Advances in valorization of sweet potato peels: A comprehensive review on the nutritional compositions, phytochemical profiles, nutraceutical properties, and potential industrial applications.

During food production, food processing, and supply chain, large amounts of food byproducts are generated and thrown away as waste, which to a great extent brings about adverse consequences on the environment and economic development. The sweet potato (Ipomoea batatas L.) is cultivated and consumed in many countries. Sweet potato peels (SPPs) are the main byproducts generated by the tuber processing. These residues contain abundant nutrition elements, bioactive compounds, and other high value-added substances; therefore, the reutilization of SPP holds significance in improving their overall added value. SPPs contain abundant phenolic compounds and carotenoids, which might contribute significantly to their nutraceutical properties, including antioxidant, antimicrobial, anticancer, prebiotic, anti-inflammatory, wound-healing, and lipid-lowering effects. It has been demonstrated that SPP could be promisingly revalorized into food industry, including: (1) applications in diverse food products; (2) applications in food packaging; and (3) applications in the recovery of pectin and cellulose nanocrystals. Furthermore, SPP could be used as promising feedstocks for the bioconversion of diverse value-added bioproducts through biological processing.

Safety and efficacy evaluation of Simo decoction and Arecae semen in herbal medicine practice.

Objective: The traditional Chinese patent medicine (TCPM), Simo decoction (Simo decoction oral solution), with its primary ingredient Arecae semen (Binglang, Areca catechu L.), known for its potential carcinogenic effects, is the subject of this study. The research aims to analyze the effectiveness and potential risks of Simo decoction, particularly as a carcinogen, and to suggest a framework for evaluating the risks and benefits of other herbal medicines. Methods: The study is based on post-marketing research of Simo decoction and Arecae semen. It utilized a wide range of sources, including ancient and modern literature, focusing on the efficacy and safety of Simo decoction. The research includes retrospective data on the sources, varieties, and toxicological studies of Arecae semen from databases such as Pubmed, Clinical Trials, Chinese Clinical Trial Registry, China National Knowledge Infrastructure, WHO-UMC Vigibase, and China National Center for ADR Monitoring. Results: Common adverse drug reactions (ADRs) associated with Simo decoction include skin rash, nausea, vomiting, abdominal pain, and diarrhea. However, no studies exist reporting the severe ADRs, such as carcinogenic effects. Arecae semen is distributed across approximately 60 varieties in tropical Asia and Australia. According to the WHO-UMC Vigibase and the National Adverse Drug Reaction Monitoring System databases, there are currently no reports of toxicity related to Arecae semen in the International System for Classification of ADRs (ISCR) or clinical studies. Conclusion: Risk-benefit analysis in TCPM presents more challenges compared to conventional drugs. The development of a practical pharmacovigilance system and risk-benefit analysis framework is crucial for marketing authorization holders, researchers, and regulatory bodies. This approach is vital for scientific supervision and ensuring the safety and efficacy of drug applications, thus protecting public health.

STAG2 mutations regulate 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme.

Inactivating mutations of genes encoding the cohesin complex are common in a wide range of human cancers. STAG2 is the most commonly mutated subunit. Here we report the impact of stable correction of endogenous, naturally occurring STAG2 mutations on gene expression, 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme (GBM). In two GBM cell lines, correction of their STAG2 mutations significantly altered the expression of ∼10% of all expressed genes. Virtually all the most highly regulated genes were negatively regulated by STAG2 (i.e., expressed higher in STAG2-mutant cells), and one of them-HEPH-was regulated by STAG2 in uncultured GBM tumors as well. While STAG2 correction had little effect on large-scale features of 3D genome organization (A/B compartments, TADs), STAG2 correction did alter thousands of individual chromatin loops, some of which controlled the expression of adjacent genes. Loops specific to STAG2-mutant cells, which were regulated by STAG1-containing cohesin complexes, were very large, supporting prior findings that STAG1-containing cohesin complexes have greater loop extrusion processivity than STAG2-containing cohesin complexes and suggesting that long loops may be a general feature of STAG2-mutant cancers. Finally, STAG2 mutation activated Polycomb activity leading to increased H3K27me3 marks, identifying Polycomb signaling as a potential target for therapeutic intervention in STAG2-mutant GBM tumors. Together, these findings illuminate the landscape of STAG2-regulated genes, A/B compartments, chromatin loops, and pathways in GBM, providing important clues into the largely still unknown mechanism of STAG2 tumor suppression.

Effects of remimazolam tosilate on gastrointestinal hormones and gastrointestinal motility in patients undergoing gastrointestinal endoscopy with sedation: a randomized control trial.

PURPOSE: To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. METHODS: A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18-65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2-0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5-2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T0), before gastrointestinal endoscopy (T1), and before leaving the Post Anesthesia Care Unit (T2); and the incidences of abdominal distension during Post Anesthesia Care Unit. RESULTS: Compared with Group P, intestinal peristalsis rating was higher in Group R (P < .001); Group R showed increased motilin and gastrin levels at T2 compared with Group P (P < .01). There was a rise in motilin and gastrin levels at T1 and T2 compared with T0 and at T2 compared with T1 in both groups (P < .01). The incidence of abdominal distension was lower in Group R (P < .05). CONCLUSION: Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility.

Assays on 3D tumor spheroids for exploring the light dosimetry of photodynamic effects under different gaseous conditions.

The multifaceted nature of photodynamic therapy (PDT) requires a throughout evaluation of a multitude of parameters when devising preclinical protocols. In this study, we constructed MCF-7 human breast tumor spheroid assays to infer PDT irradiation doses at four gradient levels for violet light at 408 nm and red light at 625 nm under normal and hypoxic oxygen conditions. The compacted three-dimensional (3D) tumor models conferred PDT resistance as compared to monolayer cultures due to heterogenous distribution of photosensitizers along with the presence of internal hypoxic region. Cell viability results indicated that the violet light was more efficient to kill cells in the spheroids under normal oxygen conditions, while cells exposed to the hypoxic microenvironment exhibited minimal PDT-induced death. The combination of 3D tumor spheroid assays and the multiparametric screening platform presented a solid framework for assessing PDT efficacy across a wide range of different physiological conditions and therapeutic regimes.

REC-NN: A reconstruction error compensation neural network for Magnetic Resonance Electrical Property Tomography (MREPT).

Electrical properties (EPs) are expected as biomarkers for early cancer detection. Magnetic resonance electrical properties tomography (MREPT) is a technique to non-invasively estimate the EPs of tissues from MRI measurements. While noise sensitivity and artifact problems of MREPT are being solved progressively through recent efforts, the loss of tissue contrast emerges as an obstacle to the clinical applications of MREPT. To solve the problem, we propose a reconstruction error compensation neural network scheme (REC-NN) for a typical analytic MREPT method, Stab-EPT. Two NN structures: one with only ResNet blocks, and the other hybridizing ResNet blocks with an encoder-decoder structure. Results of experiments with digital brain phantoms show that, compared with Stab-EPT, and conventional NN based reconstruction, REC-NN improves both reconstruction accuracy and tissue contrast. It is found that, the encoder-decoder structure could improve the compensation accuracy of EPs in homogeneous region but showed worse reconstruction than only ResNet structure for tumorous tissues unseen in the training samples. Future research is required to address overcompensation problems, optimization of NN structure and application to clinical data.

Pulmonary rehabilitation restores limb muscle mitochondria and improves the intramuscular metabolic profile.

BACKGROUND: Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated. METHODS: Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n  = 8), non-COPD/exercise ( n  = 7), COPD/rest ( n  = 7), COPD/medium exercise ( n  = 10), and COPD/intensive exercise ( n  = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). RESULTS: At the end of 90 days, COPD rats' weight gain was smaller than control by 59.48 ±â€Š15.33 g ( P  = 0.0005). The oxidative muscle fibers proportion was lower ( P  < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P  = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P  = 0.0093), myofibrils diameter (Δ0.06 µm, 95% CI: 0.02-0.10 µm, P  = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P  = 0.0434), mitochondria oxidative phosphorylate capacity ( P  < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. CONCLUSION: COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.

Physics Informed Neural Networks (PINN) for Low Snr Magnetic Resonance Electrical Properties Tomography (MREPT).

Electrical properties (EPs) of tissues facilitate early detection of cancerous tissues. Magnetic resonance electrical properties tomography (MREPT) is a technique to non-invasively probe the EPs of tissues from MRI measurements. Most MREPT methods rely on numerical differentiation (ND) to solve partial differential Equations (PDEs) to reconstruct the EPs. However, they are not practical for clinical data because ND is noise sensitive and the MRI measurements for MREPT are noisy in nature. Recently, Physics informed neural networks (PINNs) have been introduced to solve PDEs by substituting ND with automatic differentiation (AD). To the best of our knowledge, it has not been applied to MREPT due to the challenges in using PINN on MREPT as (i) a PINN requires part of ground-truth EPs as collocation points to optimize the network's AD, (ii) the noisy input data disrupts the optimization of PINNs despite the noise-filtering nature of NNs and additional denoising processes. In this work, we propose a PINN-MREPT model based on a canonical analytic MREPT model. A reference padding layer with known EPs was added to surround the region of interest for providing additive collocation points. Moreover, an optimizable diffusion coefficient was embedded in the analytic MREPT model used in the PINN-MREPT. The noise robustness of the proposed PINN-MREPT for single-sample reconstruction was tested by using numerical phantoms of human brain with extra tumor-like tissues at different noise levels. The results of numerical experiments show that PINN-MREPT outperforms two typical numerical MREPT methods in terms of reconstruction accuracy, sensitivity to the extra tissues, and the correlations of line profiles in the regions of interest. The advantage of the PINN-MREPT is shown by the results of an experiment on phantom measurement, too. Moreover, it is found that the diffusion term plays an important role to achieve a noise-robust PINN-MREPT. This is an important step moving forward to a clinical application of MREPT.

Hybrid deep learning model for risk prediction of fracture in patients with diabetes and osteoporosis.

The fracture risk of patients with diabetes is higher than those of patients without diabetes due to hyperglycemia, usage of diabetes drugs, changes in insulin levels, and excretion, and this risk begins as early as adolescence. Many factors including demographic data (such as age, height, weight, and gender), medical history (such as smoking, drinking, and menopause), and examination (such as bone mineral density, blood routine, and urine routine) may be related to bone metabolism in patients with diabetes. However, most of the existing methods are qualitative assessments and do not consider the interactions of the physiological factors of humans. In addition, the fracture risk of patients with diabetes and osteoporosis has not been further studied previously. In this paper, a hybrid model combining XGBoost with deep neural network is used to predict the fracture risk of patients with diabetes and osteoporosis, and investigate the effect of patients' physiological factors on fracture risk. A total of 147 raw input features are considered in our model. The presented model is compared with several benchmarks based on various metrics to prove its effectiveness. Moreover, the top 18 influencing factors of fracture risks of patients with diabetes are determined.

Effect of annealing and heat-moisture pretreatments on the oil absorption of normal maize starch during frying.

The impacts of two hydrothermal pretreatments, annealing (ANN) and heat moisture treatment (HMT), on oil-absorption by normal maize starch (NMS) during frying were investigated using low-field nuclear magnetic resonance (LF-NMR). The structural organizations of the fried samples were also evaluated using SEM, XRD, ATR-FTIR, and DSC, respectively. Both hydrothermal pretreatments significantly reduced the total oil content in the starch after frying, with the magnitude of the effect depending on the treatment conditions used. SEM showed that the pretreated fried starch granules preserved more of their original morphology. XRD, FTIR, and DSC showed that both pretreatments preserved more of the short-range double helices and long-range organizations within the orthorhombic crystalline structure for NMS during frying. The promoting effect of ANN/HMT on the interactions of starch molecules and the rearrangement of double helices were hypothesized to be responsible for the increased thermal stability of starch granules in the present work. As a result, fried starch pretreated by ANN/HMT were more organized and more compact than fried NMS, thus inhibiting oil absorption during frying.

Design and evaluation of novel glutaminase inhibitors.

A novel set of GAC (kidney glutaminase isoform C) inhibitors able to inhibit the enzymatic activity of GAC and the growth of the triple negative MDA-MB-231 breast cancer cells with low nanomolar potency is described. Compounds in this series have a reduced number of rotatable bonds, improved ClogPs, microsomal stability and ligand efficiency when compared to the leading GAC inhibitors BPTES and CB-839. Property improvements were achieved by the replacement of the flexible n-diethylthio or the n-butyl moiety present in the leading inhibitors by heteroatom substituted heterocycloalkanes.

A pyrazolopyran derivative preferentially inhibits the activity of human cytosolic serine hydroxymethyltransferase and induces cell death in lung cancer cells.

Serine hydroxymethyltransferase (SHMT) is a central enzyme in the metabolic reprogramming of cancer cells, providing activated one-carbon units in the serine-glycine one-carbon metabolism. Previous studies demonstrated that the cytoplasmic isoform of SHMT (SHMT1) plays a relevant role in lung cancer. SHMT1 is overexpressed in lung cancer patients and NSCLC cell lines. Moreover, SHMT1 is required to maintain DNA integrity. Depletion in lung cancer cell lines causes cell cycle arrest and uracil accumulation and ultimately leads to apoptosis. We found that a pyrazolopyran compound, namely 2.12, preferentially inhibits SHMT1 compared to the mitochondrial counterpart SHMT2. Computational and crystallographic approaches suggest binding at the active site of SHMT1 and a competitive inhibition mechanism. A radio isotopic activity assay shows that inhibition of SHMT by 2.12 also occurs in living cells. Moreover, administration of 2.12 in A549 and H1299 lung cancer cell lines causes apoptosis at LD50 34 µM and rescue experiments underlined selectivity towards SHMT1. These data not only further highlight the relevance of the cytoplasmic isoform SHMT1 in lung cancer but, more importantly, demonstrate that, at least in vitro, it is possible to find selective inhibitors against one specific isoform of SHMT, a key target in metabolic reprogramming of many cancer types.

Mathematical modeling and stability analysis of macrophage activation in left ventricular remodeling post-myocardial infarction.

BACKGROUND: About 6 million Americans suffer from heart failure and 70% of heart failure cases are caused by myocardial infarction (MI). Following myocardial infarction, increased cytokines induce two major types of macrophages: classically activated macrophages which contribute to extracellular matrix destruction and alternatively activated macrophages which contribute to extracellular matrix construction. Though experimental results have shown the transitions between these two types of macrophages, little is known about the dynamic progression of macrophages activation. Therefore, the objective of this study is to analyze macrophage activation patterns post-MI. RESULTS: We have collected experimental data from adult C57 mice and built a framework to represent the regulatory relationships among cytokines and macrophages. A set of differential equations were established to characterize the regulatory relationships for macrophage activation in the left ventricle post-MI based on the physical chemistry laws. We further validated the mathematical model by comparing our computational results with experimental results reported in the literature. By applying Lyaponuv stability analysis, the established mathematical model demonstrated global stability in homeostasis situation and bounded response to myocardial infarction. CONCLUSIONS: We have established and validated a mathematical model for macrophage activation post-MI. The stability analysis provided a possible strategy to intervene the balance of classically and alternatively activated macrophages in this study. The results will lay a strong foundation to understand the mechanisms of left ventricular remodelling post-MI.

HIV-1 Tat impairs cell cycle control by targeting the Tip60, Plk1 and cyclin B1 ternary complex.

HIV-1 Tat triggers intrinsic and extrinsic apoptosis pathways in both infected and uninfected cells and plays an important role in the pathogenesis of AIDS. Knocking down Tip60, an interactive protein of Tat, leads to the impairment of cell cycle progression, indicating a key role of Tip60 in cell cycle control. We found that Tip60 interacts with Plk1 through its ZnFMYST domain, and that this interaction is enhanced in the G 2/M phase. In addition, cyclin B1 was confirmed to interact with the ZnF domain of Tip60. Immunofluorescence imaging showed that Tip60 co-localizes with both Plk1 and cyclin B1 at the centrosome during the mitotic phase and to the mid-body during cytokinesis. Further experiments revealed that Tip60 forms a ternary complex with Plk1 and cyclin B1 and acetylates Plk1 but not cyclin B1. HIV-1 Tat likely forms a quaternary complex with Tip60, cyclin B1 and Plk1. Fluorescent microscopy showed that Tat causes an unscheduled nuclear translocation of both cyclin B1 and Plk1, causing their co-localization with Tip60 in the nucleus. Tat, Tip60, cyclin B1 and Plk1 interactions provide new a mechanistic explanation for Tat-mediated cell cycle dysregulation and apoptosis.

Strand-specific PCR of UV radiation-damaged genomic DNA revealed an essential role of DNA-PKcs in the transcription-coupled repair.

BACKGROUND: In eukaryotic cells, there are two sub-pathways of nucleotide excision repair (NER), the global genome (gg) NER and the transcription-coupled repair (TCR). TCR can preferentially remove the bulky DNA lesions located at the transcribed strand of a transcriptional active gene more rapidly than those at the untranscribed strand or overall genomic DNA. This strand-specific repair in a suitable restriction fragment is usually determined by alkaline gel electrophoresis followed by Southern blotting transfer and hybridization with an indirect end-labeled single-stranded probe. Here we describe a new method of TCR assay based on strand-specific-PCR (SS-PCR). Using this method, we have investigated the role of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase-related protein kinases (PIKK) family, in the TCR pathway of UV-induced DNA damage. RESULTS: Although depletion of DNA-PKcs sensitized HeLa cells to UV radiation, it did not affect the ggNER efficiency of UV-induced cyclobutane pyrimidine dimers (CPD) damage. We postulated that DNA-PKcs may involve in the TCR process. To test this hypothesis, we have firstly developed a novel method of TCR assay based on the strand-specific PCR technology with a set of smart primers, which allows the strand-specific amplification of a restricted gene fragment of UV radiation-damaged genomic DNA in mammalian cells. Using this new method, we confirmed that siRNA-mediated downregulation of Cockayne syndrome B resulted in a deficiency of TCR of the UV-damaged dihydrofolate reductase (DHFR) gene. In addition, DMSO-induced silencing of the c-myc gene led to a decreased TCR efficiency of UV radiation-damaged c-myc gene in HL60 cells. On the basis of the above methodology verification, we found that the depletion of DNA-PKcs mediated by siRNA significantly decreased the TCR capacity of repairing the UV-induced CPDs damage in DHFR gene in HeLa cells, indicating that DNA-PKcs may also be involved in the TCR pathway of DNA damage repair. By means of immunoprecipitation and MALDI-TOF-Mass spectrometric analysis, we have revealed the interaction of DNA-PKcs and cyclin T2, which is a subunit of the human transcription elongation factor (P-TEFb). While the P-TEFb complex can phosphorylate the serine 2 of the carboxyl-terminal domain (CTD) of RNA polymerase II and promote transcription elongation. CONCLUSION: A new method of TCR assay was developed based the strand-specific-PCR (SS-PCR). Our data suggest that DNA-PKcs plays a role in the TCR pathway of UV-damaged DNA. One possible mechanistic hypothesis is that DNA-PKcs may function through associating with CyclinT2/CDK9 (P-TEFb) to modulate the activity of RNA Pol II, which has already been identified as a key molecule recognizing and initializing TCR.

Bayesian parameter estimation for nonlinear modelling of biological pathways.

BACKGROUND: The availability of temporal measurements on biological experiments has significantly promoted research areas in systems biology. To gain insight into the interaction and regulation of biological systems, mathematical frameworks such as ordinary differential equations have been widely applied to model biological pathways and interpret the temporal data. Hill equations are the preferred formats to represent the reaction rate in differential equation frameworks, due to their simple structures and their capabilities for easy fitting to saturated experimental measurements. However, Hill equations are highly nonlinearly parameterized functions, and parameters in these functions cannot be measured easily. Additionally, because of its high nonlinearity, adaptive parameter estimation algorithms developed for linear parameterized differential equations cannot be applied. Therefore, parameter estimation in nonlinearly parameterized differential equation models for biological pathways is both challenging and rewarding. In this study, we propose a Bayesian parameter estimation algorithm to estimate parameters in nonlinear mathematical models for biological pathways using time series data. RESULTS: We used the Runge-Kutta method to transform differential equations to difference equations assuming a known structure of the differential equations. This transformation allowed us to generate predictions dependent on previous states and to apply a Bayesian approach, namely, the Markov chain Monte Carlo (MCMC) method. We applied this approach to the biological pathways involved in the left ventricle (LV) response to myocardial infarction (MI) and verified our algorithm by estimating two parameters in a Hill equation embedded in the nonlinear model. We further evaluated our estimation performance with different parameter settings and signal to noise ratios. Our results demonstrated the effectiveness of the algorithm for both linearly and nonlinearly parameterized dynamic systems. CONCLUSIONS: Our proposed Bayesian algorithm successfully estimated parameters in nonlinear mathematical models for biological pathways. This method can be further extended to high order systems and thus provides a useful tool to analyze biological dynamics and extract information using temporal data.

Free energy landscape of receptor-mediated cell adhesion.

Receptor-mediated cell adhesion plays a critical role in cell migration, proliferation, signaling, and survival. A number of diseases, including cancer, show a strong correlation between integrin activation and metastasis. A better understanding of cell adhesion is highly desirable for not only therapeutic but also a number of tissue engineering applications. While a number of computational models and experimental studies have addressed the issue of cell adhesion to surfaces, no model or theory has adequately addressed cell adhesion at the molecular level. In this paper, the authors present a thermodynamic model that addresses receptor-mediated cell adhesion at the molecular level. By incorporating the entropic, conformational, solvation, and long- and short-range interactive components of receptors and the extracellular matrix molecules, they are able to predict adhesive free energy as a function of a number of key variables such as surface coverage, interaction distance, molecule size, and solvent conditions. Their method allows them to compute the free energy of adhesion in a multicomponent system where they can simultaneously study adhesion receptors and ligands of different sizes, chemical identities, and conformational properties. The authors' results not only provide a fundamental understanding of adhesion at the molecular level but also suggest possible strategies for designing novel biomaterials.