Oxymatrine inhibits melanoma development by modulating the immune microenvironment and targeting the MYC/PD-L1 pathway.

Oxymatrine, also known as ammothamnine or oxysophoridine, is a natural compound isolated from Sophora flavescens (in Chinese, Kushen), and many previous researchers have characterized its anti-inflammatory, anti-fibrotic and anti-tumor properties. However, the underlying anti-tumor immunological mechanism of oxymatrine remains elusive. In this study, we carried out experiments both in vitro and in vivo and investigated the anti-tumor effect of oxymatrine to inhibit the proliferation and migration of melanoma B16 cells, while promoting apoptosis. Oxymatrine upregulated CD4+ T, CD8+ T and NKT cells, downregulated Treg cells, promoted TNF-α secretion, and successfully modulated the immune microenvironment and ultimately suppressed melanoma development in subcutaneous tumor models established in mice. Evidence from network pharmacology and RNAseq suggested that possible targets of oxymatrine for melanoma treatment included PD-L1 and MYC. We observed oxymatrine inhibited PD-L1 and MYC expression in melanoma cells via qRT-PCR and western blotting analysis, and found MYC potentially regulated PD-L1 to mediate anti-tumor effects. These findings provide insight into the mechanism by which oxymatrine inhibits melanoma and enhances the anti-tumor immune effect. In summary, our study proposes a novel approach to suppress melanoma by targeting the MYC/PD-L1 pathway using oxymatrine, which may develop into a less toxic and more efficient anti-tumor agent for melanoma treatment.

Effect of femtosecond laser-assisted arcuate keratotomy versus toric intraocular lens implantation on correction of astigmatism in cataract surgery: a systematic review and meta-analysis.

PURPOSE: To compare the efficacy of femtosecond laser-assisted arcuate keratotomy (FSAK) combined with non-toric intraocular lens (IOL) implantation versus Toric IOL (TIOL) implantation in correcting corneal astigmatism in cataract patients. METHODS: Relevant literature was searched in databases including PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and SinoMed. Data from the included studies were extracted. A meta-analysis was conducted to compare the correction performance of FSAK combined with non-toric IOL implantation and TIOL implantation using postoperative refractive astigmatism, correction index, and uncorrected distance visual acuity (UDVA) outcomes. Publication bias assessment and sensitivity analysis were also performed. RESULTS: Five comparative studies were ultimately included in the meta-analysis. The TIOL group had smaller postoperative refractive astigmatism and a greater correction index compared to the FSAK group. The mean differences in postoperative refractive astigmatism and correction index between the two groups were - 0.19D (95% CI = 0.12 to 0.26, P < 0.01, I2 = 7%) and - 0.09 (95% CI = - 0.18 to 0.00, P = 0.04, I2 = 0%), respectively. We found no statistically significant difference in UDVA between the two groups (95% CI = - 0.01 to 0.11, P = 0.09, I2 = 70%). CONCLUSIONS: FSAK combined with non-toric IOL implantation was found to be less effective than TIOL implantation in correcting preoperative corneal astigmatism in cataract patients. The difference in the effectiveness of astigmatism correction between the two surgical methods seems to diminish, as the degree of preoperative corneal astigmatism decreases.

Specific mating behavior of Malayan pangolin (Manis javanica) in captivity.

Pangolin is a mysterious animal in the Family Pholidota, Mammalia. Malayan pangolin (Manis javanica) is one of eight existing species and is listed in Manis. With the number of wild pangolins (Manis spp.) rapidly decreasing, captive breeding has become an important way to protect them from extinction. The research on mating behavior of pangolins is an important content to understand its reproductive characteristics and develop breeding management. From 2016 to 2022, a total of 360 mating events were observed in six males and 24 females through closed circuit television (CCTV) surveillance. The results show that males do not engage in complex courtship behavior before mating. In addition, we found that male pangolins adopted a ventrolateral mating position. Once males selected the side (left/right) of the female pangolin from which to approach to mate, they usually remained on the same side for subsequent mating, suggesting that male pangolins may have a preference in mating position. Finally, all mating events were observed at 1.72 ± 1.47 (n = 83, Mean ± SD) days after cohabitation and adjustment time before mating (from the male touching the female to intromission) took 4.98 ± 3.86 mins (n = 323). During mating, males hugged females and remained still for 47.37 ± 10.08 seconds (n = 323), which is the ejaculation and post-ejaculation quiescent time. Remarkably, we observed for the first time two peak mating times, 19:00 to 22:00 and 1:00 to 3:00, suggesting that they may have a preference for mating times. This study provides new insight into the mating behavior of M. javanica and contributes to the development of scientific conservation measures to improve the reproductive capacity of M. javanica.

Genome-Wide Analysis of the MYB-Related Transcription Factor Family in Pepper and Functional Studies of CaMYB37 Involvement in Capsaicin Biosynthesis.

Chili pepper is an important economic vegetable worldwide. MYB family gene members play an important role in the metabolic processes in plant growth and development. In this study, 103 pepper MYB-related members were identified and grouped into nine subfamilies according to phylogenetic relationships. Additionally, a total of 80, 20, and 37 collinear gene pairs were identified between pepper and tomato, pepper and Arabidopsis, and tomato and Arabidopsis, respectively. We performed promoter cis-element analysis and showed that CaMYB-related members may be involved in multiple biological processes such as growth and development, secondary metabolism, and circadian rhythm regulation. Expression pattern analysis indicated that CaMYB37 is significantly more enriched in fruit placenta, suggesting that this gene may be involved in capsaicin biosynthesis. Through VIGS, we confirmed that CaMYB37 is critical for the biosynthesis of capsaicin in placenta. Our subcellular localization studies revealed that CaMYB37 localized in the nucleus. On the basis of yeast one-hybrid and dual-luciferase reporter assays, we found that CaMYB37 directly binds to the promoter of capsaicin biosynthesis gene AT3 and activates its transcription, thereby regulating capsaicin biosynthesis. In summary, we systematically identified members of the CaMYB-related family, predicted their possible biological functions, and revealed that CaMYB37 is critical for the transcriptional regulation of capsaicin biosynthesis. This work provides a foundation for further studies of the CaMYB-related family in pepper growth and development.

Wild and Captive Environments Drive the Convergence of Gut Microbiota and Impact Health in Threatened Equids.

To explore how the living environment influences the establishment of gut microbiota in different species, as well as the extent to which changes in the living environment caused by captive breeding affect wildlife's gut microbiota and health, we used 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing to compare the gut microbiome of two species of threatened equids, the Przewalski's Horse and the Asian wild ass, in the wild and captivity. The results revealed that different species of Equidae living in the same environment showed remarkable convergence of gut microflora. At the same time, captive populations exhibited significantly "unhealthy" microbiota, such as low Alpha diversity, high levels of potentially pathogenic bacteria and biomarkers of physical or psychological disease, and enrichment of microbial functions associated with exogenous exposure and susceptibility, implying that the artificial environment created by captivity may adversely impact the health of wildlife to some extent. Our findings demonstrate the importance of the environmental factors for the establishment of gut microbiota and host health and provide new insights into the conservation of wildlife in captivity from the perspective of the microbiome.

Comparative Analysis of Microbiome Metagenomics in Reintroduced Wild Horses and Resident Asiatic Wild Asses in the Gobi Desert Steppe.

The gut microbiome offers important ecological benefits to the host; however, our understanding of the functional microbiome in relation to wildlife adaptation, especially for translocated endangered species, is lagging. In this study, we adopted a comparative metagenomics approach to test whether the microbiome diverges for translocated and resident species with different adaptive potentials. The composition and function of the microbiome of sympatric Przewalski's horses and Asiatic wild asses in desert steppe were compared for the first time using the metagenomic shotgun sequencing approach. We identified a significant difference in microbiome composition regarding the microbes present and their relative abundances, while the diversity of microbe species was similar. Furthermore, the functional profile seemed to converge between the two hosts, with genes related to core metabolism function tending to be more abundant in wild asses. Our results indicate that sympatric wild equids differ in their microbial composition while harboring a stable microbial functional core, which may enable them to survive in challenging habitats. A higher abundance of beneficial taxa, such as Akkermansia, and genes related to metabolism pathways and enzymes, such as lignin degradation, may contribute to more diverse diet choices and larger home ranges of wild asses.

Networked control strategy of dual linear switched reluctance motors based time delay tracking system.

To reduce the influence of time delay on the tracking performance of a direct-drive motion control system, this paper concentrates on stability analysis and cooperative position tracking control issues for the dual linear switched reluctance motors (LSRMs) system with network-induced time delays. The closed-loop network control system (NCS) is constructed by modeling random and bounded network-induced time delays existing in forward and feedback channels as a discrete-time Markov chain. Incremental time delay information is introduced in Lyapunov functional analysis to satisfy the high-precision movement of master and secondary motors and improve the system control performance. The time delay compensation method is proposed to compensate for the damage to the networked control system caused by random delay. With Lyapunov stability theory and LMI are applied, stability and stabilization conditions with less computational complexity and low conservatism are obtained based on incremental time delay information insertion. Finally, the numerical simulation and the experimental platform of the motor control system are built. Simulation and experiment results demonstrate that the networked control strategy can compensate the negative impact of delay on the tracking performance of LSRMs based motion control system.

Lupus gut microbiota transplants cause autoimmunity and inflammation.

BACKGROUND: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16 s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free (GF) mice. RESULTS: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to GF mice caused GF mice to develop a series of lupus-like phenotypic features, including increased serum autoimmune antibodies, imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. CONCLUSIONS: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

Dissipation of antibiotic resistance genes in manure-amended agricultural soil.

Soil antibiotic resistance due to animal manure application is of great concern in recent years. Little is known about the fate of antibiotic resistance genes (ARGs) in agricultural soils associated with long-term manure application. Here we used soil microcosms to investigate the dissipation of ARGs and the change of bacterial community in agricultural soil originated from a vegetable field which had received 24 years' swine manure application. Soil microcosms were conducted at different soil moistures and with or without biochar over a testing period of two years in lab. Results showed that continuous manure application induced an accumulation of ARGs in soil, wherein the dissipation of ARGs differed from those in non-manure amended soil. ARGs persisted in soils at least two years, although their abundance declined gradually. Meanwhile, soil moisture and biochar had significant impact on the fate of ARGs. ARGs dissipated faster in soil with higher moisture. Biochar amendment contributed to the maintenance of bacterial diversity. Within the two years of simulation experiment, biochar enhanced soil ARG retention as they dissipated slowly in the soil amended with biochar. Succession of microbial community may have sustained the transfer and resilience of ARGs. This study provides insight into the dissipation of antibiotic resistance genes in manure-applied agricultural soil.

Silk Sericin Activates Mild Immune Response and Increases Antibody Production.

To clarify whether nanoparticles of silk sericin (SS) and silk fibroin (SF) can induce inflammation and immune responses, we analyzed splenocyte proliferation, apoptosis and cytokine release to identify the effects of SS and SF on mouse splenocytes in vitro. We implanted mice with SS and SF through intraperitoneal, intramuscular, and subcutaneous routes to evaluate the innate and adaptive immune response to SS and SF in vivo. Cytokines in the serum and spleen were analyzed by Luminex and antibody array. Antigen-specific antibodies were evaluated by enzyme-linked immunosorbent assay (ELISA) at week 1 and 5 after implantation. Distinct cell populations in the spleen and bone marrow were analyzed by flow cytometry. SS suppressed the proliferation of splenocytes and CD11b+CD27- NK cells, induced splenocyte apoptosis, and increased interleukin-1 ß (IL-1 ß) and tumor necrosis factor-α (TNF-α) in the culture supernatant. SF suppressed splenocyte proliferation, induced splenocyte apoptosis, and increased the titer of TNF-α in culture supernatants. At both week 1 and 5 after implantation with SS, mouse serum interleukin-1 α (IL-1 α) and keratinocyte chemoattractant (KC) were decreased, SS-specific antibody was increased, the proportion of bone marrow CD4+ T cells was increased, and the proportion of splenic neutrophils was decreased. At week 5 after subcutaneous implantation with SF, mouse serum IL-1α, and splenic IL-6, TIMP-1, IL-4, MCP-1, IFN-γ, TCA-3, TNF-α, and IL-17 were decreased. SS was able to induce a mild immune response, as evidenced by CD4+ T cell activation, splenocyte apoptosis, and antigen-specific antibody secretion. Comparatively, SF had low immunogenicity and anti-inflammatory properties.

Microbial diversity and antibiotic resistome in swine farm environments.

Swine feedlots are recognized as a reservoir of antibiotic resistance genes (ARGs). However, the microbiome and antibiotic resistome in swine wastewater and its impact on receiving environments remain to be further explored by culture independent metagenomics. We investigated the microbial diversity of swine wastewater and the receiving environments in three swine farms by 16S rRNA gene sequencing. Metagenomic sequencing was utilized to further study the antibiotic resistome in the different depths of soils in vegetable fields, which had been fertilized with swine wastewater for at least 24 years. The 16S rRNA gene sequencing showed that the microbiome of the well water, fishpond, vegetables and the field soils was affected by the respective swine farms. Significant positive correlations were found between 20 ARGs and 41 genus of bacteria across all environmental samples. The metagenomic sequencing showed that a total of 79 types of ARGs were found in soil cores (at depth of 0-20 cm, 20-40 cm and 40-70 cm) and the irrigation water (swine wastewater). Antibiotics were detected in vertical soil profiles and wastewater. Compared with the vegetable fields without animal manure application, the soils irrigated with swine wastewater harbored higher diversity of ARGs and contained higher concentrations of antibiotics. Co-occurrence of integron-related scaffolds was found in different depths of soil cores and the swine wastewater. The results suggest that environmental microbiome was changed under the impact of swine farms, and long-term manure/wastewater application have resulted in the accumulation of ARGs in deeper soils Prudent use of antibiotics and reasonable management of animal wastes in livestock feedlots should therefore be considered to reduce the dissemination of antibiotic resistance to the environment.

Fate of veterinary antibiotics during animal manure composting.

Antibiotics are widely used in animals for disease treatment and prevention. After use, these antibiotics end up in manure. Here we investigated the fate of veterinary antibiotics in animal manure during composting and their residues in manure-applied soils. The results showed that 64.7% of the detected veterinary antibiotics were removed after composting for 171 days, which mainly occurred at the thermophilic phase in the second week, followed by a long stable stage with limited variations. The removal rates for lincomycin, trimethoprim and the macrolides during the composting were >89.7%, while those for the sulfonamides, tetracyclines and fluoroquinolones were less than <63.7%. The dissipation of antibiotics during the composting was related to the change of compost physicochemical properties, especially moisture and C/N ratio. The application of compost products with antibiotic residues could still lead to soil contamination, which may pose risks of resistance selection to the soil ecosystem.

Occurrence, fate and mass loadings of antibiotics in two swine wastewater treatment systems.

Antibiotics are widely applied in livestock industry to prevent or treat animal diseases. However, those antibiotics are poorly metabolized in livestock animals, most of them being excreted via feces or urine. Hence we need to understand the removal of antibiotics in swine farm wastewater treatment systems. This study investigated occurrence and fate of various antibiotics in two full-scale swine farm wastewater treatment systems (Farm A: anaerobic digester-A2/O-lagoon; Farm B: upflow anaerobic sludge blanket (UASB)-(A/O)2-lagoon). The results showed the presence of 25 antibiotics out of 40 target antibiotics in the wastewater and sludge samples from the two farms. In Farm A, sulfamonomethoxine, sulfachlorpyridazine, oxytetracycline and lincomycin were predominant in the influent with concentrations up to 166 ±â€¯3.64 µg/L, while in the dewatered sludge chlortetracycline, oxytetracycline, tetracycline and norfloxacin were the predominant target compounds with concentrations up to 29.2 ±â€¯3.74 µg/g. In Farm B, high concentrations (up to 3630 ±â€¯1040 µg/L) of sulfachlorpyridazine, sulfamonomethoxine and lincomycin were detected in the influent, and the predominant target antibiotics detected in the dewater sludge were similar to those in Farm A, with concentrations up to 28.6 ±â€¯0.592 µg/g. The aqueous removal rates for the total antibiotics were >99.0% in the wastewater treatment plants of both farms. Among a series of treatment units, the anaerobic digester in Farm A and UASB in Farm B made a significant contribution to the elimination of the target antibiotics from the animal wastewater. The daily mass loadings of total antibiotics in the manure, influent, dewatered sludge and effluent were 17.1, 28.0, 2.53, and 0.0730 g/d for Farm A and 24.5, 354, 3.17, and 0.293 g/d for Farm B. The full-scale swine wastewater treatment facilities could effectively remove antibiotics from swine wastewater, but the dewatered sludge needs to be further treated before disposal on land.