Innovative Approaches to Address the Technical Challenge of Hernial Sac Distension Due to Pneumoperitoneum in the Synchronous Management of Complex Hernias in Individuals With Morbid Obesity.

Although repairing ventral hernias in individuals who have undergone bariatric surgery is a common practice, persistent technical intricacies and controversies surround their management. Concurrently, addressing ventral hernias in morbidly obese patients undergoing bariatric surgery presents a significant surgical challenge, amplified by the larger intraperitoneal cavities and the presence of large hernial sacs. This technical report introduces two innovative techniques to alleviate the challenge of hernia sac distension due to pneumoperitoneum associated with simultaneous bariatric surgery and ventral hernia repair using laparoscopic technique. The methods are designed to address the complexities of the procedures, making their simultaneous execution feasible and safe. The goal is to eliminate the need for two separate interventions while ensuring the outcomes of each procedure remain uncompromised. The larger intraperitoneal cavities and the presence of large hernial sacs are managed successfully, demonstrating the feasibility and safety of the introduced methods. Importantly, the simultaneous execution of both procedures does not compromise the outcomes of either intervention. Concurrently managing ventral hernias in morbidly obese patients undergoing bariatric surgery requires innovative solutions to overcome technical challenges. The introduction of these two novel techniques proves to be a valuable approach, making simultaneous execution feasible and safe. Eliminating the need for two separate interventions streamlines the surgical process without compromising the outcomes of either bariatric surgery or ventral hernia repair.

Development, characterization, and evaluation of Zn-SA-chitosan bionanoconjugates on wheat seed, experiencing chilling stress during germination.

This study aimed to develop and characterize the chitosan bionanoconjugates (BNCs) loaded with zinc (Zn) and salicylic acid (SA) and test their efficacy on wheat seed exposed to chilling stress. BNCs developed were spherical (480 ± 6.0 nm), porous, and positively charged (+25.2 ± 2.4 mV) with regulated nutrient release properties. They possessed complexation efficiency of 78.4 and 58.9 % for Zn, and SA respectively. BET analysis further confirmed a surface area of 12.04 m2/g. Release kinetics substantiated the release rates of Zn and SA, as 0.579 and 0.559 % per hour, along with a half-life of 119.7 and 124.0 h, respectively. BNCs positively affected the germination potential of wheat seeds under chilling stress as observed by significantly (p < 0.05) reduced mean emergence time (18 %), and increased germination rate (22 %), compared to the control. Higher activities of reserve mobilizing enzymes (α-amylase- 6.5 folds, protease -10.2 folds) as well as faster reserve mobilization of starch (64.4 %) and protein (63.5 %) molecules were also observed. The application further led to increased levels of the antioxidant enzymes (SOD and CAT) and reduced oxidative damage (MDA and H2O2). Thus, it is inferred that the developed BNCs could help substantially improve the germination and reserve mobilization potential, thereby increasing the crop yield.

Postharvest handling of ethylene with oxidative and absorptive means.

Fruit ripening is an unfolding of a series of genetically-programmed modifications and tend to be highly orchestrated irrevocable phenomenon mediated by ethylene. Phytohormone ethylene also leads to over-ripening, senescence, loss of texture, microbial attack, reduced post-harvest life and other associated problems during storage and transportation of fruits. Its harmful impacts on fresh fruits, vegetables, and ornamentals result in substantial product losses even up to 80%. Curbing of this inevitable menace is therefore need of the hour. Accrual of ethylene in packaging system should fundamentally be ducked to extend the shelf-life and uphold an adequate superiority of perishables in visual and organoleptic terms. The current review discusses about properties, factors affecting and impact of ethylene, intimidation of its impact at gene vis-à-vis activity level using gene-modification/inhibition techniques, chemical/physical in conjunction with other suitable approaches. It also entails the most commercially cultivated approaches worldwide viz. KMnO4-based oxidation together with adsorption-based scrubbing of ethylene in thorough details. Future ethylene removal strategies should focus on systematic evaluation of KMnO4-based scavenging, exploring the mechanism of adsorption, adsorbent(s) behavior in the presence of other gases and their partial pressures, volatiles, temperature, relative humidity, development of hydrophobic adsorbents to turn-up under high RH, regeneration of adsorbent by desorption, improvement in photocatalytic oxidation etc. and further improvements thereof. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05777-1.

Comparison of Objectively Assessed Versus Patient-Reported Clarity of Last Rectal Effluent for the Prediction of Quality of Bowel Preparation for Colonoscopy: A Prospective, Case-Control Study.

INTRODUCTION: Colonoscopy is a crucial procedure for various clinical purposes, including screening for colorectal cancer. Adequate bowel preparation is essential for its success. Poor bowel preparation can lead to bad outcomes. An objective assessment of bowel preparation quality is typically only possible after the colonoscope is inserted. This study aimed to objectively correlate the clarity of last rectal effluent, directly collected in a transparent container, with the quality of bowel preparation, and compare it with patient-reported descriptions. METHODS: This prospective, single-centre, case-control study obtained ethical clearance and included patients aged >18 years undergoing colonoscopies. Cases included patients who collected the last rectal effluent and took photographs, while controls relied on verbal descriptions. Data collected included demographics, clinical information, bowel preparation quality, and lastly, stool clarity. A statistical analysis was performed to identify correlations and associations. RESULTS: Of the 70 included patients, 45 were male. The mean age was 35.8 ± 14.3 years. Cases had a higher mean age (37.8 ± 14.6). A higher number of cases had comorbidities (11, 68.8%). Photographic recording of the last rectal effluent was not associated with the adequacy of bowel preparation. Thin yellow fluid was the most common last-rectal effluent clarity (33, 47.1%). Thin, clear fluid was significantly associated with adequate bowel preparation. CONCLUSION: Objective assessment of last rectal effluent clarity correlates with the quality of bowel preparation. This can improve the quality of bowel preparation for colonoscopies and potentially reduce the need for repeat procedures, contributing to better patient outcomes and cost savings in healthcare systems.

Role of Angiogenesis and Its Biomarkers in Development of Targeted Tumor Therapies.

Angiogenesis plays a significant role in the human body, from wound healing to tumor progression. "Angiogenic switch" indicates a time-restricted event where the imbalance between pro- and antiangiogenic factors results in the transition from prevascular hyperplasia to outgrowing vascularized tumor, which eventually leads to the malignant cancer progression. In the last decade, molecular players, i.e., angiogenic biomarkers and underlying molecular pathways involved in tumorigenesis, have been intensely investigated. Disrupting the initiation and halting the progression of angiogenesis by targeting these biomarkers and molecular pathways has been considered as a potential treatment approach for tumor angiogenesis. This review discusses the currently known biomarkers and available antiangiogenic therapies in cancer, i.e., monoclonal antibodies, aptamers, small molecular inhibitors, miRNAs, siRNAs, angiostatin, endostatin, and melatonin analogues, either approved by the U.S. Food and Drug Administration or currently under clinical and preclinical investigations.

Acclimation response and management strategies to combat heat stress in wheat for sustainable agriculture: A state-of-the-art review.

Unpredicted variability in climate change on the planet is associated with frequent extreme high-temperature events impacting crop yield globally. Wheat is an economically and nutritionally important crop that fulfils global food requirements and each degree rise in temperature results in ∼6% of its yield reduction. Thus, understanding the impact of climate change, especially the terminal heat stress on global wheat production, becomes critically important for policymakers, crop breeders, researchers and scientists to ensure global food security. This review describes how wheat perceives heat stress and induces stress adaptation events by its morpho-physiological, phenological, molecular, and biochemical makeup. Temperature above a threshold level in crop vicinity leads to irreversible injuries, viz. destruction of cellular membranes and enzymes, generation of active oxygen species, redox imbalance, etc. To cope with these changes, wheat activates its heat tolerance mechanisms characterized by hoarding up soluble carbohydrates, signalling molecules, and heat tolerance gene expressions. Being vulnerable to heat stress, increasing wheat production without delay seeks strategies to mitigate the detrimental effects and provoke the methods for its sustainable development. Thus, to ensure the crop's resilience to stress and increasing food demand, this article circumscribes the integrated management approaches to enhance wheat's performance and adaptive capacity besides its alleviating risks of increasing temperature anticipated with climate change. Implementing these integrated strategies in the face of risks from rising temperatures will assist us in producing sustainable wheat with improved yield.

T-2 toxin induces dermal inflammation and toxicity in mice: The healing potential of menthol.

According to the World Health Organization and the Food and Agricultural Organization of the United Nations, T-2 is one of the most harmful food-toxic chemicals, penetrates intact skin. The current study examined the protective benefits of menthol topical treatment on T-2 toxin-induced cutaneous toxicity in mice. Lesions were observed on the skin of the T-2 toxin-treated groups at 72 and 120 h. The T-2 toxin (2.97 mg/kg/bw)-treated group developed skin lesions, skin inflammation, erythema, and necrosis of skin tissue in contrast to the control group. Our findings reveal that topical application of 0.25% and 0.5% MN treated groups resulted in no erythema or inflammation, and normal skin was observed with growing hairs. The 0.5% MN administered group demonstrated an 80% blister and erythema healing effect in in vitro tests. In addition, MN dose-dependently suppressed ROS and lipid peroxidation mediated by the T-2 toxin up to 120%. Histology discoveries and the immunoblotting investigations with the downregulation of i-NOS gene expression confirmed the validity of menthol activity. Further molecular docking experiments of menthol against the i-NOS protein demonstrated stable binding efficacy with conventional hydrogen bond interactions, indicating compelling evidence of menthol's anti-inflammatory effects on the T-2 toxin-induced skin inflammation.

Convalescent action of menthol against T-2 mycotoxin-induced toxicity: An in vitro study with HaCaT cells.

Only T-2 mycotoxin is emitted as an aerosol and is the most toxic fungal secondary metabolite among mycotoxins. In its clinical condition, the skin is severely irritated and painful due to lesions and alimentary toxic aleukia. Herein, we have assessed various bioactive molecules, viz. kaempferol, menthol, curcumin, and quercetin, against T-2-induced toxicity in HaCaT cells. Menthol offered exceptional protection, protecting 92% of HaCaT cells after exposure to 300 nM T-2 and reducing LDH leakage by up to 42%. Its pre-treatment provided considerable protection against T-2 toxicity, as evidenced by the assessment of mitochondrial membrane potential. Propidium iodide staining revealed a cell cycle halt at the G1, S, and M phases and a significant increase in the sub-G1 percentage in T-2-challenged cells, indicating cell death. However, pre-treatment with menthol promoted cell cycle progression in cells exposed to T-2. Immunoblotting results demonstrated that menthol resulted in a discernible down-regulation of i-NOS expression in T-2-challenged HaCaT cells.

Autism Spectrum Disorders: A Recent Update on Targeting Inflammatory Pathways with Natural Anti-Inflammatory Agents.

Autism spectrum disorder (ASD) is a heterogeneous category of developmental psychiatric disorders which is characterized by inadequate social interaction, less communication, and repetitive phenotype behavior. ASD is comorbid with various types of disorders. The reported prevalence is 1% in the United Kingdom, 1.5% in the United States, and ~0.2% in India at present. The natural anti-inflammatory agents on brain development are linked to interaction with many types of inflammatory pathways affected by genetic, epigenetic, and environmental variables. Inflammatory targeting pathways have already been linked to ASD. However, these routes are diluted, and new strategies are being developed in natural anti-inflammatory medicines to treat ASD. This review summarizes the numerous preclinical and clinical studies having potential protective effects and natural anti-inflammatory agents on the developing brain during pregnancy. Inflammation during pregnancy activates the maternal infection that likely leads to the development of neuropsychiatric disorders in the offspring. The inflammatory pathways have been an effective target for the subject of translational research studies on ASD.

Morpho-physiological and biochemical responses of cotton (Gossypium hirsutum L.) genotypes upon sucking insect-pest infestations.

The effects of sucking insect-pests on the morpho-physiological and biochemical changes in the leaves of four cotton genotypes-Bio 100 BG-II and GCH-3 (highly tolerant); KDCHH-9810 BG-II and HS-6 (highly susceptible)-were examined. Compared to tolerant genotypes, susceptible genotypes showed a decrease in relative water content, specific leaf weight, leaf area, photosynthetic rate, and total chlorophyll content, with an increase in electrolyte leakage. Hydrogen peroxide and total soluble sugar content were higher in susceptible plants. In contrast, resistant plants had higher levels of total soluble protein, total phenolic content, gossypol content, tannin content, peroxidase activity, and polyphenol oxidase. The findings demonstrated that the Bio 100 BG-II and GCH-3 genotypes effectively offset the impact of sucking insect-pests by modifying the factors mentioned above. The KDCHH-9810 BG-II and HS-6 genotypes could not completely negate the effects of sucking insect-pests. Customized metabolites and total soluble protein are more efficient in protecting cotton plants from damage brought on by infestations of sucking insects and pests. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01253-w.

Ultimate fate and possible ecological risks associated with atrazine and its principal metabolites (DIA and DEA) in soil and water environment.

Atrazine (AT) is a triazine herbicide widely used to control weeds in several crops. De-isopropylatrazine (DIA) and de-ethylatrazine (DEA) are two of the eight primary metabolites produced by AT breakdown in soil and water. The physico-chemical properties of the soil determine their final fate. So, this study aimed to assess the function of clay loam and sandy loam soils in determining their ultimate fate and the potential ecological risks to non-target species during their persistence in soil and transportation to water bodies. The soil in pots was spiked with standard solutions of AT, DEA, and DIA at 0.3 and 0.6 mg/kg for the persistence study. The leaching potential was determined by placing soils in Plexi columns and spiking them with 50 and 100 µg standard solutions. Liquid-liquid extraction was used to prepare the samples, which were then analyzed using GC-MS/MS. The dynamics of dissipation were first-order. AT, DEA and DIA disappeared rapidly in sandy loam soil, with half-lives ranging from 6.2 to 8.4 days. AT and its metabolites had a significant amount of leaching potential. In sandy loam soil, leaching was more effective, resulting in maximal residue movement up to 30-40 cm soil depth. The presence of a notable collection of residues in leachate fractions suggests the potential for surface and groundwater contamination. In particular, DEA and DIA metabolites caused springtail Folsomia candida and earthworm Eisenia fetida to have longer and greater unacceptable risks. If the residues comparable to the amount acquired in leachate fractions reach water bodies, they could cause toxicity to a variety of freshwater fish, aquatic arthropods, amphibians, and aquatic invertebrates. Future studies should take a more comprehensive approach to evaluate ecological health and dangers to non-target species.

Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury.

Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted cortex, with variable and moderate effects. In addition, the targeted circuits are inferred, rather than tested directly. In contrast, we sought to target the strong convergence between motor and sensory systems in the spinal cord. We developed spinal cord associative plasticity, precisely timed pairing of motor cortex and dorsal spinal cord stimulations, to target this interaction. We tested the hypothesis that properly timed paired stimulation would strengthen the sensorimotor connections in the spinal cord and improve recovery after spinal cord injury. We tested physiological effects of paired stimulation, the pathways that mediate it, and its function in a preclinical trial. Subthreshold spinal cord stimulation strongly augmented motor cortex evoked muscle potentials at the time they were paired, but only when they arrived synchronously in the spinal cord. This paired stimulation effect depended on both cortical descending motor and spinal cord proprioceptive afferents; selective inactivation of either of these pathways fully abrogated the paired stimulation effect. Spinal cord associative plasticity, repetitive pairing of these pathways for 5 or 30 min in awake rats, increased spinal excitability for hours after pairing ended. To apply spinal cord associative plasticity as therapy, we optimized the parameters to promote strong and long-lasting effects. This effect was just as strong in rats with cervical spinal cord injury as in uninjured rats, demonstrating that spared connections after moderate spinal cord injury were sufficient to support plasticity. In a blinded trial, rats received a moderate C4 contusive spinal cord injury. Ten days after injury, they were randomized to 30 min of spinal cord associative plasticity each day for 10 days or sham stimulation. Rats with spinal cord associative plasticity had significantly improved function on the primary outcome measure, a test of dexterity during manipulation of food, at 50 days after spinal cord injury. In addition, rats with spinal cord associative plasticity had persistently stronger responses to cortical and spinal stimulation than sham stimulation rats, indicating a spinal locus of plasticity. After spinal cord associative plasticity, rats had near normalization of H-reflex modulation. The groups had no difference in the rat grimace scale, a measure of pain. We conclude that spinal cord associative plasticity strengthens sensorimotor connections within the spinal cord, resulting in partial recovery of reflex modulation and forelimb function after moderate spinal cord injury. Since both motor cortex and spinal cord stimulation are performed routinely in humans, this approach can be trialled in people with spinal cord injury or other disorders that damage sensorimotor connections and impair dexterity.

Metabolomics and EMT Markers of Breast Cancer: A Crosstalk and Future Perspective.

Cancer cells undergo transient EMT and MET phenomena or vice versa, along with the parallel interplay of various markers, often correlated as the determining factor in decoding metabolic profiling of breast cancers. Moreover, various cancer signaling pathways and metabolic changes occurring in breast cancer cells modulate the expression of such markers to varying extents. The existing research completed so far considers the expression of such markers as determinants regulating the invasiveness and survival of breast cancer cells. Therefore, this manuscript is crosstalk among the expression levels of such markers and their correlation in regulating the aggressiveness and invasiveness of breast cancer. We also attempted to cover the possible EMT-based metabolic targets to retard migration and invasion of breast cancer.

Chitosan nanomaterials: A prelim of next-generation fertilizers; existing and future prospects.

Global agriculture is urgently seeking ways to mitigate the detrimental effects of conventional chemical fertilizers on the environment. Biodegradable, eco-friendly, renewable energy-sourced next-generation fertilizers could be an answer, allowing for improved nutrient use efficiency and a lower environmental footprint. During the last decade, agricultural research on chitosan nanomaterials (NMs) has expanded, demonstrating their usefulness in enhancing agricultural output not only as plant immune boosters but also via slow, controlled and target delivery of nutrients to plants. Chitosan NMs natively act as an abundant nutrient source of C (54.4-47.9 wt%), O (42.3-30.19 wt%), N (7.6-5.8 wt%), and P (6.1-3.4 wt%) to plants. Moreover, chitosan NMs can further functionalized by more nutrients payloads through its functional groups. The current review investigates the technical features of chitosan NMs as prospective next-generation fertilizers based on rationales. The review offers crucial insights into future directions, sources, production capacity of chitosan-based next-generation nanofertilizers for industrial-scale manufacturing.

Initial Retrocolic Endoscopic Tunnel Approach As an Ergonomic and Oncologically Apt Laparoscopic Technique for Resection of Malignant Right Colonic Lesions: An Experience from a University Hospital.

Introduction: Radical minimal access cancer surgery has demonstrated similar outcomes as open surgery of late, but with less morbidity, improving the quality of life especially in patients with colorectal cancer. Initial retrocolic endoscopic tunnel approach (IRETA) has been described in the literature by Palanivelu et al. as a laparoscopic technique for radical resection of malignant right colonic lesions (MRCL) following the modified concept of medial to lateral dissection. In this work, the authors present their experience of this ergonomic surgical technique. Materials and Methods: To begin with, retrocolic dissection was carried out to free and dissect the ascending colon up to hepatic flexure with the reflection of the peritoneum over the right colon along the white line of Toldt with abdominal wall kept intact initially to sustain intracorporeal specimen steadiness. Subsequently, the specimen is lifted medially in a distinct lymphovascular sheath, leading to high ligation of ileocolic, right colic, and the right branch of the middle colic vein with a consequent definite en bloc thorough removal of the lesion. The specimen was delivered through a transumbilical incision. Results: Ten patients (age 45.4 ± 5.6 years) underwent resection by the IRETA technique with a mean operating time of 185 ± 30 minutes and blood loss of 90 ± 20 mL. Mean hospital stay was 6 days. R0 surgical resection was achieved in all patients with proper marginal clearance. Ninety percent had adequate lymph nodal resection. One patient had an intraoperative complication and n = 3 patients developed postoperative ileus. Adjuvant chemotherapy was given and there is no recurrence on 28 months of average follow-up. Conclusion: With the increasing use of laparoscopic surgery for the management of colorectal cancers, the IRETA technique appears to be an ergonomic and oncologically robust procedure for the removal of MRCL. The presented data set needs to be increased with at least 5 years of follow-up to establish long-term surgical outcomes.

Genetic Analysis for Resistance to Sclerotinia Stem Rot, Yield and Its Component Traits in Indian Mustard [Brassica juncea (L.) Czern & Coss.].

Understanding the mode of gene action that controls seed yield and Sclerotinia stem rot resistance in Indian mustard is critical for boosting yield potential. In a line × tester mating design, ten susceptible lines and four resistant testers were used to conduct genetic analysis. The significance of general combining ability (GCA) and specific combining ability (SCA) variances revealed that both additive and non-additive gene actions were involved in the inheritance of Sclerotinia stem rot resistance and yield attributing traits. In addition to 1000-seed weight and number of primary and secondary branches/plant, the genotypes RH 1569 (line) and DRMR 2035 (tester) appeared to be the strongest general combiners for Sclerotinia stem rot resistance. RH 1657 × EC 597317 was the only cross among several that demonstrated a significant desired SCA value for Sclerotinia rot resistance. Regarding SCA effects for yield and component traits, the cross RH 1658 × EC 597328 performed best, with a non-significant but acceptable negative SCA effect for resistance. DRMR 2035, RH 1222-28, RH 1569, RH 1599-41, RH 1657, RH 1658, and EC 597328 are promising genotypes to use as parents in future heterosis breeding and for obtaining populations with high yield potential and greater resistance to Sclerotinia stem rot disease in Indian mustard, based on GCA effects of parents, per se performance, and SCA effects of hybrids. Days to 50% flowering, number of primary branches/plant, main shoot length, and 1000-seed weight all had a high genotypic coefficient of variability (GCV), broad-sense heritability (h2bs), and genetic advance as percent of the mean (GAM) values, as well as significant and desirable correlations and direct effects on seed yield. As a result, these traits have been recognized as the most critical selection criterion for Indian mustard breeding programs.

Effect of parthenolide, an NLRP3 inflammasome inhibitor, on insulin resistance in high-fat diet-obese mice.

The activation of Nod-like receptor proteins (NLRP3) containing the pyrin domain inflammasome is a hallmark of the pathogenesis of metabolic disorders. Inhibition of the NLRP3 inflammasome by phytoconstituents has been attempted as a strategy to mitigate these disorders. Therefore, the present study aimed to evaluate the efficacy of an NLRP3 inflammasome inhibitor, parthenolide (PN; 5 mg/kg i.p.) against inflammation and insulin resistance in high-fat diet (HFD) - obese mice. Treatment with PN and pioglitazone (PIO; 30 mg/kg p.o.) attenuated lipopolysaccharide (LPS; 1 ng/ml) - induced elevation of tumor necrosis factor-α and interleukin-1ß in mouse peritoneal macrophages in a dose-dependent manner. Sixty days of PN and PIO treatment marginally reduced obesity-induced insulin resistance in HFD-obese mice. PN treatment also decreased blood glucose from 14th to 60th day, supporting the hypothesis of simultaneous attenuation of inflammation and insulin resistance in obese mice. Thus, PN treatment was also evident with significant improvement in glucose tolerance and peripheral insulin resistance validated through the respective tolerance tests. Therefore, the present study suggests that PN, an NLRP3 inflammasome inhibitor, could be a possible therapeutic agent for attenuating obesity-induced insulin resistance.

Structure based prediction of a novel GPR120 antagonist based on pharmacophore screening and molecular dynamics simulations.

The G-protein coupled receptor, GPR120, has ubiquitous expression and multifaceted roles in modulating metabolic and anti-inflammatory processes. Recent implications of its role in cancer progression have presented GPR120 as an attractive oncogenic drug target. GPR120 gene knockdown in breast cancer studies revealed a role of GPR120-induced chemoresistance in epirubicin and cisplatin-induced DNA damage in tumour cells. Higher expression and activation levels of GPR120 is also reported to promote tumour angiogenesis and cell migration in colorectal cancer. Some agonists targeting GPR120 have been reported, such as TUG891 and Compound39, but to date development of small-molecule inhibitors of GPR120 is limited. Herein, following homology modelling of the receptor a pharmacophore hypothesis was derived from 300 ns all-atomic molecular dynamics (MD) simulations on apo, TUG891-bound and Compound39-bound GPR120S (short isoform) receptor models embedded in a water solvated lipid bilayer system. We performed comparative MD analysis on protein-ligand interactions between the two agonist and apo simulations on the stability of the "ionic lock" - a Class A GPCRs characteristic of receptor activation and inactivation. The detailed analysis predicted that ligand interactions with W277 and N313 are critical to conserve the "ionic-lock" conformation (R136 of Helix 3) and prevent GPR120S receptor activation. The results led to generation of a W277 and N313 focused pharmacophore hypothesis and the screening of the ZINC15 database using ZINCPharmer through the structure-based pharmacophore. 100 ns all-atomic molecular dynamics (MD) simulations were performed on 9 small molecules identified and Cpd 9, (2-hydroxy-N-{4-[(6-hydroxy-2-methylpyrimidin-4-yl) amino] phenyl} benzamide) was predicted to be a small-molecule GPR120S antagonist. The conformational results from the collective all-atomic MD analysis provided structural information for further identification and optimisation of novel druggable inhibitors of GPR120S using this rational design approach, which could have future potential for anti-cancer drug development studies.

Electromagnetic Field Stimulation Attenuates Phasic Nociception after Complete Spinal Cord Injury in Rats.

Traumatic spinal cord injury (SCI) is one of the most incapacitating pathologies, leading to huge rehabilitation challenges besides a social-economic burden on SCI patients and their families. There is no complete curative treatment available so far. Non-invasive and patient-friendly use of extremely low-frequency electromagnetic field stimulation (EMF) has emerged as a therapeutic and rehabilitation option. In this study, we tested whole-body EMF stimulation on thoracic complete SCI-induced nociception including sensorimotor deficits in rats. The EMF application significantly attenuated hyperalgesia and allodynia to thermal, electrical, and chemical stimuli from 6 weeks onwards as well as restoration of spinal reflexes, viz., H-reflex and nociceptive flexion reflex at the study endpoint (week 8). Besides, massively increased glutamate at the SCI injury site was observed in SCI rats with no treatment, which was also attenuated significantly by EMF stimulation. Spinal cord histology of the injury area showed a decrease in lesion volume and glial population in the EMF-stimulated rats. These findings indicate the beneficial role of EMF stimulation after thoracic complete SCI in adult male rats and, thereby, a beneficial patient-friendly rehabilitation tool.

Slow-release Zn application through Zn-chitosan nanoparticles in wheat to intensify source activity and sink strength.

Source activity and sink strength are important aspects to measure growth and yield in wheat. Despite zinc's extended functions in the amendment of plant metabolic activities, critical research findings are missing on mapping the elusive interplays of slow-release zinc (Zn) application from nanoparticles (NPs) in crop plants. The present study reports that slow-releasing Zn application through Zn-chitosan NPs bestows myriad effects on source activity and sink strength in wheat plants. Herein, effects of foliar application of Zn-chitosan NPs (0.04-0.16%; w/v) at booting stage of wheat crop were evaluated to quantify the source sink potential compared to ZnSO4. Zn-chitosan NPs endowed elevated source activity by up-regulating cellular redox homeostasis by improving the antioxidant status, cellular stability and higher photosynthesis. Cognately, in the field experiment, NPs (0.08-0.16%, w/v) significantly spurred sink strength by up-regulating starch biosynthesis enzymes viz. sucrose synthase (SUS), invertase (INV), ADP-glucose pyrophosphorylase (AGPase), soluble starch synthase (SSS) and accumulated more starch in developing wheat grains. Concomitantly, higher spike lengths without awns, significantly higher number of grains/spike, test weight (24% more than ZnSO4 treatment), yield (21% more than ZnSO4 treatment), biological yield and harvest index quantified the higher sink size to further validate the better sink strength in slow-release Zn application via chitosan NPs.