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Plant growth promoting rhizobacteria offer an effective and eco-sustainable solution to protect crops against phytopathogens. In the present study, Bacillus safensis STJP (NAIMCC-B-02323) from the rhizospheric soil of Stevia rebaudiana showed strong biocontrol activity against phytopathogen, Alternaria alternata. B. safensis STJP produced antifungal volatile organic compounds (AVOC). In the presence of AVOC, there was no conidia germination, mycelium growth was inhibited, and hyphae ruptured as observed by scanning electron microscopy. When mycelium of the fungus from bacterial treated plate was transferred into fresh potato dextrose agar plate, A. alternata could not grow. Extracted AVOC from B. safensis STJP were identified by thin-layer chromatography (TLC), Fourier-transform-infrared (FTIR) spectroscopy and gas-chromatography–mass spectrometry (GC–MS). In total 25 bacterial metabolites were identified by GC–MS analysis having alcohol, alkane, phenol, alkyl halide and aromatic compounds. Five of these (phenol, 2,4-bis (1,1-dimethylethyl)-, 3-hexadecanol, pyrrolo(1,2-a)pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl)-, 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo(1,2-a:1′,2′-d)pyrazine and hexadecanoic acid) inhibited the mycelium growth, controlling spore formation and conidia germination of A. alternata. This study concluded that AVOC producing B. safensis can be used as a green-fungicide against A. alternata. Bacterial metabolites could pave the way for the development of next generation biopesticides. This can be a reliable technology to enhance the quality and reliability of biopesticides.

Heavy metals are persistent and bio-accumulative, and pose potential risk to human health and ecosystem. We reviewed the current state of heavy metal contamination, the ecotoxicological and human health risk of heavy metals reported in urban road dust from various cities in different continents (Asia, Europe, Africa, America, and Australia). We compared and synthesized the findings on the methods related to sample collection, extraction, analytical tools of heavy metals, their concentrations, level of contamination, ecological risk, non-carcinogenic risk, and carcinogenic risk in road dust. Concentrations of Pb, Zn, Cu, Ni, Cd, Cr, Mn, and Fe were found to be higher than their background values in soil. As expected, the contamination levels of the heavy metals varied extensively among cities, countries, continents, and periods. A high level of contamination is observed for Pb and Cd in road dust due to operating leaded gasoline and the old vehicle population. The highest Zn contamination was observed from road dust in Europe, followed by Asia, Africa, Australia, and America (North America and South America). Cu contamination and the pollution load index ( PLI ) is found to be the highest in Europe and lowest in Africa, with in-between values of PLI in American and African cities. The potential ecological risk on different continents was observed highest in Asia, followed by Europe, Australia, America, and Africa. A comparative assessment of non-carcinogenic risk for children indicated that Australia is the most susceptible country due to high heavy metal exposure in road dust, followed by Asia. However, there is no susceptible risk in European, African, and American cities. We did not observe any potential risk to adults due to non-carcinogenic metals. Carcinogenic risk to all age groups was within the threshold limit range for all the regions worldwide.

The application of chemical fertilizers to enhance crop production is a major concern due to associated environmental pollution and health hazards. Hence, there is an urgent need to develop an eco-friendly solution to improve crop production and promote sustainable agriculture simultaneously. Stevia rebaudiana is an important medicinal crop being substitute for sugar, superior flavor outline, extensive medicinal properties, and also of agronomic interest. In the present study, bacterium STJP isolated from the rhizospheric soil of S. rebaudiana and identified as Bacillus safensis on the basis of 16S rRNA gene sequencing, showed good amount of zinc (4.4 mg/L) and potassium (5.4 mg/L) solubilization. Paneer-whey (a dairy waste) based bioformulation (P-WBF) was developed utilizing isolate B. safensis STJP (accession number NAIMCC TB-2833) and inspected for the quality and ability to enhance the growth, nutrients uptake, and stevioside content in S. rebaudiana. The application of P-WBF displayed a significantly higher concentration (153.12%) of stevioside in S. rebaudiana as compared to control. P-WBF treated Stevia plants showed significantly higher fresh and dry weight as well (as compared to control). Further, enhancement of phosphorous, nitrogen, potassium, and zinc uptake in plant tissue was also recorded by application of P-WBF. This study suggests the use of P-WBF based biofertilizer using B. safensis STJP to increase stevioside content in Stevia plant by a nutrient(s) linked mechanism. This novel approach can also be beneficial for utilization of a dairy waste in preparation of bioformulation and, for enhancement of crop yield by an ecofriendly manner leading to sustainable agriculture.Graphic abstract

The prevalence of age-related brain issues has risen in developed countries because of changes in lifestyle. Alzheimer's disease leads to a rapid and irreversible decline in cognitive abilities by damaging memory cells. A ResNet-18-based system is proposed, integrating Depth Convolution with a Squeeze and Excitation (SE) block to minimize tuning parameters. This design is based on analyses of existing deep learning architectures and feature extraction techniques. Additionally, pre-trained ResNet-18 models were created with and without the SE block to compare ROC and accuracy values across different hyperparameters. The proposed model achieved ROC values of 95% for Alzheimer's Disease (AD), 95% for Cognitively Normal (CN), and 93% for Mild Cognitive Impairment (MCI), with a maximum test accuracy of 88.51%. However, the pre-trained model with SE had 93.26% accuracy and ROC values of 98%, 99%, and 98%, while the model without SE had 94%, 97%, and 94% ROC values and 92.41% accuracy. Collecting medical data can be expensive and raises ethical concerns. Small data sets are also prone to local minima issues in the cost function. A scratch model that experiences extensive hyperparameter tuning may end up being either overfitted or underfitted. Class imbalance also reduces performance. Transfer learning is most effective with small, imbalanced datasets, and pre-trained models with SE blocks perform better than others. The proposed model introduced a method to reduce training parameters and prevent overfitting from imbalanced medical data. Overall performance findings show that the suggested approach performs better than the state-of-the-art techniques.

Technological advancements in treatment planning and delivery have propelled the use of intensity-modulated radiation therapy (IMRT) in head and neck squamous cell carcinoma (HNSCC). This review compares IMRT with conventional two-dimensional (2D) and/or three-dimensional (3D) radiotherapy (RT) in curative-intent management of HNSCC. Only randomized controlled trials (RCTs) offering curative-intent RT in patients with non-metastatic HNSCC were included. Outcome data was extracted independently by two reviewers, pooled using the Cochrane methodology, and expressed as risk ratio (RR) or hazard ratio (HR) as appropriate with 95% confidence intervals (CIs). Xerostomia was the primary outcome of interest whereas loco-regional control, overall survival and quality-of-life (QOL) were secondary endpoints. Seven RCTs involving 1155 patients directly comparing IMRT with 2D/3D-RT in HNSCC were included. The primary objective in five of seven index RCTs was reduction in xerostomia, with only one trial each using loco-regional control and overall survival as primary endpoints for sample size calculation. The use of IMRT was associated with a 36% relative risk reduction in ≥grade 2 acute xerostomia (RR = 0.64, 95%CI = 0.49-0.84; p = 0.001) compared to 2D/3D-RT. More importantly, IMRT significantly reduced the risk of ≥grade 2 late xerostomia (RR = 0.44, 95%CI = 0.34-0.57; p = 0.00001) compared to non-IMRT techniques at all time-points. Within the limitations of inadequate sample size and low statistical power, IMRT also resulted in 24% relative reduction in the risk of loco-regional relapse (HR = 0.76, 0.57-1.01; p = 0.06) and 30% relative reduction in risk of death (HR = 0.70, 95%CI = 0.57-0.88; p = 0.002) compared to 2D/3D-RT. However, this benefit of IMRT for loco-regional control and overall survival was limited to nasopharyngeal cancer patients alone, with no significant difference in efficacy between the two techniques in patients with cancers of the laryngo-pharynx in this analysis, highlighting the inconsistency in results of subgroup analyses stratified by primary site. Inadequate reporting of data precluded statistically pooling of results for QOL outcomes. There is consistent moderate-quality evidence that IMRT significantly reduces the risk of moderate to severe acute and late xerostomia compared to 2D/3D-RT in curative-intent radiotherapeutic management of HNSCC. However, the quality of evidence regarding the superiority of IMRT over conventional techniques for disease-related endpoints is rather low due to relative lack of power and inconsistency of results precluding robust conclusions.

In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail.

The present study was carried out to determine the contamination levels of heavy metals in road dust of the National Capital Territory of Delhi (NCT), India and its consequent effect on human and environment. The levels of heavy metals (Pb, Zn, Cu, Cr, Ni, Mn, and Fe) in 9 districts (Z1–Z9) of NCT were monitored and the corresponding human health risk was estimated. District-wise evaluation of heavy metal pollution in the road dust was performed. The mean concentrations of Pb, Zn, Cu, Ni, Cr, Mn, and Fe in the road dust samples over the study area were 164.2 ± 53.2, 200.7 ± 45.3, 99.9 ± 64.8, 24.7 ± 5.7, 57.7 ± 25.9, 241.4 ± 39.8, and 11113.9 ± 1669.7 mg kg −1 , respectively. PLI showed a high pollution load in the monitored nine locations, indicating an alarming condition and the urgent need for immediate remedial actions. Ecological risk assessment depicted that a 74% risk was attributed to Pb. Hazard quotient (HQ) values indicated that ingestion was the major pathway of road dust heavy metal exposure to human beings. Hazard index values showed that there was no probable non-carcinogenic risk of the heavy metals present in the road dust of the area. Children were found vulnerable to the risks of road dust metals. The findings of this study showed the alarming status of heavy metal contamination to road dust in NCT and the associated risk to human health.

Vehicle teleoperation has the ability to bridge the gap between completely automated driving and manual driving by remotely monitoring and operating autonomous vehicles when their automation fails. Among many challenges related to vehicle teleoperation, the considered ones in this work are variable time delay, saturation of actuators installed in vehicle, and environmental disturbance, which together limit the teleoperation performance. State-of-the-art predictive techniques estimate vehicle states to compensate for the delays, but the predictive states do not account for sudden disturbances that the vehicle observes, which makes the human-picked steer inadequate. This inadequacy of steer deteriorates the path-tracking performance of vehicle teleoperation. In the proposed successive reference-pose-tracking (SRPT) approach, instead of transmitting steering commands, the reference trajectory, in the form of successive reference poses, is transmitted to the vehicle. This paper introduces a method of generation of successive reference poses with a joystick steering wheel and compares the human-in-loop path-tracking performance of the Smith predictor and SRPT approach. Human-in-loop experiments (with 18 different drivers) are conducted using a simulation environment that consists of the integration of a real-time 14-DOF Simulink vehicle model and Unity game engine in the presence of bidirectional variable delays. Scenarios for performance comparison are low adhesion ground, strong lateral wind, tight corners, and sudden obstacle avoidance. Result shows significant improvement in reference tracking and in reducing human effort in all scenarios using the SRPT approach.

Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis.

Pancreatic cancer is one of the most malignant tumors with one of the worst survival rates due to its insidious onset and resistance to therapies. Most therapeutics show a desired anticancer effect in vitro; however, very poor efficacy in vivo because of the limited drug delivery and penetration into pancreatic tumors attributed to the abundance of the tumor stroma, ie, the fibrotic tumor microenvironment surrounding the cancer cells. For a better understanding of the challenges posed by the pancreatic tumor stroma, we outline the key features of the tumor microenvironment. Then we highlight major strategies used to tackle the challenges to improve drug penetration into the tumor and achieve enhanced efficacy (pre)clinically. Furthermore, we describe nanomedicine strategies to modulate the tumor stroma, degrade the extracellular matrix, and co-deliver multi-functional drugs, to improve the chemotherapeutics delivery and penetration into pancreatic tumors.