Unearthing New ccr Genes and Staphylococcal Cassette Chromosome Elements in Staphylococci Through Genome Mining.

Staphylococcal cassette chromosome mec (SCCmec) typing is crucial for investigating methicillin-resistant Staphylococcus aureus (MRSA), relying primarily on the combination of ccr and mec gene complexes. To date, 19 ccr genes and 10 ccr gene complexes have been identified, forming 15 SCCmec types. With the vast release of bacterial genome sequences, mining the database for novel ccr gene complexes and SCC/SCCmec elements could enhance MRSA epidemiological studies. In this study, we identified 12 novel ccr genes (6 ccrA, 3 ccrB, and 3 ccrC) through mining of the National Center for Biotechnology Information (NCBI) database, forming 12 novel ccr gene complexes and 10 novel SCC elements. Overexpression of 5 groups of novel Ccr recombinases (CcrA9B3, CcrA10B1, CcrC3, CcrC4, and CcrC5) in a mutant MRSA strain lacking the ccr gene and extrachromosomal circular intermediate (ciSCC) production significantly promoted ciSCC production, demonstrating their biological activity. This discovery provides an opportunity to advance MRSA epidemiological research and develop database-based bacterial typing methods.

Interguild fungal competition in litter and soil inversely modulate microbial necromass accumulation during Loess Plateau forest succession.

Microbial interactions determine ecosystem carbon (C) and nutrient cycling, yet it remains unclear how interguild fungal interactions modulate microbial residue contribution to soil C pools (SOC) during forest succession. Here, we present a region-wide investigation of the relative dominance of saprophytic versus symbiotic fungi in litter and soil compartments, exploring their linkages to soil microbial residue pools and potential drivers along a chronosequence of secondary Chinese pine (Pinus tabulaeformis) forests on the Loess Plateau. Despite minor changes in C and nitrogen (N) stocks in the litter or soil layers across successional stages, we found significantly lower soil phosphorus (P) stocks, higher ratios of soil C: N, soil N: P and soil C: P but lower ratios of litter C: N and litter C: P in old (>75 years) than young stands (<30 years). Pine stand development altered the saprotroph: symbiotroph ratios of fungal communities to favor the soil symbiotrophs versus the litter saprotrophs. The dominance of saprotrophs in litter is positively related to microbial necromass contribution to SOC, which is negatively related to the dominance of symbiotrophs in soils. Antagonistic interguild fungal competition in litter and soil layers, in conjunction with increased fungal but decreased bacterial necromass contribution to SOC, jointly contribute to unchanged total necromass contribution to SOC with stand development. The saprotroph: symbiotroph ratios in litter and soil layers are mainly driven by soil P stocks and stand parameters (e.g., stand age and slope), respectively, while substrate stoichiometries primarily regulate microbial necromass accumulation and fungal: bacterial necromass ratios. These results provide novel insights into how microbial interactions at local spatial scales modulate temporal changes in SOC pools, with management implications for mitigating regional land degradation.

Growth trends clustering: A novel method for detecting forest disturbances and extracting climate signals in tree rings.

Tree-ring widths contain valuable historical information related to both forest disturbances and climate variability and changes within forests. However, current methods are still unable to accurately distinguish between disturbances and climate signals in tree rings, especially in the case of climate anomalies. To address this issue, we developed a novel method, called Growth Trends Clustering (GTC) that uses the distribution characteristics of tree-ring widths within a stand to distinguish the effects of climate and other forest disturbances. GTC employed a Gaussian mixture model to fit the probability density distribution of annual ring-width index (RWI) in a stand. Discriminative criteria were established to cluster diverse sub-distributions from the Gaussian mixture model into categories of growth release, suppression, or normal trends. This approach allowed us to identify the occurrence, duration, and severity of forest disturbances based on percentage changes in the growth release or suppression categories of trees. And the effect of climate on tree growth was assessed according to the mean statistics of the growth normal categories. Using common forest disturbances such as defoliating insects and thinning as examples, we validated our method using tree-ring collections from six sites in British Columbia and Quebec, Canada. We found that the GTC method was superior to traditional time-series analysis methods (e.g., Radial Growth Averaging, Boundary Line, Absolute Increase, and Curve Intervention Detection) for detecting past forest disturbances and was able to significantly enhance climate signals. In summary, the GTC method presented in this study introduces a novel statistical approach for accurately distinguishing between forest disturbances and climate signals in tree rings. This is particularly important for understanding forest disturbance regimes under climate change and for developing future disturbance mitigation strategies.

Molecular dynamics study on the thermal properties of DGEBA/DETA/Ag/SWCNT-Ag composite materials.

CONTEXT: Traditional conductive adhesives based on epoxy resin system often encounter problems such as high brittleness and low heat resistance. Therefore, it is particularly important to improve the thermal and mechanical properties of the conductive adhesive. In this study, the effects of SWCNT-Ag and SWCNT fillers on the thermal properties of DGEBA/DETA/Ag conductive adhesive system were studied by using molecular dynamics to construct different cross-linking models. The final results show that the addition of SWCNT and SWCNT-Ag can significantly improve the thermal properties of the conductive adhesive. However, the nanosilver particles on the surface of SWCNT-Ag act as a bridge for the connection between SWCNT and Ag in the conductive adhesive. Therefore, SWCNT-Ag has a more positive impact on the thermal properties of DGEBA/DETA/Ag conductive adhesive system. METHODS: In this paper, the influence of SWCNT-Ag on the thermal properties of traditional DGEBA/DETA/Ag conductive adhesive system was studied by using Materials Studio software. The volume shrinkage, glass transition temperature, thermal expansion coefficient, and thermal conductivity of the material were calculated based on COMPASS force field. The thermal conductivity is calculated by using reverse non-equilibrium molecular dynamics method. Finally, it is found that SWCNT-Ag has a positive effect on the thermal properties of the conductive adhesive system by comparing several groups of calculation data.

Landscape of tumoral ecosystem for enhanced anti-PD-1 immunotherapy by gut Akkermansia muciniphila.

Gut Akkermansia muciniphila (Akk) has been implicated in impacting immunotherapy or oncogenesis. This study aims to dissect the Akk-associated tumor immune ecosystem (TIME) by single-cell profiling coupled with T cell receptor (TCR) sequencing. We adopted mouse cancer models under anti-PD-1 immunotherapy, combined with oral administration of three forms of Akk, including live Akk, pasteurized Akk (Akk-past), or its membrane protein Amuc_1100 (Amuc). We show that live Akk is most effective in activation of CD8 T cells by rescuing the exhausted type into cytotoxic subpopulations. Remarkably, only live Akk activates MHC-II-pDC pathways, downregulates CXCL3 in Bgn(+)Dcn(+) cancer-associated fibroblasts (CAFs), blunts crosstalk between Bgn(+)Dcn(+) CAFs and PD-L1(+) neutrophils by a CXCL3-PD-L1 axis, and further suppresses the crosstalk between PD-L1(+) neutrophils and CD8 T cells, leading to the rescue of exhausted CD8 T cells. Together, this comprehensive picture of the tumor ecosystem provides deeper insights into immune mechanisms associated with gut Akk-dependent anti-PD-1 immunotherapy.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

Effect of Organic, Nano, and Inorganic Zinc Sources on Growth Performance, Antioxidant Function, and Intestinal Health of Young Broilers.

The study aimed to determine the effects of different zinc sources on growth performance, antioxidant function, and intestinal health of broilers. In total, 240 Ross 308 male broilers with similar weight were randomly assigned to 4 treatments, including zinc sulfate, methionine zinc (Zn-Met), glycine zinc (Zn-Gly), and nano-zinc oxide (ZnO-NPs), with 80 mg zinc/kg diet supplementation. The experiment lasted for 21 days. Results showed dietary supplemental Zn-Gly and Zn-Met increased average daily gain during 1-14 days (P = 0.011), and Zn-Gly, Zn-Met, and ZnO-NP supplementation decreased the ratio of feed to gain during 1-21 days (P = 0.003) compared to zinc sulfate. ZnO-NPs supplementation tended to increase total SOD activity (P = 0.068) and had higher serum IgA content and lower MDA level than the other three groups (P < 0.05). Compared with zinc sulfate, Zn-Met and ZnO-NP supplementation decreased TNF-α mRNA expression (P = 0.048). However, serum biochemical indices, intestinal morphology, and mRNA expressions of tight junction proteins were not affected by different zinc sources (P > 0.05). A differential trend was observed in the beta diversity of bacterial communities among four groups (P = 0.082). The LEfSe analysis showed that bacterial genera Blautia, Ruminococcaceae, Clostridia, Anaerostipes, Eubacterium_ventriosum, Merdibacter, and Oscillospira were enriched in the ZnSO4 group, and the genera Eubacterium_hallii and Anaerotruncus were enriched in the Zn-Gly group. The genera UCG-009 and UCG010 were enriched in ZnO-NPs and Zn-Met groups, respectively. It should be stated dietary supplemental Zn-Met improved growth performance, ZnO-NPs promoted IgA production and reduced occurrences of oxidative stress and inflammation, and different zinc sources enriched different jejunal bacteria genera.

Targeting ZIP8 mediated ferroptosis as a novel strategy to protect against the retinal pigment epithelial degeneration.

The degeneration of retinal pigment epithelium (RPE) plays an important role in the development of age-related macular degeneration (AMD). However, the underlying mechanism remains elusive. In this study, we identified that ZIP8, a metal-ion transporter, plays a crucial role in the degeneration of RPE cells mediated by ferroptosis. ZIP8 was found to be upregulated in patients with AMD through transcriptome analysis. Upregulated ZIP8 was also observed in both oxidative-stressed RPE cells and AMD mouse model. Importantly, knockdown of ZIP8 significantly inhibited ferroptosis in RPE cells induced by sodium iodate-induced oxidative stress. Blocking ZIP8 with specific antibodies reversed RPE degeneration and restored retinal function, improving visual loss in a mouse model of NaIO3-induced. Interestingly, the modification of the N-glycosylation sites N40, N72 and N88, but not N273, was essential for the intracellular iron accumulation mediated by ZIP8, which further led to increased lipid peroxidation and RPE death. These findings highlight the critical role of ZIP8 in RPE ferroptosis and provide a potential target for the treatment of diseases associated with retinal degeneration, including AMD.

High preseason temperature variability drives convergence of xylem phenology in the Northern Hemisphere conifers.

Wood growth is key to understanding the feedback of forest ecosystems to the ongoing climate warming. An increase in spatial synchrony (i.e., coincident changes in distant populations) of spring phenology is one of the most prominent climate responses of forest trees. However, whether temperature variability contributes to an increase in the spatial synchrony of spring phenology and its underlying mechanisms remains largely unknown. Here, we analyzed an extensive dataset of xylem phenology observations of 20 conifer species from 75 sites over the Northern Hemisphere. Along the gradient of increase in temperature variability in the 75 sites, we observed a convergence in the onset of cell enlargement roughly toward the 5th of June, with a convergence in the onset of cell wall thickening toward the summer solstice. The increase in rainfall since the 5th of June is favorable for cell division and expansion, and as the most hours of sunlight are received around the summer solstice, it allows the optimization of carbon assimilation for cell wall thickening. Hence, the convergences can be considered as the result of matching xylem phenological activities to favorable conditions in regions with high temperature variability. Yet, forest trees relying on such consistent seasonal cues for xylem growth could constrain their ability to respond to climate warming, with consequences for the potential growing season length and, ultimately, forest productivity and survival in the future.

Partial asynchrony of coniferous forest carbon sources and sinks at the intra-annual time scale.

As major terrestrial carbon sinks, forests play an important role in mitigating climate change. The relationship between the seasonal uptake of carbon and its allocation to woody biomass remains poorly understood, leaving a significant gap in our capacity to predict carbon sequestration by forests. Here, we compare the intra-annual dynamics of carbon fluxes and wood formation across the Northern hemisphere, from carbon assimilation and the formation of non-structural carbon compounds to their incorporation in woody tissues. We show temporally coupled seasonal peaks of carbon assimilation (GPP) and wood cell differentiation, while the two processes are substantially decoupled during off-peak periods. Peaks of cambial activity occur substantially earlier compared to GPP, suggesting the buffer role of non-structural carbohydrates between the processes of carbon assimilation and allocation to wood. Our findings suggest that high-resolution seasonal data of ecosystem carbon fluxes, wood formation and the associated physiological processes may reduce uncertainties in carbon source-sink relationships at different spatial scales, from stand to ecosystem levels.