Silibinin-loaded chitosan-capped silver nanoparticles exhibit potent antimicrobial, antibiofilm, and anti-inflammatory activity against drug-resistant nosocomial pathogens.

Nanoparticles capped with natural products can be a cost-effective alternative to treat drug-resistant nosocomial infections. Therefore, silibinin-loaded chitosan-capped silver nanoparticles (S-C@AgNPs) were synthesized to evaluate their antimicrobial and anti-inflammatory potential. The S-C@AgNPs plasmon peak was found at 430 nm and had a particle size distribution of about 130 nm with an average hydrodynamic diameter of 101.37 nm. The Scanning Electron Microscopy images showed the presence of sphere-shaped homogeneous nanoparticles. The Fourier Transform Infrared Spectroscopy analysis confirmed the loading of silibinin and chitosan on the AgNPs surface. The minimum inhibitory concentration of the S-C@AgNPs was reported between 3.12 µg/ml to 12.5 µg/ml and a minimum bactericidal concentration between 6.25 µg/ml to 25 µg/ml against drug-resistant nosocomial pathogens. Moreover, concentration-dependent significant inhibition of the biofilm formation was reported against P. aeruginosa (70.21%) and K. pneumoniae (71.02%) at 30 µg/ml, and the highest destruction of preformed biofilm was observed at 100 µg/ml against P. aeruginosa (89.74%) and K. pneumoniae (77.65%) as compared to individual bacterial control. Additionally, the fluorescence live/dead assay for bacterial biofilm confirmed that 100 µg/ml effectively inhibits the biofilm formed by these pathogens. S-C@AgNPs also showed anti-inflammatory activity, which is evident by the significant decrease in the proinflammatory cytokines and chemokines level in THP1 cells treated with LPS. This study concluded that S-C@AgNPs have potent antimicrobial, antibiofilm, and anti-inflammatory properties and could be a potential option for treating drug resistant nosocomial infections.

Proanthocyanidins isolated from the leaves of Ficus glomerata evaluated on the activities of rumen enzymes: in vitro and in silico studies.

Two new proanthocyanidins (2S:3S)-(-)-epicatechin-(4α→8)4-(2R:3R)-(+)-catechin (Compound 1) and (2R, 3R)-3-O-galloyl-(+)-catechin (4ß→8)3-(2R, 3R)-3-O-galloyl-(+)-catechin (Compound 2) were isolated from Ficus glomerata and characterized by ultraviolet spectroscopy (UV), proton nuclear magnetic resonance (1H NMR), 13C NMR, and heteronuclear multiple bond correlation . The bioactivity and drug scores of isolated compounds were predicted using OSIRIS property explorer applications with drug scores of 0.03 (compound 1) and 0.05 (compound 2). Predictive drug scores provided an indication of the compounds' potential to demonstrate desired biological effects. Furthermore, the newly discovered proanthocyanidins tended to interact with protein due to their chemical structure and molecular conformation. With the aim of maintaining this focus, compounds 1 and 2 were subjected to in vitro testing against ruminal enzymes to further explore their potential impact. Both compounds showed significant inhibition activities (p < 0.01) against glutamic oxaloacetic transaminase in both protozoa and bacterial fractions, with an effective concentration (EC50) of 12.30-18.20 mg/mL. The compounds also exhibited significant inhibition (p < 0.01) of ruminal glutamic pyruvic transaminase activity, with EC50 values ranging from 9.77 to 17.38 mg/mL. Furthermore, the inhibition was recorded in R-cellulase between EC50 values of 15.85 and 23.99 mg/mL by both compounds. Additionally, both compounds led to a decrease in protease activity with increasing incubation time and concentration. In conclusion, the results indicate that these novel proanthocyanidins hold the potential to significantly impact rumen enzyme biology. Furthermore, their promising effects suggest that they could be further explored for drug development and other important applications.

Postbiotics: An alternative and innovative intervention for the therapy of inflammatory bowel disease.

Inflammatory Bowel Disease (IBD) is a persistent gastrointestinal (GI) tract inflammatory disease characterized by downregulated mucosal immune activities and a disrupted microbiota environment in the intestinal lumen. The involvement of bacterium postbiotics as mediators between the immune system and gut microbiome could be critical in determining why host-microbial relationships are disrupted in IBD. Postbiotics including Short-chain fatty acids (SCFAs), Organic acids, Proteins, Vitamins, Bacteriocins, and Tryptophan (Trp) are beneficial bioactive compounds formed via commensal microbiota in the gut environment during the fermentation process that can be used to improve consumer health. The use of metabolites or fragments from microorganisms can be a very attractive treatment and prevention technique in modern medicine. Postbiotics are essential in the immune system's development since they alter the barrier tightness, and the gut ecology and indirectly shape the microbiota's structure. As a result, postbiotics may be beneficial in treating or preventing various diseases, even some for which there is no effective causative medication. Postbiotics may be a promising tool for the treatment of IBD in individuals of all ages, genders, and even geographical locations. Direct distribution of postbiotics may provide a new frontier in microbiome-based therapy for IBD since it allows both the management of host homeostasis and the correction of the negative implications of dysbiosis. Further studies of the biological effects of these metabolites are expected to reveal innovative applications in medicine and beyond. This review attempts to explore the possible postbiotic-based interventions for the treatment of IBD.

Nano-immunomodulators: prospective applications to combat drug resistant bacterial infections and related complications.

Antimicrobial resistance (AMR) is a growing problem in our healthcare sector, it can make infections more difficult and expensive to treat and lead to treatment failure and increased risk of death. Currently, at least 700,000 people worldwide die each year from AMR. Alternative methods for mitigating drug-resistant bacterial infections are desperately needed because of the unacceptably low rate of conventional antibiotic discovery. Therefore, the implementation of various therapeutic strategies is necessary to deal with drug-resistant bacteria and immunomodulation is one of them which is highly encouraged through various studies. Immunomodulators are different biological or synthetic substances that possess the capability of inducing, suppressing, or overall modulating the innate and adaptive immune system. Some phytochemicals, including flavonoids, glycosides, polysaccharides, terpenoids, essential oils, peptides, synthetic molecules, and synthetic biomaterials, can play a crucial role in the fight against bacterial infections directly or indirectly by enhancing the activity of existing antibiotics or by boosting immunity. Nanotechnology can be used to modulate immune responses through various fabrication methods and strategies of design and for drug formulation by encapsulating potential compounds/molecules in the form of nanoparticles and by surface modification or capping of nanomaterials. This approach can improve drug solubility, stability, and bioavailability, reduce toxicity, and help to increase the effectiveness of drugs against resistant microorganisms. This review aims to provide current developments in the field of immunomodulators of different origins that can be combined with nanotechnology and exploited as potential future drugs or adjuvants to fight drug-resistant bacterial pathogens.

A Low-Latency DNN Accelerator Enabled by DFT-Based Convolution Execution Within Crossbar Arrays.

Analog resistive random access memory (RRAM) devices enable parallelized nonvolatile in-memory vector-matrix multiplications for neural networks eliminating the bottlenecks posed by von Neumann architecture. While using RRAMs improves the accelerator performance and enables their deployment at the edge, the high tuning time needed to update the RRAM conductance states adds significant burden and latency to real-time system training. In this article, we develop an in-memory discrete Fourier transform (DFT)-based convolution methodology to reduce system latency and input regeneration. By storing the static DFT/inverse DFT (IDFT) coefficients within the analog arrays, we keep digital computational operations using digital circuits to a minimum. By performing the convolution in reciprocal Fourier space, our approach minimizes connection weight updates, which significantly accelerates both neural network training and interference. Moreover, by minimizing RRAM conductance update frequency, we mitigate the endurance limitations of resistive nonvolatile memories. We show that by leveraging the symmetry and linearity of DFT/IDFTs, we can reduce the power by 1.57 × for convolution over conventional execution. The designed hardware-aware deep neural network (DNN) inference accelerator enhances the peak power efficiency by 28.02 × and area efficiency by 8.7 × over state-of-the-art accelerators. This article paves the way for ultrafast, low-power, compact hardware accelerators.

Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism.

INTRODUCTION: Even in present-day times, cancer is one of the most fatal diseases. People are overwhelmed by pricey chemotherapy, immunotherapy, and other costly cancer therapies in poor and middle-income countries. Cancer cells grow under anaerobic and hypoxic conditions. Pyruvate is the final product of the anaerobic glycolysis pathway, and many cancer cells utilize pyruvate for their growth and development. The anaerobic microbiome produces many anti-cancer substances that can act as anti-tumor agents and are both feasible and of low cost. There are different mechanisms of action of the anaerobic microbiome, such as the production of short-chain fatty acids (SCFAs), and competition for the anaerobic environment includes the metabolic product pyruvate to form lactic acid for energy. KEY FINDINGS: In this review, we have summarized the role of the metabolic approach of the anaerobic human microbiome in cancer prevention and treatment by interfering with cancer metabolite pyruvate. SCFAs possess decisive outcomes in condoning almost all the hallmarks of cancer and helping the spread of cancer to other body parts. Studies have demonstrated the impact and significance of using SCFA, which results from anaerobic bacteria, as an anti-cancer agent. Anaerobic bacteria-based cancer therapy has become a promising approach to treat cancer using obligate and facultative anaerobic bacteria because of their ability to penetrate and increase in an acidic hypoxic environment. SIGNIFICANCE: This review attempts to provide the interconnection of cancer metabolism and anaerobic microbiome metabolism with a focus on pyruvate metabolism to understand and design unique anaerobic microbiota-based therapy for cancer patients.

The study of structure and effects of two new proanthocyanidins from Anogeissus pendula leaves on rumen enzyme activities.

Two novel proanthocyanidins, (2R, 3R)-(+)-Gallocatechin-(4ß â†’ 8)4-(2R, 3R)-(+)-gallocatechin (compound 1) and 3-O-galloyl-(2S, 3S)-(-)-epicatechin-(4α → 8)-[3-O-galloyl-(2S, 3S)-(-)-epicatechin (4α → 8)]2-(2S, 3S)-(-)-epicatechin (compound 2), were structurally characterized from leaves of Anogeissus pendula. The structures were determined by ultraviolet spectroscopy (UV), proton nuclear magnetic resonance (1H NMR), 13C NMR, and heteronuclear multiple bond correlation. Molinspiration and Osiris property explorer applications were used to predict bioactivity and drug score. Drug scores of 0.08 and 0.05 were predicted for compounds 1 and 2, respectively. Predicted bioactivity scores were high. Due to their molecular weight, chemical structure, and conformation, the newly discovered proanthocyanidins possess an inclination to interact with proteins. Based on this premise, both compounds were subjected to in vitro testing against ruminal enzymes. They exhibited significant inhibition activities (p < 0.01) with a range of half maximal effective concentration (EC50) of 14.80-17.88 mg/mL of glutamic oxaloacetic transaminase in both protozoa and bacteria fractions. The ruminal glutamic pyruvic transaminase activity was significantly inhibited (p < 0.01) from EC50 12.59-16.29 mg/mL, and R-cellulase inhibition was recorded with EC50 18.20-21.98 mg/mL by compounds 1 and 2, respectively. Protease activity decreased with increasing incubation time and concentration of both compounds. The novel proanthocyanidins have potential roles in improving feed conversion ratios and in drug development.

Staphylococcus aureus vaccine strategy: Promise and challenges.

Staphylococcus aureus (S. aureus) is a leading and crucial infectious threat to global public health due to the widespread emergence of antibiotic-resistant strains such as Methicillin-Resistant S. aureus (MRSA). MRSA infects immunocompromised patients and healthy individuals and has rapidly spread from the healthcare setting to the outside community. The development of flawless vaccines become a medical need worldwide against multi-drug resistant S. aureus. Therefore, protection by an immune-based strategy may provide valuable measures to contain the spread of invasive S. aureus infections. Several vaccine candidates have been prepared which are either in the preclinical phase or in the early clinical phase, whereas several candidates have failed to show a protective efficacy in human subjects. Currently, research is focusing on identifying novel vaccine formulations able to elicit potent humoral and cellular immune responses. Several approaches have also been made to the development of monoclonal or polyclonal antibodies for passive immunization to protect against S. aureus infections. In recent years, a multi-epitope vaccine has emerged as a novel platform for subunit vaccine design by using computational approaches. Therefore, in this review, we have summarized and discussed the mechanistic overview of different strategies used to develop potential vaccine candidates and passive interventions which are in different stages of clinical trials to fight multi-drug resistant S. aureus infections.

A Low-Power DNN Accelerator Enabled by a Novel Staircase RRAM Array.

Enhancing the ubiquitous sensors and connected devices with computational abilities to realize visions of the Internet of Things (IoT) requires the development of robust, compact, and low-power deep neural network accelerators. Analog in-memory matrix-matrix multiplications enabled by emerging memories can significantly reduce the accelerator energy budget while resulting in compact accelerators. In this article, we design a hardware-aware deep neural network (DNN) accelerator that combines a planar-staircase resistive random access memory (RRAM) array with a variation-tolerant in-memory compute methodology to enhance the peak power efficiency by 5.64× and area efficiency by 4.7× over state-of-the-art DNN accelerators. Pulse application at the bottom electrodes of the staircase array generates a concurrent input shift, which eliminates the input unfolding, and regeneration required for convolution execution within typical crossbar arrays. Our in-memory compute method operates in charge domain and facilitates high-accuracy floating-point computations with low RRAM states, device requirement. This work provides a path toward fast hardware accelerators that use low power and low area.

All WSe2 1T1R resistive RAM cell for future monolithic 3D embedded memory integration.

3D monolithic integration of logic and memory has been the most sought after solution to surpass the Von Neumann bottleneck, for which a low-temperature processed material system becomes inevitable. Two-dimensional materials, with their excellent electrical properties and low thermal budget are potential candidates. Here, we demonstrate a low-temperature hybrid co-integration of one-transistor-one-resistor memory cell, comprising a surface functionalized 2D WSe2 p-FET, with a solution-processed WSe2 Resistive Random Access Memory. The employed plasma oxidation technique results in a low Schottky barrier height of 25 meV with a mobility of 230 cm2 V-1 s-1, leading to a 100x performance enhanced WSe2 p-FET, while the defective WSe2 Resistive Random Access Memory exhibits a switching energy of 2.6 pJ per bit. Furthermore, guided by our device-circuit modelling, we propose vertically stacked channel FETs for high-density sub-0.01 µm2 memory cells, offering a new beyond-Si solution to enable 3-D embedded memories for future computing systems.

Conductive bridge random access memory characteristics of SiCN based transparent device due to indium diffusion.

In this work, the transparent bipolar resistive switching characteristics of a SiCN-based ITO/SiCN/AZO structure due to In diffusion from ITO is studied. The SiCN based device is found to be 80% transparent in the visible wavelength region. This device, with AZO as both top and bottom electrodes, does not show any RRAM property due to deposition of the high quality O2-free SiCN film. Replacing the AZO top electrode with ITO in this device results in good resistive switching (RS) characteristics with a high on/off ratio and long retention. Replacing the SiCN film with ZrO2 also results in excellent RS characteristics due to the formation of an oxygen vacancies filament inside the ZrO2 film. A resistance ratio of on/off is found to be higher in the SiCN based device compared to that of the ZrO2 device. Diffusion of In from ITO into the SiCN film on application of high positive voltage during forming can be attributed to the occurrence of RS in the device, which is confirmed by the analyses of energy dispersive spectroscopy and secondary-ion mass spectrometry. This study shows a pathway for the fabrication of CBRAM based transparent devices for non-volatile memory application.

Overview of emerging nonvolatile memory technologies.

Nonvolatile memory technologies in Si-based electronics date back to the 1990s. Ferroelectric field-effect transistor (FeFET) was one of the most promising devices replacing the conventional Flash memory facing physical scaling limitations at those times. A variant of charge storage memory referred to as Flash memory is widely used in consumer electronic products such as cell phones and music players while NAND Flash-based solid-state disks (SSDs) are increasingly displacing hard disk drives as the primary storage device in laptops, desktops, and even data centers. The integration limit of Flash memories is approaching, and many new types of memory to replace conventional Flash memories have been proposed. Emerging memory technologies promise new memories to store more data at less cost than the expensive-to-build silicon chips used by popular consumer gadgets including digital cameras, cell phones and portable music players. They are being investigated and lead to the future as potential alternatives to existing memories in future computing systems. Emerging nonvolatile memory technologies such as magnetic random-access memory (MRAM), spin-transfer torque random-access memory (STT-RAM), ferroelectric random-access memory (FeRAM), phase-change memory (PCM), and resistive random-access memory (RRAM) combine the speed of static random-access memory (SRAM), the density of dynamic random-access memory (DRAM), and the nonvolatility of Flash memory and so become very attractive as another possibility for future memory hierarchies. Many other new classes of emerging memory technologies such as transparent and plastic, three-dimensional (3-D), and quantum dot memory technologies have also gained tremendous popularity in recent years. Subsequently, not an exaggeration to say that computer memory could soon earn the ultimate commercial validation for commercial scale-up and production the cheap plastic knockoff. Therefore, this review is devoted to the rapidly developing new class of memory technologies and scaling of scientific procedures based on an investigation of recent progress in advanced Flash memory devices.

Forming-free bipolar resistive switching in nonstoichiometric ceria films.

The mechanism of forming-free bipolar resistive switching in a Zr/CeOx/Pt device was investigated. High-resolution transmission electron microscopy and energy-dispersive spectroscopy analysis indicated the formation of a ZrOy layer at the Zr/CeOx interface. X-ray diffraction studies of CeOx films revealed that they consist of nano-polycrystals embedded in a disordered lattice. The observed resistive switching was suggested to be linked with the formation and rupture of conductive filaments constituted by oxygen vacancies in the CeOx film and in the nonstoichiometric ZrOy interfacial layer. X-ray photoelectron spectroscopy study confirmed the presence of oxygen vacancies in both of the said regions. In the low-resistance ON state, the electrical conduction was found to be of ohmic nature, while the high-resistance OFF state was governed by trap-controlled space charge-limited mechanism. The stable resistive switching behavior and long retention times with an acceptable resistance ratio enable the device for its application in future nonvolatile resistive random access memory (RRAM).