Toxicity and fate of cadmium in hydroponically cultivated lettuce (Lactuca sativa L.) influenced by microplastics.

Although more attention has been paid to microplastics (MPs) pollution in environment, research on the synthetic influence of microplastic and heavy metals remains limited. To help fill this information gap, we investigated the adsorption behavior of virgin polyvinyl chloride microplastics (PVCMPs) (≤450 µm white spherical powder) on cadmium (II). The effects on seed germination, seedling growth, photosynthetic system, oxidative stress indicators of lettuce, and changes in Cd bioavailability were evaluated under Cd2+ (25 µmol/L), PVCMPs (200 mg/L), and PVCMP-Cd combined (200 mg/L + 25 µmol/L) exposures in hydroponic system. The results demonstrated that the PVCMPs effectively adsorbed Cd ions, which validated by the pseudo-second-order kinetic and the Langmuir isotherm models, indicating the sorption of Cd2+ on the PVCMPs was primary chemisorption and approximates monomolecular layer sorption. Compared to MPs, Cd significantly inhibits plant seed germination and seedling growth and development. However, Surprising improvement in seed germination under PVCMPs-Cd exposure was observed. Moreover, Cd2+ and MPs alone or combined stress caused oxidative stress with reactive oxygen species (ROS) including H2O2, O2- and Malondialdehyde (MDA) accumulation in plants, and substantially damaged to photosynthesis. With the addition of PVCMPs, the content of Cd in the leaves significantly (P<0.01) decreased by 1.76-fold, and the translocation factor and Cd2+removal rate in the water substantially (P<0.01) decreased by 6.73-fold and 1.67-fold, respectively in contrast to Cd2+ stress alone. Therefore, it is concluded the PVCMP was capable of reducing Cd contents in leaves, alleviating Cd toxicity in lettuce. Notably, this study provides a scientific foundation and reference for comprehending the toxicological interactions between microplastics and heavy metals in the environment.

Strand-Specific RNA Sequencing Reveals Gene Expression Patterns in F1 Chick Breast Muscle and Liver after Hatching.

Heterosis refers to the phenomenon where hybrids exhibit superior performance compared to the parental phenotypes and has been widely utilized in crossbreeding programs for animals and crops, yet the molecular mechanisms underlying this phenomenon remain enigmatic. A better understanding of the gene expression patterns in post-hatch chickens is very important for exploring the genetic basis underlying economically important traits in the crossbreeding of chickens. In this study, breast muscle and liver tissues (n = 36) from full-sib F1 birds and their parental pure lines were selected to identify gene expression patterns and differentially expressed genes (DEGs) at 28 days of age by strand-specific RNA sequencing (ssRNA-seq). This study indicates that additivity is the predominant gene expression pattern in the F1 chicken post-hatch breast muscle (80.6% genes with additivity) and liver (94.2% genes with additivity). In breast muscle, Gene Ontology (GO) enrichment analysis revealed that a total of 11 biological process (BP) terms closely associated with growth and development were annotated in the identified DEG sets and non-additive gene sets, including STAT5A, TGFB2, FGF1, IGF2, DMA, FGF16, FGF12, STAC3, GSK3A, and GRB2. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation presented that a total of six growth- and development-related pathways were identified, involving key genes such as SLC27A4, GLUL, TGFB2, COX17, and GSK3A, including the PPAR signaling pathway, TGF-beta signaling pathway, and mTOR signaling pathway. Our results may provide a theoretical basis for crossbreeding in domestic animals.

A Microporous Mn(II) MOF Based on 5-(4H-1,2,4-triazol-4-yl) Isophthalic Acid for CO2/N2 Separation.

Removal of carbon dioxide (CO2) from a CO2/N2 mixture by utilizing CO2-selective sorbents is important from the perspective of energy security and environmental sustainability. Herein, a microporous metal-organic framework (MOF) composed of manganese(II) and a bifunctional linker 5-(4H-1,2,4-triazol-4-yl)benzene-1,3-dicarboxylic acid (H2L), [Mn(HL)2] (1) is designed and synthesized using a hydrothermal method. Characterized by single-crystal X-ray diffraction (SCXRD), a microporous channel was found in the structure of compound 1 along the a-axis. Attributed to hydrogen-binding interactions between CO2 molecules and N- and O-donor ligands in its microporous one-dimensional (1D) channel, compound 1 exhibits favorable adsorption of CO2 over N2. Further, verified by experimental breakthrough tests, the CO2/N2 mixture can be separated efficiently. This work provides potential guidance for designing CO2-selective MOFs for CO2/N2 separation.

Non-traumatic osteonecrosis of the femoral head induced by steroid and alcohol exposure is associated with intestinal flora alterations and metabolomic profiles.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives. METHODS: Utilizing fecal samples from 68 NONFH patients (32 steroid-induced, 36 alcohol-induced), high-throughput 16 S rDNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS) metabolomics analyses were conducted. Univariate and multivariate analyses were applied to the omics data, employing linear discriminant analysis effect size to identify potential biomarkers. Additionally, functional annotation of differential metabolites and associated pathways was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, Spearman correlation analysis was employed to assess the potential correlations between differential gut microbiota and metabolites. RESULTS: High-throughput 16 S rDNA sequencing revealed significant gut microbial differences. At the genus level, the alcohol group had higher Lactobacillus and Roseburia, while the steroid group had more Megasphaera and Akkermansia. LC-MS/MS metabolomic analysis indicates significant differences in fecal metabolites between steroid- and alcohol-induced ONFH patients. Alcohol-induced ONFH (AONFH) showed elevated levels of L-Lysine and Oxoglutaric acid, while steroid-induced ONFH(SONFH) had increased Gluconic acid and Phosphoric acid. KEGG annotation revealed 10 pathways with metabolite differences between AONFH and SONFH patients. Correlation analysis revealed the association between differential gut flora and differential metabolites. CONCLUSIONS: Our results suggest that hormones and alcohol can induce changes in the gut microbiota, leading to alterations in fecal metabolites. These changes, driven by different pathways, contribute to the progression of the disease. The study opens new research directions for understanding the pathogenic mechanisms of hormone- or alcohol-induced NONFH, suggesting that differentiated preventive and therapeutic approaches may be needed for NONFH caused by different triggers.

Automatic measurement of lower limb alignment in portable devices based on deep learning for knee osteoarthritis.

BACKGROUND: For knee osteoarthritis patients, analyzing alignment of lower limbs is essential for therapy, which is currently measured from standing long-leg radiographs of anteroposterior X-ray (LLR) manually. To address the time wasting, poor reproducibility and inconvenience of use caused by existing methods, we present an automated measurement model in portable devices for assessing knee alignment from LLRs. METHOD: We created a model and trained it with 837 conforming LLRs, and tested it using 204 LLRs without duplicates in a portable device. Both manual and model measurements were conducted independently, then we recorded knee alignment parameters such as Hip knee ankle angle (HKA), Joint line convergence angle (JCLA), Anatomical mechanical angle (AMA), mechanical Lateral distal femoral angle (mLDFA), mechanical Medial proximal tibial angle (mMPTA), and the time required. We evaluated the model's performance compared with manual results in various metrics. RESULT: In both the validation and test sets, the average mean radial errors were 2.778 and 2.447 (P<0.05). The test results for native knee joints showed that 92.22%, 79.38%, 87.94%, 79.82%, and 80.16% of the joints reached angle deviation<1° for HKA, JCLA, AMA, mLDFA, and mMPTA. Additionally, for joints with prostheses, 90.14%, 93.66%, 86.62%, 83.80%, and 85.92% of the joints reached that. The Chi-square test did not reveal any significant differences between the manual and model measurements in subgroups (P>0.05). Furthermore, the Bland-Altman 95% limits of agreement were less than ± 2° for HKA, JCLA, AMA, and mLDFA, and slightly more than ± 2 degrees for mMPTA. CONCLUSION: The automatic measurement tool can assess the alignment of lower limbs in portable devices for knee osteoarthritis patients. The results are reliable, reproducible, and time-saving.

Efficacy and Perioperative Safety of Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer.

Background: Esophageal cancer (EC) remains a significant global health concern. Minimally invasive surgical techniques, including robot-assisted approaches, have emerged as promising options for improving outcomes and patient recovery in EC management. Objective: This study aims to evaluate the clinical utility of robot-assisted minimally invasive esophagectomy (RAMIE) in the treatment of EC. Methods: A total of 160 EC patients undergoing treatment at our hospital were included in this study. Patients were randomly assigned to either the research group, receiving RAMIE, or the control group, undergoing thoracoscopic minimally invasive esophagectomy (MIE). Surgical outcomes, postoperative recovery, complication rates, and changes in inflammatory factors (IFs) such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were compared between the two groups. Additionally, prognostic survival and EC recurrence rates were assessed at a 1-year follow-up. Results: The research group demonstrated longer operative times, a higher number of dissected lymph nodes, reduced intraoperative bleeding, and quicker postoperative recovery compared to the control group, with significantly fewer complications (P < .05). Furthermore, the research group exhibited lower levels of postoperative IFs and MDA, along with higher levels of SOD and GSH-Px, compared to the control group (P < .05). There was no significant difference between the two groups in terms of prognostic survival and EC recurrence rates (P > .05). Conclusion: RAMIE demonstrates superior efficacy in enhancing therapeutic outcomes and accelerating postoperative recovery in patients with EC, thus establishing its value in EC treatment protocols. RAMIE is suggested as a valuable therapeutic option and warrants clinical adoption for EC management.

New advances in the treatment of chondrosarcoma under the PD-1/PD-L1 pathway.

ABSTRACT: Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma.

Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease.

INTRODUCTION: Although glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD and its sequential association with core AD biomarkers is poorly understood. METHODS: Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS) in participants with AD dementia (n = 47), mild cognitive impairment (MCI; n = 137), and normal controls (n = 235) from the Alzheimer's Disease Neuroimaging Initiative. RESULTS: ALPS index was significantly lower in AD dementia than in MCI or controls. Lower ALPS index was significantly associated with faster changes in amyloid positron emission tomography (PET) burden and AD signature region of interest volume, higher risk of amyloid-positive transition and clinical progression, and faster rates of amyloid- and neurodegeneration-related cognitive decline. Furthermore, the associations of the ALPS index with cognitive decline were fully mediated by amyloid PET and brain atrophy. DISCUSSION: Glymphatic failure may precede amyloid pathology, and predicts amyloid deposition, neurodegeneration, and clinical progression in AD. HIGHLIGHTS: The analysis along the perivascular space (ALPS) index is reduced in patients with Alzheimer's disease (AD) dementia, prodromal AD, and preclinical AD. Lower ALPS index predicted accelerated amyloid beta (Aß) positron emission tomography (PET) burden and Aß-positive transition. The decrease in the ALPS index occurs before cerebrospinal fluid Aß42 reaches the positive threshold. ALPS index predicted brain atrophy, clinical progression, and cognitive decline. Aß PET and brain atrophy mediated the link of ALPS index with cognitive decline.

An isochronous stress ratio logarithmic strain curve based clay creep model considering the effects of hardening and damage.

Creep is one of the typical mechanical properties of clay, and studying the creep mechanical properties of clay is of great significance to construction projects in clay sites. This study conducted creep tests on Chengdu clay and found that the soil mass underwent elastic deformation, decay creep deformation, steady-state creep deformation, and accelerated creep deformation. The isochronous stress ratio-logarithmic strain curves and their mathematical models were proposed to thoroughly analyze clay creep mechanical properties. Creep automatic feature points, such as linear elastic extreme point, initial yield point, long-term strength point, and plastic point, were identified on the curve. Considering the hardening and damage effects during creep loading, linear elastic and viscoelastic elements considering the time-dependent damage, a viscoplastic element considering the load hardening effect, and viscoplastic and plastic elements considering the load damage effect were established based on the element model and the Riemann-Liouville fractional derivative. Based on the mechanical properties of the whole clay creep process, the creep mechanical feature points, and the established element model, a clay creep model was proposed considering the hardening and damage effects. The rationality and regularity of the creep model were verified using the creep test data. This research accurately revealed the creep mechanical properties of clay and facilitated soil deformation prediction, thus providing technical guidance and references for construction projects in clay sites.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

Photosynthetic Responses of Racomitrium japonicum L. to Strontium Stress Evaluated through Chlorophyll a Fluorescence OJIP Transient Analysis.

Nuclides pollution and its biological effects are of great concern, especially for bryophytes during their terrestrial adaptation. Understanding PSII activity and electron transport response is vital for comprehending moss abiotic stress reactions. However, little is known about the photosynthetic performance of moss under nuclide treatment. Therefore, this study aimed to evaluate the chlorophyll fluorescence of Racomitrium japonicum L. The moss was subjected to Sr2+ solutions at concentrations of 5, 50, and 500 mg/L to evaluate chlorophyll a fluorescence using the OJIP test. Moderate and high Sr2+ stress led to inner cell membrane dissolution and reduced chlorophyll content, indicating impaired light energy absorption. At 5 mg/L Sr2+, fluorescence kinetics showed increased light energy capture, energy dissipation, and total photosynthetic driving force, thus stimulating transient photosynthetic activity of PSII and improving PSI reduction. Linear electron transfer and PSII stability significantly decreased under moderate and high Sr2+ stress, indicating potential photosynthetic center damage. Cyclic electron transfer (CEF) alleviated photosynthetic stress at 5 mg/L Sr2+. Thus, low Sr2+ levels stimulated CEF, adjusting energy flux and partitioning to protect the photosynthetic apparatus. Nevertheless, significant damage occurred due to inefficient protection under high Sr2+ stress.

Berberine alleviates concanavalin A-induced autoimmune hepatitis in mice by modulating the gut microbiota.

BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored. METHODS: BBR was orally administered at doses of 100 mg⋅kg-1⋅d-1 for 7 days to mice before concanavalin A-induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice. RESULTS: We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-α, interferon-γ, IL-1ß, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-κB pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota. CONCLUSIONS: BBR alleviated concanavalin A-induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.

[Corrigendum] Upregulation of centromere protein M promotes tumorigenesis: A potential predictive target for cancer in humans.

Subsequently to the publication of this paper, the authors' have realized that Fig. 2A on p. 3927 was published featuring an error; specifically, there was an unintentional duplication of one of the representative images chosen for the figure (the same image was selected to represent the 'BRCA/Normal' and 'Tumor/LUSC' experiments). Additionally, the sample numbers in Fig. 2A were also incorrect. The correct sample numbers are as follows: 3 samples of breast tissue, 12 samples of breast cancer tissue, 3 samples of normal cervical tissue, 9 samples of CESC, 7 samples of LIHC, 3 samples of normal lung tissue and 6 samples of LUSC. These errors were due to negligence during the storage of HPA database images.  The revised version of Fig. 2, showing the correct data for the 'Tumor/LUSC' experiment in Fig. 2A (where the error occurred), is shown on the next page. Note that this error did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to the corrigendum. The authors do stress the importance of a larger sample size to ascertain statistically significant differences in CENPM protein expression, predominantly localized in the cell nucleus. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 3922­3934, 2020; DOI: 10.3892/mmr.2020.11461].

ALKBH5 facilitates the progression of infantile hemangioma by increasing FOXF1 expression in a m6A-YTHDF2 dependent manner to activate HK-2 signaling.

Alkylation repair homolog protein 5 (ALKBH5) is reported to participate in infantile hemangioma (IH) progression. However, the underlying mechanism of ALKBH5 in IH remains unclear. Using qRT-PCR and Western blotting, ALKBH5, forkhead box F1 (FOXF1) and hexokinase 2 (HK-2) expressions in IH tissues and IH-derived endothelial cells XPTS-1 were assessed. The Me-RIP assay was used to analyze FOXF1 m6A level. CCK8, colony formation, flow cytometry and transwell assays were employed to determine IH cell viability, proliferation, apoptosis, migration and invasion. The interactions between YTH (YT521-B homology) domain 2 (YTHDF2), FOXF1 and HK-2 were analyzed by RIP, dual luciferase reporter gene assay and/or ChIP assay. The in vivo IH growth was evaluated in immunocompromised mice. FOXF1 was overexpressed in IH tissues, and its silencing inhibited IH cell proliferation, migration and invasion whereas promoting cell apoptosis in vitro. ALKBH5 upregulation facilitated FOXF1 mRNA stability and expression in IH cells in a m6A-YTHDF2-dependent manner. FOXF1 downregulation reversed the impact of ALKBH5 upregulation on IH cellular phenotypes. It also turned out that FOXF1 positively regulated HK-2 expression in IH cells through interacting with the HK-2 promoter. HK-2 upregulation abolished FOXF1 knockdown's inhibition on IH cell aggressive behaviors. ALKBH5 or FOXF1 silencing suppressed IH tumor development via HK-2 signaling in immunocompromised mice. ALKBH5 promoted FOXF1 expression m6A-YTHDF2 dependently, which in turn elevated HK-2 expression, thereby accelerating IH development.

Glycosaminoglycans: Participants in Microvascular Coagulation of Sepsis.

Sepsis represents a syndromic response to infection and frequently acts as a common pathway leading to fatality in the context of various infectious diseases globally. The pathology of severe sepsis is marked by an excess of inflammation and activated coagulation. A substantial contributor to mortality in sepsis patients is widespread microvascular thrombosis-induced organ dysfunction. Multiple lines of evidence support the notion that sepsis induces endothelial damage, leading to the release of glycosaminoglycans, potentially causing microvascular dysfunction. This review aims to initially elucidate the relationship among endothelial damage, excessive inflammation, and thrombosis in sepsis. Following this, we present a summary of the involvement of glycosaminoglycans in coagulation, elucidating interactions among glycosaminoglycans, platelets, and inflammatory cells. In this section, we also introduce a reasoned generalization of potential signal pathways wherein glycosaminoglycans play a role in clotting. Finally, we discuss current methods for detecting microvascular conditions in sepsis patients from the perspective of glycosaminoglycans. In conclusion, it is imperative to pay closer attention to the role of glycosaminoglycans in the mechanism of microvascular thrombosis in sepsis. Dynamically assessing glycosaminoglycan levels in patients may aid in predicting microvascular conditions, enabling the monitoring of disease progression, adjustment of clinical treatment schemes, and mitigation of both acute and long-term adverse outcomes associated with sepsis.

Immune-Related Molecules CD3G and FERMT3: Novel Biomarkers Associated with Sepsis.

Sepsis ranks among the most common health problems worldwide, characterized by organ dysfunction resulting from infection. Excessive inflammatory responses, cytokine storms, and immune-induced microthrombosis are pivotal factors influencing the progression of sepsis. Our objective was to identify novel immune-related hub genes for sepsis through bioinformatic analysis, subsequently validating their specificity and potential as diagnostic and prognostic biomarkers in an animal experiment involving a sepsis mice model. Gene expression profiles of healthy controls and patients with sepsis were obtained from the Gene Expression Omnibus (GEO) and analysis of differentially expressed genes (DEGs) was conducted. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to analyze genes within crucial modules. The functional annotated DEGs which related to the immune signal pathways were used for constructing protein-protein interaction (PPI) analysis. Following this, two hub genes, FERMT3 and CD3G, were identified through correlation analyses associated with sequential organ failure assessment (SOFA) scores. These two hub genes were associated with cell adhesion, migration, thrombosis, and T-cell activation. Furthermore, immune infiltration analysis was conducted to investigate the inflammation microenvironment influenced by the hub genes. The efficacy and specificity of the two hub genes were validated through a mice sepsis model study. Concurrently, we observed a significant negative correlation between the expression of CD3G and IL-1ß and GRO/KC. These findings suggest that these two genes probably play important roles in the pathogenesis and progression of sepsis, presenting the potential to serve as more stable biomarkers for sepsis diagnosis and prognosis, deserving further study.

ANP32B promotes colorectal cancer cell progression and reduces cell sensitivity to PRAP1 inhibitor through up-regulating HPF1.

ANP32B, a member of the acidic leucine-rich nuclear phosphoprotein 32 family member B, is aberrantly expressed in various cancers, including colorectal cancer. However, the function and mechanism of action of ANP32B in colorectal cancer remain unclear. The present study therefore analyzed the expression of ANP32B and its activity in colorectal cancer patient samples and colorectal cancer cell lines. ANP32B expression was found to be significantly upregulated in colorectal cancer patient samples and cell lines. Upregulation of ANP32B enhanced colorectal cancer cell proliferation and migration, whereas downregulation of ANP32B suppressed colorectal cancer cell proliferation. RNA sequencing analysis of differentially expressed genes in ANP32B silenced colorectal cancer cells showed that histone PARylation factor 1 (HPF1), which protects against DNA damage by interacting with the anti-tumor target PARP1, was significantly downregulated. Luciferase promoter assays testing the regulatory association between ANP32B and HPF1 showed that ANP32B interacted with the HPF1 promoter. Analysis of colorectal cancer samples from The Cancer Genome Atlas showed that ANP32B and HPF1 expression were positively correlated, and recovery assays showed that ANP32B promoted colorectal cancer progression by up-regulating HPF1. Overexpression of ANP32B also reduced the sensitivity of colorectal cancer cells to PARP1 inhibitor, consistent with the oncogenic role of ANP32B. ANP32B may alter the sensitivity of colorectal cancer cells to PARP1 inhibitor via a mechanism associated with the HPF1 gene. In summary, these findings showed that ANP32B acted as a tumor promoter, potentiating both colorectal cancer malignancy and drug resistance. Targeting the ANP32B/HPF1 axis may have benefit for patients with colorectal cancer.

Predictable navigation through spontaneous brain states with cognitive-map-like representations.

Just as navigating a physical environment, navigating through the landscapes of spontaneous brain states may also require an internal cognitive map. Contemporary computation theories propose modeling a cognitive map from a reinforcement learning perspective and argue that the map would be predictive in nature, representing each state as its upcoming states. Here, we used resting-state fMRI to test the hypothesis that the spaces of spontaneously reoccurring brain states are cognitive map-like, and may exhibit future-oriented predictivity. We identified two discrete brain states of the navigation-related brain networks during rest. By combining pattern similarity and dimensional reduction analysis, we embedded the occurrences of each brain state in a two-dimensional space. Successor representation modeling analysis recognized that these brain state occurrences exhibit place cell-like representations, akin to those observed in a physical space. Moreover, we observed predictive transitions of reoccurring brain states, which strongly covaried with individual cognitive and emotional assessments. Our findings offer a novel perspective on the cognitive significance of spontaneous brain activity and support the theory of cognitive map as a unifying framework for mental navigation.

Dual-Targeted Metal Ion Network Hydrogel Scaffold for Promoting the Integrated Repair of Tendon-Bone Interfaces.

The tendon-bone interface has a complex gradient structure vital for stress transmission and pressure buffering during movement. However, injury to the gradient tissue, especially the tendon and cartilage components, often hinders the complete restoration of the original structure. Here, a metal ion network hydrogel scaffold, with the capability of targeting multitissue, was constructed through the photopolymerization of the LHERHLNNN peptide-modified zeolitic imidazolate framework-8 (LZIF-8) and the WYRGRL peptide-modified magnesium metal-organic framework (WMg-MOF) within the hydrogel scaffold, which could facilitate the directional migration of metal ions to form a dynamic gradient, thereby achieving integrated regeneration of gradient tissues. LZIF-8 selectively migrated to the tendon, releasing zinc ions to enhance collagen secretion and promoting tendon repair. Simultaneously, WMg-MOF migrated to cartilage, releasing magnesium ions to induce cell differentiation and facilitating cartilage regeneration. Infrared spectroscopy confirmed successful peptide modification of nano ZIF-8 and Mg-MOF. Fluorescence imaging validated that LZIF-8/WMg-MOF had a longer retention, indirectly confirming their successful targeting of the tendon-bone interface. In summary, this dual-targeted metal ion network hydrogel scaffold has the potential to facilitate synchronized multitissue regeneration at the compromised tendon-bone interface, offering favorable prospects for its application in the integrated reconstruction characterized by the gradient structure.

Analysis of the Relation Between Balance Control Subsystems: A Structural Equation Modeling Approach.

Balance plays a crucial role in human life and social activities. Maintaining balance is a relatively complex process that requires the participation of various balance control subsystems (BCSes). However, previous studies have primarily focused on evaluating an individual's overall balance ability or the ability of each BCS in isolation, without considering how they influence (or interact with) each other. The first study used clinical scales to evaluate the functions of the four BCSes, namely Reactive Postural Control (RPC), Anticipatory Postural Adjustment (APA), Dynamic Gait (DG), and Sensory Orientation (SO), and psychological factors such as fear of falling (FOF). A hierarchical structural equation modeling (SEM) was used to investigate the relationship between the BCSes and their association with FOF. The second study involved using posturography to measure and extract parameters from the center of pressure (COP) signal. SEM with sparsity constraint was used to analyze the relationship between vision, proprioception, and vestibular sense on balance based on the extracted COP parameters. The first study revealed that the RPC, APA, DG and SO indirectly influenced each other through their overall balance ability, and their association with FOF was not the same. APA has the strongest association with FOF, while RPC has the least association with FOF. The second study revealed that sensory inputs, such as vision, proprioception, and vestibular sensing, directly affected each other, but their associations were not identical. Among them, proprioception plays the most important role in the three sensory subsystems. This study provides the first numerical evidence that the BCSes are not independent of each other and exist in direct or indirect interplay. This approach has important implications for the diagnosis and management of balance-related disorders in clinical settings and improving our understanding of the underlying mechanisms of balance control.