The gut microbe pair of Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270 confers complete protection against SARS-CoV-2 infection by activating CD8+ T cell-mediated immunity.

Despite the potential protective role of the gut microbiome against COVID-19, specific microbes conferring resistance to COVID-19 have not yet been identified. In this work, we aimed to identify and validate gut microbes at the species level that provide protection against SARS-CoV-2 infection. To identify gut microbes conferring protection against COVID-19, we conducted a fecal microbiota transplantation (FMT) from an individual with no history of COVID-19 infection or immunization into a lethal COVID-19 hamster model. FMT from this COVID-19-resistant donor resulted in significant phenotypic changes related to COVID-19 sensitivity in the hamsters. Metagenomic analysis revealed distinct differences in the gut microbiome composition among the hamster groups, leading to the identification of two previously unknown bacterial species: Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, both associated with COVID-19 resistance. Subsequently, we conducted a proof-of-concept confirmation animal experiment adhering to Koch's postulates. Oral administration of this gut microbe pair, Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, to the hamsters provided complete protection against SARS-CoV-2 infection through the activation of CD8+ T cell mediated immunity. The prophylactic efficacy of the gut microbe pair against SARS-CoV-2 infection was comparable to, or even superior to, current mRNA vaccines. This strong prophylactic efficacy suggests that the gut microbe pair could be developed as a host-directed universal vaccine for all betacoronaviruses, including potential future emerging viruses.

Dysbiosis of the gut microbiota and its effect on α-synuclein and prion protein misfolding: consequences for neurodegeneration.

Abnormal behavior of α-synuclein and prion proteins is the hallmark of Parkinson's disease (PD) and prion illnesses, respectively, being complex neurological disorders. A primary cause of protein aggregation, brain injury, and cognitive loss in prion illnesses is the misfolding of normal cellular prion proteins (PrPC) into an infectious form (PrPSc). Aggregation of α-synuclein causes disruptions in cellular processes in Parkinson's disease (PD), leading to loss of dopamine-producing neurons and motor symptoms. Alteration in the composition or activity of gut microbes may weaken the intestinal barrier and make it possible for prions to go from the gut to the brain. The gut-brain axis is linked to neuroinflammation; the metabolites produced by the gut microbiota affect the aggregation of α-synuclein, regulate inflammation and immunological responses, and may influence the course of the disease and neurotoxicity of proteins, even if their primary targets are distinct proteins. This thorough analysis explores the complex interactions that exist between the gut microbiota and neurodegenerative illnesses, particularly Parkinson's disease (PD) and prion disorders. The involvement of the gut microbiota, a complex collection of bacteria, archaea, fungi, viruses etc., in various neurological illnesses is becoming increasingly recognized. The gut microbiome influences neuroinflammation, neurotransmitter synthesis, mitochondrial function, and intestinal barrier integrity through the gut-brain axis, which contributes to the development and progression of disease. The review delves into the molecular mechanisms that underlie these relationships, emphasizing the effects of microbial metabolites such as bacterial lipopolysaccharides (LPS), and short-chain fatty acids (SCFAs) in regulating brain functioning. Additionally, it looks at how environmental influences and dietary decisions affect the gut microbiome and whether they could be risk factors for neurodegenerative illnesses. This study concludes by highlighting the critical role that the gut microbiota plays in the development of Parkinson's disease (PD) and prion disease. It also provides a promising direction for future research and possible treatment approaches. People afflicted by these difficult ailments may find hope in new preventive and therapeutic approaches if the role of the gut microbiota in these diseases is better understood.

Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation.

Autism spectrum disorder (ASD) is a neurological disorder that affects normal brain development. The recent finding of the microbiota-gut-brain axis indicates the bidirectional connection between our gut and brain, demonstrating that gut microbiota can influence many neurological disorders such as autism. Most autistic patients suffer from gastrointestinal (GI) symptoms. Many studies have shown that early colonization, mode of delivery, and antibiotic usage significantly affect the gut microbiome and the onset of autism. Microbial fermentation of plant-based fiber can produce different types of short-chain fatty acid (SCFA) that may have a beneficial or detrimental effect on the gut and neurological development of autistic patients. Several comprehensive studies of the gut microbiome and microbiota-gut-brain axis help to understand the mechanism that leads to the onset of neurological disorders and find possible treatments for autism. This review integrates the findings of recent years on the gut microbiota and ASD association, mainly focusing on the characterization of specific microbiota that leads to ASD and addressing potential therapeutic interventions to restore a healthy balance of gut microbiome composition that can treat autism-associated symptoms.

Chemico-Pharmacological Screening of the Methanol Extract of Gynura nepalensis D.C. Deciphered Promising Antioxidant and Hepatoprotective Potentials: Evidenced from in vitro, in vivo, and Computer-Aided Studies.

Gynura nepalensis D.C. (family: Asteraceae) has abundant uses in the alternative medicinal practice, and this species is commonly used in the treatment of diabetes, rheumatism, cuts or wounds, asthma, kidney stones, cough, urinary tract bleeding, gall bladder stones, hepatitis, diarrhea, hemorrhoids, constipation, vomiting, fertility problems, blood poisoning, septicemia, skin allergy, indigestion, high cholesterol levels, and so on. This study aims to investigate the hepatoprotective and antioxidant potential of the methanol extract of the Gynura nepalensis D.C. (GNME) along with chemical profiling with phytochemical screening. Moreover, prospective phytocompounds have been screened virtually to present the binding affinity of the bioactive components to the hepatic and oxidative receptors. In the hepatoprotective study, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), and lipid peroxidation (LP) and total bilirubin (TB) have been assessed, and in the antioxidant study, the DPPH free radical scavenging, total antioxidant flavonoid, and phenolic contents were determined. Moreover, the molecular binding affinity of the bioactive component of the plant has been analyzed using PyRx AutoDock Vina, Chimera, and Discovery Studio software. The plant extract showed dose-dependent hepatoprotective potential (p < 0.05, 0.01, 0.001) as well as strong antioxidant properties. Moreover, hepatoprotective and antioxidant molecular docking studies revealed a result varying from −2.90 kcal/mol to −10.1 kcal/mol. 4,5-dicaffeoylquinic acid and chlorogenic acid revealed the highest binding affinity among the selected molecules. However, the plant showed portent antioxidant and hepatoprotective properties in the in vitro, in vivo, and in silico models, and it is presumed that the hepatoprotective properties of the plant extract have occurred due to the presence of the vast bioactive chemical compounds as well as their antioxidant properties. Therefore, advanced studies are recommended to elucidate the pharmacological properties of the plant extracts.

Comparative Analysis of Original and Replaced Gut Microbiomes within Same Individuals Identified the Intestinal Microbes Associated with Weight Gaining.

The precise mechanisms of action of the host's gut microbiome at the level of its constituting bacteria are obscure in most cases despite its definitive role. To study the precise role of the gut microbiome on the phenotypes of a host by excluding host factors, we analyzed two different gut microbiomes within the same individual mouse after replacing the gut microbiome with a new one to exclude the host factors. The gut microbiome of conventional C57BL/6 mice was randomly reestablished by feeding fecal samples from obese humans to the mice, and depleting their original gut microbiome with an antibiotic and antifungal treatment. Comparison of body weight changes before and 3 months after the replacement of the gut microbiome showed that the gut microbiome replacement affected the body weight gain in three different ways: positive, medium, and negative. The differences in body weight gain were associated with establishment of a different kind of gut microbiome in each of the mice. In addition, body weight gaining was negatively associated with the Firmicutes/Bacteroidetes ratio, which is consistent with previous recent findings. Thorough statistical analysis at low taxonomic levels showed that uncultured bacteria NR_074436.1, NR_144750.1, and NR_0421101.1 were positively associated with body weight gain, while Trichinella pseudospiralis and uncultured bacteria NR_024815.1 and NR_144616.1 were negatively associated. This work shows that replacement of the gut microbiome within the same individual provides an excellent opportunity for the purpose of gut microbiome analysis by excluding the host factors.

Chemical, Pharmacological and Computerized Molecular Analysis of Stem's Extracts of Bauhinia scandens L. Provide Insights into the Management of Diarrheal and Microbial Infections.

Bauhinia scandens L. (Family: Fabaceae) is commonly used to treat cholera, diarrhea, asthma, and diabetes disorder in integrative medicine. This study aimed to screen the presence of phytochemicals (preliminary and UPLC-QTOF-M.S. analysis) and to examine the pharmacological activities of Bauhinia scandens L. stems (MEBS) stem extracts. Besides, in silico study was also implemented to elucidate the binding affinity and drug capability of the selected phytochemicals. In vivo anti diarrheal activity was investigated in mice models. In vitro, antibacterial and antifungal properties of MEBS against several pathogenic strains were evaluated using the disc diffusion method. In addition, in silico study has been employed using Discovery studio 2020, UCFS Chimera, PyRx autodock vina, and online tools. In the anti-diarrheal investigation, MEBS showed a significant dose-dependent inhibition rate in all three methods. The antibacterial and antifungal screening showed a remarkable zone of inhibition, of the diameter 14-26 mm and 12-28 mm, by MEBS. The present study revealed that MEBS has remarkable anti-diarrheal potential and is highly effective in wide-spectrum bacterial and fungal strains. Moreover, the in silico study validated the results of biological screenings. To conclude, MEBS is presumed to be a good source in treating diarrhea, bacterial and fungal infections.

Polysubstituted Hexa-cata-hexabenzocoronenes: Syntheses, Characterization, and Their Potential as Semiconducting Materials in Transistor Applications.

A series of tetra- and octa-substituted hexa-cata-hexabenzocoronenes (cata-HBCs) were synthesized from tetraryl olefins via iodine- and iron chloride-catalyzed oxidative cyclodehydrogenation reactions. The substitutions on the periphery of the parent HBC serve to modify the photophysical properties, highest occupied molecular orbital-lowest unoccupied molecular orbital gaps, and thermal stabilities of the respective derivatives. The crystal structures were determined to display multiple twists in the framework, resulting in different packing motifs depending on the position, type, and number of functional groups on the hexabenzocoronene framework. Nearly perfect co-facial packing to marginally or extensively shifted co-facial stacks were obtained due to substitution. The single crystals of parent HBC were used to fabricate single-crystal field-effect transistors, from which the highest p-channel mobility of 0.51 cm2 V-1 s-1 was measured. Thin-film transistors of selected HBCs were also prepared, and 0.61 cm2 V-1 s-1 was obtained for MeHBC-2. These results attest the potential of these materials as semiconducting materials.

The synthesis, crystal structure and charge-transport properties of hexacene.

Acenes can be thought of as one-dimensional strips of graphene and they have the potential to be used in the next generation of electronic devices. However, because acenes larger than pentacene have been found to be unstable, it was generally accepted that they would not be particularly useful materials under normal conditions. Here, we show that, by using a physical vapour-transport method, platelet-shaped crystals of hexacene can be prepared from a monoketone precursor. These crystals are stable in the dark for a long period of time under ambient conditions. In the crystal, the molecules are arranged in herringbone arrays, quite similar to that observed for pentacene. A field-effect transistor made using a single crystal of hexacene displayed a hole mobility significantly higher than that of pentacene. This result suggests that it might be instructive to further explore the potential of other higher acenes.

High mobility n-channel single-crystal field-effect transistors based on 5,7,12,14-tetrachloro-6,13-diazapentacene.

Heteroaromatic oligomer 5,7,12,14-tetrachloro-6,13-diazapentacene (TCDAP) was characterized and assessed as n-channel material in field-effect transistor applications. A single-crystal transistor based on TCDAP as the channel material exhibits a very high electron mobility of 3.39 cm(2) V(-1) s(-1) and an on/off ratio of ∼1.08 × 10(4) respectively.

High performance single-crystal field-effect transistors based on twisted polyaromatic semiconductor pyreno[4,5-a]coronene.

A novel p-channel semiconductor pyreno[4,5-a]coronene has been synthesized and characterized. The highly fused π-conjugated framework has a twisted geometry with an excellent on-top cofacial π-π stacking in the crystal structure and with a centroid-to-centroid distance of 3.808 Å. Single-crystal field effect transistors based on the molecule exhibit a high mobility of ~0.89 cm(2) V(-1) s(-1) and an on/off ratio of ~6 × 10(4).