Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Response of microbial communities to the changes in grazing intensity and season in a typical steppe.

Livestock grazing is an influencing factor playing a key role in shaping the plant community, microbial community, and soil properties in grassland ecosystems. Northern China's Loess Plateau has been used for livestock grazing for centuries and is a vulnerable ecosystem. In this study, the fates of bacterial and fungal communities of the typical steppe of the Loess Plateau were investigated under increasing grazing intensities practiced in summer and winter seasons. The results revealed changes in soil physiochemical properties, plant community properties, and microbial diversity in response to alterations in the grazing intensity. The alpha diversity of microbial communities (including bacteria and fungi) exhibited an uneven trend during summer grazing due to an increase in grazing intensity, but it decreased during winter grazing; however, the observed changes were not significant. The beta diversity of the bacterial community was highly influenced by grazing intensity, the summer community clustered near nongrazing, and the winter community presented significantly different results. The beta diversity of the fungal community was not influenced by grazing intensity or season. Grazing induced the growth of fast-growing bacteria (such as Actinobacteria and Firmicutes) and saprophytic fungi and a reduction in overall pathogenic traits. Co-occurrence network analysis and a structural equation model revealed changes in soil and plant properties (such as soil nitrogen level, soil organic carbon level, aboveground biomass, and litter biomass), with an increase in grazing intensity contributing to alterations in bacterial and fungal diversities. This finding demonstrates that grazing intensity can directly affect soil microbes and play an indirect role by modifying soil nutrients and reducing plant biomass, which eventually contributes to changes in microbial communities. Overall, implementing low grazing intensity is suggested for maintaining the microbial community structure the same as that of the native microbiome (ungrazed) in the steppe ecosystems.

Concurrent and legacy effects of sheep trampling on soil organic carbon stocks in a typical steppe, China.

Grazing plays a key role in ecosystem biogeochemistry, particularly soil carbon (C) pools. The non-trophic interactions between herbivores and soil processes through herbivore trampling have recently attracted extensive attention. However, their concurrent and legacy effects on the ecosystem properties and processes are still not clear, due to their effects being hard to separate via field experiments. In this study, we conducted a 2-year simulated-sheep-trampling experiment with four trampling intensity treatments (i.e., T0, T40, T80, and T120 for 0, 40, 80, and 120 hoofprints m-2, respectively) in a typical steppe to explore the concurrent and legacy effects of trampling on grassland ecosystem properties and processing. In 2017 (trampling treatment year), we found that trampling decreased aboveground biomass (AGB) of plant community and community-weighted mean shoot C concentration (CWM C), soil available nitrogen (N) and available phosphorus (P), but did not affect plant species diversity and belowground biomass (BGB). We show that compared with T0, trampling increased soil bulk density (BD) at T80, and decreased soil organic carbon (SOC) stocks. After the cessation of trampling for two years (i.e., in 2019), previous trampling increased plant diversity and BGB, reaching the highest values at T80, but decreased soil available N and available P. Compared with T0, previous trampling significantly increased soil BD at T120, while significantly decreased CWM C at T80 and T120, and reduced SOC stocks at T80. Compared with 2017, the trampling negative legacy effects amplified at T80 but weakened at T40 and T120. We also show that trampling-induced decreases in soil available N, AGB of Fabaceae and CWM C were the main predictors of decreasing SOC stocks in 2017, while previous trampling-induced legacy effects on soil available P, AGB of Poaceae and CWM C contributed to the variations of SOC stocks in 2019. Taken together, short-term trampling with low intensity could maintain most plant functions, while previous trampling with low intensity was beneficial to most plant and soil functions. The results of this study show that T40 caused by sheep managed at a stocking rate of 2.7 sheep ha-1 is most suitable for grassland adaptive management in the typical steppe. The ecosystem functions can be maintained under a high stocking rate through the process of providing enough time to rebuild sufficient vegetation cover and restore soil through measures such as regional rotational grazing and seasonal grazing.

OGNNMDA: a computational model for microbe-drug association prediction based on ordered message-passing graph neural networks.

In recent years, many excellent computational models have emerged in microbe-drug association prediction, but their performance still has room for improvement. This paper proposed the OGNNMDA framework, which applied an ordered message-passing mechanism to distinguish the different neighbor information in each message propagation layer, and it achieved a better embedding ability through deeper network layers. Firstly, the method calculates four similarity matrices based on microbe functional similarity, drug chemical structure similarity, and their respective Gaussian interaction profile kernel similarity. After integrating these similarity matrices, it concatenates the integrated similarity matrix with the known association matrix to obtain the microbe-drug heterogeneous matrix. Secondly, it uses a multi-layer ordered message-passing graph neural network encoder to encode the heterogeneous network and the known association information adjacency matrix, thereby obtaining the final embedding features of the microbe-drugs. Finally, it inputs the embedding features into the bilinear decoder to get the final prediction results. The OGNNMDA method performed comparative experiments, ablation experiments, and case studies on the aBiofilm, MDAD and DrugVirus datasets using 5-fold cross-validation. The experimental results showed that OGNNMDA showed the strongest prediction performance on aBiofilm and MDAD and obtained sub-optimal results on DrugVirus. In addition, the case studies on well-known drugs and microbes also support the effectiveness of the OGNNMDA method. Source codes and data are available at: https://github.com/yyzg/OGNNMDA.

Salivary microbiome is associated with the response to chemoradiotherapy in initially inoperable patients with esophageal squamous cell carcinoma.

Background: The salivary microbiome may interact with chemoradiotherapy through dynamic changes in microbial composition and systemic immunity. We aimed to explore the association between the salivary microbiome and response to chemoradiotherapy in initially inoperable patients with local advanced esophageal squamous cell carcinoma (LAESCC). Methods: Salivary and peripheral blood samples were collected before and after chemoradiotherapy. The microbiome and metabolic pathways were analyzed by 16S ribosomal RNA sequencing and liquid chromatography tandem mass spectrometry/Mass spectrometry analyses. Results: The salivary microbiome exhibited characteristic variations between patients and healthy controls. A significant correlation was found between Prevotella_salivae, Saccharibacteria_TM7_G3_bacterium_HMT_351, and Veillonellaceae_G1_bacterium_HMT_129 and pathological complete response (pCR) in initially inoperable patients who underwent surgery. The PICRUSt suggested that immune diseases and cell motility were different in tumor compared to normal groups. KEGG enrichment analysis showed enriched lipid metabolism, signal transduction, and membrane transport in the tumor group. CD3+CD8 T cells, IL6, IL10, and IFNγ exhibited an increasing trend during the treatment process of chemoradiotherapy. Conclusions: Our study demonstrated that variations in specific saliva taxa associated with host immunomodulatory cells and cytokines could be promising for early efficacy prediction of chemoradiotherapy in initially inoperable patients with LAESCC.

A nomogram based on clinical characteristics and nutritional indicators for relative and absolute weight loss during radiotherapy in initially inoperable patients with locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: Radiation for locally advanced esophageal squamous cell carcinoma often is accompanied by radiation esophagitis, which interferes with oral intake. We aimed to develop a nomogram model to identify initially inoperable patients with relative and absolute weight loss who need prophylactic nutritional supplementation. METHODS: A total of 365 initially inoperable patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy between January 2018 and December 2022 were included in the study, which was divided into discovery and validation cohorts. Receiver operating characteristic and Kaplan-Meier curve analyses were performed to compare the areas under the curve and survival benefits. RESULTS: A total of 42.2% (154 of 365) of the patients had been diagnosed with cancer cachexia. The malnourished group had a higher interruption rate of radiotherapy and number of complication diseases (P < 0.05). Meanwhile, patients with malnutrition had lower lymphocytes and prognostic nutritional index (P < 0.05). The combined index showed a higher area under the curve value (0.67; P < 0.001) than number of complication diseases (area under the curve = 0.52) and prognostic nutritional index (area under the curve = 0.49) for relative weight loss (≥ 5%). Similarly, the combined index had a higher area under the curve value (0.79; P < 0.001) than number of complication diseases (area under the curve = 0.56), treatment regimens (area under the curve = 0.56), subcutaneous fat thickness (area under the curve = 0.60), pretreatment body weight (area under the curve = 0.61), neutrophils (area under the curve = 0.56), and prognostic nutritional index (area under the curve = 0.50) for absolute weight loss (≥ 5 kg). Absolute and relative weight loss remained independent prognostic factors, with short overall survival rates compared with the normal group (P < 0.05). Patients with high nomogram scores supported by nutritional intervention had less weight loss, better nutrition scores, and increased plasma CD8+ T cells, and interferon gamma. CONCLUSIONS: We developed a nomogram model that was intended to estimate relative and absolute weight loss in initially inoperable patients with locally advanced esophageal squamous cell carcinoma during radiotherapy, which might help facilitate an objective decision on prophylactic nutritional supplementation.