retinal defects. There was a significant difference in BCVA of 0.52 ± 0.35 at 1 month and 0.64 ± 0.34 at 6 months in eyes without inner retinal defects (P < 0.001). At 6 months, cystoid resolution was observed in 28 (80%) eyes. BCVA was significantly better at 1 month (P < 0.001) and at 6 months (P = 0.001) in eyes with no DONFL. Conclusion: Macular hole indices determine the closure type. Postoperative regeneration of outer retinal layers and resolution of retinal defects significantly influence the final visual outcomes. ELM recovery is seen as a prerequisite for EZ regeneration with no new IRD after a period of 3 months.

Objective: To characterize the first patient of Perry syndrome reported from India. Methods: A 62-year-old gentleman presented with acute encephalopathy, hypercapnia, central hypoventilation, and seizures. He required ventilatory support for persistent respiratory failure even after the resolution of the encephalopathy. History revealed symptoms of orthostatic hypotension, episodes of shallow breathing, unsteadiness of gait, anxiety and depression, and significant weight loss for the previous two years. His mother and elder brother had succumbed to a similar illness. Investigations for neuromuscular diseases, including myasthenia and Pompes disease, were negative. Genetic tests for muscular dystrophies and myopathies, investigations for infectious, autoimmune, and para-neoplastic diseases were negative. Neuroimaging and electrophysiological studies were unremarkable. During his hospital stay, he developed rigidity and bradykinesia. Results: In view of the prominent respiratory failure, Parkinsonism, unexplained weight loss, and family history, he was tested for Perry syndrome. A heterozygous missense variation in Exon 2 of the DCTN1 gene that results in the substitution of Proline for Alanine at codon 45 (pA45P) was detected. This variant was not detected in his clinically unaffected brother. The clinical presentation and genetic test indicate Perry syndrome, a rare autosomal dominant fatal disease, which has never been reported from India. The patient improved with Levodopa and neurorehabilitation but eventually succumbed to his illness three years later. Conclusion: Perry syndrome, though rare, should be considered in the differential diagnosis of patients with a family history of Parkinsonism and central hypoventilation.

Abstract The medicinal properties of Ashwagandha (Withania somnifera) are attributed to triterpenoid steroidal lactones, withanolides, which are proposed to be derived from phytosterol pathway, through the action of cytochrome P450 (CYP450) enzymes. Here, we report the characterization of three transcriptome-mined CYP450 genes (WsCYP749B1, WsCYP76 and WsCYP71B10), which exhibited induced expression in response to methyl jasmonate treatment indicating their role in secondary metabolism. All three WsCYP450s had the highest expression in leaf compared to other tissues. In planta characterization of WsCYP450s through virus induced gene silencing (VIGS) and transient overexpression approaches and subsequent metabolite analysis indicated differential modulation in the accumulation of certain withanolides in W. somnifera leaves. While WsCYP749B1-vigs significantly enhanced withaferin A (~ 450%) and reduced withanolide A (~ 50%), its overexpression drastically led to enhanced withanolide A (> 250%) and withanolide B (> 200%) levels and reduced 12-deoxywithastramonolide (~ 60%). Whereas WsCYP76-vigs led to reduced withanolide A (~ 60%) and its overexpression increased withanolide A (~ 150%) and reduced 12-deoxywithastramonolide (~ 60%). Silencing and overexpression of WsCYP71B10 resulted in significant reduction of withanolide B (~ 50%) and withanolide A (~ 60%), respectively. Further, while VIGS of WsCYP450s negatively affected the expression of pathogenesis-related (PR) genes and compromised tolerance to bacteria P. syringae DC3000, their overexpression in W. somnifera and transgenic tobacco led to improved tolerance to the bacteria. Overall, these results showed that the identified WsCYP450s have a role in one or several steps of withanolides biosynthetic pathway and are involved in conferring tolerance to biotic stress.

Abstract Recently, carbon‐based metal‐free electrocatalysts (C‐MFECs) have drawn considerable research attention because of their attractive physicochemical characteristics, cost‐effectiveness, and ability to convert and store energy efficiently. Efficient intramolecular charge transfer among different parts of the carbon electrocatalyst and/or intermolecular charge transfer between electrocatalyst and electrolyte dictate the ultimate energy conversion performance. Experimental results and theoretical analyses have demonstrated that rational design of metal‐free carbon nanomaterials, coupled with proper intramolecular charge transfer through heteroatom doping, incorporation of Stone–Wales defects, and/or intermolecular charge transfer through adsorption of appropriate molecules/moieties, can promote efficient electrocatalysis. In this article, we will first provide the related theoretical principles and then present an overview on the rational design and development of C‐MFECs for efficient charge transfer, followed by elucidating charge‐transfer processes for different electrocatalytic reactions related to renewable energy conversion and environmental remediation technologies. Finally, the current challenges and future perspectives in this exciting field will be discussed.

Little millet (Panicum sumatrense) a native of Chhattisgarh, belongs to the minor millet group and is primarily known as a climate-resilient and nutritionally rich crop. However, due to the lack of enough Omic studies on the crop, the scientific community has largely remained unaware of the potential of this crop, resulting in less scope for its utilization in crop improvement programs. Looking at global warming, erratic climate change, nutritional security, and limited genetic information available, the Little Millet Transcriptome Database (LMTdb) (https://igkv.ac.in/xenom/index.aspx) was conceptualized upon completion of the transcriptome sequencing of little millet with the aim of deciphering the genetic signatures of this largely unknown crop. The database was developed with the view of providing information about the most comprehensive part of the genome, the ‘Transcriptome’. The database includes transcriptome sequence information, functional annotation, microsatellite markers, DEGs, and pathway information. The database is a freely available resource that provides breeders and scientists a portal to search, browse, and query data to facilitate functional and applied Omic studies in millet crops.

Summary: Here, we present a chromatin-immunoprecipitation-based protocol to quantify the recruitment of proteins adjacent to site-specific DNA double-strand breaks (DSBs), such as proteins involved in DSB repair. We describe steps to induce DSBs in U2OS osteosarcoma cells stably expressing the restriction endonucleases FokI or AsiSI. We then detail the procedures of chromatin isolation and immunoprecipitation, followed by protein elution and quantitative-PCR-based quantification of DNA. This protocol cannot be used on DSBs generated at random loci by DNA damaging agents.For complete details on the use and execution of this protocol, please refer to Fitieh et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Microplastics (MPs) have received increasing attention because of their ubiquitous and persisting nature and high degree of resistance to degradation, and bioaccumulation. There has been growing evidence of their direct and indirect impacts on the ecosystem's health. Although the extensive research has been carried out to assess the impact of MPs on aquatic environment, terrestrial environment is a significant research hotspot that needs to be focused more as it is highly polluted by anthropic plastic usage. The overarching aim of this study was to assess the current research trends on MPs analysis and the evaluation of the greenness of existing quantification methods, particularly in soil samples. In the last three years the trend in the quantification of MPs in soil media is found to be exponential and few studies have reported significant concentration of MPs of about 85,000 particles per kg dry weight of soil samples, raising an alarm to the policy makers to implement stringent policies. It has been observed that the existing quantification methodologies are not following the sustainable principles of green analytical chemistry due to their low score obtained from AGREE method. In this context, the electrostatic method of separation of MPs can be considered green, while the magnetic and Olive oil-based separation methods are classified as worse based on the greenness parameter. This paper attempts to provide some new information on the implementation of sustainable methods of MP quantification.

Summary: DNA end resection is a critical step in the homologous recombination pathway of repairing DNA double-strand breaks (DSBs) that can be visualized in cells by detecting the generation of single-stranded DNA (ssDNA) intermediates formed during the resection of the DSBs. Here, we describe quantitative polymerase-chain-reaction-based procedures to quantitatively measure ssDNA intermediates formed during the DNA end resection. Using the ER-AsiSI system, we use differential digestion patterns by restriction endonucleases that digest unresected double-stranded DNA at DSB sites.For complete details on the use and execution of this protocol, please refer to Fitieh et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Lack of attention to rural healthcare for livestock in the southeastern United States has led to a focus on small ruminant farming, mainly using sericea lespedeza [SL; Lespedeza cuneata (Dum-Cours) G. Don], a drought-resistant forage species with nutraceutical benefits. Climate change has increased land availability for SL cultivation, further expanding the potential of this bioactive (anti-parasitic) legume. This study aims to create a geospatial engineering and technology-assisted model for identifying suitable SL production areas for supporting profitable small ruminant farming. The cultivation of SL depends on specific weather conditions and soil properties, with minimum requirements for temperature and rainfall, non-clay soil with reduced bulk density, and open land cover. The main objective was to develop an automated geospatial model using ArcGIS Pro ModelBuilder to assess SL production suitability. This model also aimed to identify appropriate locations for small ruminant production in Georgia in the southeastern United States, characterized by increasing temperature fluctuations. A web-based geographic information system (webGIS) platform was developed using the ArcGIS Online dashboard interface, allowing agriculturalists to access decision support for SL production suitability tailored to their land. This forage production suitability analysis, conducted in the context of climate change, offers valuable guidance for pasture managers in other nations with similar environmental attributes, promoting global adaptability and resilience.

Patients presenting with pain in lower back and paresthesia in lower limbs may have tethered cord causing the symptomology. Tethered cord may be associated with intradural tumors causing symptoms due to progressive increase in size. Association of tethered cord with single intradural tumor is a common occurrence but, to date, only one case has been reported of tethered cord associated with intradural lipoma and epidermoid cyst. The authors would like to present a similar case in a middle-aged patient.

Summary: BMI-1 is an essential regulator of transcriptional silencing during development. Recently, the role of BMI-1 in the DNA damage response has gained much attention, but the exact mechanism of how BMI-1 participates in the process is unclear. Here, we establish a role for BMI-1 in the repair of DNA double-strand breaks by homologous recombination (HR), where it promotes DNA end resection. Mechanistically, BMI-1 mediates DNA end resection by facilitating the recruitment of CtIP, thus allowing RPA and RAD51 accumulation at DNA damage sites. Interestingly, treatment with transcription inhibitors rescues the DNA end resection defects of BMI-1-depleted cells, suggesting BMI-1-dependent transcriptional silencing mediates DNA end resection. Moreover, we find that H2A ubiquitylation at K119 (H2AK119ub) promotes end resection. Taken together, our results identify BMI-1-mediated transcriptional silencing and promotion of H2AK119ub deposition as essential regulators of DNA end resection and thus the progression of HR.

Carbon nanotube based multi-terminal junction configurations are of great interest because of the potential aerospace and electronic applications. Multi-terminal carbon nanotube junction has more than one carbon nanotube meeting at a point to create a 2D or 3D structure. Accurate atomistic models of such junctions are essential for characterizing their thermal, mechanical and electronic properties via computational studies. In this work, computational methodologies that uses innovative Computer-Aided Design (CAD) based optimization strategies and remeshing techniques are presented for generating such topologically reliable and accurate models of complex multi-terminal junctions (called 3-, 4-, and 6-junctions). This is followed by the prediction of structure-property relationship via study of thermal conductivity and mechanical strength using molecular dynamics simulations. We observed high degradation in the thermal and mechanical properties of the junctions compared to pristine structures which is attributed to high concentration of non-hexagonal defects in the junction. Junctions with fewer defects have better thermal transport capabilities and higher mechanical strengths, suggesting that controlling the number of defects can significantly improve inherent features of the nanostructures.

Summary: Atomically thin two-dimensional (2D) transition metal dichalcogenides (TMDCs) have attracted significant attention owing to their prosperity in material research. The inimitable features of TMDCs triggered the emerging applications in diverse areas. In this review, we focus on the tailored and engineering of the crystal lattice of TMDCs that finally enhance the efficiency of the material properties. We highlight several preparation techniques and recent advancements in compositional engineering of TMDCs structure. We summarize different approaches for TMDCs such as doping and alloying with different materials, alloying with other 2D metals, and scrutinize the technological potential of these methods. Beyond that, we also highlight the recent significant advancement in preparing 2D quasicrystals and alloying the 2D TMDCs with MAX phases. Finally, we highlight the future perspectives for crystal engineering in TMDC materials for structure stability, machine learning concept marge with materials, and their emerging applications.

Battery electric tractors (BETs) demonstrate considerable advantages over diesel-fueled tractors, including higher conversion efficiency, higher torque, less maintenance, and no tailpipe emissions. Converting to BETs also requires tradeoffs in the form of the batteries’ high cost, increased weight, limited energy capacity, finite charging cycles, and lengthy charging time. The extent to which small-scale organic vegetable, fruit and cut-flower growers are aware of these tradeoffs is unknown. Little research exists examining these growers’ perceptions, concerns, and willingness to pay for or adopt BETs. Here, we address that gap by conducting qualitative semi-structured interviews with 14 organic growers in the US Midwest, most operating in Michigan. We focus our questions on growers’ motivations, existing tractor-use patterns, and the evaluation of different configurations of a belly-mount open-station cultivating BET. Our results suggest interest in and potential for growers to transition to BETs, including an estimated willingness to pay 14 percent more for a BET compared to a diesel-fueled alternative. This premium is driven by most growers’ preferences for reduced noise, fumes, fuel, and greenhouse gases, as well as beliefs about BETs ultimately being a more sustainable long-term option than diesel-fueled tractors. Growers also identify significant concerns and uncertainty about the long-term performance, maintenance, storage, cost, safety, and weight of the tractors’ battery systems. While growers linked some environmental values and motivations to their interest in BETs, altruistic value signaling was absent, and growers focused considerably more on financial and instrumental concerns and motivations for BET adoption.

Efflux pumps in Gram-negative bacteria such as Pseudomonas aeruginosa provide intrinsic antimicrobial resistance by facilitating the extrusion of a wide range of antimicrobials. Approaches for combating efflux-mediated multidrug resistance involve, in part, developing indirect antimicrobial agents capable of inhibiting efflux, thus rescuing the activity of antimicrobials previously rendered inactive by efflux. Herein, TXA09155 is presented as a novel efflux pump inhibitor (EPI) formed by conformationally constraining our previously reported EPI TXA01182. TXA09155 demonstrates strong potentiation in combination with multiple antibiotics with efflux liabilities against wild-type and multidrug-resistant (MDR) P. aeruginosa. At 6.25 µg/mL, TXA09155, showed ≥8-fold potentiation of levofloxacin, moxifloxacin, doxycycline, minocycline, cefpirome, chloramphenicol, and cotrimoxazole. Several biophysical and genetic studies rule out membrane disruption and support efflux inhibition as the mechanism of action (MOA) of TXA09155. TXA09155 was determined to lower the frequency of resistance (FoR) to levofloxacin and enhance the killing kinetics of moxifloxacin. Most importantly, TXA09155 outperformed the levofloxacin-potentiation activity of EPIs TXA01182 and MC-04,124 against a CDC/FDA panel of MDR clinical isolates of P. aeruginosa. TXA09155 possesses favorable physiochemical and ADME properties that warrant its optimization and further development.

The emergence of multi-drug-resistant Gram-negative pathogens highlights an urgent clinical need to explore and develop new antibiotics with novel antibacterial targets. MreB is a promising antibacterial target that functions as an essential elongasome protein in most Gram-negative bacterial rods. Here, we describe a third-generation MreB inhibitor (TXH11106) with enhanced bactericidal activity versus the Gram-negative pathogens Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa compared to the first- and second-generation compounds A22 and CBR-4830, respectively. Large inocula of these four pathogens are associated with a low frequency of resistance (FOR) to TXH11106. The enhanced bactericidal activity of TXH11106 relative to A22 and CBR-4830 correlates with a correspondingly enhanced capacity to inhibit E. coli MreB ATPase activity via a noncompetitive mechanism. Morphological changes induced by TXH11106 in E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa provide further evidence supporting MreB as the bactericidal target of the compound. Taken together, our results highlight the potential of TXH11106 as an MreB inhibitor with activity against a broad spectrum of Gram-negative bacterial pathogens of acute clinical importance.

The ability to rescue the activity of antimicrobials that are no longer effective against bacterial pathogens such as Pseudomonas aeruginosa is an attractive strategy to combat antimicrobial drug resistance. Herein, novel efflux pump inhibitors (EPIs) demonstrating strong potentiation in combination with levofloxacin against wild-type P. aeruginosa ATCC 27853 are presented. A structure activity relationship of aryl substituted heterocyclic carboxamides containing a pentane diamine side chain is described. Out of several classes of fused heterocyclic carboxamides, aryl indole carboxamide compound 6j (TXA01182) at 6.25 µg/mL showed 8-fold potentiation of levofloxacin. TXA01182 was found to have equally synergistic activities with other antimicrobial classes (monobactam, fluoroquinolones, sulfonamide and tetracyclines) against P. aeruginosa. Several biophysical and genetic studies rule out membrane disruption and support efflux inhibition as the mechanism of action (MOA) of TXA01182. TXA01182 was determined to lower the frequency of resistance (FoR) of the partner antimicrobials and enhance the killing kinetics of levofloxacin. Furthermore, TXA01182 demonstrated a synergistic effect with levofloxacin against several multidrug resistant P. aeruginosa clinical isolates.