Water temperature and salt ions respectively drive the community assembly of bacterial generalists and specialists in diverse plateau lakes.

Plateau lakes (e.g., freshwater and saltwater lakes) are formed through intricate processes and harbor diverse microorganisms that mediate aquatic ecosystem functions. The adaptive mechanisms of lake microbiota to environmental changes and the ecological impacts of such changes on microbial community assembly are still poorly understood in plateau regions. This study investigated the structure and assembly of planktonic bacterial communities in 24 lakes across the Qinghai-Tibetan and Inner Mongolia Plateaus, with particular focus on habitat generalists, opportunists, and specialists. High-throughput sequencing of the 16S ribosomal RNA genes revealed that bacterial generalists had a lower species number (2196) but higher alpha diversity than the specialist and opportunist counterparts. Taxonomic dissimilarity and phylogenetic diversity analyses unraveled less pronounced difference in the community composition of bacterial generalists compared to the specialist and opportunist counterparts. Geographical scale (14.4 %) and water quality (12.6 %) emerged as major ecological variables structuring bacterial communities. Selection by water temperature and related variables, including mean annual temperature, elevation, longitude, and latitude, mainly shaped the assembly of bacterial generalists. Ecological drift coupled with selection by salt ions and related variables, including total phosphorus, chlorophyll a, and salinity, predominantly drove the assembly of bacterial specialists and opportunists. This study uncovers distinct bacterial responses to interacting ecological variables in diverse plateau lakes and the ecological processes structuring bacterial communities across various lake habitats under anthropogenic disturbance or climate change.

TGF-ß-induced lncRNA TBUR1 promotes EMT and metastasis in lung adenocarcinoma via hnRNPC-mediated GRB2 mRNA stabilization.

The transforming growth factor-ß (TGF-ß) signaling pathway is pivotal in inducing epithelial-mesenchymal transition (EMT) and promoting cancer metastasis. Long non-coding RNAs (lncRNAs) have emerged as significant players in these processes, yet their precise mechanisms remain elusive. Here, we demonstrate that TGF-ß-upregulated lncRNA 1 (TBUR1) is significantly activated by TGF-ß via Smad3/4 signaling in lung adenocarcinoma (LUAD) cells. Functionally, TBUR1 triggers EMT, enhances LUAD cell migration and invasion in vitro, and promotes metastasis in nude mice. Mechanistically, TBUR1 interacts with heterogeneous nuclear ribonucleoproteins C (hnRNPC) to stabilize GRB2 mRNA in an m6A-dependent manner. Clinically, TBUR1 is upregulated in LUAD tissues and correlates with poor prognosis, highlighting its potential as a prognostic biomarker and therapeutic target for LUAD. Taken together, our findings underscore the crucial role of TBUR1 in mediating TGF-ß-induced EMT and metastasis in LUAD, providing insights for future therapeutic interventions.

Structural analysis and blood-enriching effects comparison based on biological potency of Angelica sinensis polysaccharides.

Angelica sinensis is a long-standing medicine used by Chinese medical practitioners and well-known for its blood-tonic and blood-activating effects. Ferulic acid, ligustilide, and eugenol in Angelica sinensis activate the blood circulation; however, the material basis of their blood-tonic effects needs to be further investigated. In this study, five homogeneous Angelica sinensis polysaccharides were isolated, and their sugar content, molecular weight, monosaccharide composition, and infrared characteristics determined. Acetylphenylhydrazine (APH) and cyclophosphamide (CTX) were used as inducers to establish a blood deficiency model in mice, and organ indices, haematological and biochemical parameters were measured in mice. Results of in vivo hematopoietic activity showed that Angelica sinensis polysaccharide (APS) could elevate erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), and interleukin-3 (IL-3) serum levels, reduce tumor necrosis factor-α (TNF-α) level in mice, and promote hematopoiesis in the body by regulating cytokine levels. Biological potency test results of the in vitro blood supplementation indicated strongest tonic activity for APS-H2O, and APS-0.4 has the weakest haemopoietic activity. The structures of APS-H2O and APS-0.4 were characterized, and the results showed that APS-H2O is an arabinogalactan glycan with a main chain consisting of α-1,3,5-Ara(f), α-1,5- Ara(f), ß-1,4-Gal(p), and ß-1,4-Gal(p)A, and two branched chains of ß-t-Gal(p) and α-t-Glc(p) connected to each other in a (1→3) linkage to α-1,3,5-Ara(f) on the main chain. APS-0.4 is an acidic polysaccharide with galacturonic acid as the main chain, consisting of α-1,4-GalA, α-1,2-GalA, α-1,4-Gal, and ß-1,4-Rha. In conclusion, APS-H2O can be used as a potential drug for blood replenishment in patients with blood deficiency, providing a basis for APS application in clinical treatment and health foods, as well as research and development of new polysaccharide-based drugs.

Clonal hematopoiesis of indeterminate potential and risk of neurodegenerative diseases.

BACKGROUND: Little is known regarding the association between clonal hematopoiesis of indeterminate potential (CHIP) and risk of neurodegenerative diseases. OBJECTIVE: To estimate the risk of neurodegenerative diseases among individuals with CHIP. METHODS: We conducted a community-based cohort study based on UK Biobank and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of any neurodegenerative disease, subtypes of neurodegenerative diseases (including primary neurodegenerative diseases, vascular neurodegenerative diseases, and other neurodegenerative diseases), and specific diagnoses of neurodegenerative diseases (i.e., amyotrophic lateral sclerosis [ALS], Alzheimer's disease [AD], and Parkinson's disease [PD]) associated with CHIP. RESULTS: We identified 14,440 individuals with CHIP and 450,907 individuals without CHIP. Individuals with CHIP had an increased risk of any neurodegenerative disease (HR 1.10, 95% CI: 1.01-1.19). We also observed a statistically significantly increased risk for vascular neurodegenerative diseases (HR 1.31, 95% CI 1.05-1.63) and ALS (HR 1.50, 95% CI 1.05-2.15). An increased risk was also noted for other neurodegenerative diseases (HR 1.13, 95% CI 0.97-1.32), although not statistically significant. Null association was noted for primary neurodegenerative diseases (HR 1.06, 95% CI 0.96-1.17), AD (HR 1.04, 95% CI 0.88-1.23), and PD (HR 1.02, 95% CI 0.86-1.21). The risk increase in any neurodegenerative disease was mainly observed for DNMT3A-mutant CHIP, ASXL1-mutant CHIP, or SRSF2-mutant CHIP. CONCLUSION: Individuals with CHIP were at an increased risk of neurodegenerative diseases, primarily vascular neurodegenerative diseases and ALS, but potentially also other neurodegenerative diseases. These findings suggest potential shared mechanisms between CHIP and neurodegenerative diseases.

Aqueous VOCs in complex water environment of oil exploitation sites: Spatial distribution, migration flux, and risk assessment.

Pollution of the aqueous environment by volatile organic compounds (VOCs) has caused increasing concerns. However, the occurrence and risks of aqueous VOCs in oil exploitation areas remain unclear. Herein, spatial distribution, migration flux, and environmental risks of VOCs in complex surface waters (including River, Estuary, Offshore and Aquaculture areas) were investigated at a typical coastal oil exploitation site. Among these surface waters, River was the most polluted area, and 1,2-Dichloropropane-which emerges from oil extraction activities-was the most prevalent VOC. Positive matrix factorization showed that VOCs pollution sources changed from oil exploitation to offshore disinfection activities along River, Estuary, Offshore and Aquaculture areas. Annual volatilization of VOCs to the atmosphere was predicted to be ∼34.42 tons, and rivers discharge ∼23.70 tons VOCs into the Bohai Sea annually. Ecological risk assessment indicated that Ethylbenzene and Bromochloromethane posed potential ecological risks to the aquatic environment, while olfactory assessment indicated that VOCs in surface waters did not pose an odor exposure risk. This study provides the first assessment of the pollution characteristics of aqueous VOCs in complex aqueous environments of oil exploitation sites, highlighting that oil exploitation activities can have nonnegligible impacts on VOCs pollution profiles.

Heterogenization of microplastic communities in lakes of the Qinghai-Tibetan Plateau driven by tourism and transport activities.

The Qinghai-Tibetan Plateau has a booming tourism industry and an increasingly sophisticated road system. There is a paucity of studies quantifying the contributions of anthropogenic and natural factors to microplastic pollution in remote plateau areas. In this study, water and sediment samples were collected from eight lake tourist attractions and four remote lakes in northern and southern regions of the Qinghai-Tibetan Plateau. Microplastics were detected in all samples, with a mean abundance of 0.78 items/L in water and 44.98 items/kg in sediment. The abundance of microplastics in the study area was lower than previously observed in more populated areas of China. Small-sized (<1 mm and 1-2 mm), fiber, and transparent microplastics were predominant, with polyethylene and polypropylene microplastics as the primary polymer types. The compositions of microplastic communities indicated that tourism and road networks were the major sources of microplastics in the lakes. Distance-decay models revealed greater influence of environmental distances on microplastic community similarity than geographic distance. Compared to climate factors, urban spatial impact intensity and traffic flow impact played a leading role in the structuring of microplastic communities in lake water and sediment. Our findings provide novel quantitative insights into the role of various factors in shaping the distribution patterns of microplastic communities in plateau lakes.

Deciphering extracellular vesicles protein cargo in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) presents a significant therapeutic challenge as it is frequently diagnosed at advanced inoperable stages. Therefore, the development of a reliable screening tool for PDAC is crucial for effective prevention and treatment. Extracellular vesicles (EVs), characterized by their cup-shaped lipid bilayer structure and ubiquitous release from various cell types, offer notable advantages as an emerging liquid biopsy technique that is rapid, minimally invasive, easily sampled, and cost-effective. While EVs play a substantial role in cancer progression, EV proteins serve as direct mediators of diverse cellular behaviors and have immense potential as biomarkers for PDAC diagnosis and prognostication. This review provides an overview of EV proteins regarding PDAC diagnosis and prognostic implications as well as disease progression.

Inhibition of DEF-p65 Interactions as a Potential Avenue to Suppress Tumor Growth in Pancreatic Cancer.

The limited success of current targeted therapies for pancreatic cancer underscores an urgent demand for novel treatment modalities. The challenge in mitigating this malignancy can be attributed to the digestive organ expansion factor (DEF), a pivotal yet underexplored factor in pancreatic tumorigenesis. The study uses a blend of in vitro and in vivo approaches, complemented by the theoretical analyses, to propose DEF as a promising anti-tumor target. Analysis of clinical samples reveals that high expression of DEF is correlated with diminished survival in pancreatic cancer patients. Crucially, the depletion of DEF significantly impedes tumor growth. The study further discovers that DEF binds to p65, shielding it from degradation mediated by the ubiquitin-proteasome pathway in cancer cells. Based on these findings and computational approaches, the study formulates a DEF-mimicking peptide, peptide-031, designed to disrupt the DEF-p65 interaction. The effectiveness of peptide-031 in inhibiting tumor proliferation has been demonstrated both in vitro and in vivo. This study unveils the oncogenic role of DEF while highlighting its prognostic value and therapeutic potential in pancreatic cancer. In addition, peptide-031 is a promising therapeutic agent with potent anti-tumor effects.

Preoperative Molecular Subtype Classification Prediction of Ovarian Cancer Based on Multi-Parametric Magnetic Resonance Imaging Multi-Sequence Feature Fusion Network.

In the study of the deep learning classification of medical images, deep learning models are applied to analyze images, aiming to achieve the goals of assisting diagnosis and preoperative assessment. Currently, most research classifies and predicts normal and cancer cells by inputting single-parameter images into trained models. However, for ovarian cancer (OC), identifying its different subtypes is crucial for predicting disease prognosis. In particular, the need to distinguish high-grade serous carcinoma from clear cell carcinoma preoperatively through non-invasive means has not been fully addressed. This study proposes a deep learning (DL) method based on the fusion of multi-parametric magnetic resonance imaging (mpMRI) data, aimed at improving the accuracy of preoperative ovarian cancer subtype classification. By constructing a new deep learning network architecture that integrates various sequence features, this architecture achieves the high-precision prediction of the typing of high-grade serous carcinoma and clear cell carcinoma, achieving an AUC of 91.62% and an AP of 95.13% in the classification of ovarian cancer subtypes.

Black soldier fly larvae bioconversion and subsequent composting promote larval frass quality during pig and chicken manure transformation process.

This research systematically assessed the changes in carbon, nitrogen and microbial profiling during pig and chicken manure transformation by black soldier fly larvae (BSFL) and subsequent composting process. BSFL had higher conversion efficiency for chicken manure. The pH, phosphorus and potassium contents in fresh BSFL frass increased than raw manure, but conductivity, total-/nitrate-/ammonium-nitrogen decreased. After BSFL conversion, pig manure had a larger nitrogen loss (25 %) while chicken manure had a larger carbon loss (32 %). During subsequent composting, the indicator changes (e.g. humus, ammonium nitrogen) in frass composts basically remained stable after 20-30 days. Compared to natural composts, frass composts had higher humification degree, cellulase activities, and more cellulose-degrading bacteria. Subsequent composting further reduced potential pathogens (reduced by 98.9 %-99.7 % than raw manure), and elevated the aromaticity and humification of frass. The findings gave an insight into the maturation management of manure-sourced insect frass.

Global trends and hotspots in research on acupuncture for neurodegenerative diseases over the last decade: a bibliometric and visualization analysis.

Objectives: This study aimed to explore the current status and trends of acupuncture for neurodegenerative diseases (NDs) in the last decade and provide new insights for researchers in future studies. Methods: The publications concerning acupuncture treatment for NDs published between 2014 and 2023 were extracted from the Web of Science Core Collection. We used CiteSpace and VOSviewer to analyze data on numbers of annual publications, countries, institutions, cited journals, cited authors, cited references, keywords, and citation bursts about acupuncture for NDs. Results: A total of 635 publications were obtained from 2014 to 2023. We identified the most prolific journals, countries, institutions, authors, patterns of authorship, and the main direction of future research in the field of acupuncture for NDs in the last decade. The country, institution, and journal with the most publications are China (389 articles), Beijing University of Chinese Medicine (56 articles), and Evidence Based Complementary and Alternative Medicine (42 articles), respectively. The high-frequency keywords focused on "Alzheimer's disease," "Parkinson's disease," "acupuncture," "dementia," and "electroacupuncture." The top five keywords in terms of centrality were "cerebral ischemia," "acupuncture stimulation," "fMRI," "apoptosis," and "deep brain stimulation." Conclusion: The results from this bibliometric study provide insight into the research trends in acupuncture therapy for NDs, and the current status and trends of the past decade, which may help researchers confirm the current status, hotspots, and frontier trends in this field.

Deciphering and predicting changes in antibiotic resistance genes during pig manure aerobic composting via machine learning model.

Livestock manure is one of the most important pools of antibiotic resistance genes (ARGs) in the environment. Aerobic composting can effectively reduce the spread of antibiotic resistance risk in livestock manure. Understanding the effect of aerobic composting process parameters on manure-sourced ARGs is important to control their spreading risk. In this study, the effects of process parameters on ARGs during aerobic composting of pig manure were explored through data mining based on 191 valid data collected from literature. Machine learning (ML) models (XGBoost and Random Forest) were utilized to predict the rate of ARGs changes during pig manure composting. The model evaluation index of the XGBoost model (R2 = 0.651) was higher than that of the Random Forest (R2 = 0.490), indicating that XGBoost had better prediction performance. Feature importance was further calculated for the XGBoost model, and the XGBoost black box model was interpreted by Shapley additive explanations analysis. Results indicated that the influencing factors on the ARGs variation in pig manure were sequentially divided into thermophilic period, total composting period, composting real time, and thermophilic stage average temperature. The findings gave an insight into the application of ML models to predict and decipher the ARG changes during manure composting and provided suggestions for better composting manipulation and optimization of process parameters.

Picturing the Gap Between the Performance and US-DOE's Hydrogen Storage Target: A Data-Driven Model for MgH2 Dehydrogenation.

Developing solid-state hydrogen storage materials is as pressing as ever, which requires a comprehensive understanding of the dehydrogenation chemistry of a solid-state hydride. Transition state search and kinetics calculations are essential to understanding and designing high-performance solid-state hydrogen storage materials by filling in the knowledge gap that current experimental techniques cannot measure. However, the ab initio analysis of these processes is computationally expensive and time-consuming. Searching for descriptors to accurately predict the energy barrier is urgently needed, to accelerate the prediction of hydrogen storage material properties and identify the opportunities and challenges in this field. Herein, we develop a data-driven model to describe and predict the dehydrogenation barriers of a typical solid-state hydrogen storage material, magnesium hydride (MgH2), based on the combination of the crystal Hamilton population orbital of Mg-H bond and the distance between atomic hydrogen. By deriving the distance energy ratio, this model elucidates the key chemistry of the reaction kinetics. All the parameters in this model can be directly calculated with significantly less computational cost than conventional transition state search, so that the dehydrogenation performance of hydrogen storage materials can be predicted efficiently. Finally, we found that this model leads to excellent agreement with typical experimental measurements reported to date and provides clear design guidelines on how to propel the performance of MgH2 closer to the target set by the United States Department of Energy (US-DOE).

Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling.

Pien Tze Huang (PZH), a class I nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Chalcogen Atoms Regulate the Organic Solar Cell Performance of B-N-Based Polymer Donors.

Donor polymers play a key role in the development of organic solar cells (OSCs). B-N-based polymer donors, as new types of materials, have attracted a lot of attention due to their special characteristics, such as high E(T1), small ΔEST, and easy synthesis, and they can be processed with real green solvents. However, the relationship between the chemical structure and device performance has not been systematically studied. Herein, chalcogen atoms that regulate the OSCs performance of B-N-based polymer donors were systematically studied. Fortunately, the substitution of a halogen atom did not affect the high E(T1) and small ΔEST character of the B-N-based polymer. The absorption and energy levels of the polymer were systematically regulated by O, S, and Se atom substitution. The PBNT-TAZ:Y6-BO-based OSCs device demonstrated a high power conversion efficiency of 15.36%. Moreover, the layer-by-layer method was applied to further optimize the device performance, and the PBNT-TAZ/Y6-BO-based OSCs device yielded a PCE of 16.34%. Consequently, we have systematically demonstrated how chalcogen atoms modulated the electronic properties of B-N-based polymers. Detailed and systematic structure-performance relationships are important for the development of next-generation B-N-based materials.

Copper-Catalyzed Enantioconvergent Radical N-Alkylation of Diverse (Hetero)aromatic Amines.

The 3d transition metal-catalyzed enantioconvergent radical cross-coupling provides a powerful tool for chiral molecule synthesis. In the classic mechanism, the bond formation relies on the interaction between nucleophile-sequestered metal complexes and radicals, limiting the nucleophile scope to sterically uncongested ones. The coupling of sterically congested nucleophiles poses a significant challenge due to difficulties in transmetalation, restricting the reaction generality. Here, we describe a probable outer-sphere nucleophilic attack mechanism that circumvents the challenging transmetalation associated with sterically congested nucleophiles. This strategy enables a general copper-catalyzed enantioconvergent radical N-alkylation of aromatic amines with secondary/tertiary alkyl halides and exhibits catalyst-controlled stereoselectivity. It accommodates diverse aromatic amines, especially bulky secondary and primary ones to deliver value-added chiral amines (>110 examples). It is expected to inspire the coupling of more nucleophiles, particularly challenging sterically congested ones, and accelerate reaction generality.

Rejection Sensitivity and Reactive Aggression in Early Adults: The Mediating Role of Loneliness and Maladaptive Coping.

Reactive aggression is an aggressive response to a perceived threat or provocation. It has detrimental effects on individuals and society. Rejection sensitivity, a disposition that one tends to anxiously expect, readily perceive, and intensely react to social rejection, has been associated with reactive aggression. Considering that the mechanism underlying this link remains unclear, this study explores the mediating role of loneliness and maladaptive coping. Participants included 1104 early adults between the ages of 17-23 (Mage = 20.35, SD = 1.11, 33.6% men) in China who completed the Chinese version of the Tendency to Expect Rejection Scale, Loneliness Scale, Ways of Coping Questionnaire, and Reactive-Active Aggression Questionnaire. The serial mediation model revealed that loneliness and maladaptive coping independently mediated the association of rejection sensitivity with reactive aggression. More importantly, the chain mediating effect of "loneliness-maladaptive coping" also accounted for this link. The above findings contribute to a deeper understanding of the relationships among these factors and suggested that rejection sensitivity could positively be related to reactive aggression through loneliness and maladaptive coping.

The changes of neurogenesis in the hippocampal dentate gyrus of SAMP8 mice and the effects of acupuncture and moxibustion.

BACKGROUND: Influenced by the global aging population, the incidence of Alzheimer's disease (AD) has increased sharply. In addition to increasing ß-amyloid plaque deposition and tau tangle formation, neurogenesis dysfunction has recently been observed in AD. Therefore, promoting regeneration to improve neurogenesis and cognitive dysfunction can play an effective role in AD treatment. Acupuncture and moxibustion have been widely used in the clinical treatment of neurodegenerative diseases because of their outstanding advantages such as early, functional, and benign two-way adjustment. It is urgent to clarify the effectiveness, greenness, and safety of acupuncture and moxibustion in promoting neurogenesis in AD treatment. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice at various ages were used as experimental models to simulate the pathology and behaviors of AD mice. Behavioral experiments, immunohistochemistry, Western blot, and immunofluorescence experiments were used for comparison between different groups. RESULTS: Acupuncture and moxibustion could increase the number of PCNA+ DCX+ cells, Nissl bodies, and mature neurons in the hippocampal Dentate gyrus (DG) of SAMP8 mice, restore the hippocampal neurogenesis, delay the AD-related pathological presentation, and improve the learning and memory abilities of SAMP8 mice. CONCLUSION: The pathological process underlying AD and cognitive impairment were changed positively by improving the dysfunction of neurogenesis. This indicates the promising role of acupuncture and moxibustion in the prevention and treatment of AD.

Trophic level plays an enhanced role in shaping microbiota structure and assembly in lakes with decreased salinity on the Qinghai-Tibet and Inner Mongolia Plateaus.

Plateau lakes characterized by salinization and eutrophication are essential aquatic ecosystems. A myriad of microorganisms serve as crucial biological resources in plateau lakes and drive the elemental cycles of these ecosystems. Currently, there is a paucity of knowledge regarding the impacts of salinization and eutrophication dynamics on the microbiota in plateau lakes. Here, high-throughput sequencing of the 16S ribosomal RNA genes (V4 region) was used to characterize microbial community structure and assembly in plateau lakes with different salinities and trophic levels. Water samples were collected at 191 sites across 24 lakes on the Qinghai-Tibet and Inner Mongolia Plateaus in northern China. The results showed that high salinity considerably reduced microbial alpha-diversity and niche breadth while increasing within-group similarity among various lake types. High salinity additionally decreased the complexity of microbial networks and enhanced network robustness. The assembly of microbial communities was primarily governed by deterministic processes in high-salinity and eutrophic low-salinity lakes. At decreased salinity, trophic level played a leading role in shaping microbial community structure, and the ecological processes shifted from deterministic processes driven by high salinity to eutrophication-driven deterministic processes. The biomarkers also varied from taxa adapted to high-salinity environments (e.g., Nanoarchaeaeota, Rhodothermia) to those suited for living in freshwater and low-salinity habitats (e.g., Alphaproteobacteria, Actinobacteria). In the case of eutrophication, Actinobacteria, Chloroflexi, and Cyanobacteria became the dominant taxa. Our findings indicate that decreased salinity enables trophic level to play an enhanced role in shaping microbial community structure and assembly in plateau lakes. This study enriches our knowledge about the ecological impacts of salinization and eutrophication in plateau lakes.

Inhibition of PKM2 suppresses osteoclastogenesis and alleviates bone loss in mouse periodontitis.

BACKGROUND: Chronic periodontitis triggers an increase in osteoclastogenesis, with glycolysis playing a crucial role in this process. Pyruvate kinase M2 (PKM2) is a critical enzyme involved in glycolysis and pyruvate metabolism. Yet, the precise function of PKM2 in osteoclasts and their formation remains unclear and requires further investigation. METHODS: Bioinformatics was used to investigate critical biological processes in osteoclastogenesis. In vitro, osteoclastogenesis was analyzed using tartrate-resistant acid phosphatase (TRAP) staining, phalloidin staining, quantitative real­time PCR (RT-qPCR), and Western blotting. Small interfering RNA (siRNA) of PKM2 and Shikonin, a specific inhibitor of PKM2, were used to verify the role of PKM2 in osteoclastogenesis. The mouse model of periodontitis was used to assess the effect of shikonin on bone loss. Analyses included micro computed tomography, immunohistochemistry, flow cytometry, TRAP staining and HE staining. RESULTS: Bioinformatic analysis revealed a significant impact of glycolysis and pyruvate metabolism on osteoclastogenesis. Inhibition of PKM2 leads to a significant reduction in osteoclastogenesis. In vitro, co-culture of the heat-killed Porphyromonas gingivalis significantly promoted osteoclastogenesis, concomitant with an increased PKM2 expression in osteoclasts. Shikonin weakened the promoting effect of porphyromonas gingivalis on osteoclastogenesis. In vivo experiments demonstrated that inhibition of PKM2 by shikonin alleviated bone loss induced by periodontitis, suppressed excessive osteoclastogenesis in alveolar bone, and reduced tissue inflammation to some extent. CONCLUSION: PKM2 inhibition by shikonin, a specific inhibitor of this enzyme, attenuated osteoclastogenesis and bone resorption in periodontitis. Shikonin appears to be a promising therapeutic agent for treating periodontitis.