Genetic evidence for causal effects of leukocyte counts on risk for rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation of leukocytes and inflammatory mediators within the synovial tissue. Leukocyte counts are proposed to play a role in the pathogenesis of RA. However, the causality remains unclear. To investigate the causal relationship between various leukocytes and RA by implementing two-sample univariable Mendelian Randomization (MR) and multivariable MR. MR analysis was performed using respective genome-wide association study (GWAS) summary statistics for the exposure traits (eosinophil counts, neutrophil counts, lymphocyte counts, monocyte counts, basophil counts, and white blood cell counts) and outcome trait (RA). Summary statistics for leukocytes were extracted from the Blood Cell Consortium meta-analysis and INTERVAL studies. Public GWAS information for RA included 14,361 cases and 43,923 controls. Inverse variance weighted, weighted median, MR-Egger regression, MR pleiotropy residual sum and outlier, and multivariable MR analyses were performed in MR analysis. Univariable MR found elevated eosinophil counts (OR 1.580, 95% CI 1.389-2.681, p = 1.30 × 10-7) significantly increased the risk of RA. Multivariable MR further confirmed that eosinophil counts were a risk factor for RA. Increased eosinophils were associated with higher risk of RA. Further elucidations of the causality and mechanisms underlying are likely to identify feasible interventions to promote RA prevention.

[Effects of Simulated Acid Rain and Nitrogen Deposition on Soil Bacterial Community Structure and Diversity in the Masson Pine Forest].

By analyzing the effects of acid rain and nitrogen deposition on the structure and diversity of soil bacterial communities, the response mechanism of Masson pine forests to environmental stress was investigated, providing a theoretical reference basis for resource management and conservation in Tianmu Mountain National Nature Reserve. Four treatments of the simulated acid rain and nitrogen deposition were set up in 2017 to 2021 in Tianmu Mountain National Nature Reserve (pH value of 5.5 and 0 kg·(hm2·a)-1, CK; pH value of 4.5 and 30 kg·(hm2·a)-1, T1; pH value of 3.5 and 60 kg·(hm2·a)-1, T2; pH value of 2.5 and 120 kg·(hm2·a)-1, T3). The differences in soil bacterial community composition and structure among treatments and their influencing factors were analyzed by collecting soils from four treatments, using the Illumina MiSeq PE300 second-generation high-throughput sequencing platform. The results showed that acid rain and nitrogen deposition significantly reduced soil bacterial α-diversity (P<0.05) in a Masson pine forest. The Masson pine forest soils consisted of 36 phylum groups of mycota, with Acidobacteria, Proteobacteria, Actinobacteria, and Chloroflexi as the main bacterial phyla (relative abundance>1%) in the Masson pine forest soils. Flavobacterium, Nitrospira, Haliangium, Candidatus_Koribacter, Bryobacter, Occallatibacter, Acidipla, Singulisphaera, Pajaroellobacter, and Acidothermus, which showed significant changes in relative abundance under the four treatments, could be used as indicator species for changes in soil bacterial communities under acid rain and nitrogen deposition stress. Soil pH and total nitrogen were influential factors in the diversity of soil bacterial communities. As a result, acid rain and nitrogen deposition increased the potential ecological risk, and the loss of microbial diversity will change the ecosystem function as well as reduce the stability of the ecosystem.

Nocardia seriolae mediates liver granulomatous chronic inflammation in Micropterus salmoides through pyroptosis.

Granulomatous diseases caused by Nocardia seriously endanger the health of cultured fish. These bacteria are widely distributed, but prevention and treatment methods are very limited. Chronic granulomatous inflammation is an important pathological feature of Nocardia infection. However, the molecular mechanisms of granuloma formation and chronic inflammation are still unclear. Constructing a granuloma infection model of Nocardia is the key to exploring the pathogenesis of the disease. In this study, we established a granuloma model in the liver of largemouth bass (Micropterus salmoides) and assessed the infection process of Nocardia seriolae at different concentrations by analysing relevant pathological features. By measuring the expression of pro-inflammatory cytokines, transcription factors and a pyroptosis-related protein, we revealed the close relationship between pyroptosis and chronic inflammation of granulomas. We further analysed the immunofluorescence results and the expression of pyroptosis-related protein of macrophage infected by N. seriolae and found that N. seriolae infection induced macrophage pyroptosis in vitro. These results were proved by flow cytometry analysis of infection experiment in vivo. Our results indicated that the pyroptosis effect may be the key to inducing chronic inflammation in the fish liver and further mediating granuloma formation. In this study, we explored the molecular mechanism underlying chronic inflammation of granulomas and developed research ideas for understanding the occurrence and development of granulomatous diseases in fish.

Silicon nanowires decorated with platinum nanoparticles were applied for photothermal-enhanced sonodynamic therapy.

Sonodynamic therapy (SDT) triggered by ultrasound (US) can overcome pivotal limitations of photo-therapy owing to its high depth-penetration and low phototoxicity. However, there is still a need to develop more efficient sonosensitizes to enhance the therapy efficiency. Methods: In this study, Pt nanoparticles (Pt NPs) are reduced on silicon nanowires (SiNWs) by in situ reduction to prepare Si-Pt nanocomposites (Si-Pt NCs). Results: Si-Pt NCs can produce reactive oxygen radicals (ROS) under ultrasound (US) irradiation, which have sonodynamic therapy (SDT) effect. Meanwhile, Si-Pt NCs can convert excess hydrogen peroxide (H2O2) into ROS in the tumor microenvironment, which endow strong chemodynamic therapy (CDT) effect. Taking the advantages of the mesoporous structure of SiNWs, the SDT and CDT effects of Si-Pt NCs are stronger than those of the pure Pt NPs and SiNWs. Besides, the mild photothermal effect of Si-Pt NCs further improves the SDT&CDT activity and realizes the combined cancer therapy. Conclusion: The developed Si-Pt NCs with the ability of photothermal enhanced SDT/CDT combined therapy play a momentous role in the novel cancer treatment.

Biodegradable Fe-Doped Vanadium Disulfide Theranostic Nanosheets for Enhanced Sonodynamic/Chemodynamic Therapy.

Sonodynamic therapy (SDT), a noninvasive and highly penetrating tumor therapy, which employs ultrasound and sonosensitizers, has attracted extensive attention because of its ability to treat deep tumors. However, many current sonosensitizers have drawbacks in phototoxicity and limited sonodynamic effect. Herein, as a novel kind of sonosensitizer, iron-doped vanadium disulfide nanosheets (Fe-VS2 NSs) are constructed by a high-temperature organic-solution method and further modified with polyethylene glycol (PEG). With Fe doping, the sonodynamic effect of Fe-VS2 NSs is greatly enhanced, owing to the prolonged electron-hole recombination time. Simultaneously, such Fe-VS2-PEG NSs as a good Fenton agent can be utilized for chemodynamic therapy (CDT) by using the endogenous H2O2 in the tumor microenvironment (TME). Moreover, the multivalent Fe and V elements in the Fe-VS2 NSs can consume glutathione to amplify the reactive oxygen species-induced oxidative stress by SDT and CDT. Utilizing the strong near-infrared optical absorbance and enhanced magnetic resonance (MR) contrast by Fe-VS2 NSs, photoacoustic/MR biomodal imaging reveals a high accumulation of Fe-VS2-PEG NSs in the tumor. The great tumor suppression effect is then achieved by the in vivo combined CDT&SDT treatment. Importantly, most of the injected Fe-VS2-PEG NSs can be gradually decomposed and excreted from the mice, making them as safe sonosensitizers for cancer treatment. Our work highlights a new type of biodegradable sonosensitizer with the ability of regulating TME for applications in cancer theranostics.

Ultrasmall Iron-Doped Titanium Oxide Nanodots for Enhanced Sonodynamic and Chemodynamic Cancer Therapy.

Sonodynamic therapy (SDT), which can generate reactive oxygen species (ROS) based on sonosensitizers under ultrasound (US) to kill tumor cells, has emerged as a noninvasive therapeutic modality with high tissue-penetration depth. Herein, ultrasmall iron-doped titanium oxide nanodots (Fe-TiO2 NDs) are synthesized via a thermal decomposition strategy as a type of sonosensitizers to enhance SDT. Interestingly, the Fe doping in this system appears to be crucial in not only enhancing the US-triggered ROS generation of those NDs but also offering NDs the Fenton-catalytic function to generate ROS from tumor endogenous H2O2 for chemodynamic therapy (CDT). After polyethylene glycol (PEG) modification, Fe-TiO2-PEG NDs demonstrate good physiological stability and biocompatibility. With efficient tumor retention after intravenous injection as revealed by in vivo magnetic resonance (MR) and fluorescent imaging, our Fe-TiO2 NDs demonstrate much better in vivo therapeutic performance than commercial TiO2 nanoparticles owing to the combination of CDT and SDT. Moreover, most of those ultrasmall Fe-TiO2 NDs can be effectively excreted within one month, rendering no obvious long-term toxicity to the treated mice. Our work thus presents a type of multifunctional sonosensitizer for highly efficient cancer treatment via simply doping TiO2 nanostructures with metal ions.

Preparation of TiH1.924 nanodots by liquid-phase exfoliation for enhanced sonodynamic cancer therapy.

Metal hydrides have been rarely used in biomedicine. Herein, we fabricate titanium hydride (TiH1.924) nanodots from its powder form via the liquid-phase exfoliation, and apply these metal hydride nanodots for effective cancer treatment. The liquid-phase exfoliation is an effective method to synthesize these metal hydride nanomaterials, and its efficiency is determined by the matching of surface energy between the solvent and the metal hydrides. The obtained TiH1.924 nanodots can produce reactive oxygen species (ROS) under ultrasound, presenting a highly efficient sono-sensitizing effect. Meanwhile, TiH1.924 nanodots with strong near-infrared (NIR) absorbance can serve as a robust photothermal agent. By using the mild photothermal effect to enhance intra-tumoral blood flow and improve tumor oxygenation, a remarkable synergistic therapeutic effect is achieved in the combined photothermal-sonodynamic therapy. Importantly, most of these TiH1.924 nanodots can be cleared out from the body. This work presents the promises of functional metal hydride nanomaterials for biomedical applications.

[Effects of Simulated Acid Rain on Soil Fungi Diversity in the Transition Zone of Moso Bamboo and Broadleaf Forest].

Acid rain is an important phenomenon in the context of global climate change, and can strongly influence forest ecology. There have been many studies on the response of plants to acid rain. However, the effect of acid rain on soil microbial communities is still largely unknown. Studying the effects of acid rain on soil microbial community structure is of great significance for predicting the interactive effects of multiple climate factors on forest ecosystems in the future. Moso bamboo (Phyllostachys edulis) is often cultivated not only for its delicious shoots and versatile culms, but also as an important biomass resource in southern China. However, with its robust growth and strong rhizomes, Moso bamboo populations have been expanding rapidly into adjacent forests. Different perturbation regimes, including disturbance caused by simulated acid rain, can have significant effects on a soil fungal community in response to Moso bamboo invasion into native broadleaf forest. To explore the effect of acid rain on a mixed forest of Moso bamboo and broadleaf soil fungi diversity, and to understand the relationship between fungal community structure and acid rain stress, a mixed forest of Moso bamboo and broadleaf (transition forest) in Zhejiang Tianmu Mountain Nature Reserve was taken as the study site, and simulated acid rain was set at different acidity according to the acid rain component of Linan in recent years. The experiment consisted of three different treatments. Three gradients of simulated acid rain treatment[pH 2.5, 4.0, and CK (lake water)] were designed to determine the effects of simulated acid rain on soil bacterial community diversity in transition forest. Soil DNA was extracted from the soils for polymerase chain reaction amplification and high-throughput sequencing to study the effects of acid rain on the fungal communities of the mixed forest of Moso bamboo and broadleaf soil. We obtained 601 287 sequences across the three types of sampling sites. Sequences were affiliated to 13 different phyla throughout the dataset. The dominant fungal groups were Ascomycota, Basidiomycota, Mortierellomycota, and Mucoromycota. Simulated acid significantly increased the number of operational taxonomic units, Ace index, and Chao1 index of fungal communities (P<0.05). The results of principal coordinates analysis (PCoA) also revealed that acid rain significantly modified the structure. The changes in soil fungal community structure were mainly related to the abundance of genera Bifiguratu, Geminibasidium, Purpureocillium, and Oidiodendron, which could be utilized as indicator species to determine changes in soil fungal community structure. Redundancy and correlation analysis showed that changes in basic physicochemical factors in the soil, such as soil pH and total nitrogen, can significantly influence the composition of the fungal community (P<0.05).

Nasality Changes With Age in Normal Korean-Speaking Adults.

OBJECTIVES: This study was performed to investigate the effects of aging on nasality and the influence of age-related changes in nasal cavity volume and nasal patency on nasality. METHODS: A total of 180 healthy Korean-speaking adult volunteers, who had no nasal or voice-related complaints, were enrolled in this study. Nasometry, acoustic rhinometry, and rhinomanometry were performed to obtain the nasalance score, nasal cavity volume, and nasal resistance, respectively. Changes in these parameters with age were analyzed. RESULTS: Nasal cavity volume increased significantly, and nasal resistance decreased significantly, with age. The nasalance scores for the nasal passage and oronasal passage decreased significantly with age, while there were no age-related changes in nasalance scores for the oral passage. CONCLUSION: Nasalance scores for the passages containing nasal consonants decreased with age although significant increases were observed in nasal cavity volume and nasal patency with age. Therefore, the age-related decreases in nasalance scores may result from factors other than changes in the nasal cavity.

[Effects of target tree tending on community structure and diversity in subtropical natural secondary shrubs]. / ç›®æ ‡æ ‘æŠšè‚²å¯¹äºšçƒ­å¸¦å¤©ç„¶æ¬¡ç”ŸçŒä¸›ç¾¤è½ç»“æž„å’Œå¤šæ ·æ€§çš„å½±å“.

The typical natural secondary shrub community was chosen in Lin'an of Zhejiang Pro-vince to discover its possibility of restoration to arbor forest with three kinds of forest management models being taken, i.e., no care as control, closed forest management and target tree tending. Over four years growth, compared with control, closed forest management significantly increased average DBH and height by 130% and 50%, respectively, while 260% and 110% for target tree tending. In target tree tending plots, larger trees had been emerging with 4.5-8.5 cm diameter class and 4.5-8.5 m height class and formed a new storey of 4 m compared with control. The species biodiversity indexes at shrub layer were significantly increased in closed management plots, and did not decrease in target tree tending plots. Closed forest management did not change the tree species composition, following its previous succession direction. However, target tree tending increased the importance value of target species with the high potential succession direction of mixed coniferous-broadleaved forest. The results revealed that the secondary shrub community with target tree tending achieved more desired goals on DBH and height growth of dominant trees and species composition improvement compared with closed management. If the secondary shrub community could be managed when the operational conditions existed, target tree tending model should be selected to accelerate the restoration of shrub toward arbor forest.

[Instant response of individual size inequality indices to thinning regimes in plantation].

Four kinds of thinning treatments were designed including thinning from below, thinning from above, mechanical thinning and crop tree release with the same thinning intensity on the 14-year-old pure Cunninghamia laceolata and Pinus massoniana plantations in Guangxi, and 6 kinds of size inequality indices were applied including stand deviation, variation coefficient, skewness, Gini coefficient, Kuznetz coefficient and Lorenz asymmetry coefficient to evaluate the change of individual volume inequality after the 4 kinds of thinning regimes applied. The results showed that stand deviation, variation coefficient, Gini coefficient and Kuznetz coefficient decreased and skewness increased after thinning from below or above compared with before thinning, while after crop tree release these four indices increased and skewness was uncertain. Lorenz asymmetry coefficient increased after thinning from below while it decreased after thinning from above or crop tree release compared with before thinning. There was no distinct rule for the 6 kinds of size inequality indices after mechanical thinning. The size inequality increased after crop tree release while it decreased af- ter thinning from above or below. The study suggested that Lorenz curve, Gini coefficient and Lorenz asymmetry coefficient could be used to compare the size inequality statically and dynamically among different stands, and could be discriminated the difference of size inequality caused by the different thinning regimes. Lorenz asymmetry coefficient even could be applied to tell the size inequality was mainly from the larger or smaller individuals. Crop tree release method in close-to-nature management could lessen the competition pressures of crop trees and increase the size inequality of the stand effectively which would be helpful to maintain the dominant position of crop trees.

[Allelopathic potential of Phyllostachys edulis on two dominant tree species of evergreen broad-leaved forest in its invasive process].

In order to explore the influence of Phyllostachys edulis invasion on the surrounding forest environment,the effects of aqueous extracts from P. edulis on two dominant species (Castanopsis sclerophylla and Cyclobalanopsis glaunca)in southern China were assessed by germination bioassays. The results showed that seed germination effects depended on the concentration of aqueous extracts and the extract sources. The highest extract concentration showed significant inhibitory effects on seed germination percentage, which was 82. 3% -102. 2% of control for C. sclerophylla and 80% -90. 9% of control for C. glauca, while in the treatment with lowest extract concentration the values were 101.7% - 107.6% of control for C. sclerophylla and 94.9% - 109. 1% of control for C. glauca, respectively. The extracts had inhibitory effects on the germination speed of both species (P < 0.05) , except that no effects on C. sclerophylla were observed in the low concentration treatment. Extracts at the highest concentration reduced the root activity of C. sclerophylla by 41. 1% -62. 4% (P <0.05). There were obvious different effects among the treatments with different extract sources. Seed germination percentage was the lowest in root extract treatments. There was no obvious difference for shoot height of C. sclerophylla in different treatments(P >0.05) , while there was significant difference for C. glauca, its shoot height was higher in the leaf, root, and litter extracts treatments than in the soil extracts treatments. P. edulis possesses allelopathic potential that could possibly facilitate its invasion and monoculture formation, and does harm to the surrounding forest environment.

[Effects of UV-B radiation on the decomposition of Cunninghamia lanceolata leaf litter].

A litterbag experiment was conducted to study the decomposition of Cunninghamia lanceolata leaf litter under ambient and reduced UV-B radiation (22.1% below ambient). Comparing with ambient treatment, the reduced treatment decreased the decomposition rate of C. lanceolata leaf litter by 69.6% (P<0.001), making the relative contents of nitrogen (N), phosphorus (P), and lignin in the litter increased by 150%, 83.3%, and 13.8%, respectively, and the release of potassium (K) and carbon (C) slowed down. In the process of litter decomposition, photo-degradation of lignin didn't play crucial role. The results suggested that UV-B radiation could accelerate the decomposition rate of C. lanceolata leaf litter, promote the release of N, P, K, and C from it, and increase the nutrients turnover rate in litter layer as well as the carbon flux on the ground, giving potential effects on the function of C. lanceolata forest as a carbon source or sink in humid subtropical China.