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Kashif Asghar,1 Shaarif Bashir,2 Iftikhar Ali Rana,2 Muhammad Abu Bakar,3 Asim Farooq,1 Muhammad Hassan,1 Zukhruf Asif,1 Mahnoor Afzal,1 Iqra Masood,4 Muhammad Ishaq,2 Muhammad Tahseen,2 Sundus Bilal,5 Shafqat Mehmood,5 Nosheen Kanwal,6 Islah Ud Din,6 Asif Loya2 1Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 2Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 3Department of Cancer Registry and Clinical Data Management, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 4Department of Clinical Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 5Department of Internal Medicine (Gastroenterology), Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 6Department of Radiology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, PakistanCorrespondence: Kashif Asghar, Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, 7-A Block R-3, Johar Town, Lahore, Punjab, 54000, Pakistan, Tel +92-42-35905000, Fax +92-42-35945206, Email kashifasghar@skm.org.pkBackground/Aim: Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer that is modulated by the immune system. Programmed cell death ligand-1 (PD-L1) has emerged as a novel therapeutic target in various cancers. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that is associated with poor prognoses in various cancer types. The aim of this study was to investigate the PD-L1 expression, and clinicopathological features of non-HCV and non-HBV-associated HCC patients, including IDO expression.Patients and Methods: In this study, immunohistochemical analysis was performed to analyze the expression of PD-L1 and IDO. Formalin-fixed paraffin-embedded HCC tumor tissues (n=50) were obtained from the pathology department, at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan between 2005 and 2022. All the patients were HBV and HCV negative. Furthermore, it was a rare group of patients with no previous history of any viral hepatitis. In addition, for categorical and continuous variables chi-square or Fisher exact test and Mann–Whitney U-test was performed.Results: Of 50 tissue specimens, PD-L1+ was observed in 21 [high: 12 (24%), low: 9 (18%)] and PD-L1- was observed in 29 HCC patients. IDO+ was observed in all 50 specimens [high: 42 (84%), low: 8 (16%)]. Additionally, both PD-L1 and IDO had high expression in 11 (22%) patients. While both PD-L1 and IDO had low expression in 2 (4%) patients. Furthermore, in IDO+/PD-L1- group, 20 (69%) out of 29 patients died while in the IDO+/PD-L1+ group, 9 (43%) out of 21 patients died.Conclusion: Evaluation of IDO and PD-L1 expression may add therapeutic advantage in non-HCV and non-HBV-associated HCC patients that overexpress IDO. Further validation in a larger cohort is warranted.Keywords: programmed cell death ligand-1, indoleamine 2, 3-dioxygenase, non-HCV HCC, non-HBV HCC, immune checkpoint molecules

Tea is an economical and most widely used beverage across the globe owing to its unique fragrance and flavor. Plant microbe interaction has emerged as an important topic which got the attention of scientists to improve plant performance. Tea microbes remained a prominent research topic for scientists over the years as tea microbes helps in nutrient cycling and stress management which in turn improve the tea growth, yield and quality. The roots of tea plants are colonized by various microbes including arbuscular mycorrhizal fungi (AMF), bacterial communities, and endophytes increase root growth, development and nutrient uptake which in turn improve tea growth, yield and quality. These microbes also increase the concentration of nutrients, amino acids, soluble proteins, flavonoids, catechuic acid, glucose, fructose, sucrose contents caffeine, and polyphenols concentration in tea plants. Besides this, these microbes also protect the tea plants from harmful pest and diseases which in turn leads to an appreciable improvement in plant growth and development. The most important goal of any farming system is to establish a system with production of maximum food while minimizing impacts on the environment. The present review article highlights the role of various microbes in improving the growth, yield and quality of tea plants. In addition, we also discussed the research gaps to improve our understanding about the role of tea microbes in improving tea growth, yield, pest and diseases resistance. We believe that this review will provide a better insight into the existing knowledge of tea microbes in improving tea growth and yield.

Drought stress is significant abiotic stress that limits crop growth and productivity across the globe. The intensity of drought stress continuously rises due to rapid climate change. Drought-induced alterations in physiological and bio-chemical processes by generating membrane dis-stability, oxidative stress, nutritional imbalance and leading to substantial reduction in growth and productivity. Plants accumulate various osmolytes that protect themselves from abiotic stresses' harmful effects. Trehalose (Tre) is a non-reducing sugar found in multiple microbes ranging from bacteria to yeast and in plants and it possesses an excellent ability to improve drought tolerance. Trehalose appreciably enhanced the plant growth, and counter the drought induced damages by maintaining cellular membranes, plant water relations, stomatal regulation, photosynthetic activities, nutrient uptake, osmolyte accumulation, activating stress proteins and detoxifying the reactive oxygen species (ROS) by strengthening the anti-oxidant system. Therefore, it is essential to understand the mechanism of exogenous and endogenous Tre in mitigating the drought-induced damages and to identify the potential research questions that must be answered in the future. Therefore, to better appraise the potential benefits of Tre in drought tolerance in this review, we discussed the diverse physiological and molecular mechanisms regulated by Tre under drought stress. We have a complete and updated picture on this topic to orientate future research directions on this topic.

Kashif Asghar,1 Asif Loya,2 Iftikhar Ali Rana,2 Muhammad Tahseen,2 Muhammad Ishaq,2 Asim Farooq,3 Muhammad Abu Bakar,4 Iqra Masood5 1Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan; 2Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan; 3Department of Biomedical Engineering & Sciences, School of Mechanical & Manufacturing Engineering, National University of Sciences & Technology (NUST), Islamabad, Pakistan; 4Department of Cancer Registry and Clinical Data Management, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan; 5Department of Clinical Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan Background: Immune dysfunction in breast cancer patients is well established. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that is linked with progression of cancer. IDO is overexpressed in triple-negative breast cancer (TNBC) cases. Materials and methods: We conducted the first study to analyze IDO expression and overall survival in breast cancer cases in Pakistan. Expression of IDO, estrogen receptor (ER), progesterone receptor (PR), and human EGF receptor 2 (HER2) was evaluated by immunohistochemistry. Formalin-fixed paraffin-embedded breast cancer tissues of 100 (TNBC, n=49 and non-TNBC, n=51) patients were obtained from Shaukat Khanum Memorial Cancer Hospital and Research Centre. IDO expression was analyzed in association with clinicopathological features and overall survival. A total of 100 patients were classified based on the ordinal IDO score variables as low, medium, and high. In addition, overall mean age and SD of patients was 48.28±11.82. Results: Immunohistochemical analysis showed that high IDO was observed in the TNBC patients (65.3%) compared to that in the non-TNBC patients (33.3%). Multivariable analyses showed that TNBC was an independent risk factor for high IDO expression. Overall survival was also significantly associated with IDO score. Conclusion: Our study showed that IDO protein expression is higher in TNBC patients (P

Ahsan Saleem,1,2 Imran Masood,1 Tahir Mehmood Khan3 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Pharmacy Services Department, Integrated Medical Center, The Aga Khan University Hospital, Lahore, Pakistan; 3School of Pharmacy, Monash University, Sunway Campus, Selangor, Malaysia Background: Chronic kidney disease (CKD) alters the pharmacokinetic and pharmacodynamic responses of various renally excreted drugs and increases the risk of drug-related problems, such as drug–drug interactions.Objectives: To assess the pattern, determinants, and clinical relevancy of potential drug–drug interactions (pDDIs) in CKD patients.Materials and methods: This study retrospectively reviewed medical charts of all CKD patients admitted in the nephrology unit of a tertiary care hospital in Pakistan from January 2013 to December 2014. The Micromedex Drug-Reax® system was used to screen patient profiles for pDDIs, and IBM SPSS version 20 was used to carry out statistical analysis.Results: We evaluated 209 medical charts and found pDDIs in nearly 78.5% CKD patients. Overall, 541 pDDIs were observed, of which, nearly 60.8% patients had moderate, 41.1% had minor, 27.8% had major, and 13.4% had contraindicated interactions. Among those interactions, 49.4% had good evidence, 44.0% had fair, 6.3% had excellent evidence, and 35.5% interactions had delayed onset of action. The potential adverse outcomes of pDDIs included postural hypotension, QT prolongation, ceftriaxone–calcium precipitation, cardiac arrhythmias, and reduction in therapeutic effectiveness. The occurrence of pDDIs was found strongly associated with the age of

Background: Fine-needle aspiration cytology is an important and useful investigation and is considered next to imaging in the diagnosis of mediastinal lesions. We carried out this study in the Department of TB and respiratory diseases JNMC Aligarh from March 2000 to March 2002 with the following aims. Objectives: To make etiological diagnosis of mediastinal lesions, determine the pathological type of the tumor in cases of malignancy and evaluate the role of fine-needle aspiration cytology in staging of bronchogenic carcinoma. Materials and m0 ethods: A total of 56 patients were included in this study who had mediastinal mass with or without lung lesions on chest X-ray or computed tomography scan. Of these patients, 36 had mediastinal mass only and 20 had mediastinal mass with parenchymal lesion. Results: In the present study, of 56 patients, 36 had mediastinal masses and 20 had pulmonary mass. Conclusion: Percutaneous fine-needle aspiration is an easy and reliable method for reaching a quick tissue diagnosis in pulmonary and mediastinal masses.

This work proposes a hydrological cycle-based optimisation technique for performance enhancement of a non-negative least mean mixed norm (NNLMMN) based voltage source control (VSC) for a three-phase grid integrated wind/photovoltaic (PV) system. Water cycle algorithm (WCA) is employed to tune the proportional–integral (PI) controller parameters of VSC to regulate voltage variations at DC link generated during dynamic load and wind conditions. This results in generation of a specific loss component (Iloss) of current to boost the performance of VSC. The NNLMMN control deals with system identification troubles with a non-negativity limitation in varied Gaussian noise conditions. It generates accurate Iloss to upgrade the ability of VSC to accurately extricate weight signals and the fundamental load current component in terms of improvement in DC link voltage (vdc) and total harmonic distortion. The proposed algorithm mitigates problems like voltage fluctuations besides performing operations like reactive power compensation, enhancement of power quality, load and power balancing at the point of coupling during steady-state and dynamic conditions. In conjunction with the NNLMMN algorithm, the proposed technique reduces the surplus mean square error iteratively, resulting in a compact expression of step size. The proposed topology stands out with an improved performance of vdc under wind gusts and the well-known bell-shaped irradiance curve. For relative evaluations, the performance of non-optimised PI and particle swarm optimised PI has been added to analyse the improved response of vdc and Iloss. Extensive simulation results obtained in MATLAB/Simulink are exhibited to corroborate the efficacy of the suggested system. [ABSTRACT FROM AUTHOR]

Abstract High temperature stress influences plant growth, seed yield, and fatty acid contents by causing oxidative damage. This study investigated the potential of thiourea (TU) to mitigate oxidative stress and restoring seed oil content and quality in canola. The study thoroughly examined three main factors: (i) growth conditions—control and high temperature stress (35 °C); (ii) TU supplementation (1000 mg/L)—including variations like having no TU, water application at the seedling stage, TU application at seedling stage (BBCH Scale-39), water spray at anthesis stage, and TU application at anthesis stage (BBCH Scale-60); (iii) and two canola genotypes, 45S42 and Hiola-401, were studied separately. High temperature stress reduced growth and tissue water content, as plant height and relative water contents were decreased by 26 and 36% in 45S42 and 27 and 42% Hiola-401, respectively, resulting in a substantial decrease in seed yield per plant by 36 and 38% in 45S42 and Hiola-401. Seed oil content and quality parameters were also negatively affected by high temperature stress as seed oil content was reduced by 32 and 35% in 45S42 and Hiola-401. High-temperature stress increased the plant stress indicators like malondialdehyde, H2O2 content, and electrolyte leakage; these indicators were increased in both canola genotypes as compared to control. Interestingly, TU supplementation restored plant performance, enhancing height, relative water content, foliar chlorophyll (SPAD value), and seed yield per plant by 21, 15, 30, and 28% in 45S42; 19, 13, 26, and 21% in Hiola-401, respectively, under high temperature stress as compared to control. In addition, seed quality, seed oil content, linoleic acid, and linolenic acid were improved by 16, 14, and 22% in 45S42, and 16, 11, and 23% in Hiola-401, as compared to control. The most significant improvements in canola seed yield per plant were observed when TU was applied at the anthesis stage. Additionally, the research highlighted that canola genotype 45S42 responded better to TU applications and exhibited greater resilience against high temperature stress compared to genotype Hiola-401. This interesting study revealed that TU supplementation, particularly at the anthesis stage, improved high temperature stress tolerance, seed oil content, and fatty acid profile in two canola genotypes.

This work proposes the techno-economic analysis of a three-phase, three wire grid integrated third-generation perovskite solar cells-wind energy conversion system (PSC-WECS) controlled by a two-level voltage source converter (VSC) which is driven by the application of polynomial zero-attracting least mean square (PZA-LMS) algorithm. The proposed algorithm enhances the dynamic performance of the system by introducing sinusoidal grid currents with low total harmonic distortion (THD) which enhances system performance by providing acceptable outcomes under dynamic loading, fluctuating wind velocity, and solar insolation by compensating for load reactive power and balancing load and power demands at the point of coupling. This work replaces the conventional silicon PVs with PSCs to improve the economics of power generation thanks to their higher efficiency. For relative comparisons, the performance of the proposed 36 kW PSC-WECS is compared with the conventional silicon PV-WECS. The results reveal that the proposed system has a low net present cost (NPC) of ${\$}$ 68843 compared to the conventional system which costs ${\$}$ 160917, translating to a reduction of 58% in total cost. Sensitivity Analysis (SA) is performed to analyse the dependence of optimal solutions on the uncertainty of key variables namely NPC, cost of energy (COE), windspeed & insolation. The results show that the total NPC is more sensitive to the COE and the average wind speed as compared to the other variables. Moreover, the area covered by the proposed system is reduced by 50% while as the cost of power generation is reduced by 72% due to the high efficiency of PSCs. The results obtained in MATLAB/Simulink and HOMER to determine the optimum quantity of the renewable energy sources (RES) model demonstrate the effectiveness of the recommended system.

This present article examines the frequency control of a dual-area interconnected hybrid power system that integrates conventional as well as non-conventional sources with additional support from electric vehicles. The complicated, non-linear behavior of the system adds to the grid’s already high level of complexity. To navigate this complex environment, it becomes essential to develop a resilient controller. In this respect, a robust secondary controller is developed to handle the problem. The controller is developed while taking into account the intricate design of the contemporary power system. An extensive comparison between well-established controllers is presented to verify the efficacy of the proposed controller. An AI-based optimization technique, namely, COVID-19, is employed to obtain optimal values for different parameters of the controller. This work also investigates the effect of the FACTS device as a static synchronous series compensator (SSSC) on the dynamics of the system. Moreover, it also investigates the role of electric vehicles (EVs) and an SSSC on system stability. Further, the developed system is subjected to significant load variations and intermittent solar and wind disturbances to check the response of the optimal controller under dynamic conditions. The results demonstrate that the proposed controller reactions successfully handle system disturbances, highlighting the strength of the proposed controller design. Lastly, a case study on an IEEE-39 bus system is carried out to check the optimality of the proposed secondary controller.

Red soils are characterised by acidic pH and limitations in carbon, nitrogen, water, and soil structure. To overcome such limitations, improved soil aggregation is the key to improving the physical and chemical properties of soil. Applying organic amendments such as straw can lead to corresponding soil aggregation and stability changes. Therefore, we explored the short-term effects of rice straw amendment, either alone or in combination with biochar, on improving the carbon fractions, stability, and composition of soil aggregates in red soil with a history of vegetable planting. The study consisted of four treatments: control (no organic material, CK), biochar alone (5% homemade straw biochar, B), straw alone (12% rice straw, S), and biochar with straw (5% homemade straw biochar + 12% rice straw, BS). Our results showed that equal amounts of straw and biochar substantially reduced the number of mechanically stable aggregates (MSA), mean weight diameter (MWD), and geometric mean diameter (GMD) of the soil. BS treatment reduced >0.25 mm aggregate content (R0.25), MWD and GMD by 24.06%, 56.81%, and 62.19%, respectively, compared with that of the control. The addition of straw greatly enhanced the water-stable macromolecular content and stability coefficient of the soil, but treatment B had no obvious effect. The S treatment had the greatest effect on R0.25, MWD and GMD, increasing them by 143.94%, 246.67%, and 181.82%, respectively, compared with that of the control. Soil organic carbon (SOC) was significantly increased by straw addition and carbonisation treatment, and the effect of the BS treatment was the best, with an increase of 325.63% compared with that of the control. The organic carbon content in the aggregates of different particle sizes treated with different organic materials also increased significantly. In the soil reactive organic carbon fraction, applying biochar alone did not affect microbial biomass carbon (MBC), dissolved organic carbon (DOC), or easily oxidized organic carbon (EOC) but could increase the particulate organic carbon (POC) content. All the treatments with straw application significantly increased the MBC, DOC, EOC, and POC content, and the highest effect was obtained by applying both straw and biochar in an integrated form, i.e., the BS treatment. In conclusion, the co-application of biochar and straw sequestered more carbon and revamped soil C pools than either biochar or straw alone and could be a promising option for the sustainable use of red soils to ameliorate the aforementioned limitations associated with this soil type.