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Male infertility is a worldwide health issue, affecting 8%–12% of the global population. Oligoasthenoteratozoospermia (OAT) represents a severe type of male infertility, characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology. Using whole-exome sequencing, this study identified a novel missense mutation (c.848C>A, p.A283E) in the coiled-coil domain-containing 34 gene (CCDC34) in a consanguineous Pakistani family. This rare mutation was predicted to be deleterious and to affect the protein stability. Hematoxylin and eosin staining of spermatozoa from the patient with OAT revealed multiple morphological abnormalities of the flagella and transmission electron microscopy indicated axonemal ultrastructural defects with a lack of outer dynein arms. These findings indicated that CCDC34 plays a role in maintaining the axonemal ultrastructure and the assembly or stability of the outer dynein arms, thus expanding the phenotypic spectrum of CCDC34 missense mutations.

Abstract Global mortality data indicates cancer as the second-leading cause of death worldwide. Therefore, there’s a pressing need to innovate effective treatments to address this significant medical and societal challenge. In recent years, X-ray-induced photodynamic therapy (X-PDT) has emerged as a promising advancement, revolutionizing traditional photodynamic therapy (PDT) for deeply entrenched malignancies by harnessing penetrating X-rays as external stimuli. Recent developments in X-ray photodynamic therapy have shown a trend toward minimizing radiation doses to remarkably low levels after the proof-of-concept demonstration. Early detection and real-time monitoring are crucial aspects of effective cancer treatment. Sophisticated X-ray imaging techniques have been enhanced by the introduction of X-ray luminescence nano-agents, alongside contrast nanomaterials based on X-ray attenuation. X-ray luminescence-based in vivo imaging offers excellent detection sensitivity and superior image quality in deep tissues at a reasonable cost, due to unhindered penetration and unimpeded auto-fluorescence of X-rays. This review emphasizes the significance of X-ray responsive theranostics, exploring their mechanism of action, feasibility, biocompatibility, and promising prospects in imaging-guided therapy for deep-seated tumors. Additionally, it discusses promising applications of X-PDT in treating breast cancer, liver cancer, lung cancer, skin cancer, and colorectal cancer. Graphical Abstract

Abstract Recent developments have highlighted the critical role that computer-aided diagnosis (CAD) systems play in analyzing whole-slide digital histopathology images for detecting gastric cancer (GC). We present a novel framework for gastric histology classification and segmentation (GHCS) that offers modest yet meaningful improvements over existing CAD models for GC classification and segmentation. Our methodology achieves marginal improvements over conventional deep learning (DL) and machine learning (ML) models by adaptively focusing on pertinent characteristics of images. This contributes significantly to our study, highlighting that the proposed model, which performs well on normalized images, is robust in certain respects, particularly in handling variability and generalizing to different datasets. We anticipate that this robustness will lead to better results across various datasets. An expectation-maximizing Naïve Bayes classifier that uses an updated Gaussian Mixture Model is at the heart of the suggested GHCS framework. The effectiveness of our classifier is demonstrated by experimental validation on two publicly available datasets, which produced exceptional classification accuracies of 98.87% and 97.28% on validation sets and 98.47% and 97.31% on test sets. Our framework shows a slight but consistent improvement over previously existing techniques in gastric histopathology image classification tasks, as demonstrated by comparative analysis. This may be attributed to its ability to capture critical features of gastric histopathology images better. Furthermore, using an improved Fuzzy c-means method, our study produces good results in GC histopathology picture segmentation, outperforming state-of-the-art segmentation models with a Dice coefficient of 65.21% and a Jaccard index of 60.24%. The model’s interpretability is complemented by Grad-CAM visualizations, which help understand the decision-making process and increase the model’s trustworthiness for end-users, especially clinicians.

This comprehensive review paper delves into the multifaceted aspects of nuclear safeguards, emphasizing their indispensable role in upholding global security and preventing the illicit use of nuclear materials. Offering a fresh perspective on the nuclear safeguard system, the paper conducts a thorough examination of nuclear material accounting, underscoring the pivotal role of the International Atomic Energy Agency (IAEA) in implementing and verifying these safeguards. It provides valuable insights into the safeguarding technologies, including the utilization of sophisticated Non-Destructive Assay (NDA) equipment such as neutron counting and Gamma-ray spectroscopy, which are essential for accurately characterizing nuclear materials, elucidating the crucial role of these activities in ensuring the integrity and effectiveness of nuclear safeguards. Furthermore, the study sheds light on the complexities inherent in the nuclear fuel cycle, elucidating various stages ranging from uranium mining to waste disposal. Additionally, it discusses different fuel cycle options and their implications for non-proliferation efforts. This discussion sheds light on how safeguards are integrated into each stage of the fuel cycle to prevent the proliferation of nuclear materials. The paper delves into the Additional Protocol, emphasizing its significance in enhancing the effectiveness of nuclear safeguards by providing the IAEA with expanded inspection access and information regarding nuclear activities. This comprehensive analysis not only enhances understanding of the current safeguarding landscape but also underscores the significance of ongoing research and development in this vital realm of nuclear safety and security.

Bovine colostrum is the initial milk produced after birth that contains high levels of immunoglobulins and antimicrobial peptides. This study examined the production of bovine colostrum powder using two methods including spray- and freeze-drying. Spray-drying involves quickly drying a liquid or slurry with hot gas, while freeze-drying is a low-temperature dehydration process that preserves the product by freezing it and at reduced pressure. The aim was to compare the effectiveness of spray-drying versus freeze-drying in producing colostrum powder, focusing on protein and defensive protein content. The freeze-drying sample contained higher levels of protein and defensive proteins (IgG and IgA) compared to spray-drying. The DPPH value was high in freeze-dried samples, while higher values of FRAP, TPC, and ABTS were found in spray-dried samples. Microbiological analysis indicated freeze drying generally yielding lower counts. Sensory evaluation suggested that spray-dried colostrum scored higher for flavor and aroma, while freeze-dried samples were preferred in appearance. Overall, the study underscored the distinction between spray=drying and freeze-drying in producing bovine colostrum powder, with implications for nutritional content and sensory attributes.

Kalanchoe pinnata (Lam.) Pers. is an ethnomedicinal plant known for its antioxidant, antibacterial, and therapeutic potential. The current study was an effort to explore the impact of extraction technique on the phytochemical, antioxidant, and antibacterial profile of the plant extracts. K. pinnata leaf extracts were prepared using conventional solvent extraction (100% methanol; 50% methanol: 50% water; 100% water), microwave-assisted extraction at 700-W power (3 min; 6 min; 9 min), and supercritical fluid extraction (SFE) (3500 psi; 4500 psi; 5500 psi). Best results were attained from SFE in terms of total phenolic content (240 ± 3 mg GAE/g), total flavonoid content (165.2 ± 0.4 mg QE/g), 2,2-diphenyl-1-picrylhydrazyl radical scavenging potential (91.9 ± 0.4%), 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid assay value (8.04 ± 0.03 mMol TE/g) and ferric reducing antioxidant power assay value (471.7 ± 0.8 µg/mL). K. pinnata leaf extracts have been found to be most effective against Yersinia pseudotuberculosis (22.20 ± 0.95 mm) and least effective againstProteus vulgaris (0 ± 0 mm). High-performance liquid chromatography analysis of K. pinnata extract showed that it contains flavanol quercetin (2.0 ± 0.1 mg/g). It is evident from the findings of current study that K. pinnata extract can effectively treat bacterial infections and can cure metabolic disorders by reducing oxidative stress. Application of advance extraction techniques enhances the biological activity of plant extracts.

ABSTRACTPakistan is one of the biggest mango producing country in the world. Post-harvest losses of mango occur due to lack of storage facilities. Mango can be converted into concentrate to utilize it for longer period. In the current study, the physicochemical profile and storage stability of mango concentrate was investigated to evidence the opportunity of preservation method. Three different concentrations (0.1%, 0.2%, and 0.5%) of citric acid, sodium benzoate and potassium sorbate were applied. All chemical preservatives significantly (p ˂ 0.05) increased viscosity, total soluble solids (TS), reducing sugar (RS), non-reducing sugar (NRS), total soluble solids (TSS), and titratable acidity (TA), while the moisture content, pH, DPPH antioxidant activity, TPC (total phenolic content), TFC (total flavonoid content) and the level of texture acceptance decreased during the storage. The moisture content was decreased from 43.4% to 34.9% during storage. Phytochemical analysis showed that mango concentrate is a potential source of antioxidant compounds and has higher DPPH radical scavenging activity. Regarding preservation solution, it is suggested that sodium benzoate and citric acid might be utilized for industrial applications.

The pharmaceutical research sector’s inability to develop new drugs has made it challenging to combat microbial resistance. Secondary metabolites from plant extracts have been identified as potential protective agents against multi-drug-resistant bacteria. This study aimed to analyze hydro-ethanol extracts’ antioxidant and antimicrobial activities from various parts of the Zahidi date (whole fruit, pit powder, and flesh). Phytochemical screening of phenolic and flavonoid compounds was performed using high-performance liquid chromatography (HPLC). Total phenolic and flavonoid compounds were extracted at their maximum levels, 71.89 mg/100 g and 843.06 mg/100 g, respectively, using EoH 60%. The whole fruit had the highest concentration of flavonoid quercetin (0.83 μg/g) and phenolic compoundsinapic acid (20.03 μg/g) at the same concentration. The findings from the broth micro-dilution method showed that the whole fruit had the strongest antimicrobial effects at 60% EoHagainst Salmonella typhi (30 mg/ml), Helicobacter pylori (27 mg/ml), Escherichia coli (22 mg/ml), and Staphylococcus aureus (44 mg/ml). Zahidi whole fruit extracts showed higher antioxidant potential at EoH 60% using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging potential (78%) and ferric-reducing antioxidant power. Principal component analysis (PCA) revealed a significant negative correlation between antioxidant activity and the minimum inhibitory concentration (MIC). Evidence from this study highlights the considerable antioxidant and antimicrobial properties of Zahidi date fruit, suggesting its potential use in producing natural drugs and value-added foods to counteract contagious diseases.

ABSTRACTAscorbic acid (vitamin C) is the most crucial antioxidant for the body. The biochemical capabilities of ascorbic acid are still being studied. It acts as a cofactor for many enzymes participating in various physiological functions. This review presents how ascorbic acid is a cofactor for multiple enzymes involved in numerous human activities. Ascorbic acid protects the immune system, reduces allergic reaction severity and assists the fight against infections and other disorders. Ascorbic acid is metabolized by several procedures in the gastrointestinal tract. Eukaryotes produce ascorbic acid via L-galactose (L-Gal) and GDP-D-mannose as part of its metabolic process. It is disseminated throughout the body cells after being readily absorbed by the digestive system. This review will uncover ascorbic acid’s biological functions and metabolism in humans.

ABSTRACTThe study was designed to develop functional cucumber and pomegranate based ready-to-serve (RTS) drink as thirst quencher. To boost antioxidant activity and to add natural preservation to the drink, microwave-assisted extracts of herbs and spices; mint, lemongrass, ginger, cinnamon were incorporated either individually or collective, at an equivalent dose of 2% for comparison. In this regard, ginger extract incorporated drink maintained its storage quality owing to highest free radical scavenging potential (49 to 67%) in relevance to highest polyphenol and flavonoid contents (1203 ± 64 mg GAE/L and 178 ± 8 mg TE/L, respectively). Whereas, ascorbic acid was maximally recorded in lemongrass-based drink 22 ± 1 mg/100 mL. During 30 days storage under refrigeration, significant decrease was recorded in pH of the RTS drink along with considerable increase in acidity and browning index however, total soluble solids demonstrated non-significant pattern. Sedimentation showed an inclining trend (p˂.05) with progression in storage but comparatively less sedimentation was attributed to lemongrass incorporated drink followed by cinnamon containing drink. Turbidity also indicated significant changes but showed inverse pattern with respect to sedimentation. Additionally, ginger-based drink expressed considerably low total plate count as 2.3 ± .1 log CFU/mL with nil yeast and mold growth by all the extracts throughout storage. Further, ginger portrayed highest rate for odor, taste and consistency though, mixed herbs and spices based drink attained the best color score. Conclusively, ginger-based drink portrayed maximum antioxidant and antimicrobial properties.

ABSTRACTThe present research investigated the effectiveness of cumin and black cumin extracts as natural antioxidants in uncooked chicken nuggets stored at refrigeration temperature (4°C) for 12 days and compared the results with a control treatment. Seven treatments were formulated, including a control group (Tc), T1 (0.5% cumin), T2 (1% cumin), T3 (1.5% cumin), T4 (0.5% black cumin), T5 (1% black cumin), and T6 (1.5% black cumin). The product was evaluated for several physicochemical parameters on days 0, 3, 6, 9, and 12 of storage. The data was analyzed using a two-way factorial design under a completely randomized (CRD) design. Results showed that both treatments and storage significantly impacted all physicochemical properties, including DPPH, TPC, pH, POV, and TBARS (p 0.05). Sensory evaluation showed that T3 (1.5% cumin) was the most pleasant and preferred treatment. Conclusively, both cumin and black cumin have good antioxidant properties and can be used as natural antioxidants to increase the shelf life of food products.

ABSTRACT Kosovo, like the global trend, is experiencing a rising demand for eggs, emphasizing the necessity for stringent regulatory oversight to maintain freshness and meet increasing consumer and industrials’ needs. The research aimed to evaluate the compliance of eggs in the local market with specified quality criteria outlined in the local Administrative Directive and EC Regulation. Several quality parameters were scrutinized, including egg weight, length, width, specific gravity, air cell, Haugh units (HU), yolk and egg white weights, yolk color intensity, shell weight, and shell thickness. Key parameters varied significantly among Fresh Eggs and farms F1 to F5. Most groups displayed significantly lower egg weights, yolk, and egg white weights compared to Fresh Eggs (p 0.05). Fresh eggs outshined in all groups in relation to size and yolk color (p

ABSTRACTSaudi Arabia is the largest country in the Middle East with huge solar energy resources but has achieved minimal adoption of photovoltaic energy systems (PV). This study investigates the potential of PV systems to address pressing challenges, including water scarcity and agricultural unemployment. This study addresses the deployment of PV in contemporary agriculture such as aquaponics and hydroponics to promote sustainable water, energy, and agricultural practices. Scrutinising national goals for PV energy against ground realities. The buyback tariff, interest rates of loans, and potential future power price increases are simulated to find suitable rates to encourage PV adoption. The current government grid purchase price is 1.87 cents USD/kWh, while the national grid selling price is 4.8 cents USD/kWh. Small-scale PV plants offer local investors passive income streams if financial institutes can offer these projects at lower interest rates. Investigating the country’s educational sector reveals the need for an overhaul in technical education for solar energy systems. The simulation shows that PV use in agriculture is economically feasible for large loads even with buyback rates as low as 1.87 cents USD/kWh. This research contributes by emphasising local involvement and proposing financial mechanisms, government reforms, and sustainable agricultural development in the region.

Despite recent advancements in technology, breast cancer still poses a significant threat, often resulting in fatal consequences. While early detection and treatments have shown some promise, many breast cancer patients continue to struggle with the persistent fear of the disease returning. This fear is valid, as breast cancer cells can lay dormant for years before remerging, evading traditional treatments like a game of hide and seek. The biology of these dormant breast cancer cells presents a crucial yet poorly understood challenge in clinical settings. In this review, we aim to explore the mysterious world of dormant breast cancer cells and their significant impact on patient outcomes and prognosis. We shed light on the elusive role of the G9a enzyme and many other epigenetic factors in breast cancer recurrence, highlighting its potential as a target for eliminating dormant cancer cells and preventing disease relapse. Through this comprehensive review, we not only emphasise the urgency of unravelling the dynamics of dormant breast cancer cells to improve patient outcomes and advance personalised oncology but also provide a guide for fellow researchers. By clearly outlining the clinical and research gaps surrounding dormant breast cancer cells from a molecular perspective, we aim to inspire further exploration of this critical area, ultimately leading to improved patient care and treatment strategies.

الملخص: أهداف البحث: أجريت هذه الدراسة لتقييم تأثير فيتامين سي على جينات الاستماتة والتكاثر في خلايا ''هيب جي 2'' المصابة. طريقة البحث: في تحليل السيليكو تم إجراء استخدام الالتحام الجزيئي للمركبات الكيميائية مع بروتين عامل النمو البطاني الوعائي. الأدوات الحسابية المختلفة المستخدمة هي ''أوتودوك فينا'' و''بايوفيا ديسكفري ستوديو'' و ''بايمول''. تم تحليل تشابه الأدوية وسميتها بواسطة ''سويس أدميت''. تمت معالجة التقاء الخلايا – 60-70% بتركيزات مختلفة من ''اتش 2 أوه 2'' (100-2000 مايكرومولر) وحمض الأسكوربيك (30، 60، 90 ميكروغرام / مل). تم إجراء اختبار موت الخلايا ''ام تي تي'' لمقارنة الإمكانات التكاثرية لخلايا ''هيب جي 2'' المعالجة بـ ''اتش 2 أوه 2'' وحمض الأسكوربيك باستخدام 96 لوحة جيدة. النتائج: تمت ملاحظة أدنى طاقة ربط لـ بروتين عامل النمو البطاني الوعائي مع فيتامين سي -5,2 كيلو كالوري/مول وحمض الأسكوربيك-2 جليكوسيد -4.7 كيلو كالوري/مول في تحليل السيليكو. تم اختيار فيتامين سي لأنه يظهر تفاعلا عاليا مع بروتين عامل النمو البطاني الوعائي ويحقق قاعدة ليبينسكي، والقدرة على البقاء عن طريق الفم، والحركية الدوائية مقارنة بجليكوسيد حمض الأسكوربيك. أظهرت فحوصات صلاحية الخلية أن فيتامين سي كان له تأثيرات موت الخلايا المبرمج. بعد معالجة خلايا ''هيب جي 2'' بحمض الأسكوربيك، لوحظ انخفاض بروتين عامل النمو البطاني الوعائي (تكوين الأوعية) من خلال التعبير الجيني للموت المبرمج والتكاثري. أدى علاج حامض الأسكوربيك لخط خلايا ''هيب جي 2'' إلى تنظيم علامات التكاثر ''بي سي ان ايه'' و ''كي آي 67'' و تي أوه بي 2 ايه''. وقد لوحظت زيادة في موت الخلايا المبرمج بعد العلاج بفيتامين سي بسبب تنظيم ''بي53'' و ''أنيكسين في''. الاستنتاجات: بناء على النتائج، من الواضح أن فيتامين سي يثبط نمو الخلايا السرطانية وبالتالي يحمي خلايا ''هيب جي 2'' من الإجهاد التأكسدي. أظهر فيتامين سي نشاطا مضادا للتكاثر كما لوحظ في السيليكو، وفي المختبر، وكذلك النتائج المحتملة من تثبيط التعبير عن الجينات المشاركة في تخليق البروتين. Abstract: Objectives: This study was conducted to evaluate the effects of vitamin C on apoptotic and proliferative genes in injured HepG2 cells. Methods: In silico analysis was performed using molecular docking of chemical compounds with vascular endothelial growth factor (VEGF). The different computational tools used were AutoDock Vina, BIOVIA DISCOVERY studio, and PyMOL. Drug likeness and toxicity were analyzed by SWISS ADMET. Cells that were 60–70% confluent were treated with different concentrations of hydrogen peroxide (H2O2) (100–2000 μM) and ascorbic acid (30, 60, 90 μg/mL). The MTT cell proliferation assay was performed to compare the proliferative potential of HepG2 cells treated with H2O2 or ascorbic acid with untreated HepG2 cells using 96-well plates. Results: The lowest binding energy of VEGF with vitamin C –5.2 kcal/mol and L-ascorbic acid-2 glycoside −4.7 kcal/mol was observed by in silico analysis. Vitamin C was selected because it exhibited a high interaction with VEGF and fulfilled Lipinski's rule, and had better oral viability and pharmacokinetics compared to L-ascorbic acid-2 glycoside. Cell viability assays showed that vitamin C had significant apoptotic effects (P

Abstract Terahertz (THz) spectral region from 0.1 to 3 THz is envisaged to hold immense potential in the next generation of wireless technologies. Recently, research has focused on this terahertz gap, because of its unprecedented channel capacities. At the physical layer, the design complexities and fabrication of THz devices, especially antennas are the prime bottlenecks to realize its full potential. This article introduces a cost-effective, easy-to-fabricate, and reproducible sub-THz antenna design based on a single-layer planar printed circuit board technology. The antenna incorporates carefully designed quasi-cross slots and applied machine learning-assisted global optimization techniques to achieve the desired performance metrics. The antenna performance is elucidated through numerical simulations and verified through a rigorous in-house THz experimental framework around 100–110 GHz. The proposed antenna offers a peak gain of 13.90 dBi with less than 1 dB variation within the entire band of 100–110 GHz. The antenna holds the potential to achieve terabits per second data rates and futuristic high-resolution short-range THz imaging applications.

Abstract Background The increased socioeconomic inequality in catastrophic health expenditure (CHE) disproportionately affects disadvantaged populations, subjecting them to financial hardships, limiting their access to healthcare, and exacerbating their vulnerability to morbidity. Objectives This study examines changes in socioeconomic inequality related to CHE and analyzes the contributing factors responsible for these changes in Pakistan between 2010-11 and 2018-19. Methods This paper extracted the data on out-of-pocket health expenditures from the National Health Accounts for 2009-10 and 2017-18. Sociodemographic information was gathered from the Household Integrated Economic Surveys of 2010-11 and 2018-19. CHE was calculated using budget share and the ability-to-pay approaches. To assess socioeconomic inequality in CHE in 2010-11 and 2018-19, both generalized and standard concentration indices were used, and Wagstaff inequality decomposition analysis was employed to explore the causes of socioeconomic inequality in each year. Further, an Oaxaca-type decomposition was applied to assess changes in socioeconomic inequality in CHE over time. Results The concentration index reveals that socioeconomic inequality in CHE decreased in 2018-19 compared to 2010-11 in Pakistan. Despite the reduction in inequality, CHE was concentrated among the poor in Pakistan in 2010-11 and 2018-19. The inequality decomposition analysis revealed that wealth status was the main cause of inequality in CHE over time. The upper wealth quantiles indicated a positive contribution, whereas lower quantiles showed a negative contribution to inequality in CHE. Furthermore, urban residence contributed to pro-rich inequality, whereas employed household heads, private healthcare provider, and inpatient healthcare utilization contributed to pro-poor inequality. A noticeable decline in socioeconomic inequality in CHE was observed between 2010 and 2018. However, inequality remained predominantly concentrated among the lower socio-economic strata. Conclusion These results underscore the need to improve the outreach of subsidized healthcare and expand social safety nets.

Platelets are small anucleated cell fragments that ensure the stopping of bleeding. In blood metastasis of cancer, Platelets are essential. One of the most important aspects of cancer metastasis is the interaction between platelets and circulating tumor cells. Platelets are involved in cancer spread and constitute a hazardous collation with the cancer cells. There are various factors involved in hemostasis and thrombosis, which can be activated by several cancer-related stimuli, including extracellular matrix (ECM), adenosine diphosphate (ADP), and Toll-like receptors (TLRs). Furthermore, it has been previously published that platelets build up inside the main tumors, producing growth factors that encourage tumor growth and angiogenesis. Additionally, tumor cells can interact with platelets through aggregation, further protecting cancer cells. Platelets interact both functionally and physically with different types of tumor cells via integrin and other surface receptors. Platelet integrin’s primary function is to maintain platelet adhesion and aggregation at vascular damage sites. Pharmacological treatments that target integrin have been shown to effectively inhibit experimental metastasis. This review paper summarized the recent advances and progress of mechanisms in platelet activation and its interaction with cancer cells in metastasis.