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Iram Khatoon,1 Surrya Khanam,1 Asima Azam,2 Saima Qadeer,3 Shumaila Naz,4 Najm Ul Hassan5 1Department of Zoology, Women University Swabi, Swabi, Khyber Pakhtunkhwa, Pakistan; 2Department of Zoology, Shaheed Benazir Bhutto Women University, Peshawar, Khyber Pakhtunkhwa, Pakistan; 3Department of Zoology, Division of Science & Technology, University of Education Lahore, Lahore, Punjab, 54000, Pakistan; 4Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Punjab, Pakistan; 5Department of Microbiology, Abdul Wali Khan University, Mardan, Khyber Pakhtunkhwa, PakistanCorrespondence: Surrya Khanam, Department of Zoology, Women University Swabi, Swabi, Khyber Pakhtunkhwa, Pakistan, Tel +923348742560, Email surryiamalik@gmail.comPurpose: Urinary tract infections (UTIs) are of the most common bacterial infections in Pakistan. Rapid increase in antibiotic resistance has resulted in a limited number of treatment options available. This study aimed to determine the incidence patterns of uropathogens, their antimicrobial susceptibility pattern and risk factors for UTI among the general population.Methods: This laboratory-based cross-sectional study was conducted between November 2020 and March 2021. Urine samples were collected, cultured and bacterial isolates were identified. Bacterial isolates were tested for antimicrobial susceptibility. Data regarding socio-demographic characteristics, clinical features and risk factors were collected using structured questionnaire.Results: Of 459 urine samples, 299 (65.1%) showed positive urine cultures (105 CFU/mL). Both gram-negative and gram-positive isolates were obtained, with a prevalence of 230 (76.9%) and 69 (23%), respectively. Escherichia coli was the predominant bacteria isolated 146 (48.8%), and it showed most susceptibility to cefoperazone and imipenem. Most of the gram-negative isolates were resistant towards ampicillin. Most risk factors were not significantly associated with UTI, except for age, income, and previous history of hospitalization.Conclusion: UTI is an important problem in the study area, with a prevalence rate of 65%. All bacterial isolates developed resistance towards most antibiotics available on the market. Therefore, there is a need to develop management strategies based on susceptibility pattern of uropathogens. Additionally, proper public education regarding causes of disease transmission and control strategies is required.Keywords: antimicrobial susceptibility, risks factors, urinary tract infections, Pakistan

Shagufta Naz,1,2 Lina Tariq Al Kury,3 Humaira Nadeem,1 Fawad Ali Shah,1 Aman Ullah,1 Rehan Zafar Paracha,4 Muhammad Imran,5 Shupeng Li2 1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, 44000, Pakistan; 2State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of China; 3College of Natural and Health Sciences, Zayed University, Abu Dhabi, 49153, United Arab Emirates; 4Research Center for Modeling & Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan; 5Department of Pharmacy, IQRA University, Islamabad, 44000, PakistanCorrespondence: Humaira Nadeem, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, 44000, Pakistan, Tel +92 51-2891835, Fax +92 51-8350180, Email humaira.nadeem@riphah.edu.pk Shupeng Li, State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of China, Email lisp@pku.edu.cnIntroduction: Several studies revealed that alcohol utilization impairs memory in adults; however, the underlying mechanism is still unclear. The production of inflammatory markers and reactive oxygen species (ROS) plays a major role in neurodegeneration, which leads to memory impairment. Therefore, targeting neuroinflammation and oxidative distress could be a useful strategy for abrogating the hallmarks of ethanol-induced neurodegeneration. Moreover, several studies have demonstrated multiple biological activities of thiazolidine derivatives including neuroprotection.Methods: In the current study, we synthesized ten (10) new thiazolidine-4-carboxylic acid derivatives (P1-P10), characterized their synthetic properties using proton nuclear magnetic resonance (1H-NMR) and carbon-13 NMR, and further investigated the neuroprotective potential of these compounds in an ethanol-induced neuroinflammation model.Results: Our results suggested altered levels of antioxidant enzymes associated with an elevated level of tumor necrosis factor-alpha (TNF-α), nuclear factor-κB (p-NF-κB), pyrin domain-containing protein 3 (NLRP3), and cyclooxygenase-2 (COX-2) in ethanol-treated animals. Ethanol treatment also led to memory impairment in rats, as assessed by behavioral tests. To further support our notion, we performed molecular docking studies, and all synthetic compounds exhibited a good binding affinity with a fair bond formation with selected targets (NF-κB, TLR4, NLRP3, and COX-2).Discussion: Overall, our results revealed that these derivatives may be beneficial in reducing neuroinflammation by acting on different stages of inflammation. Moreover, P8 and P9 treatment attenuated the neuroinflammation, oxidative stress, and memory impairment caused by ethanol.Graphical Abstract: Keywords: thiazolidine, oxidative stress, neuroinflammation, neuroprotective, molecular docking, ethanol

Cardiomyopathy (CM) is a condition of cardiac dysfunction. It is one of the leading causes of mortality in which both genetic and environmental factors are involved. Cardiotrophin-1 (CT-1) level in plasma is associated with CM. It affects the cardiomyocyte differentiation. To evaluate the expression of CT-1 in cardiomyopathy, this study was done on CM subjects attending the Fatima Memorial Hospital, Lahore, Pakistan, between January and June, 2016. A total of 40 subjects were enrolled who were divided into two groups; CM group (n = 20) and a control group (n = 20). A self-designed questionnaire was filled in by each subject to collect data regarding age, body mass index (BMI) and CM history. RNA was isolated from blood after its quantification, cDNA was prepared and reverse-transcriptase-polymerase chain reaction (RT-PCR) was performed for expression of CT-1. The mean age in CM subjects was 40.1±6.03 years, while it was 35.0±3.7 years in the control group. The mean expression of CT-1 in the CM subjects was 5.2±0.66, while it was 1.00±0.001 in the control group. A highly significant difference was observed in CT-1 expression in the CM group, and expression was significantly correlated with age and BMI in CM subjects.

Physician communication is integral for improving patients’ experience and clinical outcomes. Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores are used by the Centers for Medicare & Medicaid Services to assess the quality of care provided to the patients. We conducted a prospective pre–post-intervention study from March 2018 to March 2020 and included patients and residents of the community-based university-affiliated Internal Medicine Residency Program. Residents’ communication was evaluated through resident surveys and results were shared with them and attending physicians within 48 h. To correlate with the effect over a 4-year period, 839 HCAHPS surveys were obtained for attending physicians as an outcome measure. The mean overall HCAHPS score and doctor's communication scores increased by 8.52 and 6.06 points post-intervention. The doctor's performance score for respect increased by 6.18 points, listening increased by 3.12 points, and explanation increased by 8.23 points. This study demonstrates that timely, structured, and individualized resident feedback in an academic medicine service can result in a sustainable increase in the attendings’ overall HCAHPS and doctor's communication scores.

Shagufta Naz,1,2 Fawad Ali Shah,1 Humaira Nadeem,1 Sadia Sarwar,1 Zhen Tan,3 Muhammad Imran,1 Tahir Ali,2 Jing Bo Li,2 Shupeng Li4 1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, 44000, Pakistan; 2Shenzhen University Clinical Research Center for Neurological Diseases, Health Management Center, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, People’s Republic of China; 3Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 4State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of ChinaCorrespondence: Humaira NadeemRiphah Institute of Pharmaceutical Sciences, Riphah International University, G-7/4, 7th Avenue, Islamabad, 44000, PakistanTel +92 51-2891835Fax +92 51-8350180Email humaira.nadeem@riphah.edu.pkShupeng LiState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of ChinaEmail lisp@pku.edu.cnPurpose: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate this therapeutic failure. The current study demonstrated the synthesis of 2-aminothiazole [S3(a-d) and S5(a-d)] and 2-aminopyridine [S4(a-d) and S6(a-d)] derivatives that can target multiple cellular networks implicated in cancer development.Methods: Biological assays were performed to investigate the antioxidant and anticancer potential of synthesized compounds. Redox imbalance and oxidative stress are hallmarks of cancer, therefore, synthesized compounds were preliminarily screened for their antioxidant activity using DPPH assay, and further five derivatives S3b, S3c, S4c, S5b, and S6c, with significant antioxidant potential, were selected for investigation of in vitro anticancer potential. The cytotoxic activities were evaluated against the parent (A2780) and cisplatin-resistant (A2780CISR) ovarian cancer cell lines. Further, Molecular docking studies of active compounds were performed to determine binding affinities.Results: Results revealed that S3c, S5b, and S6c displayed promising inhibition in cisplatin-resistant cell lines in comparison to parent cells in terms of both resistance factor (RF) and IC50 values. Moreover, S3c proved to be most active compound in both parent and resistant cell lines with IC50 values 15.57 μM and 11.52 μM respectively. Our docking studies demonstrated that compounds S3c, S5b, and S6c exhibited significant binding affinity with multiple protein targets of the signaling cascade.Conclusion: Anticancer activities of compounds S3c, S5b, and S6c in cisplatin-resistant cell lines suggested that these ligands may contribute as lead compounds for the development of new anticancer drugs.Keywords: thiazole, pyridine, antioxidant activity, anticancer activity, molecular docking

Bee-honey solution (BHS) is considered a plant growth multi-biostimulator because it is rich in osmoprotectants, antioxidants, vitamins, and mineral nutrients that can promote drought stress (DtS) resistance in common bean plants. As a novel strategy, BHS has been used in a few studies, which shows that the application of BHS can overcome the stress effects on plant productivity and can contribute significantly to bridging the gap between agricultural production and the steady increase in population under climate changes. Under sufficient watering (SW (100% of crop evapotranspiration; ETc) and DtS (60% of ETc)), the enhancing impacts of foliar application with BHS (0%, 0.5%, 1.0%, and 1.5%) on growth, productivity, yield quality, physiological-biochemical indices, antioxidative defense ingredients, and nutrient status were examined in common bean plants (cultivar Bronco). DtS considerably decreased growth and yield traits, green pod quality, and water use efficiency (WUE); however, application of BHS at all concentrations significantly increased all of these parameters under normal or DtS conditions. Membrane stability index, relative water content, nutrient contents, SPAD (chlorophyll content), and PSII efficiency (Fv/Fm, photochemical activity, and performance index) were markedly reduced under DtS; however, they increased significantly under normal or DtS conditions by foliar spraying of BHS at all concentrations. The negative impacts of DtS were due to increased oxidants [hydrogen peroxide (H2O2) and superoxide (O2•−)], electrolyte leakage (EL), and malondialdehyde (MDA). As a result, the activity of the antioxidant system (ascorbate peroxidase, glutathione reductase, catalase, superoxide dismutase, α-tocopherol, glutathione, and ascorbate) and levels of osmoprotectants (soluble protein, soluble sugars, glycine betaine, and proline) were increased. However, all BHS concentrations further increased osmoprotectant and antioxidant capacity, along with decreased MDA and EL under DtS. What is interesting in this study was that a BHS concentration of 1.0% gave the best results under SW, while a BHS concentration of 1.5% gave the best results under DtS. Therefore, a BHS concentration of 1.5% could be a viable strategy to mitigate the DtS impairment in common beans to achieve satisfactory growth, productivity, and green pod quality under DtS.

Cai Li, Shumaila Naz, Muhammad Aamir Shafique Khan, Basil Kusi, Majid MuradSchool of Management, Jiangsu University, Zhenjiang, Jiangsu 212013, People’s Republic of ChinaBackground: This study aimed to investigate the effect of a high-performance work system (HPWS) on employee performance and the intervening role of mediators in this relationship.Methods: The study was quantitative in nature and used a questionnaire as its instrument. Two hundred and fifty respondents from the private textile sector, located in Lahore and Faisalabad, Pakistan, were selected using a stratified sampling technique. For statistical analysis and to test the proposed research model, partial least squares–structural equation modeling was applied.Results: HPWS was positively related to employee performance. Furthermore, job satisfaction, perceived organizational support, and employee engagement positively and significantly mediated between HPWS and employee performance. Thus, the study provided evidence for the underpinning models of social exchange theory, and ability, motivation, and opportunity framework.Conclusion: The study emphasizes that practitioners should develop strategies that could foster positive work attitudes and increase perceived organizational support to achieve higher levels of performance. It further describes some limitations and gaps for future research.Keywords: high-performance work system, employee performance, job satisfaction, perceived organizational support, employee engagement

Safia Naz,1,* Mingyu Wang,1,* Yuning Han,1 Bin Hu,1 Liping Teng,2 Juan Zhou,1 Huijie Zhang,1 Jinghua Chen11Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China; 2Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China*These authors contributed equally to this workBackground: Drug delivery systems (DDS) capable of targeting both cell and organelle levels are highly desirable for effective cancer therapy. In this study, we developed a novel enzyme-responsive, multistage-targeted anticancer DDS based on mesoporous silica nanoparticles (MSNs), which possessed both CD44-targeting and mitochondrial-targeting properties.Materials and methods: Triphenylphosphine (TPP), a mitochondria-targeting compound, was grafted onto the surface of MSNs firstly. Then, Doxorubicin (Dox) was encapsulated into the pore of MSNs, followed by capping with tumor-targeting molecules hyaluronic acid (HA) through electrostatic interactions to form the final product consist of Dox loaded, TPP attached, HA capped mesoporous silica nanoparticles (MSN-DPH).Results: Our results suggested that MSN-DPH was preferentially taken up by cancer cells via CD44 receptor-mediated endocytosis. Moreover, MSN-DPH mainly accumulated in mitochondria owing to the mitochondrial-targeting ability of TPP. Degradation of HA by overexpressed HAase facilitated the release of Dox in cancer cells. Thus, MSN-DPH efficiently killed the cancer cells while exhibited much lower cytotoxicity to normal cells.Conclusion: This study demonstrates a promising multistage-targeted DDS for cancer chemotherapy.Keywords: mesoporous silica nanoparticles, drug delivery, enzyme-responsive, multistage-targeting, cancer therapy

There is an urgent need for innovative strategies to raise the performance of environmentally stressed plants. The seeds of single-cross yellow Zea mays (L.) hybrid Giza-168 were soaked in Cis-(c-Z-Ck) or trans-zeatin-type cytokinin (t-Z-Ck) solutions at a concentration of 50 or 40 µM, respectively. Salinity stress was imposed at 0, 75 or 150 mM NaCl in the Hoagland nutrient solution (full strength) used for irrigation. The total carotenoids content was negatively affected by only 150 mM NaCl, while both 75 and 150 mM NaCl negatively affected the growth and yield components, relative water content, membrane stability index, photochemical activity, gas exchange, K+ and chlorophyll contents, K+/Na+ ratio, and photosynthetic efficiency. However, all of these traits were significantly improved by c-Z-Ck pretreatment and further enhanced by t-Z-Ck pretreatment compared with the corresponding controls. Furthermore, the contents of proline, soluble sugars, ascorbate, and glutathione, as well as enzymatic antioxidant activities, were significantly elevated by both salt stress concentrations and increased more by both biostimulators compared to the control. Compared to c-Z-Ck, t-Z-Ck was superior in mitigating the harmful effects of the high H2O2 levels caused by salt stress on the levels of malondialdehyde and ion leakage compared to the control. Under normal or stress conditions, t-Z-Ck pretreatment was better than c-Z-Ck pretreatment, while both positively affected maize hormonal contents. As a result, t-Z-Ck is recommended to enhance the growth and productivity of maize plants by suppressing the effects of oxidative stress caused by saline water irrigation.

OBJECTIVE: The objective of this study was to clone and express the hepatitis B surface antigen gene (HBsAg) in Escherichia coli (E. coli), thereby aiming to develop potential local therapeutics for combating Hepatitis B virus (HBV) infection in the Pakistani community by producing HBsAg in E. coli. MATERIALS AND METHODS: Blood serum samples were collected from hepatitis B-infected patients, and their genomic DNA was extracted. Real-time and nested polymerase chain reaction (PCR) was performed to amplify the HBsAg gene. The gene of interest was cloned into the pET20b expression vector and transformed into E. coli BL21 (DE3) using Isopropyl β-D-1-thiogalactopyranoside (IPTG) induction. The gene’s precise size was confirmed with gene-specific external and internal primers (681 bp and 400 bp, respectively). RESULTS: The HBsAg gene was successfully sequenced and submitted to GenBank, exhibiting 98% homology with targeted HBV sequences worldwide. The expression of HBsAg protein was confirmed through silver staining, Coomassie staining, western blot, and dot blot analysis. CONCLUSIONS: The expressed protein clones are now available for further development as a local recombinant DNA vaccine to prevent hepatitis B viral infection in the local community. [ABSTRACT FROM AUTHOR]

Heavy metal contamination usually causes depletion in feed utilization in fish, and such disturbance may result in reduced metabolic rate and hence causing reduction in their growth. The present study assessed theharmful effect of sublethal concentrations of four different heavy metal mixturesi.e., Mix-I (Mn+Ni), Mix-II(Mn+Ni+Pb), Mix-III (Mn+Pb+Zn+Fe), and Mix-IV (Mn+Ni+Pb+Zn+Fe) on five fish species including Labeorohita, Catla catla, Cirrhinamrigala, Hypophthalmichthys molitrix, and Ctenopharyngodonidella. The experiment was carried out in triplicate for each species separately in glass aquarium for 12 weeks. The results showed a significant(p < 0.001)effect on the treated group as compared to the control group. The average weight gain was as C. catla>L. rohita>C. mrigala>C. idella>H. molitrix. The condition factor was as C. idella>C. mrigala>L. rohita>C. catla>H. molitrix. Similarly, the feed intake also reduced significantly (p>0.001) in the treated group, and the feed conversion efficiency showed significant (p>0.05) effect of metal mixtures on fish metabolism and growth activity. The current study concluded that the studied heavy metals are toxic to different fish species, even at sub-lethal concentrations, and affect different biological parameters of fish growth. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The growing bacterial resistance towards classical antibiotics demands the development of novel approaches for the effective treatment of potentially fatal bacterial infections in humans. Proteostasis is crucial for the survival of every living cell, as several important physiological functions depend on well-regulated proteostasis. Within bacteria, the regulation of proteostasis relies on AAA+ (Adenosine 5'-triphosphatases associated with diverse cellular activities), ATPases, such as the HslVU complex (heat shock locus gene products U and V), along with other proteases. The HslVU protease/chaperon complex is thought to be the progenitor of the eukaryotic proteasome that regulates proteostasis mostly in prokaryotes. This study aimed to determine the inhibitory potential of 3-substituted coumarin derivatives against Escherichia coli heat shock locus V (HslV) protease. MATERIALS AND METHODS: In this study, twenty-three derivatives of 3-substituted coumarin were assessed for their inhibitory potential against E. coli HslV protease using both in-vitro and in-silico techniques. RESULTS: Among all the tested compounds, US-I-64, US-I-66, US-I-67, and US-I-68 displayed notable inhibitory potential against the HslV protease, showing IC50 (half maximal inhibitory concentration) values ranging from 0.2 to 0.73 µM. Additionally, the inhibitory potential of these compounds against the eukaryotic proteasome was also evaluated using a separate in-silico study. It was found that these compounds did not bind with the proteasomal active site, suggesting no apparent side effects of these lead molecules. CONCLUSIONS: These identified HslV protease inhibitors can be used for the development of novel and safer anti-bacterial drugs. [ABSTRACT FROM AUTHOR]

Qaisar Maqbool,1 Mudassar Nazar,1 Sania Naz,2 Talib Hussain,3 Nyla Jabeen,4 Rizwan Kausar,5 Sadaf Anwaar,4 Fazal Abbas,6,7 Tariq Jan6 1Department of Biotechnology, Virtual University of Pakistan, Lahore, Pakistan; 2Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan; 3National Institute of Vacuum Science and Technology (NINVAST), Islamabad, Pakistan; 4Department of Biotechnology and Bioinformatics Lab., International Islamic University, Islamabad, Pakistan; 5Department of Chemistry, University of Sargodha, Sargodha, Pakistan; 6Department of Physics, International Islamic University, Islamabad, Pakistan; 7Interdisciplinary Research Organization, University of Chakwal (UOC), Chakwal, Pakistan Abstract: This article reports the green fabrication of cerium oxide nanoparticles (CeO2 NPs) using Olea europaea leaf extract and their applications as effective antimicrobial agents. O. europaea leaf extract functions as a chelating agent for reduction of cerium nitrate. The resulting CeO2 NPs exhibit pure single-face cubic structure, which is examined by X-ray diffraction, with a uniform spherical shape and a mean size 24 nm observed through scanning electron microscopy and transmission electron microscopy. Ultraviolet-visible spectroscopy confirms the characteristic absorption peak of CeO2 NPs at 315 nm. Fourier transform infrared spectroscopy reflects stretching frequencies at 459 cm-1, showing utilization of natural components for the production of NPs. Thermal gravimetric analysis predicts the successful capping of CeO2 NPs by bioactive molecules present in the plant extract. The antimicrobial studies show significant zone of inhibition against bacterial and fungal strains. The higher activities shown by the green synthesized NPs than the plant extract lead to the conclusion that they can be effectively used in biomedical application. Furthermore, reduction of cerium salt by plant extract will reduce environmental impact over chemical synthesis. Keywords: XRD, SEM, TEM, FTIR, antibacterial, antifungal, nanomedicine, green fabrication