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In recent years, there has been a growing argument attributing the primary cause of global climate change to livestock industry, which has led to the perception that the livestock industry is synonymous with greenhouse gas (GHG) emissions. However, a closer examination of the global GHG emission by sector reveals that the energy sector is responsible for the majority, accounting for 76.2% of the total, while agriculture contributes 11.9%. According to data from the Food and Agriculture Organization of the United Nations (FAO), the total GHG emissions associate with the livestock supply chain amount to 14.5%. Within this, emissions from direct sources, such as enteric fermentation and livestock manure treatment, which are not part of the front and rear industries, represent only 7%. Although it is true that the increase in meat consumption driven by global population growth and rising incomes, has contributed to higher methane (CH4) emissions resulting from enteric fermentation in ruminant animals, categorizing the livestock industry as the primary source of GHG emissions oversimplifies a complex issue and disregards objective data. Therefore, it may be a misleading to solely focus on the livestock sector without addressing the significant emissions from the energy sector, which is the largest contributor to GHG emissions. The top priority should be the objective and accurate measurement of GHG emissions, followed by the development and implementation of suitable reduction policies for each industrial sector with significant GHG emissions contributions.

Interest and investment in cultivated meat are increasing because of the realization that it can effectively supply sufficient food resources and reduce the use of livestock. Nevertheless, accurate information on the specific technologies used for cultivated meat production and the characteristics of cultivated meat is lacking. Authorization for the use of cultivated meat is already underway in the United States, Singapore, and Israel, and other major countries are also expected to approve cultivated meat as food once the details of the intricate process of producing cultivated meat, which encompasses stages such as cell proliferation, differentiation, maturation, and assembly, is thoroughly established. The development and standardization of mass production processes and safety evaluations must precede the industrialization and use of cultivated meat as food. However, the technology for the industrialization of cultivated meat is still in its nascent stage, and the mass production process has not yet been established. The mass production process of cultivated meat may not be easy to disclose because it is related to the interests of several companies or research teams. However, the overall research flow shows that equipment development for mass production and cell acquisition, proliferation, and differentiation, as well as for three-dimensional production supports and bioreactors have not yet been completed. Therefore, additional research on the mass production process and safety of cultivated meat is essential. The consumer’s trust in the cultivated meat products and production technologies recently disclosed by some companies should also be analyzed and considered for guiding future developments in this industry. Furthermore, close monitoring by academia and the government will be necessary to identify fraud in the cultivated meat industry.

ABSTRACT: This review was conducted to provide basic knowledge in developing new culture media for cultured meat production by compiling research on how the main media components affect cell proliferation and muscle differentiation. The culturing process can be divided into five processes: cell acquisition, cell proliferation, cell differentiation, myotube formation, and muscle maturation. To date, cultural media research has shown that amino acids, fatty acids, and carbohydrates mainly act as energy and nutrient sources for cell proliferation and muscle production, and minerals mainly play roles as regulators of cell proliferation and muscle production. Vitamins not only protect cells from oxidative stress but also promote cell growth and regulate cell growth-related genes. Additionally, cytokines play a role in regulating genes related to muscle proliferation and regeneration, and hormones, such as growth factors, insulin, and thyroid hormones, benefit muscle growth and regulation.

This study investigated the effect of extracts from unfertilized eggs and fertilized eggs with different culture periods as FBS substitutes for cell culture. A mixture of 5 % FBS and 20 % egg white extract or 10 % FBS and 10 % egg white extract was found to be the optimal condition for increasing cell proliferation. In particular, egg white extract obtained from unfertilized eggs was more effective in terms of increased cell viability and price competitiveness and showed similar effects to commercial FBS. In addition, when using this extract, successful proliferation of satellite cells was confirmed, as well as expression of Pax7, a protein present in muscle satellite cells. Additionally, OVF and OVA in the extract are believed to have an indirect effect on FBS replacements for chick muscle satellite cells towards cultured meat development. Egg white extract can replace up to 50–75 % of FBS. Further developments of the extracts could result in complete FBS substitution.

This study aimed to analyze the leading research materials and research trends related to livestock food in Asia in recent years and propose future research agendas to ultimately contribute to the development of related livestock species. On analyzing more than 200 relevant articles, a high frequency of studies on livestock species and products with large breeding scales and vast markets was observed. Asia possesses the largest pig population and most extensive pork market, followed by that of beef, chicken, and milk; moreover, blood and egg markets have also been studied. Regarding research keywords, “meat quality” and “probiotics” were the most common, followed by “antioxidants”, which have been extensively studied in the past, and “cultured meat”, which has recently gained traction. The future research agenda for meat products is expected to be dominated by alternative livestock products, such as cultured and plant-derived meats; improved meat product functionality and safety; the environmental impacts of livestock farming; and animal welfare research. The future research agenda for dairy products is anticipated to include animal welfare, dairy production, probiotic-based development of high-quality functional dairy products, the development of alternative dairy products, and the advancement of lactose-free or personalized dairy products. However, determining the extent to which the various research articles’ findings have been applied in real-world industry proved challenging, and research related to animal food laws and policies and consumer surveys was lacking. In addition, studies on alternatives for sustainable livestock development could not be identified. Therefore, future research may augment industrial application, and multidisciplinary research related to animal food laws and policies as well as eco-friendly livestock production should be strengthened.

The purpose of this study was to investigate the recent development of meat analog, industrialization, and the related legal changes worldwide. Summarizing the current status of the industrialization of meat analog, studies on plant-based meat, mycoprotein, and edible insects were mainly conducted to investigate their sensory properties (texture, taste, flavor, and color resembling meat), nutritional and safety evaluations, acquisition method of meat alternatives, and commercialization. Cultured meat is mainly studied for developing muscle satellite cell acquisition and support techniques or materials for the formation of structures. However, these technologies have not reached the level for active industrialization. Even though there are differences in the food categories and labeling between countries, it is common to cause confusion or to relay false information to consumers; therefore, it is important to provide accurate information. In this study, there were some differences in the food classification and food definition (labeling) contents for each country and state depending on the product shape or form, raw materials, and ingredients. Therefore, this study can provide information about the current research available on meat alternatives, improve regulation, and clarify laws related to the meat analog industry, which can potentially grow alongside the livestock industry.

Fetal bovine serum (FBS) substitution remains one of the challenges to the realization of cultured meat production in the marketplace. In this study, three methods were developed to extract a substitute for FBS using egg white extract (EWE): using 25 mM CaCl2/2.5 % ammonium sulfate/citric acid (A); ethyl alcohol (B); and 5 % ammonium sulfate/citric acid (C). B EWE can effectively replace up to 50 % of FBS in growth media (10 % of the total). Ovalbumin in the extracts can promote cell proliferation, and components along the 12 kDa protein band have the potential to inhibit cell proliferation. Chick primary muscle cells applied with B EWE, an edible material that improved the cost and time efficiency of cultured meat production, effectively proliferated/differentiated. Therefore, EWE extracted using ethyl alcohol may be used as an FBS substitute to reduce animal sacrifices and should be considered a viable alternative to FBS for cultured meat.

Cultured meat (CM) is an alternative protein food and is produced by cultivating muscle satellite (stem) cells (MSCs) derived from livestock animals (bovine, chickens, and porcine) through myogenesis leading to generate muscle mass. Myostatin (MSTN) is well well-known negative regulator of myogenesis, and in the present study, in silico screening of natural compounds was performed to identify MSTN inhibitors. Interestingly, quercetin was found to inhibit MSTN (binding energy −7.40 kcal/mol), and this was further validated by a 100 ns molecular dynamics simulation. Quercetin was added to culture media to boost myogenesis, and its potent antioxidant property helped maintain media pH. Furthermore, quercetin increased the myotube thickness and length, increased MSC differentiation, and upregulated the gene and protein expressions of myoblast determination protein 1 (MYOD), Myogenin (MYOG), and Myosin heavy chains (MYH) in vitro. In addition, quercetin inhibited the activities of MSTN, activin receptor type-2B (ACVR2B), and SMAD2 and 3, and thus significantly enhanced MSC differentiation and myotube formation. Overall, this study shows that quercetin might be useful for enhancing large-scale CM production. It is hoped that this study provides a starting point for research in the CM area aimed to enhancing product quality, nutritional values, and the efficacy of large-scale production.

The objective of this study was to investigate the protective effects of functional nutrients including various functional amino acids, vitamins, and minerals on chicken intestinal epithelial cells (cIECs) treated with oxidative stress. The cIECs were isolated from specific pathogen free eggs. Cells were exposed to 0 mM supplement (control), 20 mM threonine (Thr), 0.4 mM tryptophan (Trp), 1 mM glycine (Gly), 10 μM vitamin C (VC), 40 μM vitamin E (VE), 5 μM vitamin A (VA), 34 μM chromium (Cr), 0.42 μM selenium (Se), and 50 μM zinc (Zn) for 24 h with 6 replicates for each treatment. After 24 h, cells were further incubated with fresh culture medium (positive control, PC) or 1 mM H2O2 with different supplements (negative control, NC and each treatment). Oxidative stress was measured by cell proliferation, whereas tight junction barrier function was analyzed by fluorescein isothiocyanate (FITC)-dextran permeability and transepithelial electrical resistance (TEER). Results indicated that cell viability and TEER values were less (p < 0.05) in NC treatments with oxidative stress than in PC treatments. In addition, FITC-dextran values were greater (p < 0.05) in NC treatments with oxidative stress than in PC treatments. The supplementations of Thr, Trp, Gly, VC, and VE in cells treated with H2O2 showed greater (p < 0.05) cell viability than the supplementation of VA, Cr, Se, and Zn. The supplementations of Trp, Gly, VC, and Se in cells treated with H2O2 showed the least (p < 0.05) cellular permeability. In addition, the supplementation of Thr, VE, VA, Cr, and Zn in cells treated with H2O2 decreased (p < 0.05) cellular permeability. At 48 h, the supplementations of Thr, Trp, and Gly in cells treated with H2O2 showed the greatest (p < 0.05) TEER values among all treatments, and the supplementations of VC and VE in cells treated with H2O2 showed greater (p < 0.05) TEER values than the supplementations of VA, Cr, Se, and Zn in cells treated with H2O2. In conclusion, Thr, Trp, Gly, and VC supplements were effective in improving cell viability and intestinal barrier function of cIECs exposed to oxidative stress.

Abstract Assembly geometric error as a part of the machine tool system errors has a significant influence on the machining accuracy of the multi-axis machine tool. And it cannot be eliminated due to the error propagation of components in the assembly process, which is generally non-uniformly distributed in the whole working space. A comprehensive expression model for assembly geometric error is greatly helpful for machining quality control of machine tools to meet the demand for machining accuracy in practice. However, the expression ranges based on the standard quasi-static expression model for assembly geometric errors are far less than those needed in the whole working space of the multi-axis machine tool. To address this issue, a modeling methodology based on the Jacobian-Torsor model is proposed to describe the spatially distributed geometric errors. Firstly, an improved kinematic Jacobian-Torsor model is developed to describe the relative movements such as translation and rotation motion between assembly bodies, respectively. Furthermore, based on the proposed kinematic Jacobian-Torsor model, a spatial expression of geometric errors for the multi-axis machine tool is given. And simulation and experimental verification are taken with the investigation of the spatial distribution of geometric errors on five four-axis machine tools. The results validate the effectiveness of the proposed kinematic Jacobian-Torsor model in dealing with the spatial expression of assembly geometric errors.

Due to the aggressive scaling down of logic semiconductors, the difficulty of semiconductor component processes has increased. As the structure of components becomes more complex, the time and cost of processes and simulations have risen. Machine learning is now being used to analyze the electrical characteristics data of semiconductor components and apply the trained machine learning to next-generation semiconductor development. Machine learning trained on process data and simulation results can quickly and accurately predict which electrical characteristics change significantly when the component’s structure changes and which parameters have a significant impact on the electrical characteristic changes. This paper presents suitable machine learning models for analyzing and predicting the electrical characteristics (on-current ( $I_{on}$ ), off-current ( $I_{off}$ ), threshold voltage ( $V_{th}$ ), subthreshold swing (SS), and drain induced barrier lowering (DIBL)) and statistical distribution (mean and standard deviation of the electrical characteristics) resulting from geometrical variability (sheet thickness ( $T_{wire}$ ), sheet diameter ( $D_{wire}$ ), oxide thickness ( $T_{ox}$ ), gate length ( $L_{g}$ ), spacer length ( $L_{sp}$ ), gate metal work-function (WF)) in nanosheet field-effect transistor (NSFET), which are a next-generation logic device. Machine learning models, including regulation-based models (Ridge and LASSO) and tree-based models (decision tree (DT), random forest (RF), extreme gradient boost (XGBoost), and light gradient boost machine (LGBM)), are trained on technology computer-aided design (TCAD) simulation data. The LGBM more accurately predicts the electrical characteristics and statistical distribution of the NSFET than the other models. Additionally, we analyze the effect of geometrical variability on the NSFET based on feature importance.

Cultured meat is a potential sustainable food generated by the in vitro myogenesis of muscle satellite (stem) cells (MSCs). The self-renewal and differentiation properties of MSCs are of primary interest for cultured meat production. MSC proliferation and differentiation are influenced by a variety of growth factors such as insulin-like growth factors (IGF-1 and IGF-2), transforming growth factor beta (TGF-β), fibroblast growth factors (FGF-2 and FGF-21), platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF) and by hormones like insulin, testosterone, glucocorticoids, and thyroid hormones. In this review, we investigated the roles of growth factors and hormones during cultured meat production because these factors provide signals for MSC growth and structural stability. The aim of this article is to provide the important idea about different growth factors such as FGF (enhance the cell proliferation and differentiation), IGF-1 (increase the number of myoblasts), PDGF (myoblast proliferation), TGF-β1 (muscle repair) and hormones such as insulin (cell survival and growth), testosterone (muscle fiber size), dexamethasone (myoblast proliferation and differentiation), and thyroid hormones (amount and diameter of muscle fibers and determine the usual pattern of fiber distributions) as media components during myogenesis for cultured meat production.

This review explores the factors that improve meat protein digestibility and applies the findings to the development of home meal replacements with improved protein digestion rates in older adults. Various methods improve the digestion rate of proteins, such as heat, ultrasound, high pressure, or pulse electric field. In addition, probiotics aid in protein digestion by improving the function of digestive organs and secreting enzymes. Plant-derived proteases, such as papain, bromelain, ficin, actinidin, or zingibain, can also improve the protein digestion rate; however, the digestion rate is dependent on the plant enzyme used and protein characteristics. Sous vide processing improves the rate and extent of protein digestibility, but the protein digestion rate decreases with increasing temperature and heating time. Ultrasound, high pressure, or pulsed electric field treatments degrade the protein structure and increase the proteolytic enzyme contact area to improve the protein digestion rate.

This study was conducted to develop simple methods for the extraction of chenodeoxycholic acid (CDCA) and synthesis of ursodeoxycholic acid (UDCA) from pig by-products. The enzymatic method, which uses bile salt hydrolase (BSH) enzymes to extract CDCA, was found to be more efficient than the chemical method. The chemical method, which uses pig by-products, resulted in UDCA amounts of 6.05 mg, 0.51 mg, 3.04 mg, and 1.26 mg in 100 g of the liver, stomach, small intestine, and large intestine, respectively. The amounts of UDCA synthesized/100 g through the chemical and enzymatic methods required to extract CDCA were 3.48 g and 2.22 g, respectively. The procedure developed in this study was simplified by three stages compared to the conventional chemical method of extracting CDCA. Moreover, this study provides a technique that improves the utilization of pig by-products.

This study was conducted to determine the effect of natural ingredient seasoning on the reduction of heterocyclic amine (HCA) production that may occur when pork belly is cooked at a very high temperature for a long time. Pork belly seasoned with natural ingredients, such as natural spices, blackcurrant, and gochujang, was cooked using the most common cooking methods, such as boiling, pan fry, and barbecue. HCAs in pork belly were extracted through solid-phase extraction and analyzed via high-performance liquid chromatography. For short-term toxicity, a mouse model was used to analyze weight, feed intake, organ weight, and length; hematology and serology analysis were also performed. Results revealed that HCAs formed only when heating was performed at a very high temperature for a long time, not under general cooking conditions. Although the toxicity levels were not dangerous, the method showing the relatively highest toxicity among various cooking methods was barbecue, and the natural material with the highest toxicity reduction effect was blackcurrant. Furthermore, seasoning pork belly with natural materials containing a large amount of antioxidants, such as vitamin C, can reduce the production of toxic substances, such as HCAs, even if pork belly is heated to high temperatures.

Neutralisation assays are key to understanding immune responses to SARS-CoV-2 infection or vaccination. Here, the authors report a surrogate virus neutralization assay called Neu-SATiN, which measures neutralization directly from sera, and allows easy adaptation to variant-specific testing.

Residual antibiotics may affect human health by increasing challenges related to infection treatment due to antibiotic resistance development. Hence, determining whether residual antibiotics in the body can lead to antibiotic resistance is important. We developed a model to predict possible antibiotic resistance caused by residual antibiotics by simulating human digestion in vitro. Increased antibiotic resistance was found to be dependent on the digestion process. Ethical prediction of antibiotic resistance using fewer animals and no humans was possible by simulating the internal environment. Thus, preliminary studies to monitor antibiotic resistance that can affect human health may be safely conducted using this model.

Abstract Background Intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) is a time‐dependent treatment with a narrow therapeutic time window, in which the time delay could result from the deadline effect. Methods One hospital‐based cohort was recruited to detect the factors contributing to the deadline effect, where patients with the deadline effect were defined as those who were presented with the onset‐to‐door time (ODT) in the first 50%, while the door‐to‐needle time (DNT) was in the last quartile. DNT (in‐hospital delay) was further subdivided into several time intervals [door‐to‐examination time (DET), door‐to‐imaging time (DIT), door‐to‐laboratory time (DLT), and decision‐making time (DMT) of the patients or their proxies. Results A total of 186 IVT cases were enrolled, of which 17.2% (32/186) suffered a delay of the deadline effect. The median age was 66 years, and 35.5% were female. Baseline characteristics were similar between the two groups (all p > .05). For the comparisons of the time intervals, DIT (26 versus 15 min, p = .001) was significantly longer in the group with deadline effect, while the differences of DET, DLT, DMT, and ONT did not reach statistical significance (all p > .05). Upon multivariable adjustment in the binary logistic regression model, longer DIT [odds ratio (OR), 1.076; 95% confidence interval (CI), 1.036–1.118; p

Novel CAR T cells targeting mesothelin (MSLN) expressed on pancreatic cancer cells were developed to overcome the limit of the clinical efficacy of CAR T cell therapy for pancreatic cancer patients. Optimal single-chain variable fragments (scFv) binding to MSLN were selected based on the binding activity and the functional effectiveness of various scFv containing CAR-expressing T cells. Engineered MSLN CAR T cells showed successful anti-tumor activity specific to MSLN expression level. Furthermore, MSLN CAR T cells were evaluated for the anti-cancer efficacy in orthotopic mouse models bearing pancreatic cancer cells, MIA Paca-2, MSLN-overexpressed MIA Paca-2 or endogenously MSLN-expressing AsPC-1. Mice were randomized into control, mock treated, MS501 BBz treated, MS501 28z treated or MS501 28BBz treated group. Mice were monitored by weekly IVIS imaging and tumors were harvested and analyzed by immunohistochemical analyses. MSLN CAR T cells produced the therapeutic effect in orthotopic animal models with complete remission in significant number of mice. Histopathological analysis indicated that CD4+ and CD8+ MSLN CAR T cells infiltrated pancreatic tumor tissue and led to cancer cell eradication. Our results demonstrated the anti-tumor efficacy of MSLN CAR T cell therapy against pancreatic cancer, suggesting its therapeutic potential.

Imbalanced datasets are pervasive in classification tasks and would cause degradation of the performance of classifiers in predicting minority samples. Oversampling is effective in resolving the class imbalance problem. However, existing oversampling methods generally introduce noise examples into original datasets, especially when the datasets contain class overlapping regions. In this study, a new oversampling method named Constrained Oversampling is proposed to reduce noise generation in oversampling. This algorithm first extracts overlapping regions in the dataset. Then Ant Colony Optimization is applied to define the boundaries of minority regions. Third, oversampling under constraints is employed to synthesize new samples to get a balanced dataset. Our proposal distinguishes itself from other techniques by incorporating constraints in the oversampling process to inhibit noise generation. Experiments show that it outperforms various benchmark oversampling approaches. The explanation for the effectiveness of our method is given by studying the impact of class overlapping on imbalanced learning.

For the visual measurement of moving arm holes in complex working conditions, a histogram equalization algorithm can be used to improve image contrast. To lessen the problems of image brightness shift, image over-enhancement, and gray-level merging that occur with the traditional histogram equalization algorithm, a dual histogram equalization algorithm based on adaptive image correction (AICHE) is proposed. To prevent luminance shifts from occurring during image equalization, the AICHE algorithm protects the average luminance of the input image by improving upon the Otsu algorithm, enabling it to split the histogram. Then, the AICHE algorithm uses the local grayscale correction algorithm to correct the grayscale to prevent the image over-enhancement and gray-level merging problems that arise with the traditional algorithm. It is experimentally verified that the AICHE algorithm can significantly improve the histogram segmentation effect and enhance the contrast and detail information while protecting the average brightness of the input image, and thus the image quality is significantly increased.

(1) Background: Milnacipran is a typical serotonin–norepinephrine reuptake inhibitor and has been shown to have analgesic effects in several pain models. However, its antihyperalgesic effect in cisplatin-induced neuropathy remains unknown. We examined the effects of intraperitoneal (IP) milnacipran on allodynia in cisplatin-induced peripheral neuropathic mice. (2) Methods: Peripheral neuropathy was induced by injecting cisplatin (2.3 mg/kg/day, IP) six times, on every other day. Saline or milnacipran (10, 30, 50 mg/kg, IP) were then administered to the neuropathic mice. We examined mechanical allodynia using von Frey hairs at preadministration and at 30, 60, 90, 120, 180, 240 min and 24 h after drug administration. We also measured the dorsal root ganglion (DRG) activating transcription factor 3 (ATF3) to confirm the analgesic effects of milnacipran. (3) Results: For the milnacipran groups, the decreased paw withdrawal thresholds to mechanical stimuli were significantly reversed when compared to the preadministration values and the values in the saline-injected control group (p < 0.0001). Milnacipran administration to cisplatin-induced peripheral neuropathic mice resulted in a significant suppression of neuronal ATF3 activation (p < 0.01). (4) Conclusions: Milnacipran given via IP injection attenuates mechanical allodynia in mouse models of cisplatin-induced poly-neuropathic pain. These effects were confirmed by significant suppression of neuronal ATF3 activation in the DRG.

In the pursuit of automating the entire underground drilling process in coal mines, the automatic rod feeding technology of drilling robots plays a crucial role. However, the current lack of positional accuracy in automatic rod feeding leads to frequent accidents. To address this issue, this paper presents an algorithm for compensating positioning errors in automatic rod feeding. The algorithm is based on a theoretical mathematical model and manual teaching methods. To enhance the positioning accuracy, we first calibrate the pull rope sensor to correct its measurement precision. Subsequently, we establish a theoretical mathematical model for rod feeding positions by employing spatial coordinate system transformations. We determine the target rod feeding position using a manual teaching-based approach. Furthermore, we analyze the relationship between the theoretical rod delivery position and the target rod delivery position and propose an anisotropic spatial difference compensation technique that considers both distance and direction. Finally, we validate the feasibility of our proposed algorithm through automatic rod feeding tests conducted on a coal mine underground drilling robot. The results demonstrate that our algorithm significantly improves the accuracy of rod feeding positions for coal mine underground drilling robots.

The battery is an important part of the new energy electric vehicle, and the control of the flatness of its side plate/bottom plate is the key to quality improvement in mass production. However, there are few pieces of research on the flatness distribution form at present, and the distribution form is often assumed to be a normal distribution, which leads to a significant deviation between the tolerance design and quality control of the flatness and the reality. This paper establishes a statistical model of flatness distribution, its theoretical distribution form is deduced as a normal range distribution, and then the experimental data of the flatness distribution are collected to verify this conclusion. Determining the flatness distribution form has practical effects on improving manufacturing quality and reducing costs in battery manufacturing.

Purpose Curative treatment is challenging in patients with locally advanced rectal cancer and unresectable metastases. The aim of this study was to evaluate the clinical outcomes of short-course radiotherapy (RT) followed by systemic chemotherapy for patients with rectal cancer with mesorectal fascia (MRF) involvement and unresectable distant metastases. Methods The study included consecutive patients diagnosed as having metastatic mid-to-low rectal cancer treated with short-course RT followed by systemic chemotherapy for conversion radical or palliative surgery between 2014 and 2019 at Gil Medical Center. The patients had primary rectal tumors involving the MRF and unresectable distant metastases. The treatment strategies were determined in a multidisciplinary team discussion. Results Seven patients (five men and two women) underwent short-course RT (5×5 Gy) and preoperative systemic chemotherapy. The median age was 68 years (range, 46–84 years), and the median distance from the anal verge to the primary tumor was 6.0 cm (range, 2.0–9.0 cm). During the median follow-up period of 29.4 months, three patients underwent conversion radical surgery with R0 resection, two underwent palliative surgery, and two could not undergo surgery. No postoperative major morbidity or mortality occurred. The patients who underwent conversion complete radical surgery showed good long-term survival outcomes, with an overall survival time of 29.4–48.8 months and progression-free survival time of 14.7–41.1 months. Conclusion Short-course RT followed by systemic chemotherapy could provide patients with unresectable stage IV rectal cancer a chance to undergo to conversion radical surgery with good long-term survival outcomes.

Objective To investigate the correlation of olfactory function and cognitive function and motor symptoms in patients with primary Parkinson's disease (PD). Methods Total 152 patients with PD diagnosed and treated were recruited from August 2018 to October 2019 in The First Affiliated Hospital of Anhui Medical University. The Chinese Smell Indentification Test (CSIT) was used to evaluate the olfactory recognition function. According to the test results, patients were divided into the normal olfactory group (n=62) and the olfactory disorder group (n=90). The Unified Parkinson's Disease Assessment Scale Ⅲ (UPDRS Ⅲ) was used to evaluate the motor function, the Montreal Cognitive Assessment Scale (MoCA) Beijing edition was used to evaluate the degree of cognitive function, the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) were used to assess the patients' depression and anxiety levels. Patients' visual spatial working memory function were tested by the n⁃back test. Pearson correlation analysis and Spearman rank correlation analysis were used to investigate the correlation between olfactory function with cognitive function and motor symptoms in patients with PD. Results CSIT⁃self score (Z=⁃2.081, P=0.037) and CSIT⁃OI score (t=13.966, P=0.000) were lower in patients with anosmia than in those with normal smell. Overall MoCA score (t=3.008, P=0.003), as well as the scores of visuospatial executive function (Z=⁃2.277, P=0.023), naming (Z=⁃2.397, P=0.017), attention (Z=⁃3.203, P=0.001), language (Z=⁃2.229, P=0.026), delayed memory (Z=⁃2.426, P=0.015) were all decreased. The accuracy of 1⁃back test (t=2.341, P=0.027) and 2⁃back test (t=2.406, P=0.024) decreased, and the response time of 0⁃back test (t=⁃2.309, P=0.029) and 2⁃back test (t=⁃2.314, P=0.029) increased. Correlation analysis showed that olfactory function score was positively correlated with total MoCA score (rs=0.298, P=0.000). Conclusions The olfactory function of PD patients is closely related to cognitive function, PD patients with olfactory disorder have poor visual spatial working memory function. Therefore such patients should be paid more attention to cognitive function and visual spatial working memory function.

The three-dimensional carbon fiber fabric was densified by chemical vapor infiltration and precursor impregnation cracking composite process, and the high thermal conductivity 3D C/C composite material with density of 1.95 g/cm3 was obtained. Using SEM, XRD, thermal conductivity test, linear expansion coefficient test and three-point bending experiment to study the effect of different heat treatment temperatures of 2350,2550,2850℃ on the microscopic morphology,structure, thermal conductivity, linear expansion coefficient and bending performance of 3D C/C composites. The results show that with the increase of the heat treatment temperature, the mesophase pitch-based carbon fiber graphite sheet structure becomes more obvious, the order of the pyrolytic carbon sheets evenly wrapped around the carbon fiber increases, and the arrangement between the sheets becomes more dense; the graphitization and thermal conductivity of 3D C/C composite materials improve; in the test temperature range of 250-1400℃, the linear expansion coefficient increases slightly with the increase of the test temperature, and the 3D C/C composite after different heat treatment temperatures. The linear expansion coefficient of the materials is -1×10-6-2×10-6℃-1, showing good "zero expansion". In addition, when the heat treatment temperature increases, the bonding of the carbon fiber and the matrix of the 3D C/C composite materials are weakened, resulting in the decrease in the bending strength and flexural modulus of the materials. A large number of long fibers are pulled out on the bending fracture surface of the materials after the high temperature heat treatment at 2850℃. In general, the fracture after three different heat treatment temperatures shows "pseudoplastic" fracture characteristics.

The aim of this study was to investigate the effects of dietary sodium nitrite and meat on human health. Sodium nitrite in processed meat is known to be one of the main precursors of carcinogens, such as N-nitroso compounds. However, we previously found that processed meat is not the primary source of sodium nitrite; nitrate or the conversion of nitrate in vegetables are contribute to generate more than 70% Sodium nitrite or nitrate containing compounds in body. Although the heavy consumption of meat is likely to cause various diseases, meat intake is not the only cause of colorectal cancer. Our review indicates that sodium nitrite derived from foods and endogenous nitric oxide may exhibit positive effects on human health, such as preventing cardiovascular disease or improving reproductive function. Therefore, further epidemiological studies considering various factors, such as cigarette consumption, alcohol consumption, stress index, salt intake, and genetic factors, are required to reliably elucidate the effects of dietary sodium nitrite and meat on the incidence of diseases, such as colorectal cancer.

Objective To analyze the relevant risk factors for intracranial infection after craniotomy for resection of skull base neoplasms. Methods The clinical data of 159 patients with skull base neoplasms who underwent craniotomy from May 2010 to January 2020 in The Second Affiliated Hospital of Anhui Medical University were analyzed retrospectively. The relevant risk factors for intracranial infection were analyzed by univariate and multivariate forward Logistic regression. Results Postoperative intracranial infection occurred in 81 out of 159 patients, the infection rate was 50.94%. Multivariate forward Logistic regression analysis showed the operation time was ≥ 5 h (OR = 3.438, 95%CI: 1.371-8.625; P = 0.008), blood loss ≥ 400 ml (OR = 2.308, 95%CI: 1.115-4.777; P = 0.024), frontal sinus or mastoid air chamber breach (OR = 16.817, 95%CI: 3.689-76.658; P = 0.000) were the risk factors for intracranial infection after craniotomy for resection of skull base neoplasms. Conclusions There was a higher risk of intracranial infection after craniotomy for resection of skull base neoplasms in patients who had long operation time, more intraoperative blood loss as well as frontal sinus or mastoid air chamber breach. It is necessary to adopt effective prevention and control measures to reduce the risk of intracranial infection.

The purpose of this study was to establish a basic principal procedure for the processing of cultured meat. The first stage involved isolating satellite cells from the desired muscle of an animal using enzymatic digestion (i.e., by using proteases, collagenases, and pronases). The second stage involved culturing the isolated muscle satellite cells in a growth medium containing fetal bovine serum and penicillin/streptomycin with growth factors for an optimal period of time. The second stage involved a basic method for the isolated muscle cells to proliferate while sub-culturing to further induce differentiation in gelatin-coated culture dishes with the general culture medium. The third stage involved the induction of differentiation of muscle satellite cells or formation of myotubes using myogenic medium. Lastly, the fourth stage involved the identification of cell differentiation or myotube formation (myogenesis) using fluorescent dyes. Moreover, the principle of these protocols can be applied to perform primary culture of animal cells. This study will assist beginners with the technical aspects of culturing meat (isolation, cultivation, and differentiation of muscle satellite cells as well as identification of myotube formation for myogenesis).

Abstract Most of the traditional islanding detection methods are designed for renewable sources in AC systems and cannot be directly applied in multi‐terminal DC renewable power distribution systems. Moreover, the attenuation effect of multi‐branches makes it difficult for active methods to effectively detect complex islanding operations with multiple renewable power sources. To address the above problems, this paper proposes an active high‐frequency impedance estimation based DC islanding detection method. The impedance of converters is proved to be a constant value at high‐frequencies, and the high‐frequency impedance of the system changes significantly after islanding. Therefore, islanding operations can be accurately detected through impedance characteristics with a negligible none detection zone. The proposed islanding detection method uses DC/DC converters to inject non‐characteristic harmonics to perform high‐frequency impedance calculations without additional injection equipment. The high‐frequency impedance directly reflects structural changes of the DC system. In this case, this method has lower requirements on the disturbance intensity and will not be influenced by the attenuation effect. The injected harmonic voltage is used as an auxiliary criterion to detect complex DC islanding operations with multiple renewable sources. Simulation results prove that the proposed method has high detection accuracy and is not affected by transient conditions.

Urethral clear cell carcinoma is an aggressive tumor rarely observed in the urinary tract. To date, the diagnostic workup of such cases has not yet been standardized, and there has been no established standard treatment approach. The present study reports a rare case of urethral clear cell carcinoma successfully treated with organ preservation strategies and adjuvant chemoradiation with the goal of organ preservation. This treatment approach could be used for patients who refuse radical surgery and patients with concerns about severe morbidity from radical surgery, even in advanced-stage urethral clear cell carcinoma.

Distinguishing syncope from epileptic seizures in patients with sudden loss of consciousness is important. Various blood tests have been used to indicate epileptic seizures in patients with impaired consciousness. This retrospective study aimed to predict the diagnosis of epilepsy in patients with transient loss of consciousness using the initial blood test results. A seizure classification model was constructed using logistic regression, and predictors were selected from a cohort of 260 patients using domain knowledge and statistical methods. The study defined the diagnosis of seizures and syncope based on the consistency of the diagnosis made by an emergency medicine specialist at the first visit to the emergency room and the diagnosis made by an epileptologist or cardiologist at the first outpatient visit using the International Classification of Diseases 10th revision (ICD-10) code. Univariate analysis showed higher levels of white blood cells, red blood cells, hemoglobin, hematocrit, delta neutrophil index, creatinine kinase, and ammonia levels in the seizure group. The ammonia level had the highest correlation with the diagnosis of epileptic seizures in the prediction model. Therefore, it is recommended to be included in the first examination at the emergency room.

The surface accuracy of a multistep rotary shaft is very important in manufacturing and the assembly process of the high-speed motorized spindle of CNC machine tools, which is closely related to the machined dimensional variation induced by the turning process. This paper attempts to enhance a comprehensive understanding of the impact of different locating-error sources and machine toolpaths on the machined dimensional variation for multistep rotary parts of the high-speed motorized spindle in the turning process. A modeling method and a compensation strategy of dimensional variation are introduced in this paper and based on the relationship definition between the error sources and the machined surface using the differential motion vector and stream-of-variation methods. Validation experiments were conducted to verify the proposed model. Additionally, the relationship between locating errors and dimensional variation was investigated with varied case studies, providing a theoretical methodology for the prediction and characterization of the expected dimensional variations of the surface machined with the given conditions.

Objective To investigate the anti⁃tumoral effect of ACT001, a novel antitumor compound, on the nuclear factor⁃κB (NF⁃κB) pathway and programmed cell death protein ligand 1 (PDL1) expression in U87 glioblastoma cell line. Methods We analyzed the correlation between the expression of P65 and PDL1, pathological grade, and prognosis by introducing The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. CCK⁃8 was used to observe the effect of ACT001 on the proliferation of U87 cells, and calculate the median inhibition concentration (IC50). Immunofluorescence staining was used to detect the effect of ACT001 on nuclear translocation of the transcription factor P65. U87 cells were transfected with small interference RNA (siRNA), and P65 knockdown efficiency was determined by quantitative real⁃time polymerase chain reaction (qRT⁃PCR). The relative expression of P65, phospho⁃P65 (p⁃P65) and PDL1 in different transfected groups and drug treatment groups were determined by Western blotting. Results 1) Bioinformatics analysis showed that gliomas with higher pathological grade hourbored higher P65 and PDL1 expression (P＜0.05, for all). Moreover, patients with high expression of P65 and PDL1 mRNA predicted poor prognosis (P＜0.05, for all). 2) CCK⁃8 assay showed that treatment with different concentrations of ACT001 (5, 10, 20, 40, 80, 160 and 320 μmol/L), the inhibition rates of U87 cells were (9.01±4.75)%, (17.03±2.91)%, (28.50±4.85)%, (45.50±5.15)%, (67.67±8.46)% , (83.02±5.79)% and (94.33±1.59)% , respectively, and the IC50 was about 42.98 μmol/L. 3) Immunofluorescence staining showed that ACT001 inhibited nuclear translocation of P65. 4) qRT⁃PCR showed that the P65 mRNA expression of U87 cells in different siRNA transfected groups was statistically significant (F=164.200, P=0.000), and the mRNA expression of P65 in si⁃P65⁃1 group (t=13.290, P=0.000) and si⁃P65⁃2 group (t=12.730, P=0.000) was lower than that of si⁃NC group. 5) Western blotting showed that the relative expression of P65 (F=681.300, P=0.000), p⁃P65 (F=128.800, P=0.000) and PDL1 (F=20.470, P=0.002) in U87 cells of different siRNA transfection groups were statistically significant different. Among them, P65 (t=59.630, P=0.000; t=29.380, P=0.000), p⁃P65 (t=24.370, P=0.000; t=13.460, P=0.000) and PDL1 (t=6.025, P=0.004; t=6.728, P=0.003) in si⁃P65⁃1 group and si⁃P65⁃2 group were lower than those in si⁃NC group. 6) There were statistically significant differences in the relative expression of p⁃P65 (F=269.700, P=0.000) and PDL1 (F=128.800, P=0.000) in U87 cells treated with different concentrations of drugs. P⁃P65 (t=19.750, P=0.000; t=24.640, P=0.000) and PDL1 (t=12.690, P=0.000; t=19.230, P=0.000) in ACT001 25 μmol/L group and 50 μmol/L group were lower than those in normal control group, ACT001 50 μmol/L group were also lower than those of 25 μmol/L group (t=5.288, P=0.006; t=2.868, P=0.046). Conclusions ACT001 can inhibit the proliferation of U87 glioma cells. By inhibiting the phosphorylation and nuclear translocation of P65 in U87 cells, ACT001 decreased the expression of PDL1 to improve the immunosuppressive environment of glioblastoma and thus inhibit the progression of glioblastoma.

The authors present nanosensor chemical cytometry, based on an array of nIR fluorescent single walled carbon nanotube integrated along a microfluidic channel. The lensing effect of the flowing cells allows for extracting information, and correlating biomolecular information with physical properties.

Abstract The purpose of this study was to investigate the effects of edible halophyte Salicornia herbacea encapsulated with biopolymers on inhibition of sodium absorption in mouse. Salicornia herbacea encapsulated with four biopolymers (pectin, chitosan, cellulose and dextrin) were fed to mice for 48 hr, and inhibiting sodium absorption was measured. In primary in vitro condition, fresh Salicornia herbacea encapsulated with 1% cellulose had 40% binding rate. Juice residue Salicornia herbacea encapsulated with 1% chitosan had the highest sodium binding rate by 50%. In mouse model, fresh, juice, and juice residue of Salicornia herbacea encapsulated with 4% chitosan had the highest sodium absorption inhibitory rate by 19%. These results indicate that biopolymer‐encapsulated Salicornia herbacea could be combined with sodium under in vitro condition, and Salicornia herbacea encapsulated with biopolymers reduced sodium absorption in a mouse model. Chitosan and cellulose had the highest sodium absorption inhibitory effects compared with the other biopolymers.

Background: Colorectal cancer is the third most common malignant disease and the second leading cause of death worldwide. Previous studies showed improved bioavailability and cytotoxicity of ginsenoside-modified nanostructured lipid carrier containing curcumin (G-NLC) in human colon cancer cell lines. This study aimed to evaluate the safety and tolerability with long-term survival rates in patients with colorectal cancer with unresectable metastases after treatment with first-line bevacizumab/FOLFIRI (folinic acid, bolus/continuous fluorouracil, and irinotecan) in combination with a dietary supplement of G-NLC. Methods: This study was a prospective, observational, single-group analysis. The enrolled patients had colorectal cancer with unresectable metastases and were administered bevacizumab and FOLFIRI in combination with daily oral G-NLC as first-line treatment. Overall survival, progression-free survival, tumor response, and adverse events were evaluated. Results: A total of 44 patients were enrolled between 2015 and 2019. The median age was 65 (range 45-81) years and the sex ratio was 31:13 (male:female). The primary tumor locations were the colon (31 patients) and rectum (13 patients). The metastatic sites included, liver only (n = 20), lung only (n = 6), both liver and lung (n = 12), and others (n = 6). The median duration of curcumin supply was 7.9 (range 0.9-16.6) months. The most common grade 3 or higher adverse events were neutropenia (n = 15, 34.1%), followed by nausea (n = 4, 9.1%) and vomiting (n = 4, 9.1%). Within the median follow-up period of 22.8 months, the median overall survival was 30.7 months, and the median progression-free survival was 12.8 months. None of the patients achieved complete response (CR); however, 9 patients showed partial response (PR), and 3 patients underwent conversion surgery. Conclusions: Bevacizumab/FOLFIRI with G-NLC as first-line chemotherapy in patients with colorectal cancer with unresectable metastases presented comparable long-term survival outcomes with acceptable toxicity outcomes. Additional randomized controlled studies are needed to establish definitive conclusions regarding this new regimen for metastatic colorectal cancer.

To observe the effect of black sesame oil lecithin solution on bone metabolism in naturally grown aging mice and compare with vitamin E.8-month-old SPF Kunming mice were randomly divided into normal saline group (NS group),vitamin E group (VE group),black sesame oil group (Oil group).The experiment lasted for 10 weeks.At the end of the experiment,the mice were sacrificed.The right femurs were taken for Micro CT scan,and the left ulna for bone component content determination.Compared with the NS group,the bone calcium and bone magnesium contents in the Oil group were significantly increased,and the SMI was significantly reduced,while BV/TV,Density and Conn-Dens were increased,but the difference was not statistically significant; compared with the VE group,The content of bone calcium and bone magnesium in the Oil group were significantly increased; the three-dimensional map showed that the bone trabeculae were arranged evenly and tightly,with small gaps and good continuity.After 10 weeks of naturally-growing old mice given black sesame oil,the bone mass and microstructure of the femur of the mice increased,suggesting the potential applications for anti-osteoporosis.

Serological tests are important diagnostic and disease surveillance tools for addressing the COVID-19 pandemic. Here, the authors present a tri-part Nanoluciferase based assay to detect antibodies against SARS-CoV-2.

The carbon fiber preform is the skeleton of the carbon/carbon material. During the densification process,the pores of the preform is filled by the matrix carbon to form a carbon/carbon composite material. In order to explore the relationship between the microstructure of carbon fiber preform and densification, three kinds of three-dimensional woven preforms were used as the research objects. The microstructure of the preform was observed through a metallurgical microscope, and digital models of the theoretical structure of the preforms were established to calculate the volume content of different types of pores in the body, and to study the effect of pore structure on the densification efficiency of chemical vapor deposition. The results show that the pores in the three-dimensional woven preform are periodically and repeatedly arranged. The fiber volume fraction in the preform is related to the XY fiber layer spacing and the Z direction fiber spacing, the smaller the XY fiber layer spacing and the Z direction fiber spacing are, the higher the fiber volume content of the preform is; the preform is mainly composed of the pores in the fiber bundle and the inter-bundle pores surrounded by the X, Y, Z fiber bundles; the pore size and structure of the preform affect the densification efficiency, and the densification rate of the preform with high porosity is higher in the early stage of densification, and the preform with uniform pore structure gains weight quickly in the later stage of densification.

Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes.

Porous carbon/carbon (C/C) composites prepared by pitch-based carbon fiber and mesophase pitch were densified by chemical vapor infiltration (CVI) and precursor impregnation process (PIP). After different heat temperature treatment (HTT), the unidirectional C/C composites and bidirectional C/C composites were obtained. The microstructure of C/C composites was investigated by SEM, XRD, and the thermal conductivity was analyzed based on the thermal conductivity mechanism. The results show that unidirectional C/C composites and bidirectional C/C composites have dense structures and excellent thermal conductivity along the fiber axis. After 3000 ℃ treatment, the structure of graphite flat layers become more distinct and the graphitization degree is increased by 18.84%, leading to higher thermal conductivity. Furthermore, the thermal conductivity in X direction and Y direction of the bidirectional C/C composites can be calculated from that of unidirectional C/C composites in X direction and Z direction.

This study was conducted to develop an effective heparin extraction method by using low-cost and highly effective enzymes from six pig by-products (liver, lung, heart, stomach, small intestine, and large intestine), and analyze their bioavailability. Low-cost and highly effective enzymes (alkaline-AK and papain) and a common enzyme (trypsin) were used for the heparin extraction. The angiotensin I - converting enzyme (ACE) inhibitory activity and the antimicrobial activity of extracted heparin were analyzed to verify their bioavailability. The average amount of heparin extracted per kilogram of pig by-products was 439 mg from the liver, 127 mg from the lung, 398 mg from the heart, 261 mg from the stomach, 197 mg from the small intestine, and 239 mg from the large intestine. Various enzymes were used to extract heparin, and the amount of extracted heparin was similar. Based on 1 g of pig by-product, the enzymes trypsin, papain, and alkaline-AK could extract 1,718 mg, 1,697 mg, and 1,905 mg of heparin, respectively. Heparin extracted from pig by-products showed antihypertensive activity and antimicrobial activity against Staphylococcus aureus at low populations. These results indicated that heparin can be obtained from pig by-products at a low cost.

ObjectivesSome drugs that augment cell-intrinsic defenses or modulate cell death/survival pathways have been reported to selectively kill cells infected with HIV or Simian Immunodeficiency Virus (SIV), but comparative studies are lacking. We hypothesized that these drugs may differ in their ability to kill cells infected with intact and defective proviruses.DesignTo investigate this hypothesis, drugs were tested ex vivo on peripheral blood mononuclear cells (PBMC) from nine antiretroviral therapy (ART)-suppressed individuals.MethodsWe tested drugs currently in clinical use or human trials, including auranofin (p53 modulator), interferon alpha2A, interferon gamma, acitretin (RIG-I inducer), GS-9620/vesatolimod (TLR7 agonist), nivolumab (PD-1 blocker), obatoclax (Bcl-2 inhibitor), birinapant [inhibitor of apoptosis proteins (IAP) inhibitor], bortezomib (proteasome inhibitor), and INK128/sapanisertib [mammalian target of rapamycin mTOR] [c]1/2 inhibitor). After 6 days of treatment, we measured cell counts/viabilities and quantified levels of total, intact, and defective HIV DNA by droplet digital PCR (Intact Proviral DNA Assay).ResultsObatoclax reduced intact HIV DNA [median = 27-30% of dimethyl sulfoxide control (DMSO)] but not defective or total HIV DNA. Other drugs showed no statistically significant effects.ConclusionObatoclax and other Bcl-2 inhibitors deserve further study in combination therapies aimed at reducing the intact HIV reservoir in order to achieve a functional cure and/or reduce HIV-associated immune activation.