bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic Extraction of Sapodilla (Manilkara achras L.) Juice: Process Optimization and Characterization
Authors: Singh Sukh Veer , Singh Rakhi , Singh Anurag , Tarafdar Ayon , Thangalakshmi S. , Upadhyay Ashutosh , Kaur Barjindar P. , Chinchkar Ajay V.
Published: May 2022

Conventional treatment of sapodilla pulp yields very viscous, turbid, and low juice recovery. Sapodilla processing for juice requires liquefying enzyme that leads to rectifying flow of juice. This study was conducted to optimize the enzymatic pectolytic conditions of sapodilla fruit processing to extract maximum juice using a central composite design (CCD). The effect of processing variables on recovery of juice, total soluble solids (TSS), viscosity, clarity, and L-value along with physicochemical analysis was investigated. The optimized processing conditions were pectinase concentration (0.120%) at 42.02°C for 167.83 min resulting in juice recovery (62.08 ± 0.38%), viscosity (4.81 ± 0.02cP), TSS (21.48 ± 0.19 °Brix), clarity (0.72 ± 0.05%T), and L-value (28.79 ± 0.96). Optimized sapodilla juice showed higher filterability (24.16 ± 1.04 min−1), conductivity (69.46 ± 0.30 S/m), total phenolic content (35.86 ± 0.60 mg/100 mL), ascorbic acid (6.38 ± 0.58 mg/100 mL), moisture content (84.85 ± 0.21% WB), and titratable acidity (0.143 ± 0.0% citric acid) as compared to control sample (60.5 ± 1.80 min−1, 30.43 ± 0.35 S/m, 30.68 ± 0.85 mg/100 mL, 4.64 ± 0.0 mg/100 mL, 83.69 ± 0.18%, and 0.130 ± 0.0%). Optimized sapodilla juice was lower in sedimentation index (0.73 ± 0.11%), turbidity (13.73 ± 1.10 NTU), ash (0.57 ± 0.031%), and β-carotene (0.173 ± 0.008 μg/100 mL) as compared to control sample (1.07 ± 0.02%, 79 ± 0.75 NTU, 0.65 ± 0.031%, and 0.306 ± 0.007 μg/100 mL). The flow behavior index (n) was closer to 1 in both juice samples, which indicated Newtonian-like flow behavior. Conclusively, sapodilla juice extraction at optimal condition (0.120% of pectinase concentration) and 42.02°C/167.83 min would be potentiated to the beverage industry. The use of pectinase might reduce membrane fouling and facilitates processing operation efficiently.
[Retracted] Design, Synthesis and Activity Study of Pyridine Derivatives as Highly Effective and Selective TYK2 Inhibitors
Authors: Cheng Chaoying , Zhou Mengguang , Zhang Panpan , Qian Wenjian , Chen Lei , Chen Guorong
Published: May 2022

Due to the high homology of the ATP sites of the JAK family, the development of selective inhibitors for a certain JAK isoform is extremely challenging. Our strategy to achieve high selectivity for TYK2 relies on targeting the TYK2 pseudokinase (JH2) domain. Based on the clinical compound BMS‐986165, through structure‐activity relationship studies, a class of acyl compounds with excellent TYK2 inhibitory activity and selectivity to other subtypes of the JAK family was discovered.
Fructose-1,6-Bisphosphatase 2 Inhibits Oral Squamous Cell Carcinoma Tumorigenesis and Glucose Metabolism via Downregulation of c-Myc
Authors: Wang Liang , Wang Jinbing , Shen Yi , Zheng Zhiwei , Sun Jian
Published: May 2022

Background. Fructose-1,6-bisphosphatase 2 (FBP2), known as a rate-limiting enzyme in gluconeogenesis, is a tumor suppressor downregulated in various cancers. However, the role of FBP2 in oral squamous cell carcinoma (OSCC) remains largely unclear. Methods. The level of FBP2 in OSCC tissues and matched adjacent normal tissues was determined by western blot and RT-qPCR assays. In addition, analysis of FBP2 function in OSCC cells was assessed using both gain-of-function and loss-of-function studies. Results. In this study, we found that the expression of FBP2 was remarkably downregulated in OSCC tissues and OSCC cells. Overexpression of FBP2 suppressed the viability, proliferation, migration, and glycolysis of OSCC cells, whereas FBP2 knockdown exhibited the opposite results. Moreover, downregulation of FBP2 promoted the growth and glycolysis of OSCC cells in nude mice in a xenograft model. Specifically, FBP2 colocalizes with the c-Myc transcription factor in the nucleus. Significantly, inhibitory effects of FBP2 overexpression on the viability, proliferation, migration, and glycolysis of OSCC cells were reversed by c-Myc overexpression. Conclusion. Collectively, FBP2 could suppress the proliferation, migration and glycolysis in OSCC cells through downregulation of c-Myc. Our study revealed a FBP2-c-Myc signaling axis that regulates OSCC glycolysis and may provide a potential intervention strategy for OSCC treatment.
More on the Ridge Parameter Estimators for the Gamma Ridge Regression Model: Simulation and Applications
Authors: Yasin Ahad , Amin Muhammad , Qasim Muhammad , Muse Abdisalam Hassan , Soliman Adam Braima
Published: May 2022

The Gamma ridge regression estimator (GRRE) is commonly used to solve the problem of multicollinearity, when the response variable follows the gamma distribution. Estimation of the ridge parameter estimator is an important issue in the GRRE as well as for other models. Numerous ridge parameter estimators are proposed for the linear and other regression models. So, in this study, we generalized these estimators for the Gamma ridge regression model. A Monte Carlo simulation study and two real-life applications are carried out to evaluate the performance of the proposed ridge regression estimators and then compared with the maximum likelihood method and some existing ridge regression estimators. Based on the simulation study and real-life applications results, we suggest some better choices of the ridge regression estimators for practitioners by applying the Gamma regression model with correlated explanatory variables.
FAHP-Based Reliability Evaluation of Distributed IoT Devices in a Distribution Power Grid
Authors: You Xinhong , Zhang Pengping , Li Shuai , Wang Feng , Su Guoqiang , Zhang Shidong
Published: May 2022

Reliable operation of distributed internet of things (IoT) devices is essential for supporting two-way interaction between energy flow and information flow in a distribution power grid. Traditional reliability evaluation methods suffer from several challenges including complex evaluation indicator selection and inadaptability of fixed weights with actual reliability requirements. In this paper, we first establish a multilevel reliability evaluation indicator system, where the indicators are selected through joint consideration of comprehensiveness and effectiveness. Then, we propose a fuzzy analytic hierarchy process- (FAHP-) based reliability evaluation method, where a three-layer reliability evaluation architecture is established. Specifically, a 0.1-0.9 scaling method is adopted to establish the fuzzy judgment matrix and scale the important relationship among state-layer elements, which can be dynamically adjusted to generate the weights adapting with actual operation state. The scores of distributed IoT devices and corresponding reliability levels can be obtained through the weighted summation of the scores of each layer. Simulation results verify the effectiveness and accuracy of the proposed method through comparing with actual reliability value and two existing evaluation methods.
Mechanical, Thermal, and Ablative Properties of Silica, Zirconia, and Titania Modified Carbon-Phenol Ablative Composites
Authors: Kuppusamy Raghu Raja P. , Neogi Swati , Mohanta Santoshi , Chinnasamy Moganapriya , Rathanasamy Rajasekar , Uddin Md. Elias
Published: May 2022

The effect of nanozirconia, nanotitania, and fumed silica on the mechanical, thermal, and ablation behaviour of carbon-phenolic (C-Ph) composites is investigated. The inorganic nanofillers at different loading percentage are used to prepare nano-C-Ph panels by the compression moulding technique. The dispersion of nanofillers is confirmed through SEM analysis. After manufacturing of C-Ph laminates, the mechanical properties such as tensile strength and hardness are evaluated and the effect of these fillers is investigated. Thermal conductivity, thermal erosion, and back wall temperatures were measured to understand the thermal and ablation behaviour of nano-C-Ph laminates. Additionally, the ablation mechanism is analysed by performing SEM analysis of partially and fully burnt composite laminates. The erosion resistance and burnout time of zirconia-C-Ph panels significantly improved with increase in filler loading percentage; however, the back wall temperature rises with filler loading. Titania-filled C-Ph panels show a better control over the back wall temperature but with a poor erosion control. Silica-filled composite panels have shown a balance between decreased back wall temperature with a reasonable erosion rate and burnout time.
Evaluation of Antidiarrheal Activity of 80% Methanol Extract and Solvent Fractions of the Leaves of Withania somnifera (L.) Dunal in Swiss Albino Mice
Authors: Tessema Desta Getaye , Andargie Ferede Yared , Sisay Zewdu Woretaw , Adela Alemu Muluken
Published: May 2022

Background. Withaniasomnifera is an important medicinal plant for the treatment of diarrhea in Ethiopian folklore medicine. The aim of this study was to evaluate the antidiarrheal activity of Withania somnifera leaves in Swiss albino mice. Materials and Methods. Hydromethanolic crude extraction and solvent fractionation were done using cold maceration technique. 80% methanol was used as a solvent in crude extraction, while distilled water, n-butanol, and chloroform were employed during fractionation. Castor oil-induced diarrhea, enteropooling, and gastrointestinal motility models were employed to evaluate antidiarrheal activity. Mice were randomly divided into five groups (six mice per group): negative control, which received 2% Tween 80 in distilled water; positive control, which received 3 mg/kg loperamide; and three test groups (III, IV, and V), which were treated with 100 mg/kg, 200 mg/kg, and 400 mg/kg of crude extract and solvent fractions, respectively. Results. The crude extract, aqueous, and n-butanol fractions significantly delayed the onset of diarrhea at 200 mg/kg and 400 mg/kg dose. There was a significant reduction in the number and weight of stools at all tested doses of the crude extract and aqueous fraction, and at 200 mg/kg and 400 mg/kg of n-butanol fraction. Significant reduction in volume and weight of intestinal contents was observed at all tested doses of the crude extract, and at 200 mg/kg and 400 mg/kg of aqueous and n-butanol fractions. All tested doses of the crude extract and 200 mg/kg and 400 mg/kg of the aqueous and n-butanol fractions significantly reduced the motility of charcoal meal. Conclusion. This study demonstrated that the crude extract and solvent fractions of the Withania somnifera leaves have antidiarrheal activity and supported the folklore use of the plant.
The Clinical Observation and Mechanism of Acupuncture on Cancer-Related Fatigue of Breast Cancer Based on “Gut-Brain Axis”: Study Protocol for a Randomized Controlled Trial
Authors: Lv Zhuan , Gu Yi-Ming , Liu Rui-Dong , Su Kai-Qi , Ruan Xiao-Di , Chang Yi-Niu , Gao Jing , Li Rui-Qing , Fang Lu , Feng Xiao-Dong
Published: May 2022

Background. Cancer-related fatigue (CRF) is a painful, persistent feeling of physical and cognitive subjective fatigue related to cancer or cancer remedy. The occurrence of CRF may be related to the hypothalamic-pituitary-adrenaline (HPA) axis, inflammatory mediator theory, and gut microbiota. Moreover, acupuncture could play a vital part in the therapy of CRF. The study will evaluate whether acupuncture can improve fatigue symptoms of CRF patients after breast cancer chemotherapy by regulating the gut-brain axis. Methods/design. Seventy patients with CRF will be enrolled in this study, with 35 patients randomly assigned to each group. Blood and feces will be collected at the beginning and end of treatment. Piper fatigue scale, KPS score scale, and quality-of-life scale will be used to observe the changes of fatigue symptoms and life quality of CRF patients and to evaluate the effect of acupuncture on CRF. Then, the method of ELISA will be used to explore the regulatory effect of acupuncture on the HPA axis and inflammatory cytokines. Moreover, based on 16SrDNA, the changes of gut microbiota structure and flora of CRF patients will be observed. Ultimately, the correlation analysis of gut microbiota can be related to inflammatory cytokines, HPA axis, and clinical efficacy evaluation. Discussion. This study will identify the effect and the mechanism of acupuncture therapy in CRF. And it will offer an alternative treatment modality for the treatment of CRF after chemotherapy for breast cancer. Furthermore, it will also provide the clinical and theoretical bases for the extensive application of acupuncture therapy in tumor rehabilitation. Trial Status. Protocol version number and date: V2.0, 6 May 2021. The trial is registered with the Chinese Clinical Trial Registry on 20 June 2021 (trial identifier: ChiCTR2100047510).
Thymol Reduces agr‐Mediated Virulence Factor Phenol‐Soluble Modulin Production in Staphylococcus aureus
Authors: Lade Harshad , Chung Sung Hee , Lee Yeonhee , Kumbhar Bajarang Vasant , Joo Hwang-Soo , Kim Yun-Gon , Yang Yung-Hun , Kim Jae-Seok
Published: May 2022

Staphylococcus aureus is a major human bacterial pathogen that carries a large number of virulence factors. Many virulence factors of S. aureus are regulated by the accessory gene regulator (agr) quorum‐sensing system. Phenol‐soluble modulins (PSMs) are one of the agr‐mediated virulence determinants known to play a significant role in S. aureus pathogenesis. In the present study, the efficacy of thymol to inhibit PSM production including δ‐toxin in S. aureus was explored. We employed liquid chromatography–mass spectrometry (LC–MS) to quantify the PSMsα1–PSMα4, PSMβ1 and PSMβ2, and δ‐toxin production from culture supernatants. We found that thymol at 0.5 MIC (128 μg/mL) significantly reduced the PSMα and δ‐toxin production in S. aureus WKZ‐1, WKZ‐2, LAC USA300, and ATCC29213. Downregulation in transcription by quantitative real‐time (qRT) PCR analysis of response regulator agrA and receptor histidine kinase agrC upon 0.5 MIC thymol treatment affirmed the results of LC–MS quantification of PSMs. In silico molecular docking analysis demonstrated the binding affinity of thymol with receptors AgrA and AgrC. Transmission electron microscopy images revealed no ultrastructural alterations (cell wall and membrane) in thymol‐treated WKZ‐1 and WKZ‐2 S. aureus strains. Here, we demonstrated that thymol reduces various PSM production in S. aureus clinical isolates and reference strains with mass spectrometry.
Biodegradation of Low-Density Polyethylene (LDPE) Bags by Fungi Isolated from Waste Disposal Soil
Authors: Saira  , Abdullah  , Maroof Lalina , Iqbal Madiha , Farman Saira , Lubna  , Faisal Shah
Published: May 2022

Plastics are available in different shapes nowadays in order to enhance the living standard. But unfortunately, most of these plastics are synthetic in nature that is why they show resistance to physical and chemical degradation processes and enhance environmental hazards. The aim of the present research study was to isolate and identify beneficial fungal species from soil that have the capability to degrade plastic. Soil samples from a waste disposal site at Peshawar district were diluted and inoculated on sabouraud dextrose agar (SDA) and potato dextrose agar (PDA) for fungus isolation. After isolation, the identifications of fungal species were done using standard identification techniques such as colony morphology and microscopic examination. The isolated fungal species that were identified were Aspergillus Niger, Aspergillus flavus, Penicillium, white rot, and brown rot fungi. After isolation, a degradation experiment was conducted to evaluate the capability of fungal isolates towards degradation of plastic. For this purpose, a 2 cm2 plastic piece was treated with fungal isolates for one month in a liquid culture system. The weight loss percentage was estimated at 22.9%, 16.1%, 18.4%, and 22.7% by Aspergillus Niger, Aspergillus flavus, brown rot, and white rot, respectively, which was confirmed by the Fourier transform analysis. The obtained FTIR peaks revealed the C–H bond deformation in alkenes, ketones, and esters. It has been concluded from the study that fungal species play a significant role in the degradation of synthetic plastic which can be used in bioreactors in future studies for the degradation of complex plastic materials.
[Retracted] Effect of Warming Yang, Tonifying Kidney, and Removing Arthralgia Therapy on Cold‐Dampness Arthralgia Type Ankylosing Spondylitis and Its Influence on the Levels of Humoral Factor in Human Serum
Authors: Li Jing
Published: May 2022

Objective. This study is aimed at exploring the effect of warming Yang, tonifying kidney, and removing arthralgia therapy in the treatment of cold‐dampness arthralgia type ankylosing spondylitis (AS) and the effects on the levels of humoral factor in human serum. Method. A total of 72 patients with cold‐dampness arthralgia type AS treated in our hospital from May 2020 to June 2021 were selected and divided into the observation group (n = 36) and control group (n = 36) according to the random number table method. The clinical efficacy of the two groups was observed. The traditional Chinese medicine (TCM) syndrome scores and clinical signs of the two groups were compared, and the pain situation of the two groups was evaluated by visual analog scale (VAS). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were used to evaluate the spinal function and activity of the two groups, and the levels of CXC‐type chemokine ligand 16 (CXCL16), Dickkopf‐1(DKK‐1), interleukin‐17 (IL‐17), tumor necrosis factor‐α (TNF‐α), sclerostin (SOST) ,and bone morphogenetic protein 2(BMP‐2) in serum of the two groups were measured. Results. The total effective rate of the observation group (91.67%) was significantly higher than that of the control group (66.67%) (P < 0.05). After treatment, the degree of improvement in TCM syndrome score, clinical signs, VAS score, BASDAI, BASFI, and the levels of CXCL16, TNF‐α, IL‐17, DKK‐1, SOST, and BMP‐2 in the observation group were significantly higher than that in the control group (all P < 0.05). Conclusion. Warming Yang, tonifying kidney, and removing arthralgia therapy had a good effect on the treatment of cold‐dampness arthralgia type AS, and it could effectively improve the clinical symptoms and signs, relieve pain, improve spinal motion, and relieve inflammation of patients.
Analytical Solution for Consolidation of Vertical Drains-Impervious Columns Multiple Composite Foundation under Nonuniform Distribution of Initial Pore Pressure
Authors: Zhang Yuguo , Zhao Yamin
Published: May 2022

Based on the axisymmetric model, the consolidation control equations based on the assumption of equal strain are established for the vertical drains-impervious columns multi-composite foundation consolidation problem, and the analytical solutions are given for the drains-impervious columns multiple composite foundation consolidation with trapezoidal, rectangular, positive triangular and inverted triangular distribution of initial pore pressure. Through the degradation study and comparison with the existing analytical solutions. Using the derived consolidation analytical solution for parameter analysis, the consolidation characteristics of multivariate composite foundation are studied. The results show that: the non-uniform distribution of initial pore pressure has a significant effect on the consolidation of combined composite foundations, the trapezoidal distribution is faster than the rectangular distribution, the positive triangular distribution is the slowest and the inverted triangular distribution is the fastest. The smaller the initial pore pressure value at the base of the soil layer and the larger the vertical permeability coefficient of the soil, the faster the consolidation. The consolidation rate of the foundation increases with the increase of the replacement rate of impervious columns and the compression modulus. Compared with the foundation of a single pile type, the consolidation rate of combined composite foundations can be significantly increased. The rate of consolidation of the foundation increases with the increase in the replacement rate and compression modulus of impervious columns.
Experiment and Model Investigation on the Permeability Evolution of Granite under Triaxial Compressive Damage
Authors: Ji Zhenxing , Wu Zhide , Yang Hong , Zhang Lihua , Ouyang Zhenhua , Yi Haiyang
Published: May 2022

Deep granite is the ideal surrounding rock for nuclear waste geological disposal reservoir and its permeability is the key factor for nuclide migration. In order to study the permeability evolution characteristics of surrounding rocks in the near field of the disposal reservoir under different confining pressures during excavation, the mechanical and permeability properties of granite were explored through triaxial compression experiments associated with acoustic emission techniques. Experiment results suggest that the permeability exhibited typical pore percolation and fracture flow during the compressive damage process and it has an obvious relationship with the volumetric strain before and after dilation. According to such a relationship, a full-stage permeability model was proposed which is characterized by only 2 parameters. This permeability model was verified by the experiment data to be of good feasibility and effectiveness, exhibiting well fitness to the experiment under various confining pressures. According to the elastoplastic mechanical model that is available from other researchers, discussion was implemented and which convinced us that it is feasible to reproduce the real conditions of hydromechanical processes by combing the proposed permeability model and damage-based elastoplastic model in numerical modelling.
Bioactive Potential of Brown Algae
Authors: Remya R. R. , Samrot Antony V. , Kumar S. Suresh , Mohanavel V. , Karthick Alagar , Chinnaiyan V. Kumar , Umapathy Dhamodharan , Muhibbullah M.
Published: May 2022

Marine-derived natural products are rich source of secondary metabolites with huge potentials including novel therapeutic agents. Marine algae are considered to be a good source of secondary metabolites with versatile bioactivities. During the last few decades, researches related to natural products obtained from brown algae have remarkably escalated as they contain active compounds with varied biologically activities like antimicrobial, anticancer, antioxidant, anti-inflammatory, antidiabetic, and antiparasitic properties. The main bioactive components such as phlorotannin, fucoxanthin, alginic acid, fucoidan, and laminarin have been briefly discussed here, together with their composition and biological activities. In this review, the biological function of extracts and the metabolites of brown algae as well as their pharmacological impacts with the description of the possible mechanism of their action are described and discussed. Also, this study is expected to examine the multifunctional properties of brown algae that facilitate natural algal products, including the ability to integrate these functional properties in a variety of applications.
A New Anesthetic, Remimazolam, Is Useful in the Management of Anesthesia in Patients with Liver Cirrhosis
Authors: Onoda Anna , Suzuki Yasuyuki
Published: May 2022

Background. Management of general anesthesia in patients with liver cirrhosis is challenging because it is difficult to maintain the circulation and concentration of anesthetics within a safe range. Unlike many other anesthetics, which are metabolized by cytochrome P450 enzymes, remimazolam is metabolized by carboxylesterase. In a liver cirrhosis model, cytochrome P450 activity is suppressed by approximately 30%; however, carboxylesterase activity is maintained at approximately 60%. Also, remimazolam is less likely to inhibit circulation. A 77-year-old woman was scheduled to undergo laparoscopic cholecystectomy. The patient was diagnosed with Child-Pugh B liver cirrhosis due to type C viral hepatitis. General anesthesia with remimazolam stabilized the intraoperative circulation and resulted in rapid postoperative awakening. Conclusion. We report a case in which a patient with Child-Pugh B cirrhosis was safely managed under general anesthesia using remimazolam during laparoscopic cholecystectomy.
English Translation of Chinese Topic Sentences with Gap Subject Based on Internet Environment
Authors: Geng Yanmei
Published: May 2022

Machine translation is showing an increasingly broad application prospect as the Internet becomes more widely used. The method based on the principle of maximum entropy is primarily used in this paper to determine the subject clause for translation. Its feature set does not necessitate extensive linguistic knowledge, and it is less reliant on it than other methods. It can also add arbitrary features and flexibly combine a large amount of scattered and fragmented knowledge. As a result, the maximum entropy model is used as the classifier in this paper, and lexical and sentence features are used to effectively combine the rules and statistical knowledge. The subsentence recognition process is broken down into three stages, with different features extracted at different stages and the maximum entropy model applied multiple times. At each stage, the classifiers are trained. The translation accuracy and recall rate of Chinese gapped subject topic sentences are improved by more than 5% in a maximum entropy model, according to the results. This method of feature description is particularly useful for identifying sentence endings in Chinese subject topic sentences with gaps. Its translation is closer to the correct translation, indicating that the proposed method’s basic concept—the rationality of segmentation—is correct. The algorithm based on the maximum entropy model performs better in practice.
A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP5+, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line
Authors: Chaiswing Luksana , Yarana Chontida , St. Clair William , Tovmasyan Artak , Batinic-Haberle Ines , Spasojevic Ivan , St. Clair Daret
Published: May 2022

We have employed a redox-active MnP (MnTnBuOE-2-PyP5+, Mn(III) meso-tetrakis (N-n-butoxyethylpyridinium-2-yl) porphyrin) frequently identified as superoxide dismutase mimic or BMX-001, to explore the redox status of normal ovarian cell in relation to two ovarian cancer cell lines: OV90 human serous ovarian cancer cell and chemotherapy-resistant OV90 cell (OVCD). We identified that OVCD cells are under oxidative stress due to high hydrogen peroxide (H2O2) levels and low glutathione peroxidase and thioredoxin 1. Furthermore, OVCD cells have increased glycolysis activity and mitochondrial respiration when compared to immortalized ovarian cells (hTER7) and parental cancer cells (OV90). Our goal was to study how ovarian cell growth depends upon the redox state of the cell; hence, we used MnP (BMX-001), a redox-active MnSOD mimetic, as a molecular tool to alter ovarian cancer redox state. Interestingly, OVCD cells preferentially uptake MnP relative to OV90 cells which led to increased inhibition of cell growth, glycolytic activity, OXPHOS, and ATP, in OVCD cells. These effects were further increased when MnP was combined with carboplatin. The effects were discussed with regard to the elevation in H2O2 levels, increased oxidative stress, and reduced Nrf2 levels and its downstream targets when cells were exposed to either MnP or MnP/carboplatin. It is significant to emphasize that MnP protects normal ovarian cell line, hTER7, against carboplatin toxicity. Our data demonstrate that the addition of MnP-based redox-active drugs may be used (via increasing excessively the oxidative stress of serous ovarian cancer cells) to improve cancer patients’ chemotherapy outcomes, which develop resistance to platinum-based drugs.
Deformation Characteristics and Control Countermeasures for Surrounding Rock of Deep Roadway under Mining Disturbance: A Case Study
Authors: Qian Deyu , Deng Jinping , Wang Sujian , Yang Xingguo , Cui Qi , Li Zexiang , Jin Shengyao , Liu Wenjing
Published: May 2022

Highly efficient maintenance and control of the deep strong mining roadway’s stability is a reliable guarantee for the safe production and sustainable development of a coal mine. With return air roadway 4106 in Wenjiapo coal mine as the research background, an in situ investigation, numerical simulation, and engineering practice were carried out to reveal the stress distribution and surrounding rock deformation and failure characteristics of a strong mining roadway. The numerical simulation results show that both first mining and secondary mining are positively correlated with the deformation and failure of roadway surrounding rock. The peak abutment pressure of the coal pillar near the goaf caused by first mining and secondary mining are 28.7 and 35.6 MPa, respectively, with a 24% increase. During the first mining period, the total deformation of the roof and floor of the roadway and the two sides was 1160 and 1436 mm, respectively. During the second mining period, the total deformation of the roof and floor of the roadway in a working face advance gradually increased from 1737 mm 80 m away from the working face to 2281 mm at the working face, and the total deformation of the two sidewalls gradually increased from 2094 mm 80 m away from the working face to 2211 mm at the working face. The damage to the roadway caused by secondary mining was much greater than that caused by the first mining. The collaborative control technology of long anchorage-top-cutting blasting stress relief is proposed to control the stability of the roadway. The engineering practice shows that the deformation of the roadway is effectively controlled under strong mining disturbance, and the maximum deformations of the roof, floor and sidewall are 17, 23, and 11 mm, respectively.
Phosphoproteomics Reveals the Role of Constitutive KAP1 Phosphorylation by B-cell Receptor Signaling in Chronic Lymphocytic Leukemia
Authors: Wu Jung-Lin , Wu Hsin-Yi , Wu Shang-Ju , Tsai Ho-Yang , Weng Shao-Hsing , Lin Kuen-Tyng , Lin Liang-In , Yao Chi-Yuan , Zamanova Margarita , Lee Yi-Yuan , Angata Takashi , Tien Hwei-Fang , Chen Yu-Ju , Lin Kuo-I
Published: May 2022

Application of B-cell receptor (BCR) pathway inhibitor ibrutinib for chronic lymphocytic leukemia (CLL) is a major breakthrough, yet the downstream effects following inhibition of BCR signaling and during relapse await further clarification. By comparative phosphoproteomic profiling of B cells from patients with CLL and healthy donors, as well as CLL B cells collected at multiple time points during the course of ibrutinib treatment, we provided the landscape of dysregulated phosphoproteome in CLL and its dynamic alterations associated with ibrutinib treatment. Particularly, differential phosphorylation events associated with several signaling pathways, including BCR pathway, were enriched in patient CLL cells. A constitutively elevated phosphorylation level of KAP1 at serine 473 (S473) was found in the majority of CLL samples prior to treatment. Further verification showed that BCR activation promoted KAP1 S473 phosphorylation, whereas ibrutinib treatment abolished it. Depletion of KAP1 in primary CLL cells decelerated cell-cycle progression and ectopic expression of a KAP1 S473 phospho-mimicking mutant accelerated G2–M cell-cycle transition of CLL cells. Moreover, temporal phosphoproteomic profiles using a series of CLL cells isolated from one patient during the ibrutinib treatment revealed the dynamic changes of several molecules associated with BCR signaling in the ibrutinib responsive and recurrent stages.

Implications:

This phosphoproteomic analysis and functional validation illuminated the phosphorylation of KAP1 at S473 as an important downstream BCR signaling event and a potential indicator for the success of ibrutinib treatment in CLL.
Pan-Cancer HLA Gene-Mediated Tumor Immunogenicity and Immune Evasion
Authors: Gong Xutong , Karchin Rachel
Published: May 2022

Human leukocyte antigen (HLA) expression contributes to the activation of antitumor immunity through interactions with T-cell receptors. Pan-cancer HLA-mediated immunogenicity and immunoediting mechanisms have not been systematically studied previously. In a retrospective analysis of 33 tumor types from the Cancer Genome Atlas (TCGA), we characterized the differential expression of HLA class I and class II genes across various oncogenic pathways and immune subtypes. While HLA I genes were upregulated in all immunogenically hot tumors, HLA II genes were upregulated in an inflammatory immune subtype associated with best prognosis and were systematically downregulated in specific oncogenic pathways. A subset of immunogenically hot tumors which upregulated HLA class I but not class II genes exploited HLA-mediated escape strategies. Furthermore, with a machine learning model, we demonstrated that HLA gene expression data can be used to predict the immune subtypes of patients receiving immune checkpoint blockade and stratify patient survival. Interestingly, tumors with the highest immune infiltration did not have the best prognosis but showed significantly higher immune exhaustion.

Implications:

Taken together, we highlight the prognostic potential of HLA genes in immunotherapies and suggest that higher tumor immunogenicity mediated by HLA expression may sometimes lead to tumor escape under strong selective pressure.
MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by Upregulating NRP2-Associated Cell Adhesion
Authors: Marimuthu Saravanakumar , Lakshmanan Imayavaramban , Muniyan Sakthivel , Gautam Shailendra K. , Nimmakayala Rama Krishna , Rauth Sanchita , Atri Pranita , Shah Ashu , Bhyravbhatla Namita , Mallya Kavita , Grandgenett Paul M. , Hollingsworth Michael A. , Datta Kaustubh , Jain Maneesh , Ponnusamy Moorthy P. , Batra Surinder K.
Published: May 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer, as it commonly metastasizes to the liver resulting in an overall poor prognosis. However, the molecular mechanism involved in liver metastasis remains poorly understood. Here, we aimed to identify the MUC16-mediated molecular mechanism of PDAC-liver metastasis. Previous studies demonstrated that MUC16 and its C-terminal (Cter) domain are involved in the aggressiveness of PDAC. In this study, we observed MUC16 and its Cter expression significantly high in human PDAC tissues, PDAC organoids, and metastatic liver tissues, while no expression was observed in normal pancreatic tissues using IHC and immunofluorescence (IFC) analyses. MUC16 knockdown in SW1990 and CD18/HPAF PDAC cells significantly decreased the colony formation, migration, and endothelial/p-selectin binding. In contrast, MUC16-Cter ectopic overexpression showed significantly increased colony formation and motility in MiaPaCa2 pancreatic cancer cells. Interestingly, MUC16 promoted cell survival and colonization in the liver, mimicking an ex vivo environment. Furthermore, MUC16 enhanced liver metastasis in the in vivo mouse model. Our integrated analyses of RNA-sequencing suggested that MUC16 alters Neuropilin-2 (NRP2) and cell adhesion molecules in pancreatic cancer cells. Furthermore, we identified that MUC16 regulated NRP2 via JAK2/STAT1 signaling in PDAC. NRP2 knockdown in MUC16-overexpressed PDAC cells showed significantly decreased cell adhesion and migration. Overall, the findings indicate that MUC16 regulates NRP2 and induces metastasis in PDAC.

Implications:

This study shows that MUC16 plays a critical role in PDAC liver metastasis by mediating NRP2 regulation by JAK2/STAT1 axis, thereby paving the way for future therapy efforts for metastatic PDAC.
Tattoo Ink Market in France: A Field Study among 598 Professional Tattooists
Authors: Kluger Nicolas
Published: May 2022

Background: Tattoo ink safety is one of the main concerns surrounding tattooing practices. In order to better assess the risks and increase the safety of tattoo inks, it is important to know about the habits of tattooists in real life. Objective: We investigated the most popular inks in the French market and how professional tattooists used them in their daily practice. Methods: We performed an observational, self-reported, online survey concerning the French tattoo artists. All active professional tattooists in France were invited to take part in a six-question Internet survey regarding their tattoo inks usage habits. Results: 598 tattooists reported 36 different brands of black inks and 30 of colored inks. However, 6 brands of black inks were used by 14.2–44% of the tattooists and, for colored inks, 5 manufacturers were favored by 11.2 up to 55.7% of the tattooists. The majority of tattooists (68.9%) mixed two different colors or more to obtain a new shade while 21.7% would try to find the adequate shade within the assortment provided by a manufacturer. 54.4% had between 10 and 40 references, 31.9% had less than 10 references, 11.5% had 40–100 references, and 2.2% had >100 references. Conclusions: The market of tattoo inks in France is dominated only by a fistful of brands. Controls by official authorities should target those popular brands, even though all brands should respect the law. Toxicological studies should always precise the provenance market and which brands are tested, so we can assess their impact in real life. Tattooists should also try to lower the number of ready-made colors they require.
Creatine Phosphokinase Level Accompanied with Macro-Creatine Phosphokinase Type 1 Negatively Correlates with Plasma Glucose Control in a Patient with Type 2 Diabetes Mellitus
Authors: Kikkawa Koji , Okada Kazuya , Okada Junichi , Ohshima Kihachi , Okada Shuichi
Published: May 2022

Introduction: The macromolecular complex formed by creatine phosphokinase (CPK) is most probably an immune complex. Most of the macro-CPK migrates between CPK-MM and CPK-MB, exhibiting an atypical band on isozyme electrophoresis. Either IgA or IgG has been identified with its CPK link (termed as macro-CPK type 1). However, the biological and pathological significance of these complexes found in patients with wide-ranging disease states remains unclear. Herein, we first report a case of type 2 diabetes mellitus associated with hypercreatinekinasemia caused by macro-CPK type 1, with CPK levels negatively correlated with blood glucose control. Case Presentation: A 53-year-old Japanese woman with no complaints of muscle weakness, myalgia, and numbness of the extremities was diagnosed with hypercreatinekinasemia. Over the past years, she received empagliflozin, mitiglinide, voglibose, vildagliptin, metformin, methyl thiazide, and ezetimibe. Serum biochemistry revealed elevated CPK levels. The highest CPK value was 1,063 U/L, and the three major isozymes CPK-BB, CPK-MB, and CPK-MM accounted for 0%, 2%, and 98%, respectively. Notably, CPK isozyme electrophoresis performed on a cellulose acetate membrane detected an additional band that migrated between the CPK-MB and CPK-MM bands, suggesting macro-CPK type 1, which occupied 82% of the total CPK. The densitometric profile of the electrophoresis pattern revealed that CPK-BB, CPK-MB, and CPK-MM constituted 0%, 2%, and 16%, respectively. Moreover, serum CPK levels combined with macro-CPK showed a significant negative correlation with the HbA1c values (r = −0.498, p < 0.001). Conclusions: Serum CPK levels accompanied with macro-CPK type 1 negatively correlate with plasma glucose control. Although the pathophysiological role of macro-CPK remains unclear, our case report may provide a new viewpoint regarding macro-CPK etiology.
Call to Action for Cardiovascular Disease in Women: Epidemiology, Awareness, Access, and Delivery of Equitable Health Care: A Presidential Advisory From the American Heart Association
Authors: Wenger Nanette K. , Lloyd-Jones Donald M. , Elkind Mitchell S.V. , Fonarow Gregg C. , Warner John J. , Alger Heather M. , Cheng Susan , Kinzy Claire , Hall Jennifer L. , Roger Véronique L. ,   on behalf of the American Heart Association
Published: May 2022

Addressing the pervasive gaps in knowledge and care delivery to reduce sex-based disparities and achieve equity is fundamental to the American Heart Association’s commitment to advancing cardiovascular health for all by 2024. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders around the globe to identify and remove barriers to health care access and quality for women. A concise and current summary of existing data across the areas of risk and prevention, access and delivery of equitable care, and awareness and education provides a framework to consider knowledge gaps and research needs critical toward achieving significant progress for the health and well-being of all women.
Infarct Patterns in Patients With Symptomatic Carotid Webs
Authors: El Jamal Sleiman , Nogueira Raul G. , Bhatt Nirav R. , da Câmara Catarina Perry , Al‐Bayati Alhamza R. , Allen Jason W. , Kim Song J. , Olivé‐Gadea Marta , Frankel Michael , Nahab Fadi , Haussen Diogo C.
Published: May 2022

Background

Carotid webs (CaWs) may explain embolic strokes particularly in young patients with cerebral embolism of otherwise undetermined cause. We aim to describe the radiological patterns of infarction in patients with symptomatic CaWs.

Methods

Retrospective analysis of a symptomatic CaW database (September 2014–July 2019) from 2 comprehensive stroke centers. Magnetic resonance imaging scans were reviewed independently by 2 blinded raters. Patterns of acute infarction included territorial (involving ≥2 arterial subdivisions), cortical (affecting 1 arterial subdivision), 1or multiple small cortical infarcts, borderzone infarcts (cortical or internal), striatocapsular lacunes (<1.5 cm in size), or ≥1 deep vascular territory (involving subcortical contiguous deep structures). Different concomitant patterns could coexist. Prior strokes and leukoaraiosis severity (modified Fazekas scale) were evaluated.

Results

Forty symptomatic patients with CaW who had infarction were identified. The median age of patients was 49 years (interquartile range, 41–57 years), 22% were women, and 78% were of Black race. The median National Institute of Health Stroke Scale was 13 (interquartile range, 4–17), noncontrast Alberta Stroke Program Early CT Score was 8 (interquartile range, 7–8), and 13 (33%) patients received intravenous alteplase. Thirty‐four (85%) individuals presented with large vessel occlusion strokes (9% intracranial internal carotid artery, 62% middle cerebral artery M1 segment, 29% M2 segment). Sixty‐three percent of patients had right hemispheric strokes and 85% large vessel occlusion. Most patients (98%) had cortical infarcts: 30% were territorial, 38% affected 1 subdivision, and 63% had ≥1 small cortical infarct. Ten percent of the patients had infarcts involving borderzone areas. Fifteen percent of patients had striatocapsular lacunes, all of which had a concomitant cortical infarction. Five percent of patients had imaging evidence of previous strokes (all cortical and within the CaW vascular territory) and 20% had leukoaraiosis (18% grade 1 and 2% grade 2).

Conclusion

Acute cerebral infarction attributed to CaW were all compatible with an embolic mechanism. CaW should be considered in the workup of patients with cryptogenic strokes as a potential source of embolism.
When Poverty Reduction Meets Democracy: An Investigation into the Use of  Different Evaluation Methods for Assessing the Effectiveness of  a Social Program
Authors: Zhan Peng , Li Shi , Shen Yangyang , Wang Xiaobing
Published: May 2022

This paper evaluates the minimum living standard guarantee program (Dibao) in rural China using several methods including the income approach, the multidimensional poverty approach, and a proxy means test approach. We find that the targeting accuracy of the program appears greater the more comprehensive the evaluation method used—but all these methods find low levels of targeting accuracy. Because Dibao fund allocation is largely decided by the villagers, who take a more holistic view in selecting “poor” households than the various evaluation methods, we argue that the low targeting efficacy may be due to the lack of comprehensive evaluation method, as opposed to the low targeting of the program itself. This paper argues that the community-based targeting used by the Dibao program may be a better way to combat poverty in many developing countries, as it requires less administrative capacity and overcomes the difficulties of identifying poor households that qualify for assistance.
Predictive Coding Approximates Backprop Along Arbitrary Computation Graphs
Authors: Millidge Beren , Tschantz Alexander , Buckley Christopher L.
Published: May 2022

Backpropagation of error (backprop) is a powerful algorithm for training machine learning architectures through end-to-end differentiation. Recently it has been shown that backprop in multilayer perceptrons (MLPs) can be approximated using predictive coding, a biologically plausible process theory of cortical computation that relies solely on local and Hebbian updates. The power of backprop, however, lies not in its instantiation in MLPs but in the concept of automatic differentiation, which allows for the optimization of any differentiable program expressed as a computation graph. Here, we demonstrate that predictive coding converges asymptotically (and in practice, rapidly) to exact backprop gradients on arbitrary computation graphs using only local learning rules. We apply this result to develop a straightforward strategy to translate core machine learning architectures into their predictive coding equivalents. We construct predictive coding convolutional neural networks, recurrent neural networks, and the more complex long short-term memory, which include a nonlayer-like branching internal graph structure and multiplicative interactions. Our models perform equivalently to backprop on challenging machine learning benchmarks while using only local and (mostly) Hebbian plasticity. Our method raises the potential that standard machine learning algorithms could in principle be directly implemented in neural circuitry and may also contribute to the development of completely distributed neuromorphic architectures.
Decoding Pixel-Level Image Features From Two-Photon Calcium Signals of Macaque Visual Cortex
Authors: Zhang Yijun , Bu Tong , Zhang Jiyuan , Tang Shiming , Yu Zhaofei , Liu Jian K. , Huang Tiejun
Published: May 2022

Images of visual scenes comprise essential features important for visual cognition of the brain. The complexity of visual features lies at different levels, from simple artificial patterns to natural images with different scenes. It has been a focus of using stimulus images to predict neural responses. However, it remains unclear how to extract features from neuronal responses. Here we address this question by leveraging two-photon calcium neural data recorded from the visual cortex of awake macaque monkeys. With stimuli including various categories of artificial patterns and diverse scenes of natural images, we employed a deep neural network decoder inspired by image segmentation technique. Consistent with the notation of sparse coding for natural images, a few neurons with stronger responses dominated the decoding performance, whereas decoding of ar tificial patterns needs a large number of neurons. When natural images using the model pretrained on artificial patterns are decoded, salient features of natural scenes can be extracted, as well as the conventional category information. Altogether, our results give a new perspective on studying neural encoding principles using reverse-engineering decoding strategies.