Therapeutic Mechanisms of Berberine to Improve the Intestinal Barrier Function via Modulating Gut Microbiota, TLR4/NF-κ B/MTORC Pathway and Autophagy in Cats

BackgroundInflammatory bowel disease (IBD), a disease that seriously harms human and animal health, has attracted many researchers’ attention because of its complexity and difficulty in treatment. Most research has involved rats and dogs, and very little was cats. We should know that gut microbiota varies significantly from animal to animal. Traditional Chinese Medicine and its monomer component have many advantages compared with antibiotics used in pet clinics. Numerous studies have shown berberine (berberine hydrochloride) therapeutic value for IBD. However, the specific mechanism remains to consider.ResultsWe assessed gut pathology and analyzed fecal bacterial composition using Histological staining and 16S rRNA sequence. Dioctyl sodium sulfosuccinate (DSS) administration destroyed intestinal mucosal structure and changed the diversity of intestinal flora relative to control. RT-PCR and western blot confirmed specific molecular mechanisms that trigger acute inflammation and intestinal mucosal barrier function disruption after DSS treatment. And autophagy inhibition is typical pathogenesis of IBD. Interestingly, berberine ameliorates inflammation during the development of the intestinal by modulating the toll-like receptors 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and activating autophagy. Berberine significantly reduces tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1β expression in cats’ serum. Enhancing the antioxidant effect of IBD cats is one of the protective mechanisms of berberine. We demonstrated that berberine repairs intestinal barrier function by activating the mammalian target of rapamycin (mTOR) complex (MTORC), which inhibits autophagy.ConclusionBerberine can restore intestinal microbiota homeostasis and regulate the TLR4/NF-κB pathway, thereby controlling inflammatory responses. We propose a novel mechanism of berberine therapy for IBD, namely, berberine therapy can simultaneously activate MTORC and autophagy to restore intestinal mucosal barrier function in cats, which should be further studied to shed light on berberine to IBD

A highly effective ferritin-based divalent nanoparticle vaccine shields Syrian hamsters against lethal Nipah virus

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges

Energy‐efficient train timetabling for a medium‐speed maglev line considering propulsion and suspension energy consumption

Abstract This paper addresses the energy‐efficient train timetabling problem for MSM systems, where both propulsion and suspension energy consumption are considered. The timetable design problem is modelled as a bi‐level model for a complete two‐way MSM line. The upper level determines the train departure time at the first station, which makes train operations more convenient for passengers. The lower level uses an empirical description of the train energy consumption as a function of segment running times, and an energy‐efficient timetable optimization model is built. In doing so, all the services in both directions along a certain planning horizon are considered while attending to a known passengers’ demand. Moreover, the convenience of considering energy consumption as part of a broad objective function that includes other relevant costs is pointed out. Then, a unified sequential solution algorithm is developed for an efficient and accurate solution of the bi‐level model. Experiments show that the proposed framework can generate a holographic timetable of energy‐efficient MSM containing multi‐dimensional variables such as time, space, velocity, and electrical quantities

<i>Ganoderma lucidum</i> Ethanol Extraction Promotes Dextran Sulphate Sodium Induced Colitis Recovery and Modulation in Microbiota

Popular edible mushrooms Ganoderma lucidum and Gloeostereum incarnatum can improve physical health as a prebiotic and positively alter intestinal microbiota. Our research investigated the prebiotic effects of Ganoderma lucidum and Gloeostereum incarnatum on colon inflammation through G. lucidum water extraction polysaccharides (GLP), G. incarnatum water extraction polysaccharides (GIP), G. lucidum ethanol extraction (GLE), and G. incarnatum ethanol extraction (GIE) administered in mice after 7 days of dextran sulphate sodium (DSS) administration. Among the extracts, GLE showed reduced mortality rates, prevention of weight loss, mitigated colon length shortening, and decreased disease activity indices and histological scores. COX-2, MPO, and iNOS activities and the inflammatory cytokines’ expressions were determined to demonstrate the inhibition inflammation by GLE. Meanwhile, GLE upregulated the levels of MUC2, ZO-1, claudin-3, and occluding to protect the intestinal barrier. Furthermore, GLE modulated the composition of gut microbiota disturbed by DSS, as it decreased the abundance of Bacteroides, Staphylococcus, and Escherichia_Shigella, and increased Turicibacter and Bifidobacterium. Through cell experiment, GLE had a positive influence on adherens junction, tight junction, and TRAF6/MyD88/NF-κB signaling pathways. In conclusion, GLE supplementation promotes DSS-induced colitis recovery by regulating inflammatory cytokines, preserving the intestinal mucosal barrier, positively modulating microbiota changes, and positively influences immune response in TRAF6/MyD88/NF-κB signaling pathways

Role of dietary edible mushrooms in the modulation of gut microbiota

Edible mushrooms as valuable health foods have potential beneficial effects, and these beneficial activities are connected with the modulation of gut microbiota. In this review, we discuss the regulation of gut microbiota by edible mushroom. Ganoderma lucidum increases Bacteroides/Firmicutes ratio, and promote the growth of anti-inflammatory and short-chain fatty acid (SCFA) producing bacteria. Hericium erinaceus maintains intestinal barrier integrity, and increases the diversity and richness of gut microbiota. Lentinula edodes act as a prebiotic, increases SCFA-producing bacteria and regulates the proportion of Bacteroides/Firmicutes. Grifola frondosa increases the ratio of Bacteroides/Firmicutes, the growth of anti-inflammatory and SCFA-producing bacteria. We also discuss the effects of different edible mushrooms on the gut microbiota in different diseases and introduce a perspective application of mushrooms as adjuvant therapies for modulating gut microbiota in clinical treatments. Summarized, the statement in modulation of gut microbiota composition by edible mushrooms will provide a new perspective for further research

Sitsen: Passive sitting posture sensing based on wireless devices

Physical health diseases caused by wrong sitting postures are becoming increasingly serious and widespread, especially for sedentary students and workers. Existing video-based approaches and sensor-based approaches can achieve high accuracy, while they have limitations like breaching privacy and relying on specific sensor devices. In this work, we propose Sitsen, a non-contact wireless-based sitting posture recognition system, just using radio frequency signals alone, which neither compromises the privacy nor requires using various specific sensors. We demonstrate that Sitsen can successfully recognize five habitual sitting postures with just one lightweight and low-cost radio frequency identification tag. The intuition is that different postures induce different phase variations. Due to the received phase readings are corrupted by the environmental noise and hardware imperfection, we employ series of signal processing schemes to obtain clean phase readings. Using the sliding window approach to extract effective features of the measured phase sequences and employing an appropriate machine learning algorithm, Sitsen can achieve robust and high performance. Extensive experiments are conducted in an office with 10 volunteers. The result shows that our system can recognize different sitting postures with an average accuracy of 97.02%

Genesis of the Shirengou gold deposit, northern North China Craton, based on zircon U-Pb, fluid inclusion, sulfide compositional and S isotope data

The newly discovered vein-type Shirengou gold deposit on the northern edge of the North China Craton contains at least 8.69 tons of Au at an average grade of 9.80 g/t. Six auriferous quartz veins have been identified within Upper Jurassic rhyolitic breccia-bearing crystal-lithic tuff, and they follow NW-trending secondary faults. Gold mineralization was closely related to silicification, with pyrite as the predominant ore mineral. Four mineralization stages can be discerned, involving Stage I milky quartz, Stage II quartz-pyrite, Stage III gray quartz-polymetallic sulfide, and Stage IV quartz-calcite ± pyrite. Zircon U[sbnd]Pb dating of a pre-ore porphyryritic rhyolite dike sets an upper age limit on the gold mineralization of ~131.1 Ma. Two-phase and single-phase aqueous inclusions were observed in quartz related to all four mineralization stages. From Stage I to Stage IV, the fluid inclusion homogenization temperatures decrease from respectively 257–340 °C to 230–277 °C, 201–250 °C and 161–200 °C, with corresponding salinities of 3.39–9.21, 2.24–8.00, 1.22–7.59, and 0.18–3.55 wt% NaCl equivalent, respectively. Thus, the ore-forming fluid can be described as moderate-high temperature, moderate-low salinity H2O-NaCl fluids. The δ34S values of sulfides vary from 0.0 to 5.3 ‰, indicating that the S was derived primarily from magmatic source(s), with some contribution from the metamorphic rocks of the surrounding Jianping Group. In-situ LA-ICP-MS trace element analysis of sulfides, together with our new age data, suggest that the ore-forming fluid was initially of Early Cretaceous magmatic-hydrothermal origin, and subsequently modified by interaction with the wall rocks of the Jianping Group, extracting the ore-forming metals from these rocks into the fluids.</p

Both chimpanzee adenovirus-vectored and DNA vaccines induced long-term immunity against Nipah virus infection

Abstract Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus that poses a severe threat to humans due to its high morbidity and the lack of viable countermeasures. Vaccines are the most crucial defense against NiV infections. Here, a recombinant chimpanzee adenovirus-based vaccine (AdC68-G) and a DNA vaccine (DNA-G) were developed by expressing the codon-optimized full-length glycoprotein (G) of NiV. Strong and sustained neutralizing antibody production, accompanied by an effective T-cell response, was induced in BALB/c mice by intranasal or intramuscular administration of one or two doses of AdC68-G, as well as by priming with DNA-G and boosting with intramuscularly administered AdC68-G. Importantly, the neutralizing antibody titers were maintained for up to 68 weeks in the mice that received intramuscularly administered AdC68-G and the prime DNA-G/boost AdC68-G regimen, without a significant decline. Additionally, Syrian golden hamsters immunized with AdC68-G and DNA-G via homologous or heterologous prime/boost immunization were completely protected against a lethal NiV virus challenge, without any apparent weight loss, clinical signs, or pathological tissue damage. There was a significant reduction in but not a complete absence of the viral load and number of infectious particles in the lungs and spleen tissue following NiV challenge. These findings suggest that the AdC68-G and DNA-G vaccines against NiV infection are promising candidates for further development

Mated-Atom Nanozymes with Efficient Assisted NAD⁺ Replenishment for Skin Regeneration

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km‑NADH (16.11 μM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration