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Contents This study was conducted to determine the effect of immunization with inhibin DNA vaccine delivered by attenuated Salmonella choleraesuis on ovarian responses and fertility in cross-bred buffaloes. A total of 134 cross-bred buffaloes were divided into four groups: groups T1 ( n = 34), T2 ( n = 35) and T3 ( n = 31) were nasal immunized twice a day with 10 ml of 1 × 1010 CFU/ml of the C501 (pVAX-asd-IS) vaccine for 5, 3 and 1 day, respectively. Group C ( n = 34) was nasal immunized with 10 ml PBS for 5 days. All animals were immunized twice with an interval of 14 days and administered with 200 μg of a GnRH analogue on day 28, 0.5 mg PGF2α on day 35 and 200 μg of the same GnRH analogue on day 37. TAI was performed at 18 and 24 hr after the second GnRH treatment. Fourteen days after primary immunization, C501 (pVAX-asd-IS) elicited significant immune responses, and anti-inhibin IgG antibody titres in group T1 were significantly higher ( p < .01) than groups T3 and C. After the second GnRH treatment, the growth speed of the dominant follicles in group T1 was significantly faster ( p < .05) than groups T3 and C. The number and diameter of large follicles (≥10 mm) as well as ovulatory follicles in group T1 were the greatest in all groups, resulting in a greater conception rate in buffaloes with positive anti-inhibin antibodies. These results demonstrate that immunization with the C501 (pVAX-asd-IS) vaccine, coupled with the Ovsynch protocol, could be used as an alternative approach to improve reproductive performance in cross-bred buffaloes. [ABSTRACT FROM AUTHOR]

Huanglongbing disease (HLB) is the most severe citrus disease destroying Citrus reticulata L. 'Kinnow', the most commonly grown mandarin in Pakistan. It is caused by Candidatus Liberibacter bacterial species and it spreads through the sucking Asian citrus psyllid insect. The current study was designed to investigate the potential impact of plant extract mediated selenium nanoparticles (SeNPs) on antioxidant defense system, fruit quality and protein regulation in the fruits of HLB-infected 'Kinnow' mandarin plants. Garlic cloves extract was used as reducing and capping agent for the synthesis of SeNPs. Various concentrations of SeNPs (25, 50, 75, and 100 mg L -1 ) were exogeneously applied to HLB-positive citrus plants. SeNPs at the concentration of 75 mg L -1 affected positively fruit physio-biochemical parameters, e.g., peel thickness, peel weight, fruit weight, fruit diameter, total soluble solids, juice volume, ascorbic acid content and reduced total acidity. Furthermore, SeNPs also enhanced the amounts of total protein and total sugar as well as elevated antioxidant enzymes, e.g., superoxide dismutase, peroxidases, and catalases. Non-enzymatic antioxidant content, e.g., total phenolic and total flavonoids, was also elevated. Proteomics analysis revealed that exposure to SeNPs at the concentration of 75 mg·L -1 significantly altered in HLB infected mandarin fruting plants the expression of proteins associated with transcription, protection, cell wall biogenesis, cell wall organization, reproduction, stamen formation, embryo development, inflorescence development, as well as translation and response to oxidative stress. Our results revealed that foliar application of SeNPs influences the protein contents positively, therefore ameliorating fruit physio-biochemical quality by boosting antioxidant defense systems of HLB-infected 'Kinnow' mandarin plants., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision, (Copyright © 2024 Ikram, Raja, Mohamed, Mashwani, Omar, Gharibi and Zubarev.)

The current study aimed to investigate the effects of plant-mediated selenium nanoparticles (SeNPs) on plant growth, photosynthetic pigments, antioxidant activity, and the triacylglycerol profile of sesame ( Sesamum indicum L.). The green synthesis of SeNPs was achieved using garlic extract, resulting in spherical nanoparticles with an average size range of 70-75 nm. Three SeNP treatments (T3, 30 ppm; T4, 40 ppm; and T5, 50 ppm) were applied through seed and foliar spray on six sesame varieties (V1, TS-5; V2, TH-6; V3, Til-18; V4, Niab Millennium; V5, Niab Pearl; and V6, NS-16). All enzymatic antioxidant parameters showed an increase in the treated groups, such as SOD (74.4% in V1 at T4), POD (43% in V5 at T5), APX (62% in V1 at T3), and GPX (31.56% in V3 at T4). CAT showed the highest percentage improvement in T5 for V1, V2, V4, and V5, while V3 and V4 exhibited the highest values at T4. Likewise, seed antioxidant parameters also showed increase in antioxidant activity, highest total phenolic content (6.06 mg GAE/g) was found at T5 treatment with percent increase of 27.41%, but the highest percent increase was found to be at T4 treatments in V1 with increase of 46.83%. Percent oil yield was also noted to be higher as highest percent (60%) oil yield was obtained at T4 treatment in V3. Ultra High Performance Mass-Spectrometry (UHPLC-MS) analysis and chemometric modeling suggested a total of 10 triacylglycerol (TG) biomarkers separating untreated groups, with higher relative abundance values at T4 and T5 treatments compared to control. PCA and correlation analysis showed clustering of untreated groups from T4 and T5, which suggests that these two treatments result in higher accumulation of oil. A generalized linear model with ANOVA showed a highly significant impact of treatments on all the growth and oil parameters, with significance involvement of varieties. The interaction between variety and treatment showed no significant effect on the growth and oil biomarkers of sesame. However, it can be concluded that the T4 and T5 treatments (40 ppm and 50 ppm) of SeNPs, applied through seed and foliar methods, have a strong influence on the overall growth and oil yield of sesame. This warrants further transcriptomic and molecular analysis to gain deeper insight into the mechanisms of action of SeNPs., 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., (Copyright © 2024 Ahmad, Chen, Younas, Yousaf and Mashwani.)

This study examined the influence of different wastewater treatment processes on the physicochemical properties of Alginate-Like Exopolymers (ALE) extracted from waste sludge. Sludge samples were collected from wastewater treatment plants (WWTPs) processing both combined industrial and domestic wastewater, as well as domestic wastewater alone. Among the processes studied, aerobic granular sludge (AGS) produced the highest ALE yield (352 ± 50 mg/g-VS sludge ), significantly exceeding that from membrane bioreactor (170 ± 41 mg/g-VS sludge ) and conventional activated sludge (<130 mg/g-VS sludge ). AGS-derived ALE also had the highest uronic acid content (224 ± 14.5 mg/g-VS sludge ), with mannuronic acids playing a critical role in enhancing hydrogel cohesion and stability. The results showed that the distinct microbial consortium in the AGS system, including the presence of Pseudomonas alcaligenes , was strongly associated with increased ALE production. This establishes a novel link between microbial community composition and ALE yield. These insights are crucial for optimizing resource recovery in AGS systems and underscore the potential of ALE for various industrial applications., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rehman, Ghaani, Mohamed, Gallagher, Saikaly and Ali.)

Hemp (Cannabis sativa L.) is an annual, and dioecious herb belonging to the Cannabaceae family. This plant is native to Central and Southeast Asia. The wild races of this species are commonly growing in Khyber Pakhtunkhwa and Punjab provinces, as well as in Islamabad, Pakistan. This study provides crucial insights into how environmental variables influence the wild hemp populations, which can be utilized in for conservation and breeding. The present study was aimed at evaluating the effects of key environmental factors such as altitude, geographical location, precipitation, relative humidity, maximum, minimum, and average temperature on 16 morpho-agronomic traits of a wild population of hemp growing in the Potohar Plateau and Lesser Himalayas. Our findings indicated that high relative humidity (> 64%), low average temperature (< 15 °C), intermediate average temperature (19-22 °C), and high average temperature (> 22 °C) played significant roles in determining the distribution pattern of the wild hemp. Correlation analysis demonstrated that average annual temperature contributed a higher percentage of variation in phenotypic diversity than geographic variables. Additionally, cluster analysis indicated three groups for the selected 35 populations. Clustering and Principal Component Analysis (PCA) of the morpho-agronomic traits indicated that group 1 from the Lesser Himalayas showed high relative humidity (> 64%) and low average temperature (< 15 °C). Conversely, Group 2 populations from the Potohar Plateau demonstrated intermediate average temperature (19-22 °C). There is an existence of Group 3 in the Potohar Plateau with a high average temperature (> 22 °C) compared to Group 1 and Group 2. Our examination highlights the complex interplay between ecological factors, and morphological attributes in native landraces of Cannabis sativa, giving significant insight into knowledge for preservation and breeding initiatives. A study of genetic diversity could complement morpho-agronomic traits in future research to learn more about how genetic variation affects environmental adaptation., (© 2024. The Author(s).)

Microencapsulation is utilized to protect probiotics, such as Geotrichum candidum, ensuring their survival, stability, and targeted release. The encapsulation efficiency depends on factors such as the type and concentration of the polymers and the encapsulation method. In this study, G. candidum was encapsulated using alginate (Alg) combined with starch (AlgS) or xanthan (Alg-X) and coated with chitosan aand chitosan nanoparticles (AlgC, Alg-S-C, Alg-X-C, Alg-CN, Alg-S-CN, and Alg-X-CN) using a simple extrusion technique. The structural characteristics and surface morphology of the microcapsules were analyzed using Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Encapsulation efficiency (EE) and pH and temperature tolerances were assessed using in vitro assays. SEM results showed that the Alg-CN microcapsules were notably spherical and smooth, in contrast to the irregular and rough textures of the uncoated forms. Notably, Alg-CN exhibited the highest EE (99.3 %), followed by Alg-C (96.6 %) and Alg-X-CN (96.03 %). Moreover, chitosan-coated microcapsules, particularly Alg-CN, demonstrated superior viability at various pH levels and after exposure to 60 °C, along with extended shelf life at room temperature and 4 °C. These findings suggest that a 2 % alginate and 0.4 % chitosan combination is optimal for preserving G. candidum's viability in various applications., 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 © 2024 Elsevier B.V. All rights reserved.)

An extensive examination of the medical uses of soybean bioactive components is provided by this thorough review. It explores the possible health advantages of isoflavones with phytoestrogenic qualities, like genistein, which may lower the risk of cancer. The review highlights the different roles and possible anticancer activities of phenolic compounds, phytic acid, protease inhibitors, lignans, and saponins, among other bioactive components. It also addresses the benefits of dietary fiber and oligosaccharides derived from soybeans for intestinal health, as well as the impact of soy protein on diabetes, obesity, cancer, and cardiovascular health. Conjugated linoleic acid (CLA) has anticancer and cholesterol-lowering properties; its involvement in promoting metabolic processes is also examined. Pinitol is highlighted in the study as a blood sugar regulator with promise for controlling insulin signaling. In this review, we aim to affirm soybeans' potential as a high-functional, well-being food by examining their recently discovered therapeutic and pharmacological capabilities, rather than to improve upon the previous studies on the reported nutritional advantages of soybeans., 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., (Copyright © 2024 Rahman, Younas, Ahmad, Yousaf, Latif, Rubab, Hassan, Shafi and Mashwani.)

In the quest for sustainable energy solutions, solid oxide electrolysis cell (SOEC) emerges as a key technology for converting CO 2 into fuels and valuable chemicals. This work focuses on pure ceramic Fe x Sm 0.2 Ce 0.8 O 2- δ (xFe-SDC) as the fuel electrodes, and Sr-free ceria-based ceramic electrodes can be successfully constructed for x ≤ 0.05. The incorporation of Fe into the ceria lattice increases the oxygen vacancy concentration and promotes the formation of catalytic sites crucial for the CO 2 reduction reaction (CO 2 RR). Density functional theory calculations indicate that Fe enhances electrochemical performance by decreasing the CO 2 RR energy barrier and facilitating oxygen ion diffusion. At 800 °C and 1.5 V, single cells with 0.05Fe-SDC cathodes manifest attractive performance, attaining current densities of -1.98 and -2.26 A cm -2 under 50% CO 2 /CO and pure CO 2 atmospheres, respectively. These results suggest the great potential of xFe-SDC electrodes as promising avenues for high-performance fuel electrodes in SOEC., (© 2024 Wiley‐VCH GmbH.)

Objectives: This study aimed to compare the efficacy of dietary intake of eicosapentaenoic acid (EPA; 20:5 ω-3) and docosahexaenoic acid (DHA; 22:6 ω-3) on very short sleep duration (<5 h/night) in adults., Methods: The bootstrap method was used in the multinomial logistic regression to estimate the ORs and corresponding 95% confidence intervals (CIs) of very short sleep duration. We used rolling window method to analyze the effects of EPA and DHA dietary intakes on very short sleep durations in men and women over age. To illustrate the stability of the results for the selected window width, we built a shiny application., Results: Compared to the first quartile, the mean ORs of EPA intake on very short sleep duration and the corresponding 95% CIs for the second, third and fourth quartiles of EPA intake among men under 32 years old were 1.50 (0.56, 3.44) mg, 1.55 (0.59, 3.48) mg, and 3.99 (1.15, 10.01) mg, respectively. Among women over 44 years old, the ORs for DHA intake were 1.12 (0.81, 1.52) mg, 0.94 (0.68, 1.29) mg, and 0.62 (0.38, 0.98) mg for the second, third and fourth quartiles, respectively., Conclusions: The associations of EPA and DHA with very short sleep duration are sex- and age-dependent. In males under the age of 32, a significant positive correlation exists between dietary EPA intake and very short sleep duration. For women above 44 years of age, an increase in DHA intake can notably ameliorate issues of very short sleep duration.

Aortic stenosis (AS) is a prevalent condition among the elderly, characterized by the narrowing of the aortic valve, which, if untreated, can lead to heart failure and decreased quality of life in terms of reduced activity and high mortality in one to two years. Surgical aortic valve replacement (SAVR) has long been the standard treatment for AS. However, it poses significant risks, particularly in older patients with comorbidities. In recent years, transcatheter aortic valve replacement (TAVR) has emerged as a less invasive alternative and is increasingly used in low- and moderate-risk patients. This review seeks to assess the comparative outcomes of TAVR and SAVR in patients with moderate-risk AS. A systematic review was conducted in accordance with PRISMA guidelines, focusing on randomized controlled trials (RCTs) that compared TAVR and SAVR in this patient population. Also, the review included three major RCTs: PARTNER 2, UK TAVI, and DEDICATE. We analyzed the key outcomes of TAVR and SAVR, such as mortality, reintervention rates, complications (such as myocardial infarction, prosthetic valve endocarditis, and pacemaker implantation), and reintervention rates, to evaluate the relative efficacy and safety of TAVR and SAVR. The analysis included data from 4,359 patients across the three trials. TAVR demonstrated a lower all-cause mortality in two of the three trials, with an overall trend favoring TAVR in terms of survival. However, TAVR was associated with a higher incidence of prosthetic valve endocarditis, a greater need for pacemaker implantation, and more frequent reinterventions compared to SAVR. In conclusion, the findings suggest that TAVR may be a better option for moderate-risk AS patients, offering higher survival rates and a less invasive recovery process. While TAVR carries increased risks of endocarditis and pacemaker dependency, its overall benefits, particularly in terms of lower mortality and improved patient outcomes, make it a preferable option over SAVR for many patients. However, acknowledging potential limitations such as variations in trial design and differences in patient populations would indeed provide a more comprehensive perspective. Further research and long-term follow-up are essential to confirm these findings and refine patient selection criteria., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ajmal et al.)

Objective: This study aimed to evaluate the accuracy and reproducibility of information provided by ChatGPT, in response to frequently asked questions about radiofrequency ablation (RFA) for varicose veins., Methods: This cross-sectional study was conducted at The Aga Khan University Hospital, Karachi, Pakistan. A set of 18 frequently asked questions regarding RFA for varicose veins were compiled from credible online sources and presented to ChatGPT twice, separately, using the new chat option. Twelve experienced vascular surgeons (with >2 years of experience and ≥20 RFA procedures performed annually) independently evaluated the accuracy of the responses using a 4-point Likert scale and assessed their reproducibility., Results: Most evaluators were males (n = 10/12 [83.3%]) with an average of 12.3 ± 6.2 years of experience as a vascular surgeon. Six evaluators (50%) were from the UK followed by three from Saudi Arabia (25.0%), two from Pakistan (16.7%), and one from the United States (8.3%). Among the 216 accuracy grades, most of the evaluators graded the responses as comprehensive (n = 87/216 [40.3%]) or accurate but insufficient (n = 70/216 [32.4%]), whereas only 17.1% (n = 37/216) were graded as a mixture of both accurate and inaccurate information and 10.8% (n = 22/216) as entirely inaccurate. Overall, 89.8% of the responses (n = 194/216) were deemed reproducible. Of the total responses, 70.4% (n = 152/216) were classified as good quality and reproducible. The remaining responses were poor quality with 19.4% reproducible (n = 42/216) and 10.2% nonreproducible (n = 22/216). There was nonsignificant inter-rater disagreement among the vascular surgeons for overall responses (Fleiss' kappa, -0.028; P = .131)., Conclusions: ChatGPT provided generally accurate and reproducible information on RFA for varicose veins; however, variability in response quality and limited inter-rater reliability highlight the need for further improvements. Although it has the potential to enhance patient education and support healthcare decision-making, improvements in its training, validation, transparency, and mechanisms to address inaccurate or incomplete information are essential., Competing Interests: Disclosures None., (Copyright © 2024. Published by Elsevier Inc.)

Recent advancements in medical imaging have greatly enhanced the application of computational techniques in digital pathology, particularly for the classification of breast cancer using in situ hybridization (ISH) imaging. HER2 amplification, a key prognostic marker in 20-25% of breast cancers, can be assessed through alterations in gene copy number or protein expression. However, challenges persist due to the heterogeneity of nuclear regions and complexities in cancer biomarker detection. This review examines semi-automated and fully automated computational methods for analyzing ISH images with a focus on HER2 gene amplification. Literature from 1997 to 2023 is analyzed, emphasizing silver-enhanced in situ hybridization (SISH) and its integration with image processing and machine learning techniques. Both conventional machine learning approaches and recent advances in deep learning are compared. The review reveals that automated ISH analysis in combination with bright-field microscopy provides a cost-effective and scalable solution for routine pathology. The integration of deep learning techniques shows promise in improving accuracy over conventional methods, although there are limitations related to data variability and computational demands. Automated ISH analysis can reduce manual labor and increase diagnostic accuracy. Future research should focus on refining these computational methods, particularly in handling the complex nature of HER2 status evaluation, and integrate best practices to further enhance clinical adoption of these techniques.

In this study, a simple in situ technique followed by hydrothermal method is used to synthesize a novel tremella-like structure of ZIF-67Co(OH)F@Co 3 O 4 /CC metal-organic framework (MOF) derived from zeolite imidazole. The in situ synthesis of metal-organic frameworks (MOFs) increases their conductivity and produces more active sites for ion insertion. Their unique, scalable design not only provides more space to accommodate volume change but also facilitates electrolyte penetration into the electrode resulting in more active materials being utilized and ion-electron transfer occurring faster during the cycle. As a result, the binder-free ZIF-67Co(OH)F@Co 3 O 4 /CC supercapacitor electrode exhibits typical pseudo-capacitance behaviour, with a specific capacitance of 442 F g -1 and excellent long-term cycling stability of 90% after 5000 cycles at 10 A g -1 ., 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., (This journal is © The Royal Society of Chemistry.)

Fenestrated and branched endovascular aortic aneurysm repair (f-EVAR, b-EVAR, respectively) are technically challenging procedures that have evolved over the last decade for complex aortic aneurysms. They are alternatives to surgical repair for suprarenal and juxtarenal aortic aneurysms. A Pubmed database was reviewed by searching keywords related to f-EVAR, b-EVAR, and juxta renal abdominal aortic aneurysm (AAA) from the last five years to see current indications, contemporary techniques, and results of these techniques for juxtarenal aneurysms. Over the years, f-EVAR and b-EVAR have improved, with high technical success (>95%) and mortality rates of 1-5% for pararenal and 5-10% for thoracoabdominal aortic aneurysms. Key Words: Fenestrated-branched endovascular repair, Fenestrated EVAR, Branched EVAR, Juxtarenal aortic aneurysm.

To achieve efficient and cost-effective electrochemical water splitting, highly active and affordable nanostructured catalysts are the key requirement. The current study presents the investigations of the efficacy of metal (Mn, Fe and Ni)-doped Co(OH) 2 nanofibers towards oxygen evolution via water splitting. Notably, Ni-doped Co(OH) 2 demonstrates superior OER performance in KOH electrolyte, surpassing standard IrO 2 with a modest potential of 1.62 V at 10 mA cm -2 . The remarkable activity is attributed to the nanofiber structure, facilitating faster conduction and offering readily available active sites. Ni-doped Co(OH) 2 nanofibers displayed enduring stability even after 1000 cycles. This work underscores the importance of transition-metal based catalysts as effective electrocatalysts, providing the groundwork for the development of cutting-edge catalysts. Additionally, the electrochemical sensing capability towards ascorbic acid is evaluated, with Ni-doped Co(OH) 2 showing the most promising response, characterized by the lowest LOD and LOQ values. These findings highlight the potential of Ni-doped Co(OH) 2 nanofibers for upcoming diagnostic detection devices., Competing Interests: There are no conflict of interests to declare., (This journal is © The Royal Society of Chemistry.)

Pakistan once considered self-sufficient for edible oil production now became the major importer with 88.6% imports and producing only the minor portion. Scientific negligence in oil seed crops led to a dramatic decrease in edible oil production depending mainly on only the imports. Sesamum indicum L., "Queen of Oil seeds" with 50-55% oil, is cultivated in various geographical regions of Pakistan, but farmers are not considering this crop because of insufficient knowledge, poor crop management practices, and low yielding varieties. This study was conducted to check the nutritional, biochemical, antioxidant, and yield potentials of six major varieties, i.e., TS-5, TH-6, Til-18, NIAB-Mil, NIAB-Pearl, and NS-16, and to compare the nutritionals, oil quality, and oil yield potential of these varieties. Field experiment was conducted, and various crop growth biomarkers were analyzed. Chlorophyll content and superoxide dismutase activity were found to be highest in NIAB-Mil followed by NIAB-Pearl and comparable to those of Til-18, while APX, Cat, and GPX activity was found to be highest in Til-18 with 25.6 and 5.9 and 6.02 mg/g, respectively. Seed antioxidant parameters showed a mixed response, but NIAB-Mil, NIAB pearl, and Til-18 were found to be highest in all antioxidant parameters. UHPLC analysis of seed oil resulted in a total of 14 triacylglycerols (TAGs), and principal component analysis and OPLS-Da analysis showed seven TAG biomarkers responsible for the separation of sesame varieties. Til-18 was found to be highest in oil content (53.3%) more abundant with oleic acid, while NIAB-Pearl, NIAB-Mil, and NS-16 were found to be abundant with linoleic acid, both considered as potential TAG biomarkers for sesame oil separation. This study concluded that, in general, Til-18 variety is more resistant with high nutritional status, high antioxidant activity, and oil yielding variety, followed by NIAB-Mil and NIAB-Pearl., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background : Typhoid fever caused by Salmonella enterica serovar Typhi (S. typhi) continues to pose a significant risk to public health in developing countries, including Pakistan. This study investigated the epidemiological factors linked to suspected and confirmed S. typhi infections in Peshawar's hospital population. Methodology : A total of 5735 blood samples of patients with suspected enteric fever were collected from September 2022 to November 2023. S. typhi infection was confirmed using microbiological culture of blood samples, biochemical-based tests, and DNA-sequencing methods. Drug sensitivity testing on cultures was conducted as per the CLSI guidelines. Chi-square tests were used to analyze the clinical and epidemiologic characteristics of 5735 samples stratified by S. typhi infection status, and risk factors were assessed by applying logistic regression models to estimate odds ratios (ORs). Results : The number of confirmed typhoid fever cases in this hospital-based study population was 691 (/5735, 12.0%), more prevalent in males (447/3235 13.8%) and children (0-11 years) (429/2747, 15.6%). Compared to children, the risk of S. typhi infection was lower in adolescence (adjusted OR = 0.52; 95% CI: 0.42-0.66), adulthood (19-59 years; aOR = 0.30; 95% CI: 0.25-0.38), and older adulthood (aOR = 0.08; 95% CI: 0.04-0.18) ( p < 0.001). Compared to males, the risk of S. typhi infection was lower in females (aOR = 0.67; 95% CI = 0.56-0.80; p = 0.002). Living in a rural residence (compared to urban) was associated with a higher risk of infection (aOR = 1.38; 95% CI: 1.16-1.63; p = 0.001), while access to a groundwater source (compared to municipal water supply) led to a lower risk (aOR = 0.56; 95% CI: 0.43-0.73; p = 0.002). Vaccination demonstrated a robust protective effect (aOR = 0.069; 95% CI = 0.04-0.11, p = 0.002). For those with typhoid infections, clinical biomarker analysis revealed the presence of leucopenia (65/691, 9.4%), thrombocytopenia (130/691, 18.8%), and elevated alanine aminotransferase (ALT) (402/691, 58.2%) and C-reactive protein (CRP) (690/691, 99.9%) levels. Worryingly, among the positive S. typhi isolates, there was a high prevalence of drug resistance (653/691), including multidrug-resistant (MDR 82/691, 11.9%) and extensively drug-resistant types (XDR, 571/691, 82.6%). Conclusions : This study highlights the importance of age, sex, locality, water source, and vaccination status in shaping the epidemiological landscape of S. typhi in the Peshawar district. It implies that expanding vaccination coverage to the broader population of Khyber Pakhtunkhwa province, particularly in the district of Peshawar, would be beneficial.

Objective: To evaluate presentations, aetiologies, interventions, and outcomes of patients presenting with acute limb ischaemia (ALI)., Study Design: An observational study. Place and Duration of the Study: Department of Surgery, The Aga Khan University Hospital, Karachi, Pakistan, from January 2000 to December 2020., Methodology: Record of 104 patients who underwent surgical interventions for ALI was retrospectively evaluated. The diagnosis was confirmed on imaging (ultrasound / CTA / conventional angiography). Demographic characteristics, co-morbidities, aetiologies, and outcomes were analysed using descriptive statistics and logistic regression., Results: The cohort's mean age was 58.89 ± 12.6 years, with (54.8%, n = 57) females and (45.2%, n = 47) males. Hypertension (54.8%, n = 57), diabetes (46.2%, n = 48), and atrial fibrillation (34.6%, n = 36) were common comorbidities. Thromboembolism (67.3%, n = 70) and thrombotic occlusion (32.7%, n = 34) were primary aetiologies, predominantly affecting the lower limb (66.3%, n = 58) and femoral artery (51.9%, n = 54). The majority of cases were classified as Rutherford classification 2A (53.8%; 56 cases) and 2B (44.2%; 46 cases); 58 (55.8%) patients were classified as ASA Class III, while 36 (34.6%) patients were categorised as ASA Class IV. Embolectomy (80.8%, n = 84) was the prevailing intervention, with an amputation rate (17.3%, n = 18) and a mortality rate (5.8%, n = 6)., Conclusion: Most patients with ALI presented with Rutherford Class II and had thromboembolism aetiology. Embolectomy was the most commonly performed procedure with a high amputation rate and mortality., Key Words: Acute limb ischaemia, Embolectomy, Amputation, Thromboembolism.

Objective: To determine the frequency and pattern of different aetiologies of leg pain among patients visiting vascular surgery clinics., Study Design: Cross-sectional study. Place and Duration of the Study: Vascular Surgery Clinics of the Aga Khan University Hospital, Karachi, Pakistan, between February 2021 and June 2023., Methodology: This study examined patients presenting with leg pain for the first time at vascular surgery clinics. The socio-demographic and clinical data including the clinical symptoms, physical examination findings, and management of leg pain were noted using a specially designed proforma., Results: In a total of 142 patients (200 limbs), 82 (57.7%) were females and 60 (42.3%) were males, with a mean age of 46.8 ± 15.1 years. The patients' mean body mass index (BMI) was 30.2 ± 7.9 kg/m2. Ninety-one (64.1%) patients had a predominantly standing job compared to 51 (35.9%) patients who had a predominantly sitting job. The most common aetiology of leg pain was chronic venous insufficiency (CVI), diagnosed in 107 (53.5%) patients, followed by neurogenic pain [41 (20.5%)], musculoskeletal pain including knee osteoarthritis [30 (15.0%)], and arterial insufficiency [22 (11.0%)].  Conclusion: CVI followed by neuropathic pain was the leading cause of leg pain in vascular surgery clinics at a tertiary care hospital., Key Words: Chronic venous insufficiency, Arterial insufficiency, Vascular surgery, Leg pain, Musculoskeletal pain, Neuralgia.

This study investigated the potential of ethanolic garlic extract-loaded chitosan hydrogel film for burn wound healing in an animal model. The ethanolic garlic extract was prepared by macerating fresh ground garlic cloves in ethanol for 24 h, followed by filtration and concentration using a rotary evaporator. Hydrogels were then prepared by casting a chitosan solution with garlic extract added at varying concentrations for optimization and, following drying, subjected to various characterization tests, including moisture adsorption (MA), water vapor transmission rate (WVTR), and water vapor permeability rate (WVPR), erosion, swelling, tensile strength, vibrational, and thermal analysis, and surface morphology. The optimized hydrogel (G2) was then analyzed in vivo for its potential for healing 2nd degree burn wounds in rats, and histological examination of skin samples on day 14 of the healing period. Results showed optimized hydrogel (G2; chitosan: 2 g, garlic extract: 1 g) had MA of 56.8% ± 2.7%, WVTR and WVPR of 0.00074 ± 0.0002, and 0.000 498 946 ± 0.0001, eroded up to 11.3% ± 0.05%, 80.7% ± 0.04% of swelling index, and tensile strength of 16.6 ± 0.9 MPa, which could be attributed to the formation of additional linkages between formulation ingredients and garlic extract constituents at OH/NH and C=O, translating into an increase in transition melting temperature and enthalpy (Δ T = 238.83 °C ± 1.2 °C, Δ H = 4.95 ± 0.8 J g -1 ) of the chitosan moieties compared with blank. Animal testing revealed G2 formulation significantly reduced the wound size within 14 d of the experiment (37.3 ± 6.8-187.5 ± 21.5 mm 2 ) and had significantly higher reepithelization (86.3 ± 6.8-26.8 ± 21.5 and 38.2% ± 15.3%) compared to untreated and blank groups by hastening uniform and compact deposition of collagen fibers at the wound site, cementing developed formulation a promising platform for skin regeneration., (Creative Commons Attribution license.)

The convergence of nanotechnology with bioinformatics and the study of plant secondary metabolites hold remarkable potential for transformative scientific breakthroughs. Synergy enables a deeper understanding of the biosynthesis and functions of plant secondary metabolites, unlocking avenues to engineer novel applications in areas like pharmaceuticals, agriculture, and sustainable materials. The present study was conducted to check the effect of plant-mediated selenium nanoparticles to improve the bioactive compounds in sesame. Three varieties of sesame (TS-5, TH-6, and Till-18) were sown and got treated with different concentration of selenium nanoparticles. On the basis of antioxidant, biochemical, and physiological parameters, best performing seed samples from crop were selected and subjected to UHPLC analysis. From all 276 identified metabolites, the top 20 differentially expressed bioactive, medicinally important compounds were subjected to Swiss target prediction, KEGG, and Metascape analysis to reveal drug targets, gene targets, cell targets, and disease targets. Swiss target prediction revealed that most of the drug targets had kinases as the highest target in all the bioactive metabolites, followed by nuclear transporters, cytochrome P450, and proteins associated with electrochemical channels. Metascape analysis revealed that most of the compounds had highest enrichment in non-canonical activation of NOTCH3 followed by regulation of hormone levels. Furthermore, DisGeNET analysis revealed that most of the metabolites had strong association with impaired glucose tolerance followed by myocardial ischemia and neuralgia. Tissue and cell accumulation analysis by PaGeneBase revealed the highest accumulation in the small intestine, colon, ovary, and DRG cells. The study concluded that selenium nanoparticles has an ability to improve certain medicinally important metabolites in sesame, coupled with bioinformatics tools which revealed a great insight into the potential of those compounds, and the information can further be used in future studies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Incidences of drug-resistant tuberculosis have become common and are rising at an alarming rate. Aminoacyl t-RNA synthetase has been validated as a newer target against Mycobacterium tuberculosis . Leucyl t-RNA synthetase (LeuRS) is ubiquitously found in all organisms and regulates transcription, protein synthesis, mitochondrial RNA cleavage, and proofreading of matured t-RNA. Leucyl t-RNA synthetase promotes growth and development and is the key enzyme needed for biofilm formation in Mycobacterium. Inhibition of this enzyme could restrict the growth and development of the mycobacterial population. A database consisting of 2734 drug-like molecules was screened against leucyl t-RNA synthetase enzymes through virtual screening. Based on the docking scores and MMGBSA energy values, the top three compounds were selected for molecular dynamics simulation. The druggable nature of the top three hits was confirmed by predicting their pharmacokinetic parameters. The top three hits-compounds 1035 (ZINC000001543916), 1054 (ZINC000001554197), and 2077 (ZINC000008214483)-were evaluated for their binding affinity toward leucyl t-RNA synthetase by an isothermal titration calorimetry study. The inhibitory activity of these compounds was tested against antimycobacterial activity, biofilm formation, and LeuRS gene expression potential. Compound 1054 (Macimorelin) was found to be the most potent molecule, with better antimycobacterial activity, enzyme binding affinity, and significant inhibition of biofilm formation, as well as inhibition of the LeuRS gene expression. Compound 1054 , the top hit compound, has the potential to be used as a lead to develop successful leucyl t-RNA synthetase inhibitors.

Arachis hypogaea is the most significant oilseed nutritious legume crop in agricultural trade across the world. It is recognized as a valued crop for its contributions to nourishing food, as a cooking oil, and for meeting the protein needs of people who are unable to afford animal protein. Currently, its production, marketability, and consumption are hindered because of Aspergillus species infection that consequently contaminates the kernels with aflatoxins. Regarding health concerns, humans and animals are affected by acute and chronic aflatoxin toxicity and millions of people are at high risk of chronic levels. Most methods used to store peanuts are traditional and serve effectively for short-term storage. Now the question for long-term storage has been raised, and this promptly finds potential approaches to the issue. It is imperative to reduce the aflatoxin levels in peanuts to a permissible level by introducing detoxifying innovations. Most of the detoxification reports mention physical, chemical, and biological techniques. However, many current approaches are impractical because of time consumption, loss of nutritional quality, or weak detoxifying efficiency. Therefore, it is crucial to investigate practical, economical, and green methods to control Aspergillus flavus that address current global food security problems. Herein, a green and economically revolutionary way is a nanotechnology that has demonstrated its potential to connect farmers to markets, elevate international marketability, improve human and animal health conditions, and enhance food quality and safety by the management of fungal diseases. Due to the antimicrobial potential of nanoparticles, they act as nanofungicides and have an incredible role in the control of aflatoxins. Nanoparticles have ultrasmall sizes and therefore penetrate the fungal body and invade the pathogen machinery, leading to fungal cell death by ROS production, mutation in DNA, disruption of organelles, and membrane leakage. This is the first mechanistic overview that unveils a comprehensive insight into aflatoxin contamination in peanuts, its prevalence, health effects, and management in addition to nanotechnological interventions that serve as a triple defense approach to detoxify aflatoxins. The optimum use of nanofungicides ensures food safety and the development of goals, especially "zero hunger"., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The coordinated movement of germ layer progenitor cells reaches its peak at the dorsal side, where the Bmp signaling gradient is low, and minimum at the ventral side, where the Bmp gradient is high. This dynamic cell movement is regulated by the interplay of various signaling pathways. The noncanonical Wnt signaling cascade serves as a pivotal regulator of convergence and extension cell movement, facilitated by the activation of small GTPases such as Rho, Rab, and Rac. However, the underlying cause of limited cell movement at the ventral side remains elusive. To explore the functional role of a key regulator in constraining gastrulation cell movement at the ventral side, we investigated the Bmp4-direct target gene, sizzled (szl), to assess its potential role in inhibiting noncanonical Wnt signaling. In our current study, we demonstrated that ectopic expression of szl led to gastrulation defects in a dose-dependent manner without altering cell fate specification. Overexpression of szl resulted in decreased elongation of Activin-treated animal cap and Keller explants. Furthermore, our immunoprecipitation assay unveiled the physical interaction of Szl with noncanonical Wnt ligand proteins (Wnt5 and Wnt11). Additionally, the activation of small GTPases involved in Wnt signaling mediation (RhoA and Rac1) was diminished upon szl overexpression. In summary, our findings suggest that Bmp4 signaling negatively modulates cell movement from the ventral side of the embryo by inducing szl expression during early Xenopus gastrulation., Competing Interests: Declaration of 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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This research delves into the reproductive toxicology of zinc oxide nanoparticles (ZnO-NPs) in male Sprague Dawley rats. It specifically examines the repercussions of Zn accumulation in the testes, alterations in testosterone levels, and histopathological changes in the gonadal tissues., Aims: The primary objective of this study is to elucidate the extent of reproductive toxicity induced by ZnO-NPs in male Sprague Dawley rats. The investigation aims to contribute to a deeper understanding of the potential endocrine and reproductive disruptions caused by ZnO-NPs exposure., Methods: Characterization techniques including SEM-EDX and XRD affirmed the characteristic nature of ZnO-NPs. Twenty-five healthy post weaning rats (200-250 g) were intraperitoneally exposed to different concentrations of ZnO-NPs @ 10 or 20 or 30 mg/kg BW for 28 days on alternate days., Results: Results showed significant dose dependent decline in the body weight and testicular somatic index of rats. It also showed significant dose dependent accumulation of Zn in testis with increasing dose of ZnO-NPs. Conversely, serum testosterone level and sperm count were reduced with increasing dose of ZnO-NPs. Histological results showed dose dependent abnormalities i.e., vacuolization, edema, hemorrhage, destruction of seminiferous tubules, loss of germ cells and necrosis in rat testis., Conclusion: The findings of this study clearly indicate that high doses of zinc oxide nanoparticles (ZnO-NPs) can adversely affect the structural integrity and functional efficacy of the male reproductive system. Given these results, it becomes crucial to implement stringent precautionary measures in the utilization of ZnO-NPs, particularly in cosmetics and other relevant sectors. Such measures are imperative to mitigate the toxicological impact of ZnO-NPs on the male reproductive system and potentially on other related physiological functions. This study underscores the need for regulatory vigilance and safety assessments in the application of nanotechnology to safeguard human health., 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 © 2024 Elsevier GmbH. All rights reserved.)

The structural, mechanical, vibrational, electronic, optical, SLME, thermoelectric, and thermodynamic properties of X 2 GaAgCl 6 (X = Cs, Rb), a double perovskite material, were computed by employing Density Functional Theory (DFT). CASTEP and Quantum ESPRESSO were used to perform first-principles calculations. X 2 GaAgCl 6 possesses a cubic structure with the space-group symmetry Fm-3 m. The lattice parameters of Cs 2 GaAgCl 6 and Rb 2 GaAgCl 6 were optimized using the energy-volume curves, resulting in values of 7.357 Å and 7.365 Å, respectively. The population analysis confirmed the charge transfer among transition metals and halogen atoms. The stability of crystal X 2 GaAgCl 6 (X = Cs, Rb) is effectively demonstrated by analyzing phonon dispersion curves with no negative frequencies. The band structure calculations indicated the semiconducting nature of compounds with energy gaps of 0.96 eV and 0.88 eV for Cs 2 GaAgCl 6 and Rb 2 GaAgCl 6 , respectively. The optical characteristics results confirm that the examined materials are suitable for devices working, primarily in the electromagnetic spectrum's visible region. SLME results showed that Cs 2 GaAgCl 6 has 30% and Rb 2 GaAgCl 6 has 27% efficiency, respectively, suggesting their use in photovoltaics. The thermoelectric properties of X 2 GaAgCl 6 (X = Cs, Rb) were calculated by using the BoltzTraP code in the temperature range of 300 to 800 K. The quasi-harmonic Debye model was applied to calculate the thermodynamic characteristics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

An acute bacterial infection called avian spirochetosis is spread by ticks to a variety of birds. Clinical symptoms can vary greatly and are frequently non-specific. To diagnose a condition, the infectious spirochete must be detected. Here, we structure an epidemic model for the transmission of avian spirochetosis to visualize the interaction between tick and bird populations. The recommended dynamics of avian spirochetosis is illustrated with the help of fractional framework. We inspected the steady-states of the system of the avian spirochetosis for the stability analysis. The next-generation technique is used to evaluate the model's reproduction parameter R 0 . The infection-free and endemic steady-state of avian spirochetosis were shown to be locally asymptotically stable under the specified conditions. Through mathematical skills, the positivity of solutions is determined. Additionally, evidence supporting the existence and uniqueness of the avian spirochetosis framework solution has been shown. We conduct modified simulations of the suggested avian spirochetosis system with different input factors to study the complex phenomena of avian spirochetosis under the effect of numerous input parameters. Our outcomes illustrate the significance and plausibility of fractional parameter, and they also suggest that this input parameter may adequately account for these kinds of observations.

In vitro plant cultures have emerged as a viable source, holding auspicious reservoirs for medicinal applications. This study aims to delineate the antioxidant and hypoglycemic potential of phytosynthesized selenium nanoparticle (SeNP)- and light stress-mediated in vitro callus cultures of Caralluma tuberculata extract. The morphophysicochemical characteristics of biogenic SeNPs were assessed through a combination of analytical techniques, including UV-visible spectrophotometry, scanning electron microscopy, energy-dispersive X-rays, Fourier transform infrared spectrometry, and zeta potential spectroscopy. The antioxidative potential of the callus extract 200 and 800 μg/mL concentrations was assessed through various tests and exhibited pronounced scavenging potential in reducing power (26.29%), ABTS + scavenging (42.51%), hydrogen peroxide inhibition (37.26%), hydroxyl radical scavenging (40.23%), and phosphomolybdate (71.66%), respectively. To inspect the hypoglycemic capacity of the callus extract, various assays consistently demonstrated a dosage-dependent relationship, with higher concentrations of the callus extract exerting a potent inhibitory impact on the catalytic sites of the alpha-amylase (78.24%), alpha-glucosidase (71.55%), antisucrase (59.24%), and antilipase (74.26%) enzyme activities, glucose uptake by yeast cells at 5, 10, and 25 mmol/L glucose solution (72.18, 60.58 and 69.33%), and glucose adsorption capacity at 5, 10, and 25 mmol/L glucose solution (74.37, 83.55, and 86.49%), respectively. The findings of this study propose selenium NPs and light-stress-mediated in vitro callus cultures of C. tuberculata potentially operating as competitive inhibitors. The outcomes of the study were exceptional and hold promising implications for future medicinal applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The commercial-scale production of Caralluma tuberculata faces significant challenges due to lower seed viability and sluggish rate of root growth in natural conditions. To overcome these obstacles, using phyto-mediated selenium nanomaterials as an in vitro rooting agent in plant in vitro cultures is a promising approach to facilitate rapid propagation and enhance the production of valuable therapeutic compounds. This study aimed to investigate the impact of phytosynthesized selenium nanoparticles (SeNPs) on the morphological growth attributes, physiological status, and secondary metabolite fabrication in in vitro propagated Caralluma tuberculata. The results demonstrated that a lower dose of SeNPs (100 μg/L) along with plant growth regulators (IBA 1 mg/L) had an affirmative effect on growth parameters and promoted earliest root initiation (4.6±0.98 days), highest rooting frequency (68.21±5.12%), number of roots (6.3±1.8), maximum fresh weight (710±6.01 mg) and dry weight (549.89±6.77 mg). However, higher levels of SeNPs (200 and 400 μg/L) in the growth media proved detrimental to growth and development. Further, stress caused by SeNPs at 100 μg/L along with PGRs (IBA 1 mg/L) produced a higher level of total chlorophyll contents (32.66± 4.36 μg/ml), while cultures exposed to 200 μg/L SeNPs alone exhibited the maximum amount of proline contents (10.5± 1.32 μg/ml). Interestingly, exposure to 400 μg/L SeNPs induced a stress response in the cultures, leading to increased levels of total phenolic content (3.4 ± 0.052), total flavonoid content (1.8 ± 0.034), and antioxidant activity 82 ± 4.8%). Furthermore, the combination of 100 μg/L SeNPs and plant growth regulators (1 mg/L IBA) led to accelerated enzymatic antioxidant activities, including superoxide dismutase (SOD = 4.4 ± 0.067 U/mg), peroxidase dismutase (POD = 3.3 ± 0.043 U/mg), catalase (CAT = 2.8 ± 0.048 U/mg), and ascorbate peroxidase (APx = 1.6 ± 0.082 U/mg). This is the first report that highlights the efficacy of SeNPs in culture media and presents a promising approach for the commercial propagation of C. tuberculata with a strong antioxidant defense system in vitro., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)