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Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no-go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5 x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8-weeks post-surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC-microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight-bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself., (© 2024 Orthopaedic Research Society.)

Intervertebral disc disease (IDD) is a debilitating spine condition that can be caused by intervertebral disc (IVD) damage which progresses towards IVD degeneration and dysfunction. Recently, human pluripotent stem cells (hPSCs) were recognized as a valuable resource for cell-based regenerative medicine in skeletal diseases. Therefore, adult somatic cells reprogrammed into human induced pluripotent stem cells (hiPSCs) represent an attractive cell source for the derivation of notochordal-like cells (NCs) as a first step towards the development of a regenerative therapy for IDD. Utilizing a differentiation method involving treatment with a four-factor cocktail targeting the BMP, FGF, retinoic acid, and Wnt signaling pathways, we differentiate CRISPR/Cas9-generated mCherry-reporter knock-in hiPSCs into notochordal-like cells. Comprehensive analysis of transcriptomic changes throughout the differentiation process identified regulation of histone methylation as a pivotal driver facilitating the differentiation of hiPSCs into notochordal-like cells. We further provide evidence that specific inhibition of histone demethylases KDM2A and KDM7A/B enhanced the lineage commitment of hiPSCs towards notochordal-like cells. Our results suggest that inhibition of KDMs could be leveraged to alter the epigenetic landscape of hiPSCs to control notochord-specific gene expression. Thus, our study highlights the importance of epigenetic regulators in stem cell-based regenerative approaches for the treatment of disc degeneration.

The design of masonry structures requires accurate estimation of compressive strength (CS) of hollow concrete masonry prisms. Generally, the CS of masonry prisms is determined by destructive laboratory testing which results in time and resource wastage. Thus, this study aims to provide machine learning-based predictive models for CS of hollow concrete masonry blocks using different algorithms including Multi Expression Programming (MEP), Random Forest Regression (RFR), and Extreme Gradient Boosting (XGB) etc. A dataset of 159 experimental results was collected from published literature for this purpose. The collected dataset consisted of four input parameters including strength of masonry units ( f b ), height-to-thickness ratio (h/t), strength of mortar ( f m ), and ratio of f m / f b and only one output parameter i.e., CS. Out of all the algorithms employed in current study, only MEP and GEP expressed their output in the form of an empirical equation. The accuracy of developed models was assessed using root mean squared error (RMSE), objective function (OF), and R 2 etc. Among all algorithms assessed, XGB turned out to be the most accurate having R 2  = 0.99 and least OF value of 0.0063 followed by AdaBoost, RFR, and other algorithms. The developed XGB model was also used to conduct different explainable artificial intelligence (XAI) analysis including sensitivity and shapley analysis and the results showed that strength of masonry unit ( f b ) is the most significant variable in predicting CS. Thus, the ML-based predictive models presented in this study can be utilized practically for determining CS of hollow concrete masonry prisms without requiring expensive and time-consuming laboratory testing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Cyanine dyes are a class of organic, usually cationic molecules containing two nitrogen centers linked through conjugated polymethine chains. The synthesis and reactivity of cyanine derivatives have been extensively investigated for decades. Unlike the recently described phototruncation process, the thermal truncation (chain shortening) reaction is a phenomenon that has rarely been reported for these important fluorophores. Here, we present a systematic investigation of the truncation of heptamethine cyanines (Cy7) to pentamethine (Cy5) and trimethine (Cy3) cyanines via homogeneous, acid-base-catalyzed nucleophilic exchange reactions. We demonstrate how different substituents at the C3' and C4' positions of the chain and different heterocyclic end groups, the presence of bases, nucleophiles, and oxygen, solvent properties, and temperature affect the truncation process. The mechanism of chain shortening, studied by various analytical and spectroscopic techniques, was verified by extensive ab initio calculation, implying the necessity to model catalytic reactions by highly correlated wave function-based methods. In this study, we provide critical insight into the reactivity of cyanine polyene chains and elucidate the truncation mechanism and methods to mitigate side processes that can occur during the synthesis of cyanine derivatives. In addition, we offer alternative routes to the preparation of symmetrical and unsymmetrical meso -substituted Cy5 derivatives.

Background: Central line-associated bloodstream infections (CLABSIs) pose a significant risk to critically ill patients, particularly in intensive care units (ICU), and are a significant cause of hospital-acquired infections. We investigated whether implementation of a multifaceted intervention was associated with reduced incidence of CLABSIs., Methods: This was a prospective cohort study over nine years. We implemented a bundled intervention approach to prevent CLABSIs, consisting of a comprehensive unit-based safety program (CUSP). The program was implemented in the Neonatal ICU, Medical ICU, and Surgical ICU departments at the Aga Khan University Hospital in Pakistan., Results: The three intervention ICUs combined were associated with an overall 36% reduction in CLABSI rates and a sustained reduction in CLABSI rates for > a year (5 quarters). The Neonatal ICU experienced a decrease of 77% in CLABSI rates lasting ∼1 year (4 quarters). An attendance rate above 88% across all stakeholder groups in each CUSP meeting correlated with a better and more sustained infection reduction., Conclusions: Our multifaceted approach using the CUSP model was associated with reduced CLABSI-associated morbidity and mortality in resource-limited settings. Our findings suggest that a higher attendance rate (>85%) at meetings may be necessary to achieve sustained effects post-intervention., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Heavy-metal ATPases (HMAs) play a vital role in plants, helping to transport heavy metal ions across cell membranes.However, insufficient data exists concerning HMAs genes within the Arecaceae family.In this study, 12 AcHMA genes were identified within the genome of Areca catechu, grouped into two main clusters based on their phylogenetic relationships.Genomic distribution analysis reveals that the AcHMA genes were unevenly distributed across six chromosomes. We further analyzed their physicochemical properties, collinearity, and gene structure.Furthermore, RNA-seq data analysis exhibited varied expressions in different tissues of A. catechu and found that AcHMA1, AcHMA2, and AcHMA7 were highly expressed in roots, leaves, pericarp, and male/female flowers. A total of six AcHMA candidate genes were selected based on gene expression patterns, and their expression in the roots and leaves was determined using RT-qPCR under heavy metal stress. Results showed that the expression levels of AcHMA1 and AcHMA3 genes were significantly up-regulated under Cd2 + and Zn2 + stress. Similarly, in response to Cu 2+, the AcHMA5 and AcHMA8 revealed the highest expression in roots and leaves, respectively. In conclusion, this study will offer a foundation for exploring the role of the HMAs gene family in dealing with heavy metal stress conditions in A. catechu., (© 2024. The Author(s).)

Nanotechnology has emerged as a promising solution for tackling antibiotic resistance in monogastric animals, providing innovative methods to enhance animal health and well-being. This review explores the novel use of nanotechnology-based nanomaterials as substitutes for antibiotics in monogastric animals. With growing global concerns about antibiotic resistance and the need for sustainable practices in animal husbandry, nanotechnology offers a compelling avenue to address these challenges. The objectives of this review are to find out the potential of nanomaterials in improving animal health while reducing reliance on conventional antibiotics. We examine various forms of nanomaterials and their roles in promoting gut health and also emphasize fresh perspectives brought by integrating nanotechnology into animal healthcare. Additionally, we delve into the mechanisms underlying the antibacterial properties of nanomaterials and their effectiveness in combating microbial resistance. By shedding light on the transformative role of nanotechnology in animal production systems. This review contributes to our understanding of how nanotechnology can provide safer and more sustainable alternatives to antibiotics., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Pavel Horky reports financial support was provided by 10.13039/501100008775Mendel University in Brno. Pavel Horky reports a relationship with Mendel University in Brno that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Understanding the precursors leading to rock fracture is crucial for ensuring safety in mining and geotechnical engineering projects. To effectively discern these precursors, a collaborative monitoring approach that integrates multiple sources of information is imperative. This paper considered a rock multi-parameter monitoring loading system, incorporating infrared radiation and acoustic emission monitoring technologies to simultaneously track the rock fracture process. The study delves into the spatiotemporal evolution patterns of infrared radiation and acoustic emission in rock under loading. Utilizing stress, cumulative acoustic emission count, and average infrared radiation temperature (AIRT), the paper establishes a comprehensive evaluation model termed "acoustic-thermal-stress" fusion information, employing principal component analysis (PCA). The research reveals that the sensitivity to rock sample damage response follows the sequence of cumulative acoustic emission count, AIRT, and stress. Furthermore, a novel method for identifying rock fracture precursors is proposed, based on the first derivative of the comprehensive evaluation model. This method addresses the limitations of single physical field information, enhancing the robustness of monitoring data. It determines the average stress level of fracture precursors to be 0.77σ max . Subsequently, the study defines the probability function of rock damage during loading and fracture, enabling the realization of probability-based warnings for rock fracture. This approach introduces a new perspective on rock fracture prediction, significantly contributing to safety monitoring and warning systems in mine safety and geotechnical engineering. The findings of this research hold paramount engineering significance, offering valuable insights for enhancing safety measures in such projects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To determine the community prevalence of psychiatric disorders in adult population and describe the prevalence by age, men-women, urban-rural strata., Methods: A nationwide household survey was conducted in 2019 where adults aged 18 years and above were selected by a multicentric, stratified, systematic random approach. The Self-Reporting Questionnaire (SRQ) was used for screening purpose and screened positive individuals were interviewed by research psychiatrists and diagnosed according the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria., Results: Overall adult response rate for this survey was 90.4%. In total, of the 7270 adults, 1570 (21.6%) came positive on the SRQ. Overall prevalence of mental disorders found was 18.7% ((95% CI: 17.4%-20.0%). Women reported higher prevalence of psychiatric disorders than men (21.5% vs 15.7%). No significant difference was observed between urban and rural residents (18.9% vs 18.7%). Most common psychiatric disorders found were depressive disorders (6.7%), anxiety disorders (4.7%), somatic symptom and related disorders (2.3%), sleep-wake disorders (1%) and schizophrenia spectrum disorders (1%)., Conclusions: The study revealed that a substatial proportion of adults received diagnoses for psychiatric disorders. Once again, our findings emphasize the need for development of comprehensive mental healthcare services., Competing Interests: Declaration of Competing Interest We have no known conflict of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To determine the utility of 5-aminolevulinic acid (5-ALA) fluorescence for resection of head and neck carcinoma., Methods: In this prospective pilot trial, 5-ALA was administered as an oral suspension 3-5 h prior to induction of anesthesia for resection of head and neck squamous cell carcinoma (HNSCC). Following resection, 405 nm blue light was applied, and fluorescence of the tumor as well as the surgical bed was recorded. Specimen fluorescence intensity was graded categorically as none (score = 0), mild (1), moderate (2), or robust (3) by the operating surgeon intraoperatively and corroborated with final pathologic diagnosis., Results: Seven patients underwent resection with 5-ALA. Five (83%) were male with an age range of 33-82 years (mean = 60). Sites included nasal cavity (n = 3), oral cavity (n = 3), and the larynx (n = 1). All specimens demonstrated robust fluorescence when 5-ALA was administered 3-5 h preoperatively. 5-ALA fluorescence predicted the presence of perineural invasion, a positive margin, and metastatic lymphadenopathy. Two patients had acute photosensitivity reactions, and one patient had a temporary elevation of hepatic enzymes., Conclusions: 5-ALA induces robust intraoperative fluorescence of HNSCC, capable of demonstrating a positive margin, perineural invasion, and metastatic nodal disease. Although no conclusions are there about the safety of this drug in the head and neck cancer population, our study parallels the extensive safety data in the neurosurgical literature. Future applications may include intraoperative assessment of margin status, diagnostic accuracy, and impacts on survival., Level of Evidence: 4 Laryngoscope, 134:741-748, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Gastrointestinal stromal tumor is considered the most common mesenchymal neoplasm of the gastrointestinal tract. The majority of gastrointestinal stromal tumor cases are located in the stomach and usually affects older adults. Most of gastrointestinal stromal tumor cases are sporadic; however, few have a syndromic association, including Carney triad, Carney-Stratakis syndrome, familial gastrointestinal stromal tumor syndrome, and neurofibromatosis type 1., Case Presentation: Herein, we report a rare case of a 54-year-old Middle-Eastern female with multifocal gastrointestinal stromal tumor mixed type (epithelioid and spindle cell type) with osseous metaplasia. Fluoresce in situ hybridization analysis of platelet-derived growth factor receptor alpha revealed deletion in 42% of the tumor cells studied. Interestingly, next generation sequencing revealed platelet-derived growth factor receptor alpha exon 12 mutation (p.Y555C) and exon 14 mutation (p.N659Y)., Conclusions: In conclusion, osseous metaplasia in GIST is a very rare event and only few cases are reported in the literature. The number of reported cases is inadequate to confirm the pathogenesis and the prognosis., (© 2023. The Author(s).)

Pectinolytic enzymes are among the important group of industrial enzymes that have wide applications in different food industries. In this study, pectinase-based silica nanocarriers were synthesized using co-precipitation and cross-linking techniques. The resulting silica nanoparticles were investigated using scanning electron microscopy (SEM), energy-dispersive electron microscopy (EDEX), and X-ray diffraction (XRD) for determination of its morphology, elemental composition, and crystalline pattern. Under the optimal immobilization conditions like 1.5 % glutaraldehyde, 3000 IU/mg pectinase concentration, 90 min immobilization time and 40 °C immobilization temperature, pectinase showed maximum immobilization yield. The immobilization of pectinase onto the silica nanocarriers led to enhanced catalytic characteristics, displaying higher enzymatic activity across various temperature and pH levels compared to soluble pectinase. Moreover, the immobilization substantially improved the temperature stability of pectinase, exhibiting 100 % of its initial activity even after 120 h of pre-incubation at 50 °C. Additionally, the silica nanocarrier pectinase retained 100 % of its original activity even after being reused 10 times in a single batch of reactions. These findings indicate that the immobilization of silica nanocarriers effectively enhances pectinase's industrial capabilities, making it economically feasible for industrial use and an efficient system for various biotechnological applications., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Published by Elsevier Ltd.)

Background: Osteoarthritis (OA) is a debilitating joints disease affecting millions of people worldwide. As OA progresses, chondrocytes experience heightened catabolic activity, often accompanied by alterations in the extracellular environment's osmolarity and acidity. Nevertheless, the precise mechanism by which chondrocytes perceive and respond to acidic stress remains unknown. Recently, there has been growing interest in pH-sensing G protein-coupled receptors (GPCRs), such as GPR68, within musculoskeletal tissues. However, function of GPR68 in cartilage during OA progression remains unknown. This study aims to identify the role of GPR68 in regulation of catabolic gene expression utilizing an in vitro model that simulates catabolic processes in OA., Methods: We examined the expression of GPCR by analyzing high throughput RNA-Seq data in human cartilage isolated from healthy donors and OA patients. De-identified and discarded OA cartilage was obtained from joint arthroplasty and chondrocytes were prepared by enzymatic digestion. Chondrocytes were treated with GPR68 agonist, Ogerin and then stimulated IL1β and RNA isolation was performed using Trizol method. Reverse transcription was done using the cDNA synthesis kit and the expression of GPR68 and OA related catabolic genes was quantified using SYBR® green assays., Results: The transcriptome analysis revealed that pH sensing GPCR were expressed in human cartilage with a notable increase in the expression of GPR68 in OA cartilage which suggest a potential role for GPR68 in the pathogenesis of OA. Immunohistochemical (IHC) and qPCR analyses in human cartilage representing various stages of OA indicated a progressive increase in GPR68 expression in cartilage associated with higher OA grades, underscoring a correlation between GPR68 expression and the severity of OA. Furthermore, IHC analysis of Gpr68 in murine cartilage subjected to surgically induced OA demonstrated elevated levels of GPR68 in knee cartilage and meniscus. Using IL1β stimulated in vitro model of OA catabolism, our qPCR analysis unveiled a time-dependent increase in GPR68 expression in response to IL1β stimulation, which correlates with the expression of matrix degrading proteases suggesting the role of GPR68 in chondrocytes catabolism and matrix degeneration. Using pharmacological activator of GPR68, our results further showed that GPR68 activation repressed the expression of MMPs in human chondrocytes., Conclusions: Our results demonstrated that GPR68 was robustly expressed in human cartilage and mice and its expression correlates with matrix degeneration and severity of OA progression in human and surgical model. GPR68 activation in human chondrocytes further repressed the expression of MMPs under OA pathological condition. These results identify GPR68 as a possible therapeutic target in the regulation of matrix degradation during OA., Competing Interests: The authors declare that they have no competing interests., (© 2023 Khan et al.)

Human induced pluripotent stem cells (hiPSCs) hold immense promise in regenerative medicine as they can differentiate into various cell lineages, including adipocytes, osteoblasts, and chondrocytes. Precisely guiding hiPSC-derived mesenchymal progenitor cells (iMSCs) towards specific differentiation pathways is crucial for harnessing their therapeutic potential in tissue engineering, disease modeling, and regenerative therapies. To achieve this, we present a comprehensive and reproducible protocol for effectively differentiating iMSCs into adipocytes and osteoblasts. The differentiation process entails culturing iMSCs in tailored media supplemented with specific growth factors, which act as cues to initiate adipogenic or osteogenic commitment. Our protocol provides step-by-step guidelines for achieving adipocyte and osteoblast differentiation, ensuring the generation of mature and functional cells. To validate the success of differentiation, key assessment criteria are employed. For adipogenesis, the presence of characteristic lipid droplets within the iMSC-derived cells is considered indicative of successful differentiation. Meanwhile, Alizarin Red staining serves as a marker for the osteogenic differentiation, confirming the formation of mineralized nodules. Importantly, the described method stands out due to its simplicity, eliminating the need for specialized equipment, expensive materials, or complex reagents. Its ease of implementation offers an attractive advantage for researchers seeking robust and cost-effective approaches to derive adipocytes and osteoblasts from iMSCs. Overall, this protocol establishes a foundation for exploring the therapeutic potential of hiPSC-derived cells and advancing the field of regenerative medicine. Key features • iMSC derivation in this protocol uses embryonic body formation technique. • Adipogenesis and osteogenesis protocols were optimized for human iPSC-derived iMSCs. • Derivation of iMSC from hiPSC was developed in a feeder-free culture condition. • This protocol does not include human iPSC reprogramming strategies., Competing Interests: Competing interestsThere are no competing interests., (©Copyright : © 2023 The Authors; This is an open access article under the CC BY license.)

Physician burnout is a global concern that can lead to exhaustion, ineffectiveness, and poor health outcomes. Burnout has been linked to a variety of societal and professional variables worldwide. This cross-sectional, multi-centered study was conducted by face-to-face interviews between April 2019 and December 2021 at sixty-two (62) tertiary level hospitals to identify potential risk factors for burnout among Bangladeshi physicians, which is essential for preventing adverse impact on their well-being, improving overall quality of life, and facilitating measures to manage stress and maintain a healthy work-life balance. A simple random sampling technique in conjunction with a structured questionnaire was used to collect a total of 1434 responses, assuming 20 % of the sample as non-responsive. Univariate, bivariate, and multinomial logistic regression statistical analyses were performed to determine the risk factors and associate the level of severity. The distribution of burnout status differs significantly at distinct covariate levels, such as working place, working hour, prevalence of potential interpersonal conflicts (subsequent increase of adjusted odds ratios i.e.; 6.52, 8.82, 11.41, and 37.07 is observed for physicians having interpersonal conflicts with both co-workers & family members), job dissatisfaction, annoyed feeling while dealing with patients (adjusted odds ratios are 529.68, 518.26,983.87 and 849.57 respectively) and some other significant factors of the physicians. This study also reveals that the female physicians, physicians with age 40-49, physicians with additional liabilities, physicians with job dissatisfaction, less salary compared to the workload, less flexibility and security at the job sector as well as obese physicians are at high risk of burnout. These results are statistically significant with a p value ≤ 0.05. To reduce burnout of Bangladeshi physicians, it is necessary to address the risk factors, create supportive workplaces, maintain a healthy work-life balance, provide opportunities for self-care, and promote mental health., 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., (© 2023 The Authors.)

Induced pluripotent stem cells (iPSCs) generated from human sources are valuable tools for studying skeletal development and diseases, as well as for potential use in regenerative medicine for skeletal tissues such as articular cartilage. To successfully differentiate human iPSCs into functional chondrocytes, it is essential to establish efficient and reproducible strategies that closely mimic the physiological chondrogenic differentiation process. Here, we describe a simple and efficient protocol for differentiation of human iPSCs into chondrocytes via generation of an intermediate population of mesenchymal progenitors. These methodologies include step-by-step procedures for mesenchymal derivation, induction of chondrogenic differentiation, and evaluation of the chondrogenic marker gene expression. In this protocol, we describe the detailed procedure for successful derivation of mesenchymal progenitor population from human iPSCs, which are then differentiated into chondrocytes using high-density culture conditions by stimulating with bone morphogenetic protein-2 (BMP-2) or transforming growth factor beta-3 (TGFβ-3). The differentiated iPSCs exhibit temporal expression of cartilage genes and accumulation of a cartilaginous extracellular matrix in vitro, indicating successful chondrogenic differentiation. These detailed methodologies help effective differentiation of human iPSCs into the chondrogenic lineage to obtain functional chondrocytes, which hold great promise for modeling skeletal development and disease, as well as for potential use in regenerative medicine for cell-based therapy for cartilage regeneration. Key features • Differentiation of human iPSCs into chondrocytes using 3D culture methods. • Uses mesenchymal progenitors as an intermediate for differentiation into chondrocytes., Competing Interests: Competing interestsThe authors declare no conflicts of interest., (©Copyright : © 2023 The Authors; This is an open access article under the CC BY license.)

In this research, we focused on the production of amylose-lipid nanocomposite material (ALN) through a green synthesis technique utilizing high-speed homogenization. Our aim was to investigate this novel material's distinctive physicochemical features and its potential applications as a low-glycemic gelling and functional food ingredient. The study begins with the formulation of the amylose-lipid nanomaterial from starch and fatty acid complexes, including stearic, palmitic, and lauric acids. Structural analysis reveals the presence of ester carbonyl functionalities, solid matrix structures, partial crystallinities, and remarkable thermal stability within the ALN. Notably, the ALN exhibits a significantly low glycemic index (GI, 40%) and elevated resistance starch (RS) values. The research extends to the formulation of ALN into nanocomposite hydrogels, enabling the evaluation of its anthocyanin absorption capacity. This analysis provides valuable insights into the rheological properties and viscoelastic behavior of the resulting hydrogels. Furthermore, the study investigates anthocyanin encapsulation and retention by ALN-based hydrogels, with a particular focus on the influence of pH and physical cross-link networks on the uptake capacity presenting stearic-acid (SA) hydrogel with the best absorption capacity. In conclusion, the green-synthesized (ALN) shows remarkable functional and structural properties. The produced ALN-based hydrogels are promising materials for a variety of applications, such as medicine administration, food packaging, and other industrial purposes.

This study aims to develop a nanodrug delivery system containing podophyllotoxin (PTOX), a known anticancer drug, loaded on graphene oxide (GO). The system's ability to inhibit α-amylase and α-glucosidase enzymes was also investigated. PTOX was isolated from Podophyllum hexandrum roots with a yield of 2.3%. GO, prepared by Hummer's method, was converted into GO-COOH and surface-mobilized using polyethylene glycol (PEG) (1:1) in an aqueous medium to obtain GO-PEG. PTOX was loaded on GO-PEG in a facile manner with a 25% loading ratio. All the samples were characterized using FT-IR spectroscopy, UV/visible spectroscopy, and scanning electron microscopy (SEM). In FT-IR spectral data, GO-PEG-PTOX exhibited a reduction in acidic functionalities and there was an appearance of the ester linkage of PTOX with GO. The UV/visible measurements suggested an increase of absorbance in 290-350 nm regions for GO-PEG, suggesting the successful drug loading on its surface (25%). GO-PEG-PTOX exhibited a rough, aggregated, and scattered type of pattern in SEM with distinct edges and binding of PTOX on its surface. GO-PEG-PTOX remained potent in inhibiting both α-amylase and α-glucosidase with IC 50 values of 7 and 5 mg/mL, closer to the IC 50 of pure PTOX (5 and 4.5 mg/mL), respectively. Owing to the 25% loading ratio and 50% release within 48 h, our results are much more promising. Additionally, the molecular docking studies confirmed four types of interactions between the active centers of enzymes and PTOX, thus supporting the experimental results. In conclusion, the PTOX-loaded GO nanocomposites are promising α-amylase- and α-glucosidase-inhibitory agents when applied in vitro and have been reported for the first time., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The tumor microenvironment (TME), which includes both cellular and non-cellular elements, is now recognized as one of the major regulators of the development of primary tumors, the metastasis of which occurs to specific organs, and the response to therapy. Development of immunotherapy and targeted therapies have increased knowledge of cancer-related inflammation Since the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCB) limit immune cells from entering from the periphery, it has long been considered an immunological refuge. Thus, tumor cells that make their way "to the brain were believed to be protected from the body's normal mechanisms of monitoring and eliminating them. In this process, the microenvironment and tumor cells at different stages interact and depend on each other to form the basis of the evolution of tumor brain metastases. This paper focuses on the pathogenesis, microenvironmental changes, and new treatment methods of different types of brain metastases. Through the systematic review and summary from macro to micro, the occurrence and development rules and key driving factors of the disease are revealed, and the clinical precision medicine of brain metastases is comprehensively promoted. Recent research has shed light on the potential of TME-targeted and potential treatments for treating Brain metastases, and we'll use that knowledge to discuss the advantages and disadvantages of these approaches., 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 © 2023 Khan, Khan, Sala, Khan, Ud Din, Khan, Hassan, Khan and Liu.)

Many bacteria possess dynamic filaments called Type IV pili (T4P) that perform diverse functions in colonization and dissemination, including host cell adhesion, DNA uptake, and secretion of protein substrates-exoproteins-from the periplasm to the extracellular space. The Vibrio cholerae toxin-coregulated pilus (TCP) and the enterotoxigenic  Escherichia coli  CFA/III pilus each mediates export of a single exoprotein, TcpF and CofJ, respectively. Here, we show that the disordered N-terminal segment of mature TcpF is the export signal (ES) recognized by TCP. Deletion of the ES disrupts secretion and causes TcpF to accumulate in the V. cholerae periplasm. The ES alone can mediate export of Neisseria gonorrhoeae FbpA by V. cholerae in a T4P-dependent manner. The ES is specific for its autologous T4P machinery as CofJ bearing the TcpF ES is exported by V. cholerae , whereas TcpF bearing the CofJ ES is not. Specificity is mediated by binding of the ES to TcpB, a minor pilin that primes pilus assembly and forms a trimer at the pilus tip. Finally, the ES is proteolyzed from the mature TcpF protein upon secretion. Together, these results provide a mechanism for delivery of TcpF across the outer membrane and release into the extracellular space.

Goats are generally called a "poor man's cow" because they not only provide meat and milk but also other assistance to their owners, including skins for leather production and their waste, which can be used as compost for fertilizer. Multiple ovulation and embryo transfer (MOET) is an important process in embryo biotechnology, as it increases the contribution of superior female goats to breeding operations. The field of assisted reproductive biotechnologies has seen notable progress. However, unlike in cattle, the standard use of superovulation and other reproductive biotechnologies has not been widely implemented for goats. Multiple intrinsic and extrinsic factors can alter the superovulatory response, significantly restricting the practicability of MOET technology. The use of techniques to induce superovulation is a crucial step in embryo transfer (ET), as it accelerates the propagation of animals with superior genetics for desirable traits. Furthermore, the conventional superovulation techniques based on numerous injections are not appropriate for animals and are labor-intensive as well as expensive. Different approaches and alternatives have been applied to obtain the maximum ovarian response, including immunization against inhibin and the day-0 protocol for the synchronization of the first follicular wave. While there are several studies available in the literature on superovulation in cattle, research on simplified superovulation in goats is limited; only a few studies have been conducted on this topic. This review describes the various treatments with gonadotropin that are used for inducing superovulation in various dairy goat breeds worldwide. The outcomes of these treatments, in terms of ovulation rate and recovery of transferrable embryos, are also discussed. Furthermore, this review also covers the recovery of oocytes through repeated superovulation from the same female goat that is used for somatic cell nuclear transfer (SCNT)., 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 © 2023 Khan, Jamal, Khan, Ullah, Jabbar, Khan and Liu.)

Due to functional and physicochemical properties, starch in its native state has limited range of applications. Simultaneously, information on effects of different sugars and their interactions with modified starch on gluten-free model dough is also limited. To better overcome these restrictions, the effects of sucrose, trehalose, maltose and xylose on rheology, water mobility and microstructure of gluten-free dough prepared with high hydrostatic pressure (HHP) treated maize (MS), potato (PS) and sweet potato starch (SS) were investigated. MS, PS and SS dough with trehalose exhibited a lower degree of dependence of G' on frequency sweep (z'), higher strength (K) and relative elastic part of maximum creep compliance (J e /J max ), suggesting stable network structure formation. Total gas production (V T ) of MS dough with maltose, PS dough with sucrose and SS dough with trehalose was increased from 588 to 1454 mL, 537 to 1498 mL and 637 to 1455 mL respectively. Higher weakly bound water (T 22 ) was found in the dough with trehalose at 60 min of fermentation, suggesting more hydrogen bonds and stable network. Thus, trehalose might be a potential improver in HHP treated starch-based gluten-free products., 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 © 2023 Elsevier B.V. All rights reserved.)

To investigate the effect of water on the mechanical properties and acoustic emission (AE) characteristics of coal in the failure and deformation processes. Coal samples of different content were subjected to uniaxial compression tests and AE signals were monitored. The characteristics of the AE signals were further analyzed using fractal analysis. The results show that saturated coal samples have substantially reduced mechanical properties such as uniaxial compressive strength (UCS), dissipation energy, peak stress, and elastic modulus. Under loading, stress-strain curves are characterized by five distinct stages: (1) compaction; (2) linear elastic; (3) crack stable propagation; (4) crack accelerating propagation; and (5) post-peak and residual stages. Using phase-space theory, a novel Grassberger Procaccia (GP) algorithm was utilized to find the AE fractal characteristics of coal samples in different stages. It is significant to note that AE energy does not exhibit fractal characteristics in either the first or second stages. Contrary to the first two stages, the third stage showed obvious fractal characteristics. Fractal analysis of AE time sequences indicates that fractal dimension values change as stress increases, indicating the initiation of complex microcracks in coal. In the fourth stage, the fractal dimension rapidly declines as the strength reaches its limit, indicating the occurrence of macrocracks. However, fractal dimensions continued to decrease further or increased slightly in the fifth stage. Consequently, the coal begins to collapse, potentially resulting in a disaster and failure. It is, therefore, possible to accurately predict coal and rock dynamic failures and microcrack mechanisms by observing the subsequent sudden drop in the correlation dimension of the AE signals in response to different stages of loading., (© 2023. The Author(s).)

Legumain (LGMN) has been demonstrated to be overexpressed not just in breast, prostatic, and liver tumor cells, but also in the macrophages that compose the tumor microenvironment. This supports the idea that LGMN is a pivotal protein in regulating tumor development, invasion, and dissemination. Targeting LGMN with siRNA or chemotherapeutic medicines and peptides can suppress cancer cell proliferation in culture and reduce tumor growth in vivo . Furthermore, legumain can be used as a marker for cancer detection and targeting due to its expression being significantly lower in normal cells compared to tumors or tumor-associated macrophages (TAMs). Tumor formation is influenced by aberrant expression of proteins and alterations in cellular architecture, but the tumor microenvironment is a crucial deciding factor. Legumain (LGMN) is an in vivo-active cysteine protease that catalyzes the degradation of numerous proteins. Its precise biological mechanism encompasses a number of routes, including effects on tumor-associated macrophage and neovascular endothelium in the tumor microenvironment. The purpose of this work is to establish a rationale for thoroughly investigating the function of LGMN in the tumor microenvironment and discovering novel tumor early diagnosis markers and therapeutic targets by reviewing the function of LGMN in tumor genesis and progression and its relationship with tumor milieu., 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 © 2023 Khan, Khan, Khan, Ud Din, Khan, Khan and Liu.)

Induced pluripotent stem cells (iPSCs) are potential cell sources for regenerative medicine. The iPSCs exhibit a preference for lineage differentiation to the donor cell type indicating the existence of memory of origin. Although the intrinsic effect of the donor cell type on differentiation of iPSCs is well recognized, whether disease-specific factors of donor cells influence the differentiation capacity of iPSC remains unknown. Using viral based reprogramming, we demonstrated the generation of iPSCs from chondrocytes isolated from healthy (AC-iPSCs) and osteoarthritis cartilage (OA-iPSCs). These reprogrammed cells acquired markers of pluripotency and differentiated into uncommitted mesenchymal-like progenitors. Interestingly, AC-iPSCs exhibited enhanced chondrogenic potential as compared OA-iPSCs and showed increased expression of chondrogenic genes. Pan-transcriptome analysis showed that chondrocytes derived from AC-iPSCs were enriched in molecular pathways related to energy metabolism and epigenetic regulation, together with distinct expression signature that distinguishes them from OA-iPSCs. Our molecular tracing data demonstrated that dysregulation of epigenetic and metabolic factors seen in OA chondrocytes relative to healthy chondrocytes persisted following iPSC reprogramming and differentiation toward mesenchymal progenitors. Our results suggest that the epigenetic and metabolic memory of disease may predispose OA-iPSCs for their reduced chondrogenic differentiation and thus regulation at epigenetic and metabolic level may be an effective strategy for controlling the chondrogenic potential of iPSCs., Competing Interests: NK, MD, SC, PP, PB, LM, RG, HD No competing interests declared

To increase its operational stability and ongoing reusability, B. subtilis pectinase was immobilized on iron oxide nanocarrier. Through co-precipitation, magnetic iron oxide nanoparticles were synthesized. Scanning electron microscopy (SEM) and energy dispersive electron microscopy (EDEX) were used to analyze the nanoparticles. Pectinase was immobilized using glutaraldehyde as a crosslinking agent on iron oxide nanocarrier. In comparison to free pectinase, immobilized pectinase demonstrated higher enzymatic activity at a variety of temperatures and pH levels. Immobilization also boosted pectinase's catalytic stability. After 120 h of pre-incubation at 50 °C, immobilized pectinase maintained more than 90% of its initial activity due to the iron oxide nanocarrier, which improved the thermal stability of pectinase at various temperatures. Following 15 repetitions of enzymatic reactions, immobilized pectinase still exhibited 90% of its initial activity. According to the results, pectinase's catalytic capabilities were enhanced by its immobilization on iron oxide nanocarrier, making it economically suitable for industrial use.

Diseases affecting the brain and spinal cord fall under the umbrella term "central nervous system disease". Most medications used to treat or prevent chronic diseases of the central nervous system cannot cross the blood-brain barrier (BBB) and hence cannot reach their intended target. Exosomes facilitate cellular material movement and signal transmission. Exosomes can pass the blood-brain barrier because of their tiny size, high delivery efficiency, minimal immunogenicity, and good biocompatibility. They enter brain endothelial cells via normal endocytosis and reverse endocytosis. Exosome bioengineering may be a method to produce consistent and repeatable isolation for clinical usage. Because of their tiny size, stable composition, non-immunogenicity, non-toxicity, and capacity to carry a wide range of substances, exosomes are indispensable transporters for targeted drug administration. Bioengineering has the potential to improve these aspects of exosomes significantly. Future research into exosome vectors must focus on redesigning the membrane to produce vesicles with targeting abilities to increase exosome targeting. To better understand exosomes and their potential as therapeutic vectors for central nervous system diseases, this article explores their basic biological properties, engineering modifications, and promising applications.

Background: To describe the key findings and lessons learned from an international pilot study that surveyed spinal cord injury programs in acute and rehabilitation facilities to understand the status of spinal cord injury care., Methods: An online survey with two questionnaires, a 74-item for acute care and a 51-item for rehabilitation, was used. A subset of survey items relevant to the themes of specialized care, timeliness, patient-centeredness, and evidence-based care were operationalized as structure or process indicators. Percentages of facilities reporting the structure or process to be present, and percentages of indicators met by each facility were calculated and reported separately for facilities from high-income countries (HIC) and from low and middle-income countries (LMIC) to identify "hard to meet" indicators defined as those met by less than two-thirds of facilities and to describe performance level., Results: A total of 26 acute and 26 rehabilitation facilities from 25 countries participated in the study. The comparison of the facilities based on the country income level revealed three general observations: 1) some indicators were met equally well by both HIC and LMIC, such as 24-hour access to CT scanners in acute care and out-patient services at rehabilitation facilities; 2) some indicators were hard to meet for LMIC but not for HIC, such as having a multidisciplinary team for both acute and rehabilitation settings; and 3) some indicators were hard to meet by both HIC and LMIC, including having peer counselling programs. Variability was also observed for the same indicator between acute and rehabilitation facilities, and a wide range in the total number of indicators met among HIC facilities (acute 59-100%; rehabilitation 36-100%) and among LMIC facilities (acute: 41-82%; rehabilitation: 36-93%) was reported., Conclusions: Results from this international pilot study found that the participating acute and rehabilitation facilities on average adhered to 74% of the selected indicators, suggesting that the structure and processes to provide ideal traumatic spinal cord injury care were broadly available. Recruiting a representative sample of SCI facilities and incorporating regional attributes in future surveys will be helpful to examine factors affecting adherence to indicators., (© 2022. The Author(s).)

Micro RNAs (miRNAs) have been recognized as important regulators that are indispensable for testicular development and spermatogenesis. miRNAs are endogenous transcriptomic elements and mainly regulate the gene expression at post-transcriptional levels; however, the key role of miRNA in bovine testicular growth is not clearly understood. Thus, supposing to unveil the transcriptomics expression changes in the developmental processes of bovine testes, we selected three immature calves and three sexually mature bulls of the local Wandong breed for testicular-tissue sample collection. The cDNA libraries of experimental animals were established for RNA-sequencing analysis. We detected the miRNA expression in testes by using high-throughput sequencing technology, and bioinformatics analysis followed. The differentially expressed (DE) data showed that 151 miRNAs linked genes were significantly DE between immature and mature bull testes. Further, in detail, 64 were significantly up-regulated and 87 were down-regulated in the immature vs. mature testes ( p -value < 0.05). Pathway analyses for miRNA-linked genes were performed and identified JAG2, BCL6, CFAP157, PHC2, TYRO3, SEPTIN6 , and BSP3 ; these genes were involved in biological pathways such as TNF signaling, T cell receptor, PI3KAkt signaling, and functions affecting testes development and spermatogenesis. The DE miRNAs including MIR425, MIR98, MIR34C, MIR184, MIR18A, MIR136, MIR15A, MIR1388 and MIR210 were associated with cattle-bull sexual maturation and sperm production. RT-qPCR validation analysis showed a consistent correlation to the sequencing data findings. The current study provides a good framework for understanding the mechanism of miRNAs in the development of testes and spermatogenesis.

The genome contributes to the uniqueness of an individual breed, and enables distinctive characteristics to be passed from one generation to the next. The allelic heterogeneity of a certain breed results in a different response to a pathogen with different genomic expression. Disease resistance in chicken is a polygenic trait that involves different genes that confer resistance against pathogens. Such resistance also involves major histocompatibility (MHC) molecules, immunoglobulins, cytokines, interleukins, T and B cells, and CD4+ and CD8+ T lymphocytes, which are involved in host protection. The MHC is associated with antigen presentation, antibody production, and cytokine stimulation, which highlight its role in disease resistance. The natural resistance-associated macrophage protein 1 (Nramp-1), interferon (IFN), myxovirus-resistance gene, myeloid differentiation primary response 88 (MyD88), receptor-interacting serine/threonine kinase 2 (RIP2), and heterophile cells are involved in disease resistance and susceptibility of chicken. Studies related to disease resistance genetics, epigenetics, and quantitative trait loci would enable the identification of resistance markers and the development of disease resistance breeds. Microbial infections are responsible for significant outbreaks and have blighted the poultry industry. Breeding disease-resistant chicken strains may be helpful in tackling pathogens and increasing the current understanding on host genetics in the fight against communicable diseases. Advanced technologies, such as the CRISPR/Cas9 system, whole genome sequencing, RNA sequencing, and high-density single nucleotide polymorphism (SNP) genotyping, aid the development of resistant breeds, which would significantly decrease the use of antibiotics and vaccination in poultry. In this review, we aimed to reveal the recent genetic basis of infection and genomic modification that increase resistance against different pathogens in chickens., 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 © 2022 Gul, Habib, Khan, Rahman, Khan, Wang, Khan and Liu.)

The COVID-19 series is obviously one of the most volatile time series with lots of spikes and oscillations. The conventional integer-valued auto-regressive time series models (INAR) may be limited to account for such features in COVID-19 series such as severe over-dispersion, excess of zeros, periodicity, harmonic shapes and oscillations. This paper proposes alternative formulations of the classical INAR process by considering the class of high-ordered INAR models with harmonic innovation distributions. Interestingly, the paper further explores the bivariate extension of these high-ordered INARs. South Africa and Mauritius' COVID-19 series are re-scrutinized under the optic of these new INAR processes. Some simulation experiments are also executed to validate the new models and their estimation procedures., 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., (© 2022 The Author(s).)

The current studies were focused on the phytochemical profiling of two local wild Artemisia species, Artemisia scoparia and Artemisia absinthium leaves’ essential oils, extracted via the hydro distillation method along with evaluation of their antioxidant as well as antimicrobial effects. The constituents of EOs were identified using a combined gas chromatography-mass spectrometric (GC-MS) technique. A total of 25 compounds in A. scoparia essential oil (EOAS) were identified, and 14 compounds with percentage abundance of >1% were tabulated, the major being tocopherol derivatives (47.55%). A total of nine compounds in Artemisia absinthium essential oil (EOAA) were enlisted (% age > 1%), the majority being oleic acid derivatives (41.45%). Strong antioxidant effects were pronounced by the EOAS in DPPH (IC50 = 285 ± 0.82 µg/mL) and in ABTS (IC50 = 295 ± 0.32 µg/mL) free radical scavenging assays. Both the EOs remained potent in inhibiting the growth of bacterial species; Escherichia coli (55−70%) and Shigella flexneri (60−75%) however remained moderately effective against Bacillus subtilis as well as Staphylococcus aureus. Both EOAS and EOAA strongly inhibited the growth of the tested fungal species, especially Aspergillus species (up to 70%). The oils showed anti-cholinesterase potential by inhibiting both Acetylcholinesterase (AChE; IC50 = 30 ± 0.04 µg/mL (EOAS), 32 ± 0.05 µg/mL (EOAA) and Butyrylcholinesterase (BChE; IC50 = 34 ± 0.07 µg/mL (EOAS), 36 ± 0.03 µg/mL (EOAA). In conclusion, the essential oils of A. scoparia and A. absinthium are promising antioxidant, antimicrobial and anticholinergic agents with a different phytochemical composition herein reported for the first time.

Background: Intervertebral disc (IVD) degeneration is strongly associated with low back pain and is highly prevalent in the elderly population. Hallmarks of IVD degeneration include cell loss and extracellular matrix degradation. The PH domain leucine-rich-repeats protein phosphatase (PHLPP1) is highly expressed in diseased cartilaginous tissues where it is linked to extracellular matrix degradation. This study explored the ability of PHLPP1 deficiency to protect against age-related spontaneous IVD degeneration., Methods: Lumbar IVDs of global Phlpp1 knockout (KO) and wildtype (WT) mice were collected at 5 months (young) and 20 months (aged). Picrosirius red-alcian blue staining (PR-AB) was performed to examine IVD structure and histological score. The expression of aggrecan, ADAMTS5, KRT19, FOXO1 and FOXO3 was analyzed through immunohistochemistry. Cell apoptosis was assessed by TUNEL assay. Human nucleus pulposus (NP) samples were obtained from patients diagnosed with IVD degeneration. PHLPP1 knockdown in human degenerated NP cells was conducted using small interfering RNA (siRNA) transfection. The expression of PHLPP1 regulated downstream targets was analyzed via immunoblot and real time quantitative PCR., Results: Histological analysis showed that Phlpp1 KO decreased the prevalence and severity of age-related IVD degeneration. The deficiency of PHLPP1 promoted the increased expression of NP phenotypic marker KRT19, aggrecan and FOXO1, and decreased levels of ADMATS5 and cell apoptosis in the NP of aged mice. In degenerated human NP cells, PHLPP1 knockdown induced FOXO1 protein levels while FOXO1 inhibition offset the beneficial effects of PHLPP1 knockdown on KRT19 gene and protein expression., Conclusions: Our findings indicate that Phlpp1 deficiency protected against NP phenotypic changes, extracellular matrix degradation, and cell apoptosis in the process of IVD degeneration, probably through FOXO1 activation, making PHLPP1 a promising therapeutic target for treating IVD degeneration., Competing Interests: The authors have no conflict of interest associated with this work., (© 2022 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Fatigue cracks are a major defect in metal alloys, and specifically, their study poses defect evaluation challenges in aluminum aircraft alloys. Existing inline inspection tools exhibit measurement uncertainties. The physical-based methods for crack growth prediction utilize stress analysis models and the crack growth model governed by Paris' law. These models, when utilized for long-term crack growth prediction, yield sub-optimum solutions and pose several technical limitations to the prediction problems. The metaheuristic optimization algorithms in this study have been conducted in accordance with neural networks to accurately forecast the crack growth rates in aluminum alloys. Through experimental data, the performance of the hybrid metaheuristic optimization-neural networks has been tested. A dynamic Levy flight function has been incorporated with a chimp optimization algorithm to accurately train the deep neural network. The performance of the proposed predictive model has been tested using 7055 T7511 and 6013 T651 alloys against four competing techniques. Results show the proposed predictive model achieves lower correlation error, least relative error, mean absolute error, and root mean square error values while shortening the run time by 11.28%. It is evident through experimental study and statistical analysis that the crack length and growth rates are predicted with high fidelity and very high resolution.

Many metabolic bone diseases arise as a result excessive osteoclastic bone resorption, which has motivated efforts to identify new molecular targets that can inhibit the formation or activity of these bone-resorbing cells. Mounting evidence indicates that the transcription factor Runx1 acts as a transcriptional repressor of osteoclast formation. Prior studies using a conditional knockout approach suggested that Runx1 in osteoclast precursors acts as an inhibitor of osteoclastogenesis; however, the effects of upregulation of Runx1 on osteoclast formation remain unknown. In this study, we investigated the skeletal effects of conditional overexpression of Runx1 in preosteoclasts by crossing novel Runx1 gain-of-function mice (Rosa26-LSL-Runx1) with LysM-Cre transgenic mice. We observed a sex-dependent effect whereby overexpression of Runx1 in female mice increased trabecular bone microarchitectural indices and improved torsion biomechanical properties. These effects were likely mediated by delayed osteoclastogenesis and decreased bone resorption. Transcriptomics analyses during osteoclastogenesis revealed a distinct transcriptomic profile in the Runx1-overexpressing cells, with enrichment of genes related to redox signaling, apoptosis, osteoclast differentiation, and bone remodeling. These data further confirm the antiosteoclastogenic activities of Runx1 and provide new insight into the molecular targets that may mediate these effects., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Final adult height is a useful proxy measure of childhood nutrition and disease burden. Tall stature has been previously associated with decreased risk of all-cause mortality, decreased risk of major cardiovascular events and an increased risk of cancer. However, these associations have primarily been derived from people of European and East Asian backgrounds, and there are sparse data from other regions of the world., Methods: The Prospective Urban-Rural Epidemiology study is a large, longitudinal population study done in 21 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years. Height was measured in a standardized manner, without shoes, to the nearest 0.1 cm. During a median follow-up of 10.1 years (interquartile range 8.3-12.0), we assessed the risk of all-cause mortality, major cardiovascular events and cancer., Results: A total of 154 610 participants, enrolled since January 2003, with known height and vital status, were included in this analysis. Follow-up event data until March 2021 were used; 11 487 (7.4%) participants died, whereas 9291 (6.0%) participants had a major cardiovascular event and 5873 (3.8%) participants had a new diagnosis of cancer. After adjustment, taller individuals had lower hazards of all-cause mortality [hazard ratio (HR) per 10-cm increase in height 0.93, 95% confidence interval (CI) 0.90-0.96] and major cardiovascular events (HR 0.97, 95% CI 0.94-1.00), whereas the hazard of cancer was higher in taller participants (HR 1.23, 95% CI 1.18-1.28). The interaction p-values between height and country-income level for all three outcomes were <0.001, suggesting that the association with height varied by country-income level for these outcomes. In low-income countries, height was inversely associated with all-cause mortality (HR 0.88, 95% CI 0.84-0.92) and major cardiovascular events (HR 0.87, 95% CI 0.82-0.93). There was no association of height with these outcomes in middle- and high-income countries. The respective HRs for cancer in low-, middle- and high-income countries were 1.14 (95% CI 0.99-1.32), 1.12 (95% CI 1.04-1.22) and 1.20 (95% CI 1.14-1.26)., Conclusions: Unlike high- and middle-income countries, tall stature has a strong inverse association with all-cause mortality and major cardiovascular events in low-income countries. Improved childhood physical development and advances in population-wide cardiovascular treatments in high- and middle-income countries may contribute to this gap. From a life-course perspective, we hypothesize that optimizing maternal and child health in low-income countries may improve rates of premature mortality and cardiovascular events in these countries, at a population level., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Two-Dimensional (2D) object detection has been an intensely discussed and researched field of computer vision. With numerous advancements made in the field over the years, we still need to identify a robust approach to efficiently conduct classification and localization of objects in our environment by just using our mobile devices. Moreover, 2D object detection limits the overall understanding of the detected object and does not provide any additional information in terms of its size and position in the real world. This work proposes an object localization solution in Three-Dimension (3D) for mobile devices using a novel approach. The proposed method works by combining a 2D object detection Convolutional Neural Network (CNN) model with Augmented Reality (AR) technologies to recognize objects in the environment and determine their real-world coordinates. We leverage the in-built Simultaneous Localization and Mapping (SLAM) capability of Google's ARCore to detect planes and know the camera information for generating cuboid proposals from an object's 2D bounding box. The proposed method is fast and efficient for identifying everyday objects in real-world space and, unlike mobile offloading techniques, the method is well designed to work with limited resources of a mobile device.

This study reports the isolation of three new C 20 diterpenoid alkaloids, Chitralinine A-C ( 1 - 3 ) from the aerial parts of Delphinium chitralense . Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds ( 1 - 3 ) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC 50 value of 11.64 ± 0.08 μM against AChE, and 24.31 ± 0.33 μM against BChE, respectively. The molecular docking reflected a binding free energy of -16.400 K Cal-mol -1 for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer's disease.

This study was designed to evaluate the emulsifying and rheological properties of acorn protein isolate (API) in different pH mediums (pH 3, 7 and 9) and in the presence of ionic salts (1 M NaCl and 1 M CaCl2). API shows higher solubility in distilled water at pH 7, while at the same pH, a decrease in solubility was observed for API in the presence of CaCl2 (61.30%). A lower emulsifying activity index (EAI), lower stability index (ESI), larger droplet sizes and slight flocculation were observed for API in the presence of salts at different pHs. Importantly, CaCl2 treated samples showed relevantly higher EAI (252.67 m2/g) and ESI (152.67 min) values at all pH as compared to NaCl (221.76 m2/g), (111.82 min), respectively. A significant increase in interfacial protein concentration (4.61 mg/m2) was observed for emulsion at pH 9 with CaCl2, while the major fractions of API were observed in an interfacial layer after SDS-PAGE analysis. All of the emulsion shows shear thinning behavior (τc > 0 and n < 1), while the highest viscosity was observed for emulsion prepared with CaCl2 at pH 3 (11.03 ± 1.62). In conclusion, API, in the presence of ionic salts at acidic, neutral and basic pH, can produce natural emulsions, which could be substitutes for synthetic surfactants for such formulations.

In the emerging field of intramolecular charge transfer induced counterion migration, we report the new insights into photophysical features of luminescent donor-acceptor phosphonium dyes (D-π-) n A + [X - ] (π=-(C 6 H 4 ) x -). The unique connectivity of the phosphorus atom affords multipolar molecules with a variable number of arms and the electronic properties of the acceptor group. In the ion-paired form, the transition from dipolar to quadrupolar configuration enhances the low energy migration-induced band by providing the additional pathways for anion motion. The multipolar architecture, adjustable lengths of the π-spacers and the nature of counterions allow for efficient tuning of the emission and achieving nearly pure white light with quantum yields around 30 %. The methyl substituent at the phosphorus atom reduces the rate of ion migration and suppresses the red shifted bands, simultaneously improving total emission intensity. The results unveil the harnessing of the multiple emission of phosphonium fluorophores by anion migration via structure and branching of donor-acceptor arms., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

This report is devoted to the study of the flow of MHD nanofluids through a vertical porous plate with a temperature-dependent surface tension using the Cattaneo-Christov heat flow model. The energy equation was formulated using the Cattaneo-Christov heat flux model instead of Fourier's law of heat conduction. The Tiwari-Das model was used to take into account the concentration of nanoparticles when constructing the momentum equation. The problem is described mathematically using the boundary layer approach as a PDE, which is then converted into an ODE with the help of the transformation process. The solution finding process was completed by running the bvp4c code in MATLAB. A quantitative analysis of the influence of some newly occurring parameters on physical quantities was carried out using graphics. The addition of nanoparticles to the base fluid leads to an increase in both skin friction and thermal conductivity. The increase in thermal conductivity is the advantage, while the increase in skin friction is the disadvantage of the nanoparticle concentration. Marangoni convection has proven to be one of the most cost-effective tools available that can reduce skin friction. Marangoni convection improves the heat transfer coefficient during suction but decreases the heat transfer coefficient during the injection., (© 2022. The Author(s).)

Green synthesis has been introduced as an alternative to chemical synthesis due to the serious consequences. Metal nanoparticles synthesized through green approach have different pharmaceutical, medical and agricultural applications. The present study followed a green and simple route for the preparation of potentially bioactive gold nanoparticles (Au NPs). Au NPs were prepared via green synthesis approach using crude basic alkaloidal portion of the tuber of Delphinium chitralense. The green synthesized Au NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) fourier transform infrared (FTIR), and UV-Visible spectrophotometer. Morphological analysis shows that Au NPs have cubic geometry with different sizes. UV-Vis spectroscopic analysis confirmed the synthesis of Au NPs while XRD proved their pure crystalline phase. The Au NPs showed promising dose dependent inhibition of both AChE and BChE as compared to the crude as well as standard drug.

Microcephaly (MCPH) is a developmental anomaly of the brain known by reduced cerebral cortex and underdeveloped intellectual disability without additional clinical symptoms. It is a genetically and clinically heterogenous disorder. Twenty-five genes (involved in spindle positioning, Wnt signaling, centriole biogenesis, DNA repair, microtubule dynamics, cell cycle checkpoints, and transcriptional regulation) causing MCPH have been identified so far. Pakistani population has contributed in the identification of many MCPH genes. WES of three large consanguineous families revealed three pathogenic variants of MCPH1 , CENPJ , and CASK . One novel (c.1254delT) deletion variant of MCPH1 and one known (c.18delC) deletion variant of CENPJ were identified in family 1 and 2, respectively. In addition to this, we also identified a missense variant (c.1289G>A) of CASK in males individuals in family 3. Missense mutation in the CASK gene is frequent in the boys with intellectual disability and autistic traits which are the common features that are associated with FG Syndrome 4. The study reports novel and reported mutant alleles disrupting the working of genes vital for normal brain functioning. The findings of this study enhance our understanding about the genetic architecture of primary microcephaly in our local pedigrees and add to the allelic heterogeneity of 3 known MCPH genes. The data generated will help to develop specific strategies to reduce the high incidence rate of MCPH in Pakistani population., Competing Interests: The authors declare that they have no conflict of interests., (Copyright © 2022 Niaz Muhammad Khan et al.)

Objective: The COVID-19 pandemic has affected the mental health of children, adolescents, and their parents. This study aimed to assess the emotional and behavioural changes in children and adolescents and their association with parental depression during the COVID-19 pandemic in Bangladesh., Methods: On 7 May 2020 during COVID-19 lockdown, an online questionnaire was distributed through social media and made available for 10 days. Data were collected from parents of children aged 4 to 17 years. The Bangla version of the parent-rated version of the Strengths and Difficulties Questionnaire (SDQ) was used to determine the behavioural and emotional disturbances of the children and adolescents. The Bangla version of the Patient Health Questionnaire (PHQ-9) was used to assess the depression status of parents., Results: There were 512 participants. 21.5% of children and adolescents had emotional and behavioural problems. More boys than girls had abnormal peer relationship problems (21.1% vs 15.4%, p = 0.03). Of the parents, 16.2% had moderate depression, 5.5% moderately severe depression, and 2.9% severe depression. 8.2% and 2.9% of parents reported that it was very difficult and extremely difficult, respectively, to do work, take care of things at home, or get along with other people; the proportion was higher in mothers than fathers (χ 2 = 11.4, df = 3, p = 0.01). The PHQ-9 total score of parents mildly correlated with the SDQ score of children and adolescents ( r = 0.51, p = 0.01). In multiple linear regression, a combination of parent sex (β = 0.08, p < 0.001), child's history of developmental/psychiatric problems (β = 0.02, p = 0.67), and the SDQ total score of children and adolescents (β = 0.52, p = 0.03) accounted for 27% of the variability in PHQ total score of parents., Conclusion: During lockdown, the prevalence of psychiatric disorder among children and adolescents and their parents increased. The depression status of parents mildly correlated with the behavioural and emotional disturbances of children and adolescents. We recommend opening the schools as soon as the situation improves and developing interventions such as virtual mental health assessment for children and adolescents and their parents., Competing Interests: All authors have disclosed no conflicts of interest.

Aim: The novel coronavirus disease 2019 (COVID-19) is present in Bangladesh, and various control measures have been taken to flatten the epidemic curve. Due to the current demographic distribution in Bangladesh, young adults comprise almost one-third of the total population of the country. Therefore, their precautionary behavior is very important to ensure the success of preventive policies. This exploratory study examined the differences in the adoption of precautionary behaviors among young adults, and estimated and compared the predictors of precautionary behavior adoption among young adults living in the capital city Dhaka and a nearby district, Tangail., Subject and Methods: A total of 350 respondents from each district participated in the study. ANOVA and two-sample t-tests were utilized to detect differences in precautionary behavior across demographic groups of young adults, and quantile regression modeling was used to find the predictors of adopting precautionary behaviors and to compare these predictors between the two districts., Results: Individuals who had a postgraduate education and had good mental health tended to show better precautionary behaviors in Dhaka. Female respondents from Tangail who had no psychological distress took precautionary behaviors more often than their male counterparts. However, no significant differences in the adoption of precautionary behaviors to prevent COVID-19 among young adults were found between the two districts. Better self-control ability, higher education and good mental health emerged as factors that significantly shaped the precautionary behaviors of young adults in this study., Conclusion: Having better knowledge did not ensure better adoption of precautionary behaviors among the participants. In effect, the government's strong intervention to keep people maintaining social distance and a strict lockdown in severely affected areas are probable immediate solutions., Competing Interests: Conflict of interestThe authors declare that they do not have any conflict of interest., (© The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature 2021.)

Objectives: The number of modern healthcare providers in Bangladesh has increased and they are well equipped with modern medical instruments and infrastructures. Despite this development, patients seeking treatment from alternative healthcare providers are ongoing. Hence, this study aims to determine the underlying predictors of patients' choosing modern healthcare providers and health facilities for getting treatments., Setting: Data from the nationally representative Household Income and Expenditure Survey 2016-2017 conducted by the Bangladesh Bureau of Statistics were used., Participants: 34 512 respondents sought treatment for their illnesses from different types of available healthcare providers., Primary and Secondary Outcome Measure: Patients' choice of healthcare providers (primary) and predictors of patients' choice of modern healthcare providers (secondary)., Results: The study found that 40% of the patients visit modern healthcare providers primarily on having symptoms of illness, and the remainder goes to alternative healthcare providers. Patients living in urban areas (adjusted OR (AOR)=1.11, 95% CI 1.05 to 1.17, p<0.01), and if the travel time was between 1 and 2 hours (AOR=1.11, 95% CI 1.00 to 1.22, p<0.05) compared with travel time less than 1 hour, were positively associated to utilisation of modern healthcare facilities for their first consultation. The statistical models show that the predisposing and need factors do not significantly impact patients' choice of modern healthcare providers., Conclusions: The distribution of modern healthcare providers should be even across the country to eliminate the rural-urban divide in modern healthcare utilisation. Enhancing the digital provision of modern healthcare services could reduce travel time, omit transportation costs and save waiting time for treatment by the modern healthcare providers. Policymakers can think of introducing a national health insurance programme in Bangladesh as a potential policy instrument., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cognitive decline in dementia is associated with deficiency of the cholinergic system. In this study, five mono-carbonyl curcumin analogs were synthesized, and on the basis of their promising in vitro anticholinesterase activities, they were further investigated for in vivo neuroprotective and memory enhancing effects in scopolamine-induced amnesia using elevated plus maze (EPM) and novel object recognition (NOR) behavioral mice models. The effects of the synthesized compounds on the cholinergic system involvement in the brain hippocampus and their binding mode in the active site of cholinesterases were also determined. Compound h2 ( p < 0.001) and h3 ( p < 0.001) significantly inhibited the cholinesterases and reversed the effects of scopolamine by significantly reducing TLT ( p < 0.001) in EPM, while ( p < 0.001) increased the time exploring the novel object. The % discrimination index (DI) was significantly increased ( p < 0.001) in the novel object recognition test. The mechanism of cholinesterase inhibition was further validated through molecular docking study using MOE software. The results obtained from the in vitro, in vivo and ex vivo studies showed that the synthesized curcumin analogs exhibited significantly higher memory-enhancing potential, and h3 could be an effective neuroprotective agent. However, more study is suggested to explore its exact mechanism of action.

Wandong cattle are an autochthonous Chinese breed used extensively for beef production. The breed tolerates extreme weather conditions and raw feed and is resistant to tick-borne diseases. However, the genetic basis of testis development and sperm production as well as breeding management is not well established in local cattle. Therefore, improving the reproductive efficiency of bulls via genetic selection is crucial as a single bull can breed thousands of cows through artificial insemination (AI). Testis development and spermatogenesis are regulated by hundreds of genes and transcriptomes. However, circular RNAs (circRNAs) are the key players in many biological developmental processes that have not been methodically described and compared between immature and mature stages in Bovine testes. In this study, we performed total RNA-seq and comprehensively analyzed the circRNA expression profiling of the testis samples of six bulls at 3 years and 3 months of developmental age. In total, 17,013 circRNAs were identified, of which 681 circRNAs ( p -adjust < 0.05) were differentially expressed (DE). Among these DE circRNAs, 579 were upregulated and 103 were downregulated in calf and bull testes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that the identified target genes were classified into three broad functional categories, including biological process, cellular component, and molecular function, and were enriched in the lysine degradation, cell cycle, and cell adhesion molecule pathways. The binding interactions between DE circRNAs and microRNAs (miRNAs) were subsequently constructed using bioinformatics approaches. The source genes ATM , CCNA1 , GSK3B , KMT2C , KMT2E , NSD2 , SUCLG2, QKI , HOMER1 , and SNAP91 were found to be actively associated with bull sexual maturity and spermatogenesis. In addition, a real-time quantitative polymerase chain reaction (RT-qPCR) analysis showed a strong correlation with the sequencing data. Moreover, the developed model of Bovine testes in the current study provides a suitable framework for understanding the mechanism of circRNAs in the development of testes and spermatogenesis., 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 © 2021 Khan, Liu, Zhuang, Khan, Zhang, Chen, Xu, Avalos, Zhou and Zhang.)