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Nucleotide-binding Oligomerization Domain 1 (NOD1) is a cytosolic pattern recognition receptor that senses specific bacterial peptidoglycan moieties, leading to the induction of inflammatory response. Besides, sensing peptidoglycan, NOD1 has been reported to sense metabolic disturbances including the ER stress-induced unfolded protein response (UPR). However, the underpinning crosstalk between the NOD1 activating microbial ligands and the metabolic cues to alter metabolic response is not yet comprehensively defined. Here, we show that underlying ER stress aggravated peptidoglycan-induced NOD1-mediated inflammatory response in hepatoma cells. The HepG2 cells, undergoing ER stress induced by thapsigargin exhibited an amplified inflammatory response induced by peptidoglycan ligand of NOD1 (i.e. iE-DAP). This aggravated inflammatory response disrupted lipid and glucose metabolism, characterized by de novo lipogenic response, and increased gluconeogenesis in HepG2 cells. Further, we characterized that the aggravation of NOD1-induced inflammatory response was dependent on inositol-requiring enzyme 1-α (IRE1-α) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) activation, in conjunction with calcium flux. Altogether, our findings suggest that differential UPR activation makes liver cells more sensitive towards bacterial-derived ligands to pronounce inflammatory response in a NOD1-dependent manner that impairs hepatic nutrient metabolism., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the quest for the discovery of antidiabetic compounds, a series of 27 1,4-dihydropyridine-indole derivatives were synthesized using a diversity approach. These compounds were systematically evaluated for their antidiabetic activity, starting with an in vitro assessment for GLUT4 translocation stimulation in L6-GLUT4 myc myotubes, followed by in vivo antihyperglycemic activity evaluation in a streptozotocin (STZ)-induced diabetic rat model. Among the synthesized compounds, 12 , 14 , 15 , 16 , 19 , 27 , and 35 demonstrated significant potential to stimulate GLUT4 translocation in skeletal muscle cells. Compound 19 exhibited the highest potency and was selected for in vivo evaluation. A notable reduction of 21.6% ( p < 0.01) in blood glucose levels was observed after 5 h of treatment with compound 19 in STZ-induced diabetic rats. Furthermore, pharmacokinetic studies affirmed that compound 19 was favorable to oral exposure with suitable pharmacological parameters. Overall, compound 19 emerged as a promising lead compound for further structural modification and optimization.

Waterlogging stress causes substantial destruction to plant growth and production under climatic fluctuations globally. Plants hormones have been widely explored in numerous crops, displaying an imperative role in crop defense and growth mechanism. However, there is a paucity of research on the subject of plant hormones regulating waterlogging stress responses in wheat crop. In this study, we clarified the role of 6-BA in waterlogging stress through inducing phenylpropanoid biosynthesis in wheat. The application of 6-BA (6-benzyladenine) enhanced the growth and development of wheat plants under waterlogging stress, which was accompanied by reduced electrolyte leakage, high chlorophyll, and soluble sugar content. ROS scavenging was also enhanced by 6-BA, resulting in reduced MDA and H 2 O 2 accumulation and amplified antioxidant enzyme activities. Additionally, under the effect of 6-BA, the acceleration of lignin content and accumulation in the cell walls of wheat tissues, along with the activation of PAL (phenylalanine ammonia lyase), TAL (tyrosine ammonia lyase), and 4CL (4-hydroxycinnamate CoA ligase) activities and the increase in the level of transcription of the TaPAL and Ta4CL genes, were observed under waterlogging stress. Also, 6-BA improved the root growth system under waterlogging stress conditions. Further qPCR analysis revealed increased auxin signaling ( TaPR1 ) in 6-BA-treated plants under waterlogging stress that was consistent with the induction of endogenous IAA hormone content under waterlogging stress conditions. Here, 6-BA also reduced yield loss, as compared to control plants. Thus, the obtained data suggested that, under the application of 6-BA, phenylpropanoid metabolism (i.e., lignin) was stimulated, playing a significant role in reducing the negative effects of waterlogging stress on yield, as evinced by the improved plant growth parameters.

In the context of China's transportation sector, which has faced escalating challenges in carbon emissions, this study delves into the intricate nexus between sustainable finance strategies and the imperative of achieving carbon neutrality. Spanning the years 2010-2022 across 30 provinces of China and employing a rigorous Panel Model methodology, our research sets out to achieve several pivotal objectives. These include assessing the tangible impact of sustainable finance initiatives on curtailing carbon emissions within the transportation domain, discerning the pivotal drivers that influence the trajectory of carbon neutrality endeavors, and critically evaluating the efficacy of policy interventions aimed at fostering sustainability. Our findings unearth a compelling narrative. Firstly, we observe a discernible positive correlation between the implementation of sustainable finance mechanisms-such as green bonds, sustainable investment portfolios, and innovative financial instruments-and the tangible reduction of carbon emissions within the transportation sector. Secondly, our analysis underscores the indispensable role of key drivers, ranging from technological advancements and regulatory frameworks to evolving consumer behavior and public consciousness, in steering the course towards carbon neutrality. Thirdly, our research underscores the pivotal impact of targeted policy interventions, emphasizing the efficacy of measures aimed at incentivizing sustainable practices, fostering stakeholder collaborations, and bolstering industry-wide accountability frameworks. In light of these insights, our study advocates for a nuanced policy landscape characterized by a multifaceted approach. By aligning financial incentives with sustainability goals, fostering technological innovation, and fostering robust regulatory frameworks, policymakers can catalyze a paradigm shift towards carbon neutrality in the transportation sector., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

STAT3 is a crucial member within a family of seven essential transcription factors. Elevated STAT3 levels have been identified in various cancer types, notably in breast cancer (BC). Consequently, inhibiting STAT3 is recognized as a promising and effective strategy for therapeutic intervention against breast cancer. We herein synthesize a library of isoxazole (PAIs) from piperic acid [2E, 4E)-5-(2H-1,3-Benzodioxol-5-yl) penta-2,4-dienoic acid] on treatment with propargyl bromide followed by oxime under prescribed reaction conditions. Piperic acid was obtained by hydrolysis of piperine extracted from Piper nigrum. First, we checked the binding potential of isoxazole derivatives with breast cancer target proteins by network pharmacology, molecular docking, molecular dynamic (MD) simulation and cytotoxicity analysis as potential anti-breast cancer (BC) agents. The multi-source databases were used to identify possible targets for isoxazole derivatives. A network of protein-protein interactions (PPIs) was generated by obtaining 877 target genes that overlapped gene symbols associated with isoxazole derivatives and BC. Molecular docking and MD modelling demonstrated a strong affinity between isoxazole derivatives and essential target genes. Further, the cell viability studies of isoxazole derivatives on the human breast carcinoma cell lines showed toxicity in all breast cancer cell lines. In summary, our study indicated that the isoxazole derivative showed the significant anticancer activity. The results highlight the prospective utility of isoxazole derivatives as new drug candidates for anticancer chemotherapy, suggesting route for the continued exploration and development of drugs suitable for clinical applications., Competing Interests: Declaration of competing interest No conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of -30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity., (© 2024 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

Transgenic Arabidopsis thaliana (ecotype Columbia) was successfully transformed with the gene fructose-1,6-bisphosphatase (FBPas e) and named as AtFBPase plants. Transgenic plants exhibited stable transformation, integration and significantly higher expressions for the transformed gene. Morphological evaluation of transgenic plants showed increased plant height (35cm), number of leaves (25), chlorophyll contents (28%), water use efficiency (increased from 1.5 to 2.6μmol CO2 μmol-1 H2 O) and stomatal conductance (20%), which all resulted in an enhanced photosynthetic rate (2.7μmolm-2 s-1 ) compared to wild type plants. This study suggests the vital role of FBPase gene in the modification of regulatory pathways to enhance the photosynthetic rate, which can also be utilised for economic crops in future.

The detrimental impact of reactive oxygen species on D.N.A. repair processes is one of the contributing factors to colon cancer. The idea that oxidative stress may be a significant etiological element for carcinogenesis is currently receiving more and more support. The goal of the current study is to evaluate the anti-inflammatory and anticancer activity of three powerful phytocompounds-sitosterol, amyrin, and epiafzelechin-alone and in various therapeutic combinations against colon cancer to identify the critical mechanisms that mitigate nickel's carcinogenic effect. To evaluate the ligand-protein interaction of four selected components against Vascular endothelial growth factor (VEGF), Matrix metalloproteinase-9 (MMP9) inhibitor and Interleukin-10 (IL-10) molecular docking approach was applied using PyRx bioinformatics tool. For in vivo analysis, hundred albino rats were included, divided into ten groups, each containing ten rats of weight 160-200 g. All the groups were injected with 1 ml/kg nickel intraperitoneally per week for three months, excluding the negative control group. Three of the ten groups were treated with β-sitosterol (100 mg/kg b wt), β-amyrin (100 mg/kg b wt), and epiafzelechin (200 mg/kg b wt), respectively, for one month. The later four groups were fed with combinatorial treatments of the three phyto compounds for one month. The last group was administered with commercial drug Nalgin (500 mg/kg b wt). The biochemical parameters Creatinine, Protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), VEGF, MMP-9 Inhibitor, and IL-10 were estimated using ELISA kits and Glutathione (G.S.H.), Superoxide dismutase (S.O.D.), Catalase (C.A.T.) and Nitric Oxide (NO) were analyzed manually. The correlation was analyzed through Pearson's correlation matrix. All the parameters were significantly raised in the positive control group, indicating significant inflammation. At the same time, the levels of the foresaid biomarkers were decreased in the serum in all the other groups treated with the three phytocompounds in different dose patterns. However, the best recovery was observed in the group where the three active compounds were administered concomitantly. The correlation matrix indicated a significant positive correlation of IL-10 vs VEGF (r = 0.749**, p = 0.009), MMP-9 inhibitor vs SOD (r = 0.748**, p = 0.0 21). The study concluded that the three phytocompounds β-sitosterol, β-amyrin, and epiafzelechin are important anticancer agents which can target the cancerous biomarkers and might be used as a better therapeutic approach against colon cancer soon., (© 2023. The Author(s).)

Purpose: This study aimed to explore patients' experiences of palliative chemotherapy for non-small cell lung cancer (NSCLC), how patients adapt to their new and challenging life after chemotherapy, their beliefs, and their quality of life., Patients and Methods: The study used an exploratory descriptive qualitative approach that was designed to explore the experiences and side effects of NSCLC patients on chemotherapy in Pakistan. The study was designed to obtain a deeper understanding of 22 NSCLC patients' experiences, using a face-to-face approach and interviews were conducted. Patients who have completed chemotherapy agreed to participate in semi-structured interviews., Results: The data were arranged into five themes: hospital facilities and environment, patient's beliefs in alternative treatments, presenting a positive/negative face, life is for living, and health insurance coverage. The major complaints related to bad experiences of chemotherapy-induced side effects, but these patients still managed to complete the full course of their respective chemotherapy. Additionally, the current study revealed the real experience of patients with NSCLC which had been less studied. The patient's experience was summarized into four themes and several subthemes., Conclusion: This study aid healthcare providers when deciding on treatment options that will improve shared decision-making between clinicians and treatment outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zubair et al.)

Ethnopharmacological Relevance: Moringa oleifera is a valued plant with wide distribution in tropical and subtropical regions of the world. It is traditionally used for the treatment of fever, infections, rheumatism, cancer, improving cardiac, renal and hepatic functions, and regulating blood glucose level. The plant has been scientifically reported for the anti-inflammatory, antioxidant, renoprotective, and anti-diabetic properties. Diabetic patients are prone to develop end-stage renal diseases due to incidence of diabetes-induced renal dysfunctions. Given that, increased production and accumulation of advanced glycation end-products (AGEs) play a conspicuous role in the development of diabetes-linked renal dysfunctions, nature-based interventions with AGEs inhibitory activity can prevent renal dysfunctions leading to renoprotection., Aim of the Study: The study aimed to demonstrate the preventive effects of the ethanolic extract of the leaves of Moringa oleifera (EEMO) on protein glycation and its further assessment for the renoprotective effect in diabetic rats., Materials and Methods: Antiglycation activity of EEMO was assessed in vitro using bovine serum albumin. For reno-protective activity assessment, streptozotocin (STZ)-induced diabetic rats were orally treated with EEMO (100 mg/kg) or standard antiglycation agent aminoguanidine (100 mg/kg) for consecutive 8 weeks. The effects on glucose homeostasis, renal functions, and renal morphology were assessed by clinical biochemistry, molecular and histological examination., Results: Presence of EEMO efficiently prevented glucose-, fructose- or methylglyoxal-mediated glycation of protein. Under in vivo set-up, compared to diabetic control rats, EEMO treatment effectively improved the glucose tolerance and body weight, and reduced the serum levels of triglycerides and total cholesterol. Additionally, EEMO administration significantly ameliorated renal dysfunctions in diabetic rats characterized by improved levels of creatinine, urea nitrogen, and uric acid in serum, and total protein level in urine, accompanied by improved kidney morphology. The diabetes-associated pro-inflammatory response characterized by upregulated expression of the inducible nitric oxide synthase (iNos), activation of nuclear factor kappa B (NF-κB) and the raised levels of inflammatory factors, interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in renal tissue was significantly attenuated in EEMO-treated rats. Moreover, EEMO treatment diminished renal reactive oxygen species (ROS) levels in diabetic animals., Conclusions: Our study demonstrated that EEMO prevented AGEs formation and ameliorated renal dysfunctions in diabetic rats by blocking inflammatory/oxidative pathways. Our observations justify M. oleifera as a potential source of therapeutic interventions for diabetic nephropathy management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Activation of specific innate immune receptors has been characterized to modulate nutrient metabolism in individual metabolic tissue directly or indirectly via secretory molecules. Activation of the nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in adipocytes has been reported to induce lipolysis linked with insulin resistance and inflammatory response. These cues are positioned to modulate metabolic action in distal organs through paracrine/endocrine signaling. Here, we assessed the role of NOD1-mediated lipolysis and inflammatory response in adipocytes to affect lipid metabolism in hepatocytes., Main Methods: Human hepatoma cells (HepG2) were exposed to conditioned medium obtained from 3 T3-L1 adipocytes pretreated with NOD1 ligand (iE-DAP) and the effects on lipid accumulation, inflammation and insulin response were assessed. Activation of mechanisms leading to hepatic lipid accumulation was investigated by gene expression analysis., Key Findings: The conditioned medium from NOD1-activated 3 T3-L1 adipocytes (CM-DAP) induced lipid accumulation in HepG2 cells, driven by both lipolysis and inflammatory responses. The CM-DAP-induced lipid accumulation was independent to de novo lipogenesis and resulted from the enhanced transport of fatty acids inside and consequent increase in rate of triglycerides synthesis in hepatocytes. Moreover, CM-DAP-induced lipid accumulation instigated the expression of the markers of fatty acid oxidation and VLDL assembly for the export of triglycerides from hepatocyte. Furthermore, CM-DAP-induced lipid accumulation was associated with induction of inflammatory response and impairment of insulin signaling in HepG2 cells., Significance: Beyond showing liver-specific mechanisms to adipocytes-derived factors, our findings support the involvement of adipose tissue as a mediator in NOD1-mediated biological responses to modulate hepatic metabolism., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

High fructose flux enhances hepatocellular triglyceride accumulation (hepatic steatosis), which is a prime trigger in the emergence of hepatic ailments. Nevertheless, the pathophysiology underlying the process is not completely understood. Emerging evidences have revealed the inputs from multiple cues including inflammation, oxidative stress, and endoplasmic reticulum (ER) stress in the development of hepatic steatosis. Here, we substantiated the role of NLRP3 inflammasome and its convergence with oxidative and ER stress leading to hepatic steatosis under high fructose diet feeding. Male SD rats were fed on 60% high fructose diet (HFrD) for 10 weeks and treated with antioxidant quercetin or NLRP3 inflammasome inhibitor glyburide during the last 6 weeks, followed by metabolic characterization and analysis of hepatic parameters. HFrD-induced hepatic steatosis was associated with the activation of NLRP3 inflammasome, pro-inflammatory response, oxidative, and ER stress in liver. Treatment with quercetin abrogated HFrD-induced oxidative stress, along with attenuation of NLRP3 activation in the liver. On the other hand, inhibition of NLRP3 signaling by glyburide suppressed HFrD-induced oxidative and ER stress. Both glyburide or quercetin treatment significantly attenuated hepatic steatosis, associated with mitigated expression of the lipogenic markers in liver. Our findings verified the association of NLRP3 inflammasome with oxidative and ER stress in fructose-induced lipogenic response and indicate that in addition to be a target of oxidative/ER stress, NLRP3 can act as a trigger for oxidative/ER stress to activate a vicious cycle where these cues act in a complex manner to propagate inflammatory response, leading to hepatic steatosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adipose tissue plays a crucial role in energy intake and regulation of metabolic homeostasis. Fructose consumption implicates in development and progression of metabolic dysfunctions. Fructose is a lipogenic sugar known to induce inflammatory response. However, the role of specific inflammatory signal such as nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) in fructose-induced inflammatory response and its relevance to lipogenesis in adipose tissue are elusive. We assessed NLRP3 activation and its significance in inflammatory response and lipogenesis in epididymal adipose tissue of 60% fructose diet (HFrD)-fed rats. The long-term consumption of HFrD led to impairment of glucose metabolism, development of visceral adiposity, insulin resistance, and elevation of serum triglycerides level, accompanied by activation of NLRP3 in adipose tissue. NLRP3 inflammasome activation in adipose tissue was associated with up-regulated expression of Nlrp3, Asc, and Caspase-1, and raised caspase-1 activity, which resulted in increased expression of IL-1β and IL-18 and secretion of IL-1β. Moreover, lipid accumulation and expression of transcription factors exacerbating accumulation of lipids were augmented in adipose tissue of HFrD-fed rats. Treatment with glyburide, quercetin or allopurinol corrected HFrD-induced dyslipidemia or hyperuricemia, and blocked NLRP3 activation, leading to mitigated inflammatory signaling and lipid accumulation in adipose tissue, improved glucose tolerance and insulin sensitivity in HFrD-fed rats. These data suggest the role of NLRP3 inflammasome to establish linkage among inflammation, lipid accumulation and insulin resistance in adipose tissue, and targeting NLRP3 inflammasome may be a plausible approach for prevention and management for fructose-induced metabolic impairments., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Innate immune components participate in obesity-induced inflammation, which can contribute to endocrine dysfunction during metabolic diseases. However, the chronological activation of specific immune proteins such as Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) and relevance to cellular crosstalk during the progression of obesity-associated insulin resistance (IR) is not known., Methods: The NOD1 signaling in various insulin-sensitive metabolic tissues during the progression of diet-insulin resistance was assessed in C57BL/6J mice fed with 60% high-fat diet (HFD) for 4, 8, 12, and 16 weeks. Intestinal permeability was measured using FITC-dextran. NOD1 activating potential was analyzed using HEK-Blue mNOD1 cells., Results: HFD-fed mice showed progressive induction of glucose intolerance and impairment of insulin signaling in key metabolic tissues. We found a time-dependent increase in intestinal permeability coupled with transport and accumulation of NOD1 activating ligand in the serum of HFD-fed mice. We also observed a progressive accumulation of γ-D-glutamyl-meso-diaminopimelic acid (DAP), a microbial peptidoglycan ligand known to activate NOD1, in serum samples of the HFD-fed mice. There was also a progressive increase in transcripts levels of NOD1 in bone marrow-derived macrophages during HFD-feeding. In addition, skeletal muscle, adipose and liver, the key insulin sensitive metabolic tissues also had a time-dependent increase in transcripts of NOD1 and Rip2 and a corresponding activation of pro-inflammatory responses in these tissues., Conclusion: These data highlight the correlation of inflammation and insulin resistance to NOD1 activation in the bone marrow derived macrophages and insulin responsive metabolic tissues during high fat diet feeding in mice., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The purpose of this study is to explore energy prices and their impact on household consumption under the condition of Keynesian consumption theory in South Asian countries over the 1995-2020 periods. By employing the panel ordinary least square model estimation technique, the study attempted to find the relationship between household income and consumption under the theory of Keynesian consumption function. Furthermore, we investigated the relationship between household consumption and environmental sustainability, policy mix variables, and energy pricing. First of all, this study confirms the existence of Keynesian consumption theory in these economies of South Asia. Furthermore, energy pricing, environmental sustainability, and inflation rate are the factors that inducing toward high household consumption in South Asia. Considering the policy mix factors, inflation rate contribution positively while tax rate inducing this consumer for low household consumption. Based on the empirical analysis, this study suggested some parameters to these Asian economies particularly and other similar economies generally., Competing Interests: The authors have declared that no competing interests exist.

The construction of green finance index is a three-tiered process that involves macroeconomic, ecological, and monetary indicators. Therefore, this research is one of the first thorough assessments of the impacts of green financing regulations in China, examining 30 provinces during the period of 2010 to 2017. Data envelopment analysis models for 30 provinces in China have been tested by using non-radial models and longitudinal datasets. The findings demonstrate that between 2010 and 2017, the efficiency of China's provinces such as Beijing, Fujian, Guangdong, Hainan, Hebei, Jiangsu, Liaoning, Shandong, Shanghai, Tianjin, and Zhejiang and provinces of central regions as well as western provinces of country green economies has increased with distinct geographical disparities becoming more apparent. The geographical distribution of economic efficacy in the green economy is greatest in the eastern parts and poorest in the Chongqing, Gansu, Guangxi, Guizhou, Inner Mongolia, Ningxia, Qinghai, Shaanxi, Sichuan, Tibet, Xinjiang, and Yunnan. The study revealed that sustainable financial growth may be accomplished via the creation of green financing, which can be achieved by employing different solutions across the macroeconomic, institutional, and ecological considerations. The western and central areas, however, have a significant negative association. There are substantial variations in factors at the state and federal level from the viewpoint of dependent variables. Eventually, the research offers some suggestions for future ecological impact of China, along with the creation of new environmental legislation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Chiari malformations are a group of clinicopathological entities with a variety of clinical presentations, different pathophysiology, and variable outcomes. It has a typical set of clinical presentation. In this study is to observe the different clinical presentations of the patients with Chiari malformation in our population. As the time of initial presentation is delayed that might change the sign and symptoms with which patient initially presents., Materials and Methods: This was a cross-sectional observational study with prospectively collected data of 46 patients with Chiari malformation. The duration of the study is from 2017 to 2020. Patient's data will be compiled and analyzed through Statistical Package for Social Sciences (SPSS) Version 25. Qualitative variables are presented as frequencies and percentages. Quantitative variables are presented as mean ± standard deviation. Effect modifiers are controlled through stratification. The Chi-square test is used for finding association between categorical variables. P ≤ 0.05 is considered as statistically significant., Results: According to our data 36% of our patients presented with motor weakness which is followed by sensory deficit, however in previous literature headache was the commonest clinical presentation., Conclusion: Clinical presentation in our population differs from other studies and the reason behind this is the delayed presentation of the patient and lack of awareness of disease and ultimately it will alter the outcome of disease and treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Asian Journal of Neurosurgery.)

Drought stress causes heavy damages to crop growth and productivity under global climatic changes. Transcription factors have been extensively studied in many crops to play important roles in plant growth and defense. However, there is a scarcity of studies regarding WRKY transcription factors regulating drought responses in maize crops. Previously, ZmWRKY79 was identified as the regulator of maize phytoalexin biosynthesis with inducible expression under different elicitation. Here, we elucidated the function of ZmWRKY79 in drought stress through regulating ABA biosynthesis. The overexpression of ZmWRKY79 in Arabidopsis improved the survival rate under drought stress, which was accompanied by more lateral roots, lower stomatal aperture, and water loss. ROS scavenging was also boosted by ZmWRKY79 to result in less H 2 O 2 and MDA accumulation and increased antioxidant enzyme activities. Further analysis detected more ABA production in ZmWRKY79 overexpression lines under drought stress, which was consistent with up-regulated ABA biosynthetic gene expression by RNA-seq analysis. ZmWRKY79 was observed to target ZmAAO3 genes in maize protoplast through acting on the specific W-boxes of the corresponding gene promoters. Virus-induced gene silencing of ZmWRKY79 in maize resulted in compromised drought tolerance with more H 2 O 2 accumulation and weaker root system architecture. Together, this study substantiates the role of ZmWRKY79 in the drought-tolerance mechanism through regulating ABA biosynthesis, suggesting its broad functions not only as the regulator in phytoalexin biosynthesis against pathogen infection but also playing the positive role in abiotic stress response, which provides a WRKY candidate gene to improve drought tolerance for maize and other crop plants.

Activation of innate immune components promotes cell autonomous inflammation in adipocytes. Oxidative stress links pattern recognition receptor-mediated detection of inflammatory ligands and the immune response. Reactive oxygen species (ROS) may mediate the effect of nucleotide-binding oligomerization domain protein-1 (NOD1) activation on inflammation in adipocytes. Here, we define the potential role of NADPH oxidase (NOX)-derived ROS in NOD1-mediated inflammatory response in adipocytes. Differentiated 3T3-L1 adipocytes were treated with NOD1 activating ligand D-gamma-Glu-meso-diaminopimelic acid (iE-DAP) to evaluate the oxidative stress and contribution of NOX as source of intracellular ROS. NOD1 activation potently induced ROS generation in 3T3-L1 adipocytes. Of the NOX family members, expression of NOX1 and NOX4 was increased upon NOD1 activation, in a PKCδ-dependent manner. siRNA-mediated down-regulation of NOX1 or NOX4 inhibited NOD1-mediated ROS production and increased the expression of antioxidant defense enzyme catalase and superoxide dismutase (SOD). siRNA-mediated lowering of NOX1 or NOX4 also suppressed NOD1-mediated activation of JNK1/2 and NF-κB, and consequent activation of inflammatory response in 3T3-L1 adipocytes. In summary, our findings demonstrate that NOD1 activation provokes oxidative stress in adipocytes via NOX1/4 and that oxidative stress, at least in part, contributes to induction of inflammatory response. Defining the source of ROS after immune response engagement may lead to new therapeutic strategies for adipose tissue inflammation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Traumatic brain injuries represent a significant cause of morbidity and mortality worldwide and road traffic crashes account for a significant proportion of these injuries. It is one of the leading causes of death, especially among young adults, and, according to the World Health Organization, this will surpass many diseases as the major cause of death and disability by the year 2020 and lifelong disability is common in those who survive. It is also known as the silent epidemic. Many CT scan scoring systems for brain injury have been developed but none of them are validated. These scores are based on structural findings of CT scan to predict the prognosis. Marshall and Rotterdam are the two most widely used scoring systems., Method: This was an observational study with prospectively collected data. 903 consecutive patients with TBI. This study aimed to compare the Helsinki CT scoring system with the Rotterdam scoring system to find out the better score for the prognostic purpose by using the Glasgow outcome score., Results: Helsinki CT scoring system was found to be the most accurate score among the others in predicting the outcome of the patient based on morphological findings in CT scan. These scores also guided us regarding the treatment plan and patients with the good prognostic outcome are usually treated aggressively. Also these scores guide clinicians whether to opt for a conservative approach or any intervention., Conclusion: In this study we compared, Rotterdam vs. Helsinki CT Scoring System. We observed that the Helsinki score was a better outcome predictor for TBI than the Rotterdam score and can be used as a single validated score in predicting outcome and guiding the treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Endoscopic third ventriculostomy (ETV) is an advanced surgical procedure and plays a major role in the management of hydrocephalus. The complications associated with this procedure are grave and unforgiving. Image guidance system (IGS) can help reduce these complications. This technical note describes the technique for utilizing image guidance in carrying out ETV with safety and efficacy., Methods: The authors have performed ETV on more than 75 cases. We describe a step-by-step technique for the implication of image guidance while performing ETV including the trajectory planning, coregistration, approach, and third ventricular floor perforation. For illustration, we present the case of a 54-year-old female with moderate-intensity headache and central vertigo for 2 months presented with no significant findings on examination. Magnetic resonance imaging (MRI) showed dilated lateral and third ventricles with normal sized fourth ventricle. A diagnosis of aqueductal stenosis was made and ETV was performed under image guidance., Results: Since 2012, we performed 78 cases of ETV with the help of image guidance. None of the patients had any episode of intraoperative hemorrhage. Two patients (2.56%) had fornix contusions., Conclusion: Image guidance can help reduce complications and is becoming an essential tool in performing ETV. IGS ETV technique may benefit young neurosurgeons the most and can help them overcome the learning curve with safety., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

Background: Delay in seeking health care by breast cancer patients is associated with advanced stage of disease at presentation and poor survival rates. This study aimed to identify the reasons for delayed presentation and their association with various sociodemographic variables., Methods: A total of 200 female patients with abnormal clinical findings, ie, lump or palpable mass, were consecutively invited for this study. Diagnostic delay was defined as a consultation with a health care provider more than 3 months from the appearance of the first symptoms. Sociodemographic variables, presenting symptoms, knowledge about diseases and its symptoms, time between seeking medical attention after appearance of symptoms and causes of delayed presentation were investigated. Chi-squared and logistic regression tests for significance and associations were used., Results: Among 125 women with breast cancer fulfilling the inclusion criteria, aged 24-75 years, 88.8% (n=111) presented late (≥3 months) and 59% presented with advanced stage of disease (stage III/IV). The majority (65.6%) were older than 40 years of age, 99.2% were married, 60.8% had <8 years of education, 67.2% had poor social status, and 64.8% had a negative family history of any cancer type. Almost all patients (96%) complained about the presence of a painless lump in their breast. Ignorance of disease or the presence of painless lumps in the breast and low financial resources for therapy (81.1%) were the main variables associated with delayed presentation. Educational factors ( P <0.001, OR 4.682) and social status ( P <0.001, OR 1.8) were also associated with delayed presentation., Conclusion: Our study highlighted the variables associated with delayed presentation in Pakistani breast cancer patients. A significant number of patients presented late owing to misconceptions and poor knowledge about the disease and its symptoms, while illiteracy and poor social status were the major contributing factors for delayed presentation, resulting in an advanced presentation of disease and ultimately a decreased survival rate., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The present study was to develop a stable and sustained-release delivery system of tacrolimus (TCM). TCM is a macrolide antibiotic used as an immunosuppressant. It is formulated as a microsponge, which is a safe and effective delivery system with reduced side effects., Materials and Methods: The method used to prepare ethyl cellulose (EC) and xanthan gum (XG)-facilitated EC-based microsponges employed emulsification and modified double emulsification techniques. TCM-containing microsponges were prepared using varying concentrations followed by evaluation of micromeritics, compatibility of drug and excipients, production yield, drug content and entrapment efficiency, zeta potential, size distribution and drug release., Results: The results showed excellent flow properties with adequate entrapment efficiency of the system and satisfactory release of active pharmaceutical ingredient. In vitro dissolution studies, which were conducted to determine the amount of drug released, illustrated a pronounced sustained effect up to 8 h. Zeta size and zeta potential analysis of microsponges confirmed the existence of micro-sized (1.99-3.09 µm) and stable particles (-15.33 to -3.38 mV), respectively., Conclusion: Conclusively, the applied technique and selected combination of ingredients were found suitable for the preparation of TCM-containing sustained-release microsponges., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Wastewater treatment based on ecological principles is a low cost and highly desirable solution for the developing countries like Pakistan. The present study evaluated the effectiveness of biological treatment systems including Internal Circulation (IC) anaerobic bioreactor and constructed wetlands (CWs) containing macrophytes and mixed algal cultures for industrial wastewater treatment. The IC bioreactor reduced COD (52%), turbidity (89%), EC (24%) of the industrial wastewater. However, the effluents of IC bioreactor did not comply with National Environmental Quality Standards (NEQS) of Pakistan. Post-treatment of IC bioreactor effluents was accomplished in CW containing macrophytes (Arundo donax and Eichhornia crassipes) and mixed algal culture. The CWs planted with macrophytes lowered the concentrations of COD (89%) and turbidity (99%). CWs with algal biomass were not effective in further polishing the effluent. Inhibition of algal biomass growth was observed due to physicochemical characteristics of wastewater. The integrated treatment system consisting of IC bioreactor and macrophytes was found more suitable option for industrial wastewater treatment.

Medicinal plants are the main natural pools for the discovery and development of new drugs. In the modern era of computer-aided drug designing (CADD), there is need of prompt efforts to design and construct useful database management system that allows proper data storage, retrieval and management with user-friendly interface. An inclusive database having information about classification, activity and ready-to-dock library of medicinal plant's phytochemicals is therefore required to assist the researchers in the field of CADD. The present work was designed to merge activities of phytochemicals from medicinal plants, their targets and literature references into a single comprehensive database named as Medicinal Plants Database for Drug Designing (MPD3). The newly designed online and downloadable MPD3 contains information about more than 5000 phytochemicals from around 1000 medicinal plants with 80 different activities, more than 900 literature references and 200 plus targets. The designed database is deemed to be very useful for the researchers who are engaged in medicinal plants research, CADD and drug discovery/development with ease of operation and increased efficiency. The designed MPD3 is a comprehensive database which provides most of the information related to the medicinal plants at a single platform. MPD3 is freely available at: http://bioinform.info .