bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of preoperative neoadjuvant chemotherapy on postoperative delirium in patients with gynecological tumor surgery: an observational study
Authors: Yang Yiwen , Chen Jiahui , Wen Qian , Jin Guangshan , Liu Fuqiang , Yu Ling , He Jianhua
Published: October 2024

Purpose: To investigate whether NACT increases the incidence of POD in patients with gynecological tumors undergoing radical hysterectomy.
Methods: This study included 60 patients in the neoadjuvant chemotherapy exposure group and 60 in the non-exposure group. Preoperative cognitive function, the incidence of POD and other physiological parameters were assessed on POD-1, and POD1-POD3. Additionally, preoperative olfactory function was evaluated using an olfactory detection kit on POD-1. The primary outcome was the incidence of POD within three days after surgery.
Results：The incidence of POD was 28.3% in the exposed group and 8.3% in the non-exposed group (P = 0.005). Compared to the non-exposed group, the exposed group had higher rate of cognitive dysfunction (33.33% vs 13.33%; P = 0.010), and a higher rate of OD (25.0% vs 10.0%; P = 0.031). A restricted cubic spline analysis revealed a non-linear relationship between olfactory test scores and MoCA scores (P for overall < 0.001, P for nonlinear = 0.001). Logistic regression identified NACT, mild and moderate cognitive dysfunction, OD, and depression as independent risk factors for POD, with all factors showing significant associations (P < 0.05). The AUC of OD for predicting POD was 0.783 (95%CI: 0.656-0.909).
Conclusions: This single-blind observational study suggests that NACT increases the incidence of POD in patients with gynecological tumors undergoing radical hysterectomy. Moreover, the results indicate that preoperative OD may reflect preoperative cognitive dysfunction, and have predictive value for the incidence of POD.
Effects of aquarobics participation on back pain disability index, sleep disturbance, and subjective memory impairment in female older adults with chronic back pain
Authors: Lee MoonSook , Kim Jiyoun
Published: October 2024

Background
Pain is a notable risk factor for cognitive decline in older adults. Aims: This study aimed to evaluate the effect of an aquarobics exercise program on three critical health outcomes—back Pain Disability Index (BPDI), sleep disturbance (SD), and subjective memory impairment (SMI) —in female older adults with chronic low back pain. Methods: In total, 152 participants were recruited and randomly assigned to either the experimental group (n = 68), which participated in a structured aquarobics program for three months, or the control group (n = 84), which did not engage in any structured exercise intervention. Results: Participation in the aquarobics program resulted in a statistically significant reduction in BPDI scores, indicating a marked decrease in functional limitations associated with chronic back pain. Participants in the experimental group exhibited significant improvements in sleep quality and decreased subjective memory impairment, both of which were positively correlated with reduced BPDI. SEM analysis confirmed that improvements in BPDI mediated positive effects on sleep and memory, suggesting that physical pain alleviation contributes to enhanced cognitive and psychological well-being. Discussion: These findings underscore the potential of aquarobics as a viable non-pharmacological intervention for elderly women with chronic low back pain, offering comprehensive benefits beyond pain relief, including enhancements in sleep and cognitive function. Conclusions: Future research should explore the long-term sustainability of these benefits and consider the integration of aquarobics into broader rehabilitation and wellness programs for older adults.
Identification of Fatty acid metabolism-Related Genes in the Progression from Non-Alcoholic Fatty Liver to Nonalcoholic fatty liver disease
Authors: Xie Xuancheng , Xiong Tao , Zhai Yue , Liu Xingli , Song Wei , Gao Meng , He Xiao , Fan Hongjie , Wang Gang
Published: October 2024

Aim
To elucidate the regulatory mechanisms of fatty acid metabolism-related genes (FAMRGs) and the gene expression clustering in nonalcoholic fatty liver disease (NAFLD).
Methods
The NAFLD dataset was sourced from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified and their specific functions analyzed. Biomarkers were identified using machine learning and Weighted Gene Co-Expression Network Analysis. CIBERSORT evaluated immune cell infiltration and the relationship between biomarkers and immune cells. Fatty acid metabolism-related DEGs (FAMRDEGs) were identified, and consensus clustering differentiated NAFLD patients into two clusters. Clinical differences between subtypes were compared. Principal component analysis calculated cluster-specific gene scores, and single sample gene set enrichment analysis assessed the proportion of immune cells between clusters.
Results
A total of 2124 DEGs were identified, primarily associated with immune-related pathways. Among 44 FAMRDEGs, FMO1 was identified as a biomarker for NAFLD and validated using an independent dataset, qRT-PCR, and WB. Immune cell infiltration analysis suggested that NAFLD may be co-regulated by immune cells and FMO1. Clustering of NAFLD individuals based on the 44 FAMRDEGs revealed that genes in cluster A were predominantly related to immune pathways, while those in cluster B were associated with metabolic pathways. Disease severity was higher in cluster A, which also had a larger proportion of differing immune cells compared to cluster B.
Conclusion
FMO1 was identified as a biomarker for NAFLD. High expression of PPT1 and PTGS2 correlated with disease severity. The identification of NAFLD subgroups based on has enhanced our knowledge of NAFLD etiology.
Association between sarcopenia and parity in American women based on data from the National Health and Nutrition Examination Surveys (NHANES) 2011–2018
Authors: Hou Xuefeng , Chen Dong , Shen Yuchen , Jiang Jian , Xu Kangjie , Dai Bin
Published: October 2024

Background: Muscle atrophy is a condition characterized by a decrease in muscle mass, and it is more prevalent among females than males. Currently, there is limited research on the relationship between parity (number of pregnancies) and muscle atrophy. Therefore, this study aims to investigate the association between parity and muscle loss among Americans.
Materials and Methods: Clinical data from 3,530 participants of the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 were analyzed. Restricted quadratic spline models were utilized in dose-response analyses to assess the relationship between parity and muscle atrophy. Propensity score matching (PSM) was used to balance confounding factors between the muscle atrophy group and the non-muscle atrophy group.
Results: Among the 3,530 participants, 330 (9.3%) were diagnosed with muscle atrophy. Our study revealed that factors such as older age, Mexican-American descent, low educational level, married status, poverty, physical inactivity, and higher parity were associated with muscle loss. The dose–response analyses showed a positive correlation between increasing parity and muscle atrophy, signifying that a higher number of pregnancies is linked to an increased risk of muscle atrophy. The results of PSM analysis further supported the positive association between parity and muscle atrophy, even after adjusting for other confounding variables.
Conclusion: Expanding on our research, we observed a positive correlation between higher parity and an elevated likelihood of experiencing muscle atrophy in postmenopausal American women. Engaging in regular exercise might reduce this risk.
Correcting Autoinflammation in STING-Associated Vasculopathy with Onset in Infancy (SAVI) by Human Stem Cell Genome-Editing
Authors: Pavel-Dinu Mara , Viel Sebastien , Selvaraj Sridhar , Gastou Marc , Feist William , Perret Magali , Rouvet Isabelle , Nombel Anais , Hacein-Bey-Abina Salima , Belot Alexandre , Porteus Matthew
Published: October 2024

Type I interferonopathies comprise a large group of Mendelian autoinflammatory diseases that generally lack effective treatments. STING-associated Vasculitis with onset in Infancy (SAVI) is a severe autosomal dominant disease due to gain-of-functon(GOF) mutations in the gene STING1, encoding for the Stimulator of Interferon Response CGAMP Interactor 1 (STING1). SAVI leads to a severe multisystemic disease comprising systemic vasculitis and lung fibrosis. A possible therapeutic approach is to engineer the patient’s hematopoietic system to restore interferon homeostasis, thereby preventing chronic inflammation and organ damage and halting disease development. Here, we describe a “universal” genome editing correction strategy using CRISPR/Cas9 that targets the stimulator of interferon response cGAMP interactor 1 (STING1) gene at the endogenous locus in SAVI patient-derived induced pluripotent stem cells (iPSCs) and in human CD34+ hematopoietic stem and progenitor cells (HSPCs). The engineered SAVI-iPSCs express normal levels of STING1 protein following differentiation into monocytes and macrophages and no longer produce interferon-alpha (IFN-α) at a basal state. Using SAVI-gene-engineered HSPCs, we determined the minimum fraction of mutant alleles required to induce spontaneous IFN-α production, thus establishing the threshold of genome correction necessary to rescue the disease. Finally, we demonstrated engineered CD34+ HSPCs at the STING1 locus retain regenerative potential by supporting long-term repopulating capacity and multi-lineage differentiation potential following transplantation into immunocompromised mice. Together, these studies established the rationale for the clinical translation of SAVI genome editing and a therapeutic framework for correcting other type I interferonopathies.
1,000,000 on/off ratio in sub-1nm channel length CNT/monolayer MoS2/CNT vertical transistors
Authors: Yu Woo Jong , Do Van Dam , Duong Ngoc Thanh , Vu Van Tu , Nguyen Minh Chien , Dat Vu Khac , Duong Hai Phuong , Do Dinh Phuc , Phan Thanh Luan , Yun Hong Won , Lim Seong Chu
Published: October 2024

Vertical field effect transistors (VFETs) using graphene and transition metal dichalcogenides (TMDs) heterostructures are promising for downsizing the channel length to a monolayer TMD thickness of 0.65 nm. However, graphene/monolayer TMD/metal VFETs struggle with a low on/off ratio due to gate field screening by the graphene layer and a high off-state tunneling current caused by the large contact area. Here, we propose a 0.65 nm channel length VFET with a very high on/off current ratio made by cross-stacking top and bottom carbon nanotubes (CNTs) with a monolayer TMD in between. The ultra-narrow junction area in the CNT/monolayer TMD/CNT VFET can significantly reduce the off-state tunneling current. Additionally, the gate field is transmitted from the sidewall of the bottom CNT to the monolayer MoS2 vertical channel between the two CNTs without field screening, thus achieving very strong gate modulation. Unlike the BH change (< 92 meV) of the graphene/MoS2/metal junction, which is fully dependent on the Fermi level (EF) shift of graphene, the CNT/MoS2/CNT junction exhibits a larger BH change (370 meV) than the typical EF shift (20 meV with Vg = -30 ~ 20 V) of semi-metallic CNTs. As a result, our CNT/monolayer MoS2/CNT VFETs exhibit about 105 times higher on/off ratio (= 106), 105 times lower off current (= 10− 13 A), and 100 times lower SS (= 0.4 V.dec− 1) compared to graphene/monolayer TMD/metal VFETs. In the comparison between multilayer MoS2 and monolayer MoS2 VFETs, rigid multilayer MoS2 forms a large air gap at the multilayer MoS2/CNT/substrate heterostructure, which reduces electric field transmission. In contrast, monolayer MoS2 bends significantly along the sidewall of the CNT, resulting in minimal air gap formation and enhancing the electric field effect in the channel. As a result, CNT/monolayer MoS2/CNT VFET shows 10 times higher on-current saturation and on/off ratio compared to the CNT/multilayer MoS2/CNT VFET.
Neutrophil NADPH oxidase breaks the inflammatory IL-1β/IL-17A circuit to enhance pathogen clearance during respiratory virus infections.
Authors: Warnatsch Annika , Sofoluwe Aderonke , Petropoulos Angelos , Goomanee Abhilesh , Ali-Khan Zehra
Published: October 2024

Respiratory virus infections are invariably accompanied by an increase in oxidative stress, characterised by elevated production of Reactive Oxygen Species (ROS) in the lung, which plays a pivotal role in both pathogenesis and host defence. Using a mouse model, neutrophil NADPH Oxidase 2 (Nox2) emerges as a key player, primarily responsible for generation of ROS during the early phases of Influenza A Virus (IAV) infection. Neutrophil Nox2-derived ROS display a multifaceted role, not only unleashing oxidative stress but in turn curbing neutrophil-derived IL-1β signalling. Absence of neutrophil Nox2 triggered heightened production of IL-1β, promoting the proliferation of IL-17-producing gamma delta (γδ) T cells. This early self-amplified augmentation of the IL-1β/IL-17 axis counteracted the antiviral interferon response against IAV infection in mice. We extended our findings to humans. Similar patterns of ROS production and cytokine regulation were observed in human neutrophils when exposed to virus analogue poly(I:C) and SARS-CoV-2. Our discovery highlights that ROS, often associated with harm, play a dual role by regulating cytokine signalling and thus influencing the immune response against respiratory viruses.
Immune perturbations induced by SARS-CoV2 in infants vary with disease severity and differ from adults’ responses
Authors: Ramilo Octavio , Nehar-Belaid Djamel , Mejias Asuncion , Xu Zhaohui , Marches Radu , Yerrabelli Rushil , Chen Guo , Mertz Sara , Ye Fang , Sanchez Pablo , Aydillo Teresa , Miorin Lisa , cupic Anastasija , Garcia-Sastre Adolfo , Ucar Duygu , Banchereau Jacques , Pascual Virginia
Published: October 2024

Differences in immune profiles of children and adults with COVID-19 have been previously described. However, no systematic studies have been reported from infants hospitalized with severe disease. We applied a multidimensional approach to decipher the immune responses of SARS-CoV-2 infected infants (n=26; 10 subacute, 11 moderate and 5 severe; median age=~1.6 months) and matched controls (n=14; median age=~2 months). Single cell (scRNA-seq) profiling of PBMCs revealed substantial alterations in cell composition in SARS-CoV-2 infected infants; with most cell-types switching to an interferon-stimulated gene (ISGhi) state including: (i) CD14+ monocytes co-expressing ISGs and inflammasome-related molecules, (ii) ISGhi naïve CD4+ T cells, (iii) ISGhi proliferating cytotoxic CD8+ T cells, and (iv) ISGhi naïve and transitional B cells. Concurrently, we observed increased serum concentrations of both interferons and inflammatory cytokines in infected infants. Antibody responses to SARS-CoV-2 were also consistently detected in the absence of anti-IFN autoantibodies. Compared with infected adults, infants displayed a similar ISG signature in monocytes but a markedly enhanced ISG signature in T and B cells. These findings provide new insights into the distinct immune responses to SARS-CoV-2 in the first year of life and underscore the importance of further defining the unique features of early life immunity.
Antioxidant, Antidiabetic, Analgesic, and Antibacterial Properties of Chrysopogon zizanioides Leaf Extract: An In Vivo, In Vitro, and In Silico Evaluation
Authors: Akash Sajidur , Akter Most. Afrin , Talukder Chayan , Mim Sumaya Alam , Rahman Md. Atikur , Obaid Md. Abdullah Al , Islam Md.Mirajul , Himu Jahidul Islam , Aziz Tareq , Rashid M A , Jahan Mst. Lubna , Ali Md. Sarafat
Published: October 2024

Chrysopogon zizanioides, commonly known as vetiver, has long been utilized in traditional medicine for its therapeutic properties. This study investigated Chrysopogon zizanioides leaf extract's antioxidant, antibacterial, analgesic, and antidiabetic properties. A diclofenac sodium standard and control group were used to compare the extract's analgesic impact in an animal model. The extract was 66.08% analgesic, whereas diclofenac sodium was 91.11%. Antibacterial activity was assessed against various bacterial pathogens, showing strong inhibition of gram-positive bacteria, particularly Staphylococcus aureus, with an inhibition zone of 30 ± 4.39 mm. The extract also demonstrated notable activity against gram-negative bacteria, with Escherichia coli exhibiting the highest inhibition of 22 ± 1.93 mm.
Antioxidant activity was measured using DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assays. The extract had an IC50 of 257.23 µg/ml, whereas ascorbic acid had an IC50 of 7.8 µg/ml. Moreover, GC-MS analysis identified 63 phytoconstituents and the antidiabetic activity showed as in silico model where in molecular docking 9,19-Cyclolanostan-3-ol acetate (3.beta.) showing the highest binding scores with proteins such as 5NN5 (-9.6820 kcal/mol) and 4GQR (-10.2851 kcal/mol). Additionally, Phytol demonstrated a Glide docking value of -9.1677 kcal/mol with protein 5F19. ADMET analysis showed the extract's non-carcinogenicity and good absorption, whereas PASS predictions and drug-likeness data suggested significant oral bioavailability, antioxidant, and anti-inflammatory properties.
These findings highlight the therapeutic potential of Chrysopogon zizanioides leaf extract as a natural pharmacological agent. Further research, including clinical trials and isolation of active compounds, is needed to fully understand its mechanisms and confirm its efficacy and safety for human use.
Prefrontal Cortical NR2B-Containing NMDA Receptors are Essential for Spatial Working Memory Performance
Authors: Li Baoming , Peng Jiyun , Wang Gongwu , Han Yingying , Qu Lili , Wang Min , Arnsten Amy , Cai Jingxia
Published: October 2024

NR2A and NR2B are the major GluR2 subunits of N-methyl-D-aspartate (NMDA) receptor. NR2B-containing NMDA receptor was found exclusively expressed in prefrontal cortical (PFC) layer III post-synapses of pyramidal neurons. Many studies have suggested the importance of PFC NR2B-containing NMDA receptor for working memory, especially for the persistent delay cell firing. However, direct evidence for the necessity of PFC NR2B-containing NMDA receptor on working memory is still absent, especially in non-human primates. Here, we directly evaluated the necessity of PFC synaptic NR2B in both rats and monkeys. We first examined the synaptosome expression ratio of NR2B/2A in the PFC, hippocampus and visual cortex and confirmed a relatively higher expression ratio in the PFC than in the hippocampus and visual cortex in both species. We then investigated the effect of intra-PFC blockade of NR2B on the performance of spatial working memory task and found that the spatial working memory, but not pattern discrimination, was robustly impaired in a delay length-dependent way upon NR2B blockade in both species. The present study provided behavioral and neuropharmacological evidence for the critical role of PFC NR2B-containing receptor in primate PFC.
Environmental Degradation and Fragmentation of Microplastics: Dependence on Polymer Type, Humidity, UV Dose and Temperature
Authors: Pfohl Patrizia , Santizo Katherine , Sipe Joana , Wiesner Mark , Harrison Sam , Svendsen Claus , Wohlleben Wendel
Published: October 2024

Depending on the environmental compartment, plastics are subjected to various stressors, including UV light, water, microbial exudates (enzymes), and temperature. Among these, stress on plastics from photo-chemical processes was identified as a leading exposure pathway of plastics, e.g., in the atmosphere or on the water surface. While the focus of earlier studies mainly was on deterioration of the chemical and mechanical properties, more recent studies demonstrate how photo-oxidation leads to fragmentation and release of secondary micro- and nanoplastic fragments, as well as low-molecular weight species. These studies tend to focus on a single exposure condition and a limited number of polymer types. Therefore, this study focuses on systematically evaluating the influence of temperature and relative humidity during simulated UV exposure on the fragmentation and degradation of five types of pristine microplastic powders: polypropylene, low density polyethylene, polyamide 6, high impact polystyrene and thermoplastic polyurethane. We quantified the dose-dependent release of water-soluble organics, as well as secondary micro- and nanoplastics (including their particle size distributions) and found that the polymer identity dictated the type and quantity of species released rather than the aging protocol. With this systematic assessment the generated data can be used in mechanistic microplastic fragmentation models to determine fragmentation rates and fragment size distributions.
Research on subsurface damage of CFRP cutting with biomimetic gradient micro-textured tools
Authors: Gao Mengxue , Zhang Xu , Hu Liangfei , Song Yue , Yao Peiwei , Zhang Liqiang , Zhang Xuechang
Published: October 2024

CFRP (Carbon fiber reinforced polymer) exhibits anisotropy and low interlaminar shear strength, which makes it prone to inducing defects, especially at the fiber cutting angle of 135°, where subsurface damage is especially severe. This article constructs a 3D microscopic finite element model for CFRP cutting and analyzes the cutting mechanism of micro-textured tools at a 135° fiber cutting angle, and proposes use micro-textured tools with varying depths for cutting. Concurrently, incorporating the "crescent-shaped depression" morphology of bamboo rats' incisors, it is able to effectively mitigate subsurface damage during CFRP cutting while maintaining the structural strength of the cutting tool. The biomimetic gradient micro-textured tools proposed in this study can effectively reduce the overall subsurface damage during CFRP processing at various angles. Compared to non-textured and equal-depth micro-textured tools, the overall maximum subsurface damage is reduced by 44.92% and 21.99% respectively, providing an effective solution to reduce subsurface damage.
A new human spine model for use in cinematographic gait analysis
Authors: Tabor Piotr , Palczewska Iwona , Grygiel Rafał , Olszewska Elżbieta , Chwała Wiesław , Mastalerz Andrzej
Published: October 2024

Purpose
The aim of this study was to compare the accuracy of two spine models: the broken curve model and a new four tangent circles model. The modification concerns the adaptation of data acquisition to kinematic methods used in e.g. gait and running analysis.
Method
Plastic, movable spine model of human with flexible intervertebral discs (manufactured by Erler Zimmer GE3014) was used as the study material. Markers with a diameter of 5mm were glued to each spinous process (from C7 to L5). The recording was performed with a 6-camera Vicon system. Two spine models were created: a broken curve model used, among others, in the Diers scanner, and an own model of 4 circles, similar to the model of circles used in X-ray and CT analysis.
Results
The errors in the position of the spinous processes were significantly smaller in the 4-circle model than in the broken curve model. They ranged from 0.01 to 6.5 mm in the lumbar section, from 0.004 to 3.1 mm in the thoracic section. The practical possibilities of using the four-circle model during the cinematographic analysis of gait and run should be checked.
Conclusion
The four-circle model is more accurate than the broken curve model and can be used in the cinematographic analysis of the human spine movement.
Optimizing Lassa Fever Outbreak Control: A Comparative Study on the Efficacy of Contact Tracing Integration in Epidemiological Models
Authors: Ajala Bolarinwa Olumide , Adejumo Adebowale Olusola , Akinyemi Joseph Adekunle , Ekum Matthew Iwada , Barrah Vincent , Barrah-Ajala Jennifer Uzodinma , Nwanya Julius Chigozie
Published: October 2024

Lassa fever, an acute viral hemorrhagic illness endemic to West Africa, presents significant public health challenges because of its high mortality rate and potential for rapid spread. Accurate models are crucial for effective outbreak management and resource allocation. As such, this study examines the modelling of Lassa fever transmission through a comparative analysis of two epidemiological models: one incorporating contact tracing and the other without. By integrating epidemiological data and mathematical models, contact tracing and noncontact tracing are performed to investigate the dynamics of the Lassa fever model through reproduction number (R 0). The uniqueness of the solution is tested and confirmed via an invariant property, and through the next generation matrix, the reproduction number is determined. Our findings indicate that the model with integrated contact tracing significantly enhances early detection, reduces the number of secondary infections, and provides a more precise understanding of transmission dynamics. This model also supports more efficient allocation of healthcare resources and bolsters public confidence in health interventions. In contrast, the model without contact tracing tends to underestimate the spread of the virus and fails to optimize resource deployment. The comparative analysis underscores the importance of incorporating contact tracing into Lassa fever models, highlighting its critical role in controlling outbreaks, reducing transmission , and improving public health outcomes. This research advocates the widespread adoption of contact tracing in the modelling and management of Lassa fever and similar infectious diseases.
Super-Lubricous Polyethylene Glycol Hydrogel Microspheres for Use in Knee Osteoarthritis Treatments
Authors: Stealey Samuel , Dharmesh Ether , Bhagat Maitreyi , Tyagi Abdul Malik , Schab Andrew , Hong Mellissa , Osbourn Damon , Abu-Amer Yousef , Jelliss Paul A. , Zustiak Silviya Petrova
Published: October 2024

Knee osteoarthritis (OA) is characterized by cartilage degeneration and significant reduction in lubrication. One strategy to recover the natural lubrication of the synovial fluid is the injection of hydrogel microspheres, which offer both reduction in friction and the potential to encapsulate therapeutic cargo. Here, we have fabricated polyethylene glycol (PEG)-based hydrogel microspheres via a modified electrospraying setup and Michael-type addition crosslinking. To improve throughout, crosslinking of PEG droplets was delayed until after droplet formation was complete. Microsphere diameter could be easily tuned based on syringe needle diameter. A custom-synthesized super-lubricious copolymer consisting of adhesive dopamine methacrylate (DMA) and zwitterionic sulfobetaine methacrylate (SBMA) was used to dip-coat the PEG microspheres. The lubricious copolymer also incorporated rhodamine B, allowing for easy visualization and tracking. The copolymer coating exhibited in vitro stability for over 21 d and did not significantly affect cell proliferation. Lubricity was measured with a custom tribo-rheology setup and mechanical properties were tested with rheology. Super-lubricious PEG microspheres coated with the copolymer reduced coefficient of friction by 57% compared to simulated synovial fluid, indicating beneficial lubrication properties. The copolymer coating did not affect microsphere stiffness, and both coated-and uncoated microspheres showed shear-thinning properties, allowing for easy injection. When injected into C57BL6 mice, PEG microspheres exhibited stability for up to 26 d and did not adversely affect mouse behavior. These super-lubricious PEG microspheres offer great promise to reduce the friction that is a hallmark of progressive OA, potentially mitigating the need for total knee arthroplasty.
Immunosuppression by tetrahydrobiopterin increases the proliferation of regulatory T-cells and mast cells and modulates the cytokine expression in a murine heart transplant model
Authors: Ebner Susanne , Texler Bernhard , Nardin Florian , Troppmair Maria R , Nguyen Anh Vu , Cardini Benno , Troppmair Jakob , Schäfer Georg , Thalhammer-Thurner Gudrun C , Nirtl Kerstin , Lackner Katharina , Alenina Natalia , Öfner Dietmar , Schneeberger Stefan , Watschinger Katrin , Brandacher Gerald , Werner Ernst R , Maglione Manuel
Published: October 2024

Administration of tetrahydrobiopterin (BH4) has been shown to attenuate acute allograft rejection in a murine heart transplantation model in a manner similar to that of cyclosporine A. However, its mechanism of action on immune cells remains largely unknown. A fully MHC-mismatched (C3H/He to C57BL/6) mouse heart transplant model was used in this study. The recipients were treated with BH4 or Cyclosporine A six days. The degree of acute rejection was assessed by histopathological analysis, splenocytes were analyzed by flow cytometry, and cytokine production was estimated based on the level of protein and RNA in sera and grafts and in vitro in T cell cultures. Proliferation of regulatory T cells and mast cells, suppressor capacity of Tregs, and MLR of T cells were conducted in vitro. Survival curves confirmed the significant improvement observed in the BH4-treated animals. BH4-treatment resulted in a substantial increase in Tregs and mast cells in the secondary lymphoid organs. In vitro assays showed increased proliferation of BH4-treated Tregs and mast cells. Cytokine production in vivo and in vitro in BH4-treated animals revealed an increase in the expression of IL-10, IL-5 and IL-4. BH4-dependent mast cell-derived tryptophan hydroxylase-1 could be excluded as a treatment target in recipient knockout mice. These data suggest that BH4 modulates the innate and adaptive immune systems, resulting in increased proliferation of regulatory T and mast cells accompanied by a modulation of anti-inflammatory cytokines.
Abrupt changes in heatwave evolution in Mediterranean Chile and California
Authors: Carrillo Hugo , Mendoza Mauro , Lambert Fabrice , Wout Elwin van ’t
Published: October 2024

Heatwaves are extreme weather events with significant impacts on natural ecosystems, human health, and socio-economic systems. While global trends indicate an increase in the frequency, duration, and intensity of heatwaves due to climate change, regional studies are essential to understand local variations and impacts. This study aims to address the gap in knowledge regarding the evolution of heatwaves in Central Chile and California, two regions with similar Mediterranean climates but located in different hemispheres.
We analyzed temperature data from meteorological stations in Central Chile and California over the past five decades. Using various heatwave definitions and indices, we quantified trends in heatwave frequency, duration, and intensity. The number of heatwave events per year in Central Chile increased by approximately one event every 15 years, while in California we register an average increase of one event per decade, although regional variations exist. These trends have accelerated over the last two decades, with abrupt changes in heatwave behavior detected around 2010 in both regions. We suggest that strong reductions in anthropogenic aerosol emissions around this time removed atmospheric aerosol cooling and may have abruptly amplified heatwaves post-2010.
These findings highlight the accelerating impact of changing climate conditions on heatwave characteristics in Central Chile and California, and indicate possible unintended consequences of air quality improvements. Our results underscore the urgent need for adaptive measures to mitigate the adverse effects of increasing heatwaves.
Evaluation of Mixed Chuihui (Modified Mortar) Material on the Chest and Abdomen of Leshan Giant Buddha
Authors: Sun Bo , Liang Yuyuan , Shi Wentao , Peng Ningbo , Wu Guopeng
Published: October 2024

As a traditional repair material, Chuihui has been maturely used in the restoration work of the Leshan Giant Buddha many times. Fundamentally, it is a kind of mortar processed by "hammering". Over the years, it is mainly divided into traditional Chuihui, mixed Chuihui and modified Chuihui. This study tested and evaluated the mixed Chuihui material on the chest and abdomen of the Leshan Giant Buddha in 2001. By measuring the thickness, surface hardness, density, and longitudinal wave velocity of the mixed Chuihui, and combining the results of X-ray diffraction analysis, infrared spectroscopy analysis, micro-drilling damping detection, micro-morphological characteristics, and mercury intrusion porosimetry, the macroscopic physical indicators and microscopic characteristics were analyzed and its performance was evaluated. The results show that among the three-layer structure (surface layer, middle layer, and cushion layer) of the mixed Chuihui material, the cushion layer has greater thickness and porosity, lower wave velocity and hardness, the lowest average drilling force value, the highest proportion of cracks, and the worst overall performance. At the same time, the existence of the hydration product C-S-H proves that there is a cement component in each layer of Chuihui. Since the surface layer of mixed Chuihui uses higher quality raw materials and is protected by carbonation, the physical and mechanical properties of the surface layer are at a relatively high level compared with the other two layers. Moreover, according to the order from air to bedrock, the mechanical properties of the three-layer structure of Chuihui material show a gradually decreasing trend. When encountering external damage or natural shedding, the Chuihui layer can act as a sacrificial layer and be damaged, thus avoiding damage to the bedrock. The strength of the surface layer also ensures its ability to resist weathering.
Uptake of heavy metals from aqueous media onto the blend of sodium alginate and kernel powder
Authors: Sardar Muhammad Hamza , Saddique Muhammad Tahir
Published: October 2024

Heavy metal poisoning is widely recognized as a serious problem for both the environment and human health. The damage caused by these metals has raised concerns for global public health and ecology, prompting a significant focus on developing effective materials for heavy metal removal. This study presents a method for creating an environmentally friendly adsorbent for removing metal ions from aqueous solutions, using sodium alginate/mango seed kernel blend beads (SA/MSK). The goal was to develop a low-cost, beneficial adsorbent by utilizing mango seed kernel (MSK), an agricultural waste product, as a resource to manufacture material for the removal of specific heavy metals. Adsorption, one of the most promising techniques, was employed in this work. Batch studies were conducted to examine the effects of pH, dosage, initial metal ion concentration, adsorbent particle size, and contact time on the percentage removal of Cd²⁺, Cu²⁺, and Pb²⁺ ions. FTIR, SEM, and XRD analyses demonstrated that carboxyl and hydroxyl functional groups were involved in the sorption of Cu²⁺, Cd²⁺, and Pb²⁺ ions. The efficacy of SA/MSK beads in eliminating metal ions from effluent samples showed that the beads were able to remove all three metal ions to varying degrees. Physicochemical and spectroscopic methods revealed that the binding sites involved were ether, carboxyl, hydroxyl, and amine groups. These findings suggest that SA/MSK beads hold great potential for applications in heavy metal removal and could become a sustainable method for removing metal ions from effluent.
The Synergistic effects and mechanism of recombinant viral vector-mediated co-expression plasmids stat1 and stat3-siRNA on glioma in vivo and in vitro
Authors: Hu Xin long , Li Hong , Zhang Guodong , Lin Chao , Huang Ping , Chen Xiufeng , Wan Fang , Dou Changwu , Ju Haitao
Published: October 2024

Objective
To investigate the Synergistic effects and mechanism of recombinant viral vector-mediated co-expression plasmids stat1 and stat3-siRNA on glioma in vivo and in vitro
Methods
We constructed the co-expression plasmid stat1/stat3-SiRNA and packaged it into lentivirus and adenovirus for cell and animal experiments. Real-time PCR and Western blot analyses were used to detect the expression of STAT1 and STAT3 at the gene and protein levels. CCK-8, TUNEL, flow cytometry, and cell scratching assays were established to detect the therapeutic effect of the co-expression plasmid stat1/stat3-SiRNA on glioma in vivo and in vitro, and we used transcriptome sequencing to further explore the possible mechanism.
Results
After we treated gliomas with the co-expression plasmid stat1/stat3-SiRNA, STAT1 increased and STAT3 decreased significantly in mRNA and protein expression levels, Compared with the single-gene stat1 and stat3-SiRNA groups, stat1/stat3-siRNA group inhibited the proliferation and migration of U251 cells, and the tumor growth in nude mice more significantly. The analysis of the transcriptome sequencing results suggested that changing multiple nodes in the FOXO signaling pathway may be the main mechanism for co-expression of lenti-stat1/stat3-SiRNA than the single genome stat1 or stat3-SiRNA to inhibit the proliferation of U251 cells and induce their apoptosis, but awaiting further research and discussion.
Conclusions
The co-expression plasmid stat1/stat3-siRNA inhibits the growth of glioma and induces its apoptosis more significantly than the single genome stat1 and stat3-siRNA. The possible mechanism is to change multiple nodes in the FOXO signaling pathway.
Exploring the Relationship Between Physical Activity and Multimorbidity: Insights from the CHARLS Database
Authors: Mou Chuan , Wang Zhihua , Ke Zhifei
Published: October 2024

Background
Physical activity has been widely recognized for its important role in preventing cardiovascular and other chronic diseases. However, the specific relationship between different levels of physical activity and various chronic diseases, including multimorbidity, remains unclear, which require further investigation.
Methods
This study utilized the China Health and Retirement Longitudinal Study (CHARLS) database to classify physical activity levels based on metabolic equivalents (MET). The analysis focused on the relationship between low, moderate, and high physical activity levels and various chronic diseases, as well as the co-occurrence of multiple diseases. Multivariable logistic regression models were employed to assess the association between different activity levels and the risk of chronic diseases, while stratified analyses explored the impact of demographic factors on these associations. Additionally, a restricted cubic spline (RCS) model was applied to investigate potential nonlinear relationships between total MET and chronic disease risks.
Results
The results showed that compared to low activity levels, moderate and high levels of physical activity significantly reduced the risk of cardiovascular diseases and respiratory diseases, with a nonlinear dose-response relationship. High levels of physical activity also significantly lowered the risk of multimorbidity, particularly the coexistence of three or more chronic diseases (OR = 0.55, 95% CI: 0.47, 0.65, P < 0.01). However, moderate activity levels were associated with increased risks of dyslipidemia and diabetes, while high levels of activity were linked to higher risks of arthritis and kidney diseases. Stratified analyses revealed that demographic factors influenced the association between physical activity and disease risk.
Conclusion
Moderate and high levels of physical activity provide significant protection against cardiovascular and respiratory diseases and effectively reduce the risk of multimorbidity. However, the increased risk of certain metabolic and joint diseases with higher activity levels warrants further attention. Future research should clarify the impact of physical activity on different populations and chronic diseases, with randomized controlled trials needed to verify causality.
Generative AI based Predictive Maintenance in Aviation: A Systematic Literature Review
Authors: Khan Zeeshan Ullah , Nasim Bisma , Rasheed Zeehasham
Published: October 2024

Predictive maintenance (PdM) is a critical tool in aviation, promoting sustainability, safety, and cost-effectiveness. However, a significant challenge in implementing predictive maintenance framework is limited run-to-failure data due to frequent preventive maintenance. Generative AI (GAI) offers a promising solution to this challenge by generating synthetic data, enabling more accurate predictions of aircraft system health. The recent surge in scientific publications exploring GAI's potential for aviation predictive maintenance emphasizes the need for a comprehensive review. This research addresses this gap by conducting a systematic literature review (SLR), employing an active learning open-source tool to thoroughly analyze papers sourced from four scientific databases. These papers focus on predictive maintenance of aircraft systems through generative AI models. The findings of this review examine various aspects of GAI-powered predictive maintenance, including its objectives, the diversity of models employed, areas of application, datasets used for model validation, and the prevailing challenges and emerging trends. The review identified that most commonly used GAI models in aircraft PdM are GANs (Generative Adversarial Networks), VAEs (Variational Autoencoders) or combination of these models. However, knowledge sharing, model integration and specificity are the key challenges associated with the implementation of these models. This strong knowledge-base will be a valuable resource for researchers, engineers, and practitioners aiming to improve their knowledge and implementation of GAI-driven models for predictive maintenance in the aviation industry.
Arsenic and Heavy metals levels into edible fresh meat (chicken, goat, and beef) and associated health risks
Authors: Shah Syed Sayyam Abbas , Eqani Syed Ali Musstjab Akber Shah , Nawaz Ismat , Ali Nadeem , Rajah Nisreen , Rasheed Iqra , Ali Syeda Maria , Orif Muhammad I , Shen Heqing
Published: October 2024

The current study (very first) measured the concentrations (dry weight; µg/kg) of arsenic (As) and selected heavy metals (Cr, Ni, Mn, Pb, Cd, Cu, Zn) by using ICP-MS in muscle and liver samples of chicken, mutton, and beef from different areas (Peshawar, Islamabad, Gujrat, Lahore) of Pakistan. In general, the occurrence trend of studied toxic elements in liver and muscle samples were as follows: Zn > Cu > Mn > Cr > Ni > Pb > As > Cd. As, Cd, Pb (µg/kg) and Cu (mg/kg) were significantly higher in beef liver (110.2, 100, 358.6, and 115.1, respectively) than those of mutton (51.3, 63.3, 234.9 and 74.5) and chicken liver (41.3, 29.3, 115.5 and 11.3). On the other hand, As, Pb (µg/kg), and Zn (mg/kg) concentrations were significantly higher in the muscles of mutton (121.6, 247.7, 146.6, respectively) and beef (117.2,227.2 and 166.4) followed by chicken (44.5, 141.1, 41.3). Similarly, organ-wise levels of the studied toxic elements (particularly Mn, and Cu) were higher in liver samples than those of muscles of all types of animals except for As (high in mutton muscle) and Cr, Ni, Zn (high in beef muscle). Our results highlighted that beef (liver and muscle) is the most contaminated type of meat than those of mutton and chicken (liver and muscle). Correlation analysis and principal component analysis (PCA) highlighted that studied toxic metals exposure may be linked to the contaminated soil/dust (Mn, Pb, Cd, Ni), water (As, Cr, Pb) and food (Zn, Cu, Cd, Ni) at different locations of Indus floodplain. Chronic exposure of the studied toxic metals (HQ > 1 for As, Cr, Cu, and Zn) through meat (particularly beef liver and muscle) consumption may be harmful for human health and may pose significant threat to the consumer’s health.
QbD-Driven Development and Validation of an Optimized HPTLC Method for Simultaneous Estimation of Berberine and Conessine
Authors: Naik Archana , Chhaya Gadgoli , Yadav Sriniwas , Nagargoje Rutuja , Patil Siddhika
Published: October 2024

Berberine, an isoquinoline-derivative alkaloid from Berberis aristata, and conessine, an alkaloid found in the stem bark of Holarrhena antidysenterica, have long been used in traditional medicine to treat gastrointestinal and reproductive issues. This study focused on developing a high-performance thin-layer chromatography (HPTLC) method for the simultaneous quantification of berberine and conessine, optimized using a Quality by Design (QbD) approach. The method development involved the systematic optimization of critical method parameters (CMPs) such as mobile phase ratio, saturation time, distance travelled, and derivatizing agent concentration, using a Box-Behnken design. The critical analytical attributes (CAAs) evaluated included peak area and retardation factor as indicators of method robustness. Optimal chromatographic separation was achieved with a mobile phase of ethyl acetate, methanol, and diethyl amine in a ratio of 6.5:1.0:0.3 v/v on Silica gel 60GF 254 plates. Berberine and conessine were detected densitometrically at 350 nm and 620 nm, respectively, with Rf values of 0.22 and 0.85. The method was validated as per the ICH recommended conditions, which revealed high degree of linearity, accuracy, precision, sensitivity and robustness. The method was demonstrated to be simple, fast, accurate, resilient, and exact. Also, the method was applied for the estimation of berberine and conessine in inhouse formulations, which indicated no significant change in the retention time. In a nutshell, the studies demonstrated successful development of the HPTLC method for simultaneous estimation of berberine and conessine with improved understanding of the relationship among the influential variables for enhancing the method performance.
Revisiting the long-run and short-run relationship between economic growth, exchange rate, money supply, and government expenditure: empirical evidence from India using the NARDL approach.
Authors: Husain Shah , baig Imran Ali , Rana Minakshi , Khalid Bushra
Published: October 2024

The prior research that examined at how exchange rate fluctuations affected economic growth were based on the symmetric method, which predicted that the impact on GDP would be the same for both overvalued and undervalued exchange rates. However, recent research has shown that important economic variables like trade flows and economic growth are typically affected asymmetrically by the exchange rate. The primary aim of the present study is to examine the long term and short-term association among economic growth, exchange rate changes, money supply and government expenditure for a period of 1980-2022 in India. The study employed nonlinear autoregressive distributed lag model (NARDL) to examine the asymmetric relationship among the scrutinised variables. Furthermore, we used Granger causality test to check the direction of causal association. The results of NARDL confirm the long-term relationship among economic growth, exchange rate changes, money supply and government expenditure. The findings show that undervaluation affect economic growth negatively in the case of the Indian economy whereas overvaluation promotes it. Moreover, we found asymmetric impact of exchange rate change on economic growth in India. The Wald test confirms the asymmetrical relationship between exchange rate and economic growth for both short-run and long-run. The results of causality test show bidirectional causality among exchange rate, government expenditure and economic growth. While, one-way causal effects run from money supply to economic growth. The findings of the study have some policy implications. Exchange rate governing organisation should place a priority on restoring stability and work towards developing more robust exchange rates in order to achieve the goal of sustained economic growth and, ultimately, sustainable development
JEL: B22, CO1, E51, H50