Exercise training decreases lactylation and prevents myocardial ischemia-reperfusion injury by inhibiting YTHDF2.

Exercise improves cardiac function and metabolism. Although long-term exercise leads to circulating and micro-environmental metabolic changes, the effect of exercise on protein post-translational lactylation modifications as well as its functional relevance is unclear. Here, we report that lactate can regulate cardiomyocyte changes by improving protein lactylation levels and elevating intracellular N6-methyladenosine RNA-binding protein YTHDF2. The intrinsic disorder region of YTHDF2 but not the RNA m6A-binding activity is indispensable for its regulatory function in influencing cardiomyocyte cell size changes and oxygen glucose deprivation/re-oxygenation (OGD/R)-stimulated apoptosis via upregulating Ras GTPase-activating protein-binding protein 1 (G3BP1). Downregulation of YTHDF2 is required for exercise-induced physiological cardiac hypertrophy. Moreover, myocardial YTHDF2 inhibition alleviated ischemia/reperfusion-induced acute injury and pathological remodeling. Our results here link lactate and lactylation modifications with RNA m6A reader YTHDF2 and highlight the physiological importance of this innovative post-transcriptional intrinsic regulation mechanism of cardiomyocyte responses to exercise. Decreasing lactylation or inhibiting YTHDF2/G3BP1 might represent a promising therapeutic strategy for cardiac diseases.

The role of the cartilaginous to osseous acetabular angle ratio in children with developmental dysplasia of the hip.

Purpose: This study aims to demonstrate the use of the cartilaginous to osseous acetabular angle ratio (AAR) in surgical decision-making for hip dysplasia. Methods: Data were collected from patients who underwent an MRI of the hip after conservative treatment for developmental dysplasia of the hip between August 2019 and 2022. The data included demographic information as well as an anteroposterior pelvic radiograph. The osseous acetabular index (OAI) was measured using x-ray, while the cartilaginous acetabular index (CAI) and the cartilaginous acetabulum head index (CAHI) were measured using MRI. The square of the CAI to OAI, AAR, was calculated. The patients in the residual hip dysplasia (RHD) group were categorized as having an OAI above 20°. During the postoperative follow-up, we evaluated the patients in this group who underwent Bernese triple pelvic osteotomy. Data on surgical patients with an observation period that exceeded 1 year were collected and analyzed. The distribution of the AAR among the different groups was analyzed. A receiver operating characteristic (ROC) predictive model was constructed using the AAR of the patients in the normal and surgical groups to evaluate the need for surgery. Results: It was found that there was a significant difference in the OAI, CAI, CAHI, and AAR between the RHD group (OAI 26.15 ± 3.90°, CAI 11.71 ± 4.70°, CAHI 79.75 ± 6.27%, and AAR 5.88 ± 4.24) and the control group patients (OAI 16.77 ± 5.39°, CAI 6.16 ± 3.13°, CAHI 85.05 ± 4.91%, and AAR 2.71 ± 2.08) (p < 0.001). A total of 93.5% of the control group patients had an AAR ≤5, while only 6.5% had an AAR >5. The results of postoperative imaging follow-up were "excellent" in 52 patients and "good" in 3, while the functional follow-up results were excellent in 53 and good in 2. In 15 patients, the observation period exceeded 1 year. The mean observation period was 633.1 ± 259.6 days and the preoperative CAHI was 71.7 ± 4.8%. Of the patients with an AAR >5, a substantial 94.8% (55/58) of them were reported to have undergone surgery, while all patients with an AAR less than or equal to 5 did not undergo surgery (91/91). Based on the ROC, a cutoff value of 5.09 was identified for the need for surgery in children with RHD. Conclusions: A surgical decision for residual hip dysplasia can be based on the AAR. An AAR >5 may be a potential indicator for surgical intervention in patients with RHD.

Decreased Electrically and Increased Ionically Conducting Scaffolds for Long-Life, High-Rate and Deep-Capacity Lithium-Metal Anodes.

Lithium (Li) metal batteries are deemed as promising next-generation power solutions but are hindered by the uncontrolled dendrite growth and infinite volume change of Li anodes. The extensively studied 3D scaffolds as solutions generally lead to undesired "top-growth" of Li due to their high electrical conductivity and the lack of ion-transporting pathways. Here, by reducing electrical conductivity and increasing the ionic conductivity of the scaffold, the deposition spot of Li to the bottom of the scaffold can be regulated, thus resulting in a safe bottom-up plating mode of the Li and dendrite-free Li deposition. The resulting symmetrical cells with these scaffolds, despite with a limited pre-plated Li capacity of 5 mAh cm-2, exhibit ultra-stable Li plating/stripping for over 1 year (11 000 h) at a high current density of 3 mA cm-2 and a high areal capacity of 3 mAh cm-2. Moreover, the full cells with these scaffolds further demonstrate high cycling stability under challenging conditions, including high cathode loading of 21.6 mg cm-2, low negative-to-positive ratio of 1.6, and limited electrolyte-to-capacity ratio of 4.2 g Ah-1.

Epiberberine: a potential rumen microbial urease inhibitor to reduce ammonia release screened by targeting UreG.

Rumen microbial urease inhibitors have been proposed for regulating nitrogen emission and improving nitrogen utilization efficiency in ruminant livestock industry. However, studies on plant-derived natural inhibitors of rumen microbial urease are limited. Urease accessory protein UreG, plays a crucial role in facilitating urease maturation, is a new target for design of urease inhibitor. The objective of this study was to select the potential effective inhibitor of rumen microbial urease from major protoberberine alkaloids in Rhizoma Coptidis by targeting UreG. Our results showed that berberine chloride and epiberberine exerted superior inhibition potential than other alkaloids based on GTPase activity study of UreG. Berberine chloride inhibition of UreG was mixed type, while inhibition kinetics type of epiberberine was uncompetitive. Furthermore, epiberberine was found to be more effective than berberine chloride in inhibiting the combination of nickel towards UreG and inducing changes in the second structure of UreG. Molecular modeling provided the rational structural basis for the higher inhibition potential of epiberberine, amino acid residues in G1 motif and G3 motif of UreG formed interactions with D ring of berberine chloride, while interacted with A ring and D ring of epiberberine. We further demonstrated the efficacy of epiberberine in the ruminal microbial fermentation with low ammonia release and urea degradation. In conclusion, our study clearly indicates that epiberberine is a promising candidate as a safe and effective inhibitor of rumen microbial urease and provides an optimal strategy and suitable feed additive for regulating nitrogen excretion in ruminants in the future. KEY POINTS: • Epiberberine is the most effective inhibitor of rumen urease from Rhizoma Coptidis. • Urease accessory protein UreG is an effective target for design of urease inhibitor. • Epiberberine may be used as natural feed additive to reducing NH3 release in ruminants.

A new isopropyl esterification method for quantitative profiling of short-chain fatty acids in human and cow milk by gas chromatograph-mass spectrometer.

Short-chain fatty acids (SCFAs) content in milk may have been underestimated due to the neglect of the esterified SCFAs content and the lack of an accurate detection method, especially for C1:0, C2:0, and C3:0 SCFAs. In this study, an accurate gas chromatography-mass spectrometry profiling method was established for 10 SCFAs. A 2-step esterification, including alkaline saponification (60°C for 30 min) and acid-catalyzed esterification (80°C for 150 min) in water/isopropyl/hexane (1:2:1, volume ratio), was found to be the most suitable for the quantification of esterified and nonesterified SCFAs analysis. The validation results demonstrate satisfactory linearity, sensitivity, matrix effects, precision, and accuracy. The recoveries of nonesterified and esterified SCFAs ranged from 82.78% to 112.49%, respectively. Human milk is distinguished from cow milk by its higher C1:0 and C2:0 content and lower C4:0 and C6:0 content. This method successfully accomplished qualitative and quantitative estimation of all 10 SCFAs in milk, including both nonesterified and esterified SCFAs. Furthermore, whether our method is applicable for the determination of SCFAs in serum, rumen fluid, and feces remains to be explored.

Enhanced mechanical and long-lasting antibacterial properties of starch/PBAT blown films via designing of reactive micro-crosslinked starch.

A functional starch (TPS-E) was designed and constructed by incorporating epoxy soybean oil (ESO) and an antibacterial agent polyhexamethylene guanidine hydrochloride (PHMG), then the film was prepared by reaction extrusion and blow molding using TPS-E and poly(butylene adipate-co-terephthalate) (PBAT). The micro-crosslinking structure, forming through ring-opening reaction between the epoxy active site of TPS-E and the end group of PBAT, improved the compatibility of starch/PBAT blend and reduce the dispersed starch phase size, leading to significantly increase the tensile strength. Compared to starch/PBAT films, the tensile strength of TPS-E/PBAT in the longitudinal direction increase by 112% with the same starch content of 30%. Furthermore, these TPS-E/PBAT films demonstrated long-lasting antibacterial performance with a 98% inhibition ratio even after 10 cycles, without any observed leaching of the antibacterial agent, highlighting the high coupling efficiency of PHMG. TPS-E with the degradable ESO also promotes the degradation of PBAT. Thus, an important method of synergistic improving the mechanical, degradable and antibacterial properties of blown films through the design of reactive micro-crosslinked starch structures was established.

Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy.

Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1. The resultant fibrous glue is capable of normalizing tumoral vasculature as well as restricting immune escape. The pre-GP1 retains a 6-fold higher penetration depth than that of antibody in the multicellular spheroids (MCSs) model. It also shows remarkable tumor growth inhibition (TGI) from 19% to 61% in a murine advanced large tumor model compared to the clinical combination therapy. In addition, in the orthotopic renal tumor preclinical model, the lung metastatic nodules are reduced by 64% compared to the clinically used combination. This pre-GP1 provides a promising strategy to control the progression and metastasis of advanced renal carcinoma.

Combined BRAF and PIM1 inhibitory therapy for papillary thyroid carcinoma based on BRAFV600E regulation of PIM1: Synergistic effect and metabolic mechanisms.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, and its incidence has increased rapidly in recent years. The BRAF inhibitor vemurafenib is effective against BRAFV600E-positive PTC; however, acquired resistance to single agent therapy frequently leads to tumor recurrence and metastasis, underscoring the need to develop tailored treatment strategies. We previously showed that the oncogenic kinase PIM1 was associated with the malignant phenotype and prognosis of PTC. In this study, we showed that sustained expression of the PIM1 protein in PTC was affected by the BRAFV600E mutation. Based on this regulatory mechanism, we tested the synergistic effects of inhibitors of BRAF (BRAFi) and PIM1 in BRAFV600E-positive PTC cell lines and xenograft tumors. LC-MS metabolomics analyses suggested that BRAFi/PIMi therapy acted by restricting the amounts of critical amino acids and nucleotides required by cancer cells as well as modulating DNA methylation. This study elucidates the role of BRAFV600E in the regulation of PIM1 in PTC and demonstrates the synergistic effect of a novel combination, BRAFi/PIMi, for the treatment of PTC. This discovery, along with the pathways that may be involved in the powerful efficacy of BRAFi/PIMi strategy from the perspective of cell metabolism, provides insight into the molecular basis of PTC progression and offers new perspectives for BRAF-resistant PTC treatment.

Willed Attentional Selection of Visual Features: An EEG Study.

Visual selective attention studies generally tend to apply cuing paradigms to instructively direct observers' attention to certain locations, features or objects. However, in real situations, attention in humans often flows spontaneously without any specific instructions. Recently, a concept named "willed attention" was raised in visuospatial attention, in which participants are free to make volitional attention decisions. Several ERP components during willed attention were found, along with a perspective that ongoing alpha activity may bias the subsequent attentional choice. However, it remains unclear whether similar neural mechanisms exist in feature- or object-based willed attention. Here, we included choice cues and instruct cues in a feature-based selective attention paradigm, allowing participants to freely choose or to be instructed to attend a color for the subsequent target detection task. Pre-cue ongoing alpha oscillations, cue-evoked potentials and target-related steady-state visual evoked potentials (SSVEPs) were simultaneously measured as markers of attentional processing. As expected, SSVEP responses were similarly modulated by attention between choice and instruct cue trials. Similar to the case of spatial attention, a willed-attention component (Willed Attention Component, WAC) was isolated during the cue-related choice period by comparing choice and instruct cues. However, pre-cue ongoing alpha oscillations did not predict the color choice (yellow vs blue), as indicated by the chance level decoding accuracy (50%). Overall, our results revealed both similarities and differences between spatial and feature-based willed attention, and thus extended the understanding toward the neural mechanisms of volitional attention.

FGF21 ameliorates septic liver injury by restraining proinflammatory macrophages activation through the autophagy/HIF-1α axis.

INTRODUCTION: Sepsis, a systemic immune syndrome caused by severe trauma or infection, poses a substantial threat to the health of patients worldwide. The progression of sepsis is heavily influenced by septic liver injury, which is triggered by infection and cytokine storms, and has a significant impact on the tolerance and prognosis of septic patients. The objective of our study is to elucidate the biological role and molecular mechanism of fibroblast growth factor 21 (FGF21) in the process of sepsis. OBJECTIVES: This study was undertaken in an attempt to elucidate the function and molecular mechanism of FGF21 in therapy of sepsis. METHODS: Serum concentrations of FGF21 were measured in sepsis patients and septic mice. Liver injury was compared between mice FGF21 knockout (KO) mice and wildtype (WT) mice. To assess the therapeutic potential, recombinant human FGF21 was administered to septic mice. Furthermore, the molecular mechanism of FGF21 was investigated in mice with myeloid-cell specific HIF-1α overexpression mice (LyzM-CreDIO-HIF-1α) and myeloid-cell specific Atg7 knockout mice (Atg7△mye). RESULTS: Serum level of FGF21 was significantly increased in sepsis patients and septic mice. Through the use of recombinant human FGF21 (rhFGF21) and FGF21 KO mice, we found that FGF21 mitigated septic liver injury by inhibiting the initiation and propagation of inflammation. Treatment with rhFGF21 effectively suppressed the activation of proinflammatory macrophages by promoting macroautophagy/autophagy degradation of hypoxia-inducible factor-1α (HIF-1α). Importantly, the therapeutic effect of rhFGF21 against septic liver injury was nullified in LyzM-CreDIO-HIF-1α mice and Atg7△mye mice. CONCLUSIONS: Our findings demonstrate that FGF21 considerably suppresses inflammation upon septic liver injury through the autophagy/ HIF-1α axis.

Relationships among bacterial cell size, diversity, and taxonomy in rumen.

Introduction: The rumen microbial community plays a crucial role in the digestion and metabolic processes of ruminants. Although sequencing-based studies have helped reveal the diversity and functions of bacteria in the rumen, their physiological and biochemical characteristics, as well as their dynamic regulation along the digestion process in the rumen, remain poorly understood. Addressing these gaps requires pure culture studies to demystify the intricate mechanisms at play. Bacteria exhibit morphological differentiation associated with different species. Based on the difference in size or shape of microorganisms, size fractionation by filters with various pore sizes can be used to separate them. Methods: In this study, we used polyvinylidene difluoride filters with pore sizes of 300, 120, 80, 40, 20, 8, 6, 2.1, and 0.6 µm. Bacterial suspensions were successively passed through these filters for the analysis of microbial population distribution using 16S rRNA gene sequences. Results: We found that bacteria from the different pore sizes were clustered into four branches (> 120 µm, 40-120 µm, 6-20 µm, 20-40 µm, and < 0.6 µm), indicating that size fractionation had effects on enriching specific groups but could not effectively separate dominant groups by cell size alone. The species of unclassified Flavobacterium, unclassified Chryseobacterium, unclassified Delftia, Methylotenera mobilis, unclassified Caulobacteraceae, unclassified Oligella, unclassified Sphingomonas, unclassified Stenotrophomonas, unclassified Shuttleworthia, unclassified Sutterella, unclassified Alphaproteobacteria, and unclassified SR1 can be efficiently enriched or separated by size fractionation. Discussion: In this study, we investigated the diversity of sorted bacteria populations in the rumen for preliminary investigations of the relationship between the size and classification of rumen bacteria that have the potential to improve our ability to isolate and culture bacteria from the rumen in the future.

Knowledge, concerns, and vaccine acceptance related to Mpox (Monkeypox) among university students in North and Northeast China: An online cross-sectional study.

The growing number of Mpox cases in China has posed a challenge to public health. The prevalence of men who have sex with men behaviors among students has been consistently increasing each year in China, accompanied by a high frequency of unprotected anal sex. As crowded places, schools are highly likely to cause an Mpox outbreak among students through long-term close contact. Understanding university students' perceptions about Mpox and willingness to vaccinate play a vital role in implementing preventive measures in schools. This study aimed to assess knowledge, concerns, and vaccine acceptance toward Mpox among university students in North and Northeast China. A cross-sectional study was conducted among 3831 university students from seven universities in North and Northeast China between September 10 and September 25, 2023. This study found a relative insufficiency in Mpox knowledge among university students (71.60%), with less than half expressing concern about the Mpox outbreak (39.57%), and the majority exhibiting a positive attitude to vaccination (76.30%). Multivariate regression analysis revealed that a good knowledge level was associated with age, study discipline, education level, and a high level of concern about Mpox. Male, elderly, or highly educated participants had a low level of concern about Mpox. Participants with a high level of knowledge toward Mpox were more likely to have the vaccination willingness. This study might help governments and schools to understand students' Mpox perceptions and vaccination intentions, enabling them to implement effective measures in addressing the issue of inadequate understanding regarding Mpox among university students.

Evaluation of omadacycline regimens for community-acquired bacterial pneumonia patients infected with Staphylococcus Aureus by pharmacokinetic/pharmacodynamic analysis.

Omadacycline is an FDA-approved agent for community-acquired bacterial pneumonia (CABP). The purpose of this study is to evaluate the effectiveness of omadacycline for treating CABP patients infected with Staphylococcus aureus, including Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA), using pharmacokinetic/pharmacodynamic (PK/PD) analysis. Monte Carlo simulations (MCSs) were performed by utilizing omadacycline pharmacokinetic (PK) parameters, minimum inhibitory concentration (MIC) data, and in vivo PK/PD targets to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) values for different dose regimens against MRSA and MSSA in CABP patients. A dosage regimen with a PTA or CFR expectation value greater than 90% was considered optimal. For all recommended dose regimens, PTA values for MRSA MIC ≤1 and MSSA MIC ≤4 on days 1, 4, and 7 were greater than 90%. Based on the MIC distribution of Staphylococcus aureus, all dose regimens had CFR values greater than 90% for both MRSA and MSSA. CFR values for different bacterial strains were still greater than 90% within the range of PK/PD target values less than 40, although they gradually decreased with increasing PK/PD target values. PK/PD modeling demonstrated that all recommended dose regimens of omadacycline are highly effective against CABP patients infected with MRSA and MSSA. The study provides theoretical support for the efficacy of omadacycline in different dose regimens.

Ammonia distribution and ecological risk assessment in nine fresh lakes in China.

With the development of industry and economy, ammonia nitrogen pollutions in surface water are of great concern worldwide. This study investigated the historical contents of total ammonia nitrogen (TAN) and unionized ammonia molecules (NH3) in nine fresh lakes in China during 2014-2022. Three different classification methods (flood season, season, and geographical distribution) were used to analyze the concentration variation of TAN and NH3. The concentration of TAN first decreased and then increased in the flood season, showing a lower concentration in summer and a higher concentration in winter. The variation trend of NH3 was in an opposite way with TAN. Correlation analysis between ammonia and 10 water quality parameters and 4 pollution emission and treatment parameters showed that the correlation coefficient between TAN and total phosphorus (total nitrogen) was 0.44 (0.43), respectively. The correlation coefficients between average annual TAN concentration and total emissions (waste water treatment input) were 0.35 (0.53), respectively. Combined with ecotoxicity data from a series of aquatic species, the ecological risks of TAN and NH3 in lakes were evaluated using hazard quotient and joint probability curve methods. From 2014 to 2022, the probability of 5% species affected in the acute ecological risk of TAN and NH3 is lower than 0.01, but for the chronic ecological risk of TAN and NH3, the probabilities of 5% species affected are 0.003-0.030 and 0.04-0.14, respectively. The chronic ecological risks were higher than the acute ecological risks, and high risks in plateau lakes like Dianchi Lake should be paid more attention to.

Clinical characteristics and surgical outcomes of low-grade epilepsy-associated brain tumors.

Background: Low-grade epilepsy-associated brain tumors (LEATs) are found to be the second most common lesion-related epilepsy. Malignant potential of LEATs is very low and the overall survival is good, so the focus of treatment is focused more on seizure outcome rather than oncological prognosis. Objectives: This study was conducted to evaluate the risk factors of seizure outcomes after resection in patients with LEATs. Design: A retrospective study. Methods: A retrospective analysis of patients with LEATs who underwent resective surgery in our three epilepsy centers between October 2010 and April 2023 with a minimum follow-up of 1 year. Demography, clinical characters, neurophysiology, and molecular neuropathology were assessed for association with postoperative seizure outcomes at 1-, 2-, and 5-year follow-up. Synthetic minority oversampling technique (SMOTE) algorithm model was performed to handle the imbalance of data distribution. Gaussian Naïve Bayes (GNB) algorithms were created as a basis for classifying outcomes according to observation indicators. Results: A total of 111 patients were enrolled in the cohort. The most common pathology was ganglioglioma (n = 37, 33.3%). The percentage of patients with seizure freedom was 91.0% (101/111) at 1-year follow-up, 87.5% (77/88) at 2-year follow-up, and 79.1% (53/67) at 5-year follow-up. Partial resection had a significantly poor seizure outcome compared to total resection and supratotal resection (p < 0.05). The epileptiform discharge on post-resective intraoperative electrocorticography (ECoG) or postoperative scalp electroencephalography (EEG) were negative factors on postoperative seizure freedom at 1-, 2-, or 5-year follow-ups (p < 0.05). The area under the receiver-operating characteristic curve value of the GNB-SMOTE model was 0.95 (95% CI, 0.876-1.000), 0.892 (95% CI, 0.656-0.934), and 0.786 (95% CI, 0.491-0.937) at 1-, 2-, and 5-year follow-up, respectively. Conclusion: The partial resection, post-resective intraoperative ECoG, and postoperative scalp EEG were valuable indicators of poor seizure outcomes. The utilization of post-resective intraoperative ECoG is beneficial to improve seizure outcomes. Based on the data diversity and completeness of three medical centers, a multivariate correlation analysis model was established based on GNB algorithm.

Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma.

Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research.

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We investigated the changes of soil nutrients and plant communities in the artificial sand fixation forests of Caragana korshinskii with different ages. The results showed that soil organic carbon and soil total nitrogen contents increased with the stand ages, and were significantly higher in 40 and 50 year-old than other ages. Soil organic carbon and total nitrogen contents recovered much faster in the surface layer (0-10 cm) than in others. Soil nutrient stoichiometric ratios (C:P, N:P) in the 0-10 cm soil layer differed significantly among different stand ages. With the increases of stand age, C and N contents in C. korshinskii leaves increased significantly, and reached the maximum at 50 year-old. Leaf P content increased first and then decreased, being maximum at 18 year-old. Leaf C:N first increased and then decreased, being maximum at 12 year-old. The contents of photosynthetic pigments and leaf C:P and N:P decreased first and then increased, being minimum at 18 year-old. C. korshinskii was mainly influenced by N availability before 40 year-old, but mainly limited by P after. The species number, density, and vegetation cover of annual and perennial herbaceous plants increased with stand ages, and the community shifted from a simple shrub plant community to a complex shrub-herb community. The biomass of C. korshinskii and herbaceous plants increased significantly with stand age, and had a significant positive correlation with the contents of soil organic carbon, total nitrogen and N:P.

Development and validation of a nomogram for predicting 28-day in-hospital mortality in sepsis patients based on an optimized APACHE II score.

PURPOSE: The objective of this study is to establish a nomogram that correlates optimized APACHE II score with sepsis-related indicators, aiming to provide a robust model for early prediction of sepsis prognosis in clinical practice and serve as a valuable reference for improved diagnosis and treatment strategies. METHODS: This retrospective study extracted sepsis patients meeting the inclusion criteria from the MIMIC-IV database to form the training group. An optimized Acute Physiology and Chronic Health Evaluation (APACHE) II score integrated with relevant indicators was developed using a nomogram for predicting the prognosis of sepsis patients. External validation was conducted using data from the Intensive Care Unit at Lanzhou University Second Hospital. RESULTS: The study enrolled 1805 patients in the training cohort and 203 patients in the validation cohort. A multifactor analysis was conducted to identify factors affecting patient mortality within 28 days, resulting in the development of an Optimized Score by simplifying evaluation indicators from APACHE II score. The results showed that the Optimized Score (AUC = 0.715) had a higher area under receiver operating characteristic curve than SOFA Score (AUC = 0.637) but slightly lower than APACHE II score (AUC = 0.720). Significant indicators identified through multifactor analysis included platelet count, total bilirubin level, albumin level, prothrombin time, activated partial thromboplastin time, mechanical ventilation (MV) use and renal replacement therapy (RRT) use. These seven indicators were combined with Optimized Score to construct a nomogram Based on these seven indicators. The nomogram demonstrated good clinical predictive value in both training cohort (AUC = 0.803) and validation cohort (AUC = 0.750). Calibration curves and decision curve analyses also confirmed its good predictive ability, surpassing the APACHE II score and SOFA score in identifying high-risk patients. CONCLUSIONS: The Nomogram was established in this study using the MIMIC-IV database and validated with external data, demonstrating its robust discriminability, calibration, and clinical practicability for predicting 28-day mortality in sepsis patients. These findings aim to provide substantial support for clinicians' decision-making.

RTC_TongueNet: An improved tongue image segmentation model based on DeepLabV3.

Objective: Tongue segmentation as a basis for automated tongue recognition studies in Chinese medicine, which has defects such as network degradation and inability to obtain global features, which seriously affects the segmentation effect. This article proposes an improved model RTC_TongueNet based on DeepLabV3, which combines the improved residual structure and transformer and integrates the ECA (Efficient Channel Attention Module) attention mechanism of multiscale atrous convolution to improve the effect of tongue image segmentation. Methods: In this paper, we improve the backbone network based on DeepLabV3 by incorporating the transformer structure and an improved residual structure. The residual module is divided into two structures and uses different residual structures under different conditions to speed up the frequency of shallow information mapping to deep network, which can more effectively extract the underlying features of tongue image; introduces ECA attention mechanism after concat operation in ASPP (Atrous Spatial Pyramid Pooling) structure to strengthen information interaction and fusion, effectively extract local and global features, and enable the model to focus more on difficult-to-separate areas such as tongue edge, to obtain better segmentation effect. Results: The RTC_TongueNet network model was compared with FCN (Fully Convolutional Networks), UNet, LRASPP (Lite Reduced ASPP), and DeepLabV3 models on two datasets. On the two datasets, the MIOU (Mean Intersection over Union) and MPA (Mean Pixel Accuracy) values of the classic model DeepLabV3 were higher than those of FCN, UNet, and LRASPP models, and the performance was better. Compared with the DeepLabV3 model, the RTC_TongueNet network model increased MIOU value by 0.9% and MPA value by 0.3% on the first dataset; MIOU increased by 1.0% and MPA increased by 1.1% on the second dataset. RTC_TongueNet model performed best on both datasets. Conclusion: In this study, based on DeepLabV3, we apply the improved residual structure and transformer as a backbone to fully extract image features locally and globally. The ECA attention module is combined to enhance channel attention, strengthen useful information, and weaken the interference of useless information. RTC_TongueNet model can effectively segment tongue images. This study has practical application value and reference value for tongue image segmentation.

Arsenic trioxide suppresses lung adenocarcinoma stem cell stemness by inhibiting m6A modification to promote ferroptosis.

Arsenic trioxide (ATO) is well known for its inhibitory effects on cancer progression, including lung adenocarcinoma (LUAD), but the molecular mechanism remains elusive. This study aimed to investigate the roles of ATO in regulating LUAD stem cells (LASCs) and the underlying mechanisms. To induce LASCs, cells cultured in an F12 medium, containing B27, epidermal growth factor, and basic fibroblast growth factor, induced LASCs. LASCs stemness was assessed through tumor sphere formation assay, and percentages of CD133+ cells were detected by flow cytometry. The Cell Counting Kit-8 method was used to assess LASCs viability, while reactive oxygen species (ROS) and iron ion levels were quantitated by fluorescence microscopy and spectrophotometry, respectively, and total m6A levels were measured by dot blot. Additionally, LASCs mitochondrial alterations were analyzed via transmission electron microscopy. Finally, the tumorigenicity of LASCs was assessed using a cancer cell line-based xenograft model. Tumor sphere formation and CD133 expression were used to validate the successful induction of LASCs from A549 and NCI-H1975 cells. ATO significantly inhibited proliferation, reduced ZC3H13 expression and total m6A modification levels, and increased ROS and iron ion content, but repressed sphere formation and CD133 expression in LASCs. ZC3H13 overexpression or ferrostatin-1 treatment abrogated LASCs stemness inhibition caused by ATO treatment, and interference with ZC3H13 inhibited LASCs stemness. Furthermore, the promotion of LASCs ferroptosis by ATO was effectively mitigated by ZC3H13 overexpression, while interference with ZC3H13 further promoted ferroptosis. Moreover, si-ZC3H13 promoted ferroptosis and impaired stemness in LASCs, which ferrostatin-1 abrogated. Finally, ZC3H13 overexpression alleviated the inhibitory effects of ATO on LASCs tumorigenicity. Taken together, ATO treatment substantially impaired the stemness of LUAD stem cells by promoting the ferroptosis program, which was mediated by its ZC3H13 gene expression inhibition to suppress m6A medication.