Wide Variety Research Articles

Insight into the Nutraceutical Potential of Garcinia Species

Background:: A wide variety of Garcinia species have been used over decades, as traditional home remedies starting from their use in flavored food to the treatment of various ailments. The presence of the essential primary and secondary metabolite with curative properties in Garcinia has enhanced its value in the therapeutic world. These have captivated the use of Garcinia in expanding nutritional values and adding extra health benefits. Hereby, observing the potential of different Garcinia species for their use as nutraceuticals. Objective:: The present-day lifestyle and current health trends are the reasons why the public has accumulated a lot of interest in the nutraceutical food market. Traditionally the various remedies used from plants, fruits, and fruit extracts used in the cure of multiple ailments since antiquity have now made their way into pharmaceutical nutraceuticals. The fruits of Garcinia species have many culinary, nutritional, and pharmaceutical uses. Therefore, the paper aims to focus on the different Garcinia species having nutritional potential along with various therapeutic properties. Methods:: Studies of different Garcinia species are reviewed, with a focus on their nutritional and medicinal actions on ailments that are the reason for today's lifestyles and current health trends. Results:: Different varieties of Garcinia species are found to have various potential primary and secondary metabolites which have curative properties like anti-diabetic, anti-obesity, anti-microbial, anti-cancer, anti-inflammation, and anti-bacterial potential. Conclusion:: The natural occurrences of the plant product with nutraceutical value have boosted the quality of life. The Garcinia species containing the essential primary and secondary constituents are accountable for numerous biological activities. Many of the Garcinia species are marketed these days for a better and healthy life. Thus, Garcinia could be used as a nutraceutical to alleviate several disease conditions.

Role of Vitamin D in Gynecological Cancer: State of the Art

: Vitamin D and Vitamin D Receptors have gained more importance beyond their roles in bone metabolism and calcium homeostasis. Several epidemiological studies have confirmed that vitamin D has a specific function in a wide variety of gynecological cancers, such as ovarian cancer, endometrial cancer, cervical cancer, uterine fibroid, and vulvar cancer. The different anti-cancer mechanisms exerted by vitamin D on tumor cells are cell proliferation, cancer progression, angiogenesis, cell cycle arrest, and inflammation. The role of vitamin D is well emphasized in ovarian cancer and uterine fibroids, with limited studies available on cervical cancer and other types of gynecological cancers. Overall, most epidemiological data support that inadequate or low levels of vitamin D in the circulation are associated with risk and poor prognosis in several types of gynecological cancer. It is evident that vitamin D plays a prominent role as an anticancer agent against numerous types of cancer. This review focuses on the etiology and role of vitamin D and the Vitamin D Receptor in various types of gynecological cancer, as well as the mechanism of Vitamin D and its metabolites in the management of gynecological cancer.

BehaviorMate: An Intranet of Things Approach for Adaptable Control of Behavioral and Navigation-Based Experiments.

Investigators conducting behavioral experiments often need precise control over the timing of the delivery of stimuli to subjects and to collect the precise times of the subsequent behavioral responses. Furthermore, investigators want fine-tuned control over how various multi-modal cues are presented. behaviorMate takes an "Intranet of Things" approach, using a networked system of hardware and software components for achieving these goals. The system outputs a file with integrated timestamp-event pairs that investigators can then format and process using their own analysis pipelines. We present an overview of the electronic components and GUI application that make up behaviorMate as well as mechanical designs for compatible experimental rigs to provide the reader with the ability to set up their own system. A wide variety of paradigms are supported, including goal-oriented learning, random foraging, and context switching. We demonstrate behaviorMate's utility and reliability with a range of use cases from several published studies and benchmark tests. Finally, we present experimental validation demonstrating different modalities of hippocampal place field studies. Both treadmill with burlap belt and virtual reality with running wheel paradigms were performed to confirm the efficacy and flexibility of the approach. Previous solutions rely on proprietary systems that may have large upfront costs or present frameworks that require customized software to be developed. behaviorMate uses open-source software and a flexible configuration system to mitigate both concerns. behaviorMate has a proven record for head-fixed imaging experiments and could be easily adopted for task control in a variety of experimental situations.

Real Face Value: The Processing of Naturalistic Facial Expressions in the Macaque Inferior Temporal Cortex.

For primates, expressions of fear are thought to be powerful social signals. In laboratory settings, faces with fearful expressions have reliably evoked valence effects in inferior temporal cortex. However, because macaques use so called "fear grins" in a variety of different contexts, the deeper question is whether the macaque inferior temporal cortex is tuned to the prototypical fear grin, or to conspecifics signaling fear? In this study, we combined neuroimaging with the results of a behavioral task to investigate how macaques encode a wide variety of fearful facial expressions. In Experiment 1, we identified two sets of macaque face stimuli using different approaches; we selected faces based on the emotional context (i.e., calm vs. fearful), and we selected faces based on the engagement of action units (i.e., neutral vs. fear grins). We also included human faces in Experiment 1. Then, using fMRI, we found that the faces selected based on context elicited a larger valence effect in the inferior temporal cortex than faces selected based on visual appearance. Furthermore, human facial expressions only elicited weak valence effects. These observations were further supported by the results of a two-alternative, forced-choice task (Experiment 2), suggesting that fear grins vary in their perceived pleasantness. Collectively, these findings indicate that the macaque inferior temporal cortex is more involved in social intelligence than commonly assumed, encoding emergent properties in naturalistic face stimuli that transcend basic visual features. These results demand a rethinking of theories surrounding the function and operationalization of primate inferior temporal cortex.

Potential Impact of Bioactive Compounds as NLRP3 Inflammasome Inhibitors: An Update.

The inflammasome NLRP3 comprises a caspase recruitment domain, a pyrin domain containing receptor 3, an apoptosis-linked protein like a speck containing a procaspase-1, and an attached nucleotide domain leucine abundant repeat. There are a wide variety of stimuli that can activate the inflammasome NLRP3. When activated, the protein NLRP3 appoints the adapter protein ASC. Adapter ASC protein then recruits the procaspase-1 protein, which causes the procaspase- 1 protein to be cleaved and activated, which induces cytokines. At the same time, abnormal activation of inflammasome NLRP3 is associated with many diseases, such as diabetes, atherosclerosis, metabolic syndrome, cardiovascular and neurodegenerative diseases. As a result, a significant amount of effort has been put into comprehending the mechanisms behind its activation and looking for their specific inhibitors. In this review, we primarily focused on phytochemicals that inhibit the inflammasome NLRP3, as well as discuss the defects caused by NLRP3 signaling. We conducted an in-depth research review by searching for relevant articles in the Scopus, Google Scholar, and PubMed databases. By gathering information on phytochemical inhibitors that block NLRP3 inflammasome activation, a complicated balance between inflammasome activation or inhibition with NLRP3 as a key role was revealed in NLRP3-driven clinical situations.

CSAIL2019 Crypto-Puzzle Solver Architecture

tThe CSAIL2019 time-lock puzzle is an unsolved cryptographic challenge introduced by Ron Rivest in 2019, replacing the solved LCS35 puzzle. Solving these types of puzzles requires large amounts of intrinsically sequential computations, with each iteration performing a very large (3,072-bit for CSAIL2019) modular multiplication operation. The complexity of each iteration is several times greater than known field-programmable gate array (FPGA) implementations, and the number of iterations has been increased by about 1,000x compared with LCS35. Because of the high complexity of this new puzzle, a number of intermediate, or milestone, versions of the puzzle have been specified. In this article, we present several FPGA architectures for the CSAIL2019 solver, which we implement on a medium-sized Intel Agilex device. We develop a new multi-cycle modular multiplication method, which is flexible and can fit on a wide variety of sizes of current FPGAs. We introduce a class of multi-cycle squarer-based architectures that allow for better resource and area trade-offs. We also demonstrate a new approach for improving the fitting and timing closure of large, chip-filling arithmetic designs. We used the solver to compute the first 23 out of 28 milestone solutions of the puzzle, which are the first reported results for this problem.

Prospective Approaches of Herbal Novel Delivery System with Special Reference to the Herbal Nanosciences

: Medicinal and culinary uses of plants date back centuries. Projects on a global scale are conducting laboratory research to identify plants with therapeutic properties, with the ultimate goal of developing such compounds into medicines with acceptable drug delivery mechanisms and bringing them to market. Non-synthetic medications derived from plant or herbal sources have attracted a lot of interest because of their high tolerability and low likelihood of adverse medication reactions. All diseases, the theory goes, can be cured by something found in nature. Medicines can be taken in a wide variety of forms, including tablets, capsules, powders, semi-liquid extracts, tinctures, decoctions, medicinal teas, solutions, and more. Longer release, patient adherence, and other objectives necessitate adjustments to herbal medications. Researchers into novel drug delivery systems had hitherto overlooked herbal remedies due to a lack of scientific validation and the challenges inherent in processing, standardizing, extracting, and identifying them. Transdisciplinary research and cuttingedge isolation, purification, and identification techniques have led to the development of novel herbal compositions. Bioactive plant extracts and phytoconstituents are used in a wide variety of Nano- Emulsions, microspheres, transferosomes, implants, and ethosomes. Compared to herbal remedies, novel formulations fared better. Among these advantages are increased solubility, bioavailability, toxicity, pharmacological activity, stability, delivery duration, and resistance to physical and chemical degradation. As a result, the pharmacokinetic and pharmacodynamic properties of herbal medications can be enhanced by the use of novel drug delivery systems, making them safer and more effective. : This article aims to provide a concise description of the many new drug delivery techniques that have been created for the administration of herbal medications. The ultimate goal is to increase the efficacy of therapies and to learn more about their significance and worldwide appeal.

A Literature Review Focusing on the Antiviral Activity of [1,2,4] and [1,2,3]-triazoles.

Out of a variety of heterocycles, triazole scaffolds have been shown to play a significant part in a wide array of biological functions. Many drug compounds containing a triazole moiety with important antimicrobial, anticancer and antidepressant properties have been commercialized. In addition, the triazole scaffold exhibits remarkable antiviral activity either incorporated into nucleoside analogs or non-nucleosides. Many synthetic techniques have been produced by scientists around the world as a result of their wide-ranging biological function. In this review, we have tried to summarize new synthetic methods produced by diverse research groups as well as provide a comprehensive description of the function of [1,2,4] and [1,2,3]-triazole derivatives as antiviral agents. Antiviral triazole compounds have been shown to target a wide variety of molecular proteins. In addition, several strains of viruses, including the human immunodeficiency virus, SARS virus, hepatitis B and C viruses, influenza virus, Hantavirus, and herpes virus, were discovered to be susceptible to triazole derivatives. This review article covered the reports for antiviral activity of both 1,2,3- and 1,2,4-triazole moieties up to 2022.

Explainable Detection of Fake News on Social Media Using Pyramidal Co-Attention Network

In today’s world, fake news on social media is a universal trend and has severe consequences. There has been a wide variety of countermeasures developed to offset the effect and propagation of Fake News. The most common are linguistic-based techniques, which mostly use deep learning (DL) and natural language processing (NLP). Even government-sponsored organizations spread fake news as a cyberwar strategy. In literature, computational-based detection of fake news has been investigated to minimize it. The initial results of these studies are good but not significant. However, we argue that the explainability of such detection, particularly why a certain news item is detected as fake, is a vital missing element of the studies. In real-world settings, the explainability of the system’s decisions is just as important as its accuracy. This article explores explainable fake news detection and proposes a sentence-comment-based co-attention sub-network model. The proposed model uses user comments and news contents to mutually apprehend top- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$k$</tex-math> </inline-formula> explainable check-worthy user comments and sentences for detecting fake news. The experimental result on real-world datasets shows that our proposed model outperforms state-of-the-art techniques by 5.56% in the <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$F$</tex-math> </inline-formula> 1 score. In addition, our model outperforms other baselines by 16.4% in normalized cumulative gain (NDCG) and 22.1% in Precision in identifying top- <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$k$</tex-math> </inline-formula> comments from users, which indicates why a news article can be fake.

MeshWGAN: Mesh-to-Mesh Wasserstein GAN With Multi-Task Gradient Penalty for 3D Facial Geometric Age Transformation.

As the metaverse develops rapidly, 3D facial age transformation is attracting increasing attention, which may bring many potential benefits to a wide variety of users, e.g., 3D aging figures creation, 3D facial data augmentation and editing. Compared with 2D methods, 3D face aging is an underexplored problem. To fill this gap, we propose a new mesh-to-mesh Wasserstein generative adversarial network (MeshWGAN) with a multi-task gradient penalty to model a continuous bi-directional 3D facial geometric aging process. To the best of our knowledge, this is the first architecture to achieve 3D facial geometric age transformation via real 3D scans. As previous image-to-image translation methods cannot be directly applied to the 3D facial mesh, which is totally different from 2D images, we built a mesh encoder, decoder, and multi-task discriminator to facilitate mesh-to-mesh transformations. To mitigate the lack of 3D datasets containing children's faces, we collected scans from 765 subjects aged 5-17 in combination with existing 3D face databases, which provided a large training dataset. Experiments have shown that our architecture can predict 3D facial aging geometries with better identity preservation and age closeness compared to 3D trivial baselines. We also demonstrated the advantages of our approach via various 3D face-related graphics applications.

Synthesis and Gas Permeation Properties of Functionalized Norbornene-Based Polymers

Abstract: Functionalized polynorbornenes are very important specialty materials for a wide variety of practical and industrial applications. In the membrane technology field, polynorbonene derivatives play a main role in gas transport since they can be systematically and easily functionalized, thus affecting the membrane performance in gas separation processes. Thus, several methodologies have been employed to yield macromolecular architectures with tailored gas permeation properties. This review is intended to provide different synthesis routes of substituted polynorbornenes as well as the effects of the polymer chemical structures on their gas permeation properties, among others.

Hydrogel-based Drug Delivery System in Diabetes Management.

It is estimated that there are over 200 million people living with diabetes mellitus (DM) all over the world. It is a metabolic condition caused by decreased insulin action or secretion. Diabetes Mellitus is also known as Type 2 Diabetes Mellitus. Type 1 diabetes mellitus and type 2 diabetes mellitus are the two most common types of DM. Treatment for type 1 diabetes often consists of insulin replacement therapy, while treatment for type 2 diabetes typically consists of oral hypoglycemics. Conventional dosing schedules for the vast majority of these medications come with a number of drawbacks, the most common of which are frequent dosing, a short half-life, and low bioavailability. Thus, innovative and regulated oral hypoglycemic medication delivery methods have been developed to reduce the limitations of standard dose forms. The studies and reviews published under the title were looked up in several databases (including PubMed, Elsevier, and Google Scholar). Hydrogels made from biopolymers are three-dimensional polymeric networks that can be physically or chemically crosslinked. These networks are based on natural polymers and have an inherent hydrophilic quality because of the functional groups they contain. They have a very high affinity for biological fluids in addition to a high water content, softness, flexibility, permeability, and biocompatibility. The fact that these features are similar to those of a wide variety of soft living tissues paves the way for several potentials in the field of biomedicine. In this sense, hydrogels offer excellent platforms for the transport of medications and the controlled release of those drugs. Additionally, biopolymer-based hydrogels can be put as coatings on medical implants in order to improve the biocompatibility of the implants and to prevent medical diseases. The current review focuses on the most recent advancements made in the field of using biopolymeric hydrogels that are physically and chemically crosslinked, in addition to hydrogel coatings, for the purpose of providing sustained drug release of oral hypoglycemics and avoiding problems that are associated with the traditional dosage forms of oral hypoglycemics.

Microbes with higher metabolic independence are enriched in human gut microbiomes under stress.

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health versus IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

“When I started teaching you wouldn’t notice any of that’: teachers’ perceptions of the issues facing children and adolescents’ mental health and well-being”

PurposeThe purpose of this paper was to establish how the phenomenon of mental health issues among young people has translated into the reality of Irish schools through the lens of Irish teachers.Design/methodology/approachThis wholly qualitative study adopted a post-positivist and phenomenological approach to gathering data by way of semi-structured interviews of 16 participants, 8 from primary backgrounds and 8 from post-primary backgrounds. Analysis of the data highlighted what teachers perceive to be ongoing issues with the mental health and well-being of pupils and the challenges that both teachers and pupils must overcome.FindingsInterviewing the participants unearthed three sub-themes with regard to mental health in Irish schools, namely, the prevalence of psychiatric disorders/symptoms of mental ill-health among Irish children and adolescents, the barriers preventing help-seeking and the role of mental health support services in Irish schools.Research limitations/implicationsOne limitation in this study was that a wider variety in sample could have yielded a more in-depth volume of results. Furthermore, the study by semi-structured interview presented challenges, such as the use of other people’s viewpoints to support the perceptions of the participants, which could not be validated.Practical implicationsAmong the recommendations made by the participants were that schools engage in policy development to combat mental health and well-being issues, that teachers engage in continuous professional development in the area and that mental health support services are sufficiently staffed and funded.Social implicationsThe general public should engage more in activities that promote a healthy dialogue around the topic of mental health to reduce stigma. It is recommended that campaigns to raise awareness are continued and bolstered.Originality/valueIrish teachers are being confronted by a contemporary discourse that has materialised as a by-product of an evolving society. Cultural development has led to increased focus on mental health and well-being in recent years, with this body of research exploring its emergence into school life from teachers’ perspectives.

A New Multiplex TaqMan qPCR for Precise Detection and Quantification of Clavibacter michiganensis in Seeds and Plant Tissue.

Bacterial canker of tomato caused by Clavibacter michiganensis (Cm) is one of the most devastating bacterial diseases affecting the tomato industry worldwide. As the result of Cm colonization of the xylem, the susceptible host shows typical symptoms of wilt, marginal leaf necrosis, stem cankers, and ultimately plant death. However, what makes Cm an even more dangerous pathogen is its ability to infect seeds and plants without causing symptoms. Unfortunately, there are no resistant cultivars or effective chemical or biological control methods available to growers against Cm. Its control relies heavily on prevention. The implementation of a rapid and accurate detection tool is imperative to monitor the presence of Cm and prevent its spread. In this study, we developed a specific and sensitive multiplex TaqMan qPCR assay to detect Cm and distinguish it from related bacterial species that affect tomato plants. Two Cm chromosomal virulence-related genes, rhuM and tomA, were used as specific targets. The plant internal control tubulin alpha-3 was included in each of the multiplexes to improve the reliability of the assay. Specificity was evaluated with 37 bacterial strains including other Clavibacter spp. and related and unrelated bacterial pathogens from different geographic locations affecting a wide variety of hosts. Results showed that the assay is able to discriminate Cm strains from other related bacteria. The assay was validated on tissue and seed samples following artificial infection, and all tested samples accurately detected the presence of Cm. The tool described here is highly specific, sensitive, and reliable for the detection of Cm and allows the quantification of Cm in seeds, roots, stems, and leaves. The diagnostic assay can also be adapted for multiple purposes such as seed certification programs, surveillance, biosafety, the effectiveness of control methods, border protection, and epidemiological studies.[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Whole genome sequencing of a family with autosomal dominant features within the oculoauriculovertebral spectrum.

Oculoauriculovertebral Spectrum (OAVS) encompasses abnormalities on derivatives from the first and second pharyngeal arches including macrostomia, hemifacial microsomia, micrognathia, preauricular tags, ocular and vertebral anomalies. We present genetic findings on a three-generation family affected with macrostomia, preauricular tags and uni- or bilateral ptosis following an autosomal dominant pattern. We generated whole genome sequencing data for the proband, affected parent and unaffected paternal grandparent followed by Sanger sequencing on 23 family members for the top 10 candidate genes: KCND2, PDGFRA, CASP9, NCOA3, WNT10A, SIX1, MTF1, KDR/VEGFR2, LRRK1, and TRIM2 We performed parent and sibling-based transmission disequilibrium tests and burden analysis via a penalized linear mixed model, for segregation and mutation burden respectively. Next, via bioinformatic tools we predicted protein function, mutation pathogenicity and pathway enrichment to investigate the biological relevance of mutations identified. Rare missense mutations in SIX1, KDR/VEGFR2, and PDGFRA showed the best segregation with the OAV phenotypes in this family. When considering any of the 3 OAVS phenotypes as an outcome, SIX1 had the strongest associations in parent-TDTs and sib-TDTs (p=0.025, p=0.052) (unadjusted p-values). Burden analysis identified SIX1 (RC=0.87) and PDGFRA (RC=0.98) strongly associated with OAVS severity. Using phenotype-specific outcomes, sib-TDTs identified SIX1 with uni- or bilateral ptosis (p=0.049) and ear tags (p=0.01), and PDGFRA and KDR/VEGFR2 with ear tags (both p<0.01). SIX1, PDGFRA, and KDR/VEGFR2 are strongly associated to OAVS phenotypes. SIX1 has been previously associated with OAVS ear malformations and is co-expressed with EYA1 during ear development. Efforts to strengthen the genotype-phenotype co-relation underlying the OAVS are key to discover etiology, family counseling and prevention.

New Horizons in Diabetic Neuropathies: An Updated Review on their Pathology, Diagnosis, Mechanism, Screening Techniques, Pharmacological, and Future Approaches.

One of the largest problems for global public health is diabetes mellitus (DM) and its micro and macrovascular consequences. Although prevention, diagnosis, and treatment have generally improved, its incidence is predicted to keep rising over the coming years. Due to the intricacy of the molecular mechanisms, which include inflammation, oxidative stress, and angiogenesis, among others, discovering treatments to stop or slow the course of diabetic complications is still a current unmet need. The pathogenesis and development of diabetic neuropathies may be explained by a wide variety of molecular pathways, hexosamine pathways, such as MAPK pathway, PARP pathway, oxidative stress pathway polyol (sorbitol) pathway, cyclooxygenase pathway, and lipoxygenase pathway. Although diabetic neuropathies can be treated symptomatically, there are limited options for treating the underlying cause. Various pathways and screening models involved in diabetic neuropathies are discussed, along with their possible outcomes. Moreover, both medicinal and non-medical approaches to therapy are also explored. This study highlights the probable involvement of several processes and pathways in the establishment of diabetic neuropathies and presents in-depth knowledge of new therapeutic approaches intended to stop, delay, or reverse different types of diabetic complications.

A DRL-Based Reactive Scheduling Policy for Flexible Job Shops With Random Job Arrivals

In real-life production systems, arrivals of jobs are usually unpredictable, which makes it necessary to develop solid reactive scheduling policies to meet delivery requirements. Deep reinforcement learning (DRL) based scheduling methods are capable of quickly responding to dynamic events by learning from the training data. However, most of policy networks in DRL algorithms are trained to choose priority dispatching rules (PDR), thus, to some extent, the efficiency of obtained scheduling plans is limited by the performance of PDRs. This paper investigates a dynamic flexible job shop scheduling problem with random job arrivals for the total tardiness minimization. A DRL-based reactive scheduling method, proximal policy optimization with attention-based policy network (PPO-APN), is proposed to make real-time decisions for the dynamic scheduling environment, where the attention-based policy network (APN) is able to directly select pending jobs distinguished from the action space that consists of PDRs. Additionally, a global/local reward function (GLRF) is designed to address the reward sparsity issue during training processes. The proposed PPO-APN is tested on randomly generated instances with different production configurations, and is compared with frequently-used PDRs and DRL-based methods. Numerical experimental results indicate that APN and GLRF components significantly improve the training efficiency, and the PPO-APN shows better overall performance compared with other methods. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —This work is motivated by a typical production scenario in discrete manufacturing systems, where orders randomly arrive at the shop floor and require to be scheduled in a short time to ensure the on-time delivery. Previous research work tends to apply DRL algorithms to choose suitable dispatching rules for the ease of implementation. Nevertheless, the jobs that can be selected by dispatching rules are rather limited, thus many possible high-quality scheduling plans are ignored. This work first sorts all the unscheduled jobs by a heuristic algorithm, and puts some of top-ranked jobs to a pool. When a machine becomes available, it will directly choose a job from the pool as the next processing task. The job selection policy is represented by a novel attention-based network, and is trained by a powerful DRL algorithm. The aforementioned process is repeatedly executed in a simulation environment to collect the training data. Therefore, after being trained for a certain period of time, the policy will become smarter and can be applied to make right decisions in real-time. The proposed reactive scheduling method has been proved to be more efficient than dispatching rules and DRL-based approaches, and is effective in the production scheduling for a wide variety of discrete manufacturing scenarios, such as automobile and electronics industries. Moreover, the proposed method can be further extended to address dynamic scheduling problems with some production characteristics via adding constraints for the job selection or re-defining calculations for the completion time of operations accordingly.

Acetaldehyde and Butyrate: Their Biological Effects on the Liver and the Gut Axis

Abstract: The gut is the most accommodating environment in the human body for bacteria. The microbial community there is both dense and varied. The gut microbe forms an axis with the human liver, according to the theory of liver disease causation. The portal vein, systemic circulation, and biliary tract all provide bidirectional connections between the liver and the intestines. The liver secretes bile acid and a wide variety of bioactive mediators into the biliary tract and general circulation. : On the other hand, the portal vein carries microbial-produced endogenous compounds from the colon to the liver, where they might disrupt liver function. Acetyl-aldehyde and butyrate are two of the many byproducts produced by the microbiota in the human gut in response to indigestible food. In addition, these two waste products alter liver function and play an important role in maintaining intestinal health in humans. This paper reviews the literature on the link between butyrate and acetyl-aldehyde production in the human gut and the organ's role in the development of liver disease. Butyrate, acetyl-aldehyde, and liver disease all play roles in the gut-liver axis.

Target-specific requirements for RNA interference can arise through restricted RNA amplification despite the lack of specialized pathways.

Since double-stranded RNA (dsRNA) is effective for silencing a wide variety of genes, all genes are typically considered equivalent targets for such RNA interference (RNAi). Yet, loss of some regulators of RNAi in the nematode C. elegans can selectively impair the silencing of some genes. Here we show that such selective requirements can be explained by an intersecting network of regulators acting on genes with differences in their RNA metabolism. In this network, the Maelstrom domain-containing protein RDE-10, the intrinsically disordered protein MUT-16, and the Argonaute protein NRDE-3 work together so that any two are required for silencing one somatic gene, but each is singly required for silencing another somatic gene, where only the requirement for NRDE-3 can be overcome by enhanced dsRNA processing. Quantitative models and their exploratory simulations led us to find that (1) changing cis-regulatory elements of the target gene can reduce the dependence on NRDE-3, (2) animals can recover from silencing in non-dividing cells and (3) cleavage and tailing of mRNAs with UG dinucleotides, which makes them templates for amplifying small RNAs, is enriched within 'pUG zones' matching the dsRNA. Similar crosstalk between pathways and restricted amplification could result in apparently selective silencing by endogenous RNAs.