The feasibility and clinical significance of lateral approach thyroidectomy.

BACKGROUND: By comparing the three lateral approaches to thyroidectomy, the feasibility and clinical effects were analyzed, and the advantages of the lateral approach were summarized. METHODS: From January 2022 to January 2023, 52 patients with thyroid cancer admitted to our department were selected and subjected to Lateral approach for thyroidectomy. Among them, 31 patients underwent thyroidectomy via the supraclavicular approach, 13 patients underwent endoscopic thyroidectomy via the subclavicular approach, and 8 patients underwent endoscopic thyroidectomy via the axillary approach. The basic conditions, surgical conditions, complications, postoperative pain scores and postoperative satisfaction of patients in the three approach surgery groups were recorded and analyzed. RESULTS: There were no significant differences among the three approach groups in terms of patient characteristics, number of central lymph node dissections, intraoperative blood loss, postoperative drainage volume, duration of drainage tube placement, length of hospital stay, postoperative pain, satisfaction, and complications. However, the operation time was longest in the subclavicular approach group, followed by the axillary approach group, and shortest in the supraclavicular approach group. The total hospitalization cost was highest in the axillary approach group, followed by the subclavicular approach group, and lowest in the supraclavicular approach group. CONCLUSION: The lateral approach for thyroidectomy is deemed a safe and effective method. The three different approach paths gradually increase in length, allowing for the accumulation of anatomical experience. This approach has a shorter learning curve for clinical doctors and is a favorable choice for patients seeking aesthetic benefits.

Suppression of NSCLC progression via the co-administration of Danusertib, an AURK inhibitor, and KRIBB11, an HSF1 inhibitor.

Aurora kinase (AURK) and heat shock factor 1 (HSF1) are commonly overexpressed in non-small cell lung cancer (NSCLC), correlating with poor prognosis. This study aims to assess the therapeutic potential of combining the Danusertib (Danu, AURK inhibitor) and KRIBB11 (HSF1 inhibitor) for NSCLC treatment. The effects of this combination were investigated in A549 cells and a tumor xenograft mouse model. The findings demonstrate that concurrent administration of Danu and KRIBB11 effectively impedes cell proliferation, induces apoptosis, and triggers G2/M cell cycle arrest. Moreover, the combination treatment upregulates pro-apoptotic proteins (Cleaved-caspase3, Cleaved-PARP, and Bax) while downregulating anti-apoptotic proteins (Bcl-2), as well as G2/M-related proteins (CDC2 and cyclin B1). Additionally, the combination treatment elevates reactive oxygen species (ROS) levels, decreases mitochondrial membrane potential, and activates the DNA damage pathway. Interestingly, we discovered that the PI3K/AKT pathway is involved in mediating the effects of both Danu and KRIBB11. Furthermore, the combination treatment inhibits tumor growth and AKT signaling in the xenograft mouse model, increases levels of the tumor tissue oxidation product malondialdehyde (MDA), and induces DNA damage. To summarize, a potential therapeutic approach for NSCLC may involve dual inhibition of AURK and HSF1, resulting in the downregulation of the PI3K/AKT signaling pathway, and the activation of ROS-mediated mitochondrial and DNA damage pathways.

SET domain containing 2 promotes megakaryocyte polyploidization and platelet generation through methylation of α-tubulin.

BACKGROUND: Megakaryocytes (MKs) are polyploid cells responsible for producing ∼1011 platelets daily in humans. Unraveling the mechanisms regulating megakaryopoiesis holds the promise for the production of clinical-grade platelets from stem cells, overcoming significant current limitations in platelet transfusion medicine. Previous work identified that loss of the epigenetic regulator SET domain containing 2 (SETD2) was associated with an increased platelet count in mice. However, the role of SETD2 in megakaryopoiesis remains unknown. OBJECTIVES: Here, we examined how SETD2 regulated MK development and platelet production using complementary murine and human systems. METHODS: We manipulated the expression of SETD2 in multiple in vitro and ex vivo models to assess the ploidy of MKs and the function of platelets. RESULTS: The genetic ablation of Setd2 increased the number of high-ploidy bone marrow MKs. Peripheral platelet counts in Setd2 knockout mice were significantly increased ∼2-fold, and platelets exhibited normal size, morphology, and function. By knocking down and overexpressing SETD2 in ex vivo human cell systems, we demonstrated that SETD2 negatively regulated MK polyploidization by controlling methylation of α-tubulin, microtubule polymerization, and MK nuclear division. Small-molecule inactivation of SETD2 significantly increased the production of high-ploidy MKs and platelets from human-induced pluripotent stem cells and cord blood CD34+ cells. CONCLUSION: These findings identify a previously unrecognized role for SETD2 in regulating megakaryopoiesis and highlight the potential of targeting SETD2 to increase platelet production from human cells for transfusion practices.

MRI-Based Radiomics and Deep Learning in Biological Characteristics and Prognosis of Hepatocellular Carcinoma: Opportunities and Challenges.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. HCC exhibits strong inter-tumor heterogeneity, with different biological characteristics closely associated with prognosis. In addition, patients with HCC often distribute at different stages and require diverse treatment options at each stage. Due to the variability in tumor sensitivity to different therapies, determining the optimal treatment approach can be challenging for clinicians prior to treatment. Artificial intelligence (AI) technology, including radiomics and deep learning approaches, has emerged as a unique opportunity to improve the spectrum of HCC clinical care by predicting biological characteristics and prognosis in the medical imaging field. The radiomics approach utilizes handcrafted features derived from specific mathematical formulas to construct various machine-learning models for medical applications. In terms of the deep learning approach, convolutional neural network models are developed to achieve high classification performance based on automatic feature extraction from images. Magnetic resonance imaging offers the advantage of superior tissue resolution and functional information. This comprehensive evaluation plays a vital role in the accurate assessment and effective treatment planning for HCC patients. Recent studies have applied radiomics and deep learning approaches to develop AI-enabled models to improve accuracy in predicting biological characteristics and prognosis, such as microvascular invasion and tumor recurrence. Although AI-enabled models have demonstrated promising potential in HCC with biological characteristics and prognosis prediction with high performance, one of the biggest challenges, interpretability, has hindered their implementation in clinical practice. In the future, continued research is needed to improve the interpretability of AI-enabled models, including aspects such as domain knowledge, novel algorithms, and multi-dimension data sources. Overcoming these challenges would allow AI-enabled models to significantly impact the care provided to HCC patients, ultimately leading to their deployment for clinical use. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Habitat Radiomics Based on MRI for Predicting Platinum Resistance in Patients with High-Grade Serous Ovarian Carcinoma: A Multicenter Study.

RATIONALE AND OBJECTIVES: This study aims to explore the feasibility of MRI-based habitat radiomics for predicting response of platinum-based chemotherapy in patients with high-grade serous ovarian carcinoma (HGSOC), and compared to conventional radiomics and deep learning models. MATERIALS AND METHODS: A retrospective study was conducted on HGSOC patients from three hospitals. K-means algorithm was used to perform clustering on T2-weighted images (T2WI), contrast-enhanced T1-weighted images (CE-T1WI), and apparent diffusion coefficient (ADC) maps. After feature extraction and selection, the radiomics model, habitat model, and deep learning model were constructed respectively to identify platinum-resistant and platinum-sensitive patients. A nomogram was developed by integrating the optimal model and clinical independent predictors. The model performance and benefit was assessed using the area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 394 eligible patients were incorporated. Three habitats were clustered, a significant difference in habitat 2 (weak enhancement, high ADC values, and moderate T2WI signal) was found between the platinum-resistant and platinum-sensitive groups (P < 0.05). Compared to the radiomics model (0.640) and deep learning model (0.603), the habitat model had a higher AUC (0.710). The nomogram, combining habitat signatures with a clinical independent predictor (neoadjuvant chemotherapy), yielded a highest AUC (0.721) among four models, with positive NRI and IDI. CONCLUSION: MRI-based habitat radiomics had the potential to predict response of platinum-based chemotherapy in patients with HGSOC. The nomogram combining with habitat signature had a best performance and good model gains for identifying platinum-resistant patients.

O, N Coordination-Mediated Nickel Single-Atom Catalysts for High-Efficiency Generation of H2O2.

Electrochemical selective two-electron oxygen reduction shows great potential for on-site electrochemical production of hydrogen peroxide (H2O2). Herein, we demonstrated the synthesis of Ni single-atom sites coordinated by three oxygen atoms and one nitrogen atom (i.e., Ni-N1O3) supported by oxidized carbon black (OCB) by pyrolyzing nickel-(pyridine-2,5-dicarboxylate) coordination complexes. Aberration-corrected scanning transmission electron microscopy (AC-STEM) combined with X-ray absorption spectroscopy (XAS) proves the presence of atomically dispersed Ni atoms attached on OCB (labeled as Ni-SACs@OCB), in which Ni single atoms are stabilized by a N, O-mediated coordination configuration. This Ni-SACs@OCB catalyst shows high H2O2 selectivity (95%) in a range of 0.2-0.7 V undergoing a two-electron oxygen reduction process, with a kinetic current density of 2.8 mA cm-2 and a mass activity of 24 A gcat.-1 at 0.65 V (vs RHE). In practice, H-cells with Ni-SACs@OCB as catalysts displayed a high H2O2 production rate of 98.5 mmol gcat.-1 h-1 with negligible current loss during testing, suggesting the high H2O2 generation efficiency and robust stability. DFT theoretical calculations revealed that Ni single-atom sites coordinated by O, N coordination exhibit advantages in oxygen adsorption and increased reactivity toward the intermediate species, *OOH, which is beneficial to high selectivity for H2O2 production. This work provides a novel N, O-mediated four-coordinate nickel single-atom catalyst as a promising candidate for practical decentralized production of H2O2.

Mixture effect assessment applying in vitro bioassays to in-tissue silicone extracts of traditional foods prepared from beluga whale blubber.

We complement an earlier study on the nutrient and environmental contaminant levels in Arctic beluga whale traditional foods by mixture effect assessment using in vitro bioassays. Mixtures were extracted by in-tissue sampling of raw blubber and several traditional food preparations including Muktuk and Uqsuq using silicone (polydimethylsiloxane, PDMS) as sampler. PDMS extracts persistent and degradable neutral organic chemicals of a wide range of hydrophobicity with defined lipid-PDMS partition ratios. The solvent extracts of PDMS were dosed in various reporter gene assays based on human cell lines. Cytotoxicity was consistent across all cell lines and was a good indicator of overall chemical burden. No hormone-like effects on the estrogen receptor, the progesterone receptor and the glucocorticoid receptor were observed but a few samples activated the androgen receptor, albeit with low potency. The peroxisome-proliferator activated receptor (PPARγ) was the most sensitive endpoint followed by activation of oxidative stress response and activation of the arylhydrocarbon (AhR) receptor. The detected pollutants only explained a small fraction of the experimental mixture effects, indicating additional bioactive pollutants. The effect levels of the extracted mixtures were higher than those observed in blubber extracts of dugongs living off the shore of Australia. Roasting over an open fire or food preparation near a smokehouse led to increased PAH levels that were reflected in increased oxidative stress response and activation of the AhR. So far in vitro assays have only been used to quantify persistent dioxin-like chemicals in food and feed but this pilot study demonstrates a much broader potential for food safety evaluations complementing chemical analytical monitoring.

Efficacy of pulsed dye laser combined with fractional CO2 laser in the treatment of pediatric burn scars.

OBJECTIVE: The present study aimed to investigate the efficacy and safety of pulsed dye laser (PDL) combined with fractional CO2 laser in the treatment of burn scars in pediatric patients. METHODS: The present retrospective study enrolled 60 pediatric patients with burn scars from July 2017 to June 2021. In the 4-month treatment period, all patients received PDL treatment every 1 month and received fractional CO2 laser treatment every 3 months. The Patient and Observer Scar Assessment Scale (POSAS) was used to evaluate the scar condition before the treatment as well as 6 months after the whole treatment. The satisfaction of the patient's parents was collected and recorded 6 months after the treatment. Complications were recorded during the treatment period and at follow-up visits. RESULTS: Among all patients, 38 (63.33%) cases were scald-induced scars and 22 (36.67%) cases were burn-induced scars. The mean diameter of the scar area was 107.53 ± 2.92 cm2 . For the measurement of the patient part of POSAS, all indices of pain, itching, color, stiffness, thickness, and irregularity, as well as the total scores were remarkably lower after 6 months of the treatment compared with the baseline (p < 0.05). For the observer part of POSAS, the indices of vascularization, pigmentation, thickness, relief, pliability, and surface area, as well as the total scores were markedly decreased after treatment (p < 0.05). The total satisfactory rate was 96.67% (58/60). No severe complications nor scar aggravation was observed. CONCLUSION: The combination of PDL and fractional CO2 laser showed good efficacy in the treatment of pediatric patients with burn scars with no severe complications and can be recommended in clinical application.

LncRNA AC093850.2 predicts poor outcomes in patients with triple-negative breast cancer and motivates tumor progression by sponging miR-4299.

BACKGROUND: Accumulating evidence displays that non-coding RNAs (ncRNAs) are involved in the progression of triple-negative breast cancer (TNBC). This study aimed to investigate the role of lncRNA AC093850.2 in TNBC. METHODS: The AC093850.2 levels were compared using RT-qPCR in TNBC tissues and corresponding normal tissues. The Kaplan-Meier curve method was conducted to assess the clinical significance of AC093850.2 in TNBC. Bioinformatic analysis was used to predict potential miRNA. Cell proliferation and invasion assays were carried out to explore the function of AC093850.2/miR-4299 in TNBC. RESULTS: lncRNA AC093850.2 expression is raised in TNBC tissues and cell lines, which is related to the shorter overall survival of patients. AC093850.2 is directly bound to miR-4299 in TNBC cells. Downregulation of AC093850.2 reduces tumor cell proliferation, migration, and invasion abilities, while miR-4299 silence attenuated AC093850.2 silencing induced inhibition of cellular activities in TNBC cells. CONCLUSION: In general, the findings suggest that lncRNA AC093850.2 was closely related to the prognosis and progression of TNBC by sponging miR-4299, which might be a prognosis predictor and potential target for treating TNBC patients.

Multi-Sequence and Multi-Regional MRI-Based Radiomics Nomogram for the Preoperative Assessment of Muscle Invasion in Bladder Cancer.

BACKGROUND: Whether bladder cancer (BCa) invades muscle is a determinant of management. However, the accuracy of preoperative diagnosis of muscle invasion is not satisfactory. PURPOSE: To investigate the value of multi-sequence and multi-regional magnetic resonance imaging (MRI)-based radiomics nomogram for assessing muscle invasion of BCa. STUDY TYPE: Retrospective. POPULATION: 342 BCa patients, divided into a training set (239 cases), a validation set (68 cases), and a test set (35 cases). FIELD STRENGTH/SEQUENCE: 3.0 T/T2 -weighted image, diffusion-weighted imaging, and dynamic contrast-enhanced imaging. ASSESSMENT: Patients were divided into muscle-invasive (79 cases) and non-muscle-invasive (263 cases). Two radiologists delineated the whole tumor, tumor body, and muscle layer of BCa, respectively, and extracted radiomic features. STATISTICAL TESTS: Recursive feature elimination, Pearson correlation coefficient, logistic regression, least absolute shrinkage and selection operator (Lasso) regression analysis, and 5-fold cross-validation were used to screen features and build a radiomics model. The clinical data were collected to construct a clinical model and a radiomics-clinical nomogram. RESULTS: 23,688 features were extracted. After screening, the radiomics scoring model was constructed using nine radiomics features with area under curve (AUC) values of 0.933, 0.913, and 0.931 in the training, validation, and test sets, respectively. The clinical model was constructed using five clinical independent risk factors; the AUC values in the training, validation, and test set were 0.876, 0.859, and 0.824, respectively. After logistic regression analysis, the AUC values of the radiomics-clinical nomogram were made up of four clinical independent risk factors and radiomics scores were 0.955, 0.922, and 0.935 for the training, validation, and test sets, respectively. The DeLong test between clinical model and radiomics-clinical nomogram shows P < 0.001. CONCLUSION: Multi-sequence and multi-regional MRI-based radiomics models could effectively assess the state of BCa muscular invasion. The radiomics-clinical nomogram is superior to clinical model for assessing BCa muscular invasion. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Bioinspired nanovehicle of furoxans-oxaliplatin improves tumoral distribution for chemo-radiotherapy.

The spatiotemporal distribution of therapeutic agents in tumors remains an essential challenge of radiation-mediated therapy. Herein, we rationally designed a macrophage microvesicle-inspired nanovehicle of nitric oxide donor-oxaliplatin (FO) conjugate (M-PFO), aiming to promote intratumor permeation and distribution profiles for chemo-radiotherapy. FO was responsively released from M-PFO in intracellular acidic environments, and then be activated by glutathione (GSH) into active oxaliplatin and NO molecules in a programmed manner. M-PFO exhibited notable accumulation, permeation and cancer cell accessibility in tumor tissues. Upon radiation, the reactive peroxynitrite species (ONOO-) were largely produced, which could diffuse into regions over 400 µm away from the tumor vessels and be detectable after 24 h of radiation, thereby exhibiting superior efficacy in improving the spatiotemporal distribution in tumors versus common reactive oxygen species (ROS). Moreover, M-PFO mediated chemo-radiotherapy caused notable inhibition of tumor growth, with an 89.45% inhibition in HT-29 tumor models and a 92.69% suppression in CT-26 tumor models. Therefore, this bioinspired design provides an encouraging platform to improve intratumor spatiotemporal distribution to synergize chemo-radiotherapy.

Microvesicle-inspired oxygen-delivering nanosystem potentiates radiotherapy-mediated modulation of tumor stroma and antitumor immunity.

The efficacy of radiotherapy is greatly challenged by intense hypoxia, intricate stroma and suppressive immune microenvironments in tumors. Herein, we rationally designed a microvesicle-inspired oxygen-delivering polyfluorocarbon nanosystem loading DiIC18(5) and halofuginone (M-FDH) with prominent capacity of improving tumor oxygenation and intratumor distribution, synergizing radiation to disrupt tumor stroma and boost antitumor immunity for combinational cancer therapy. M-FDH produced a 10.98-fold enhancement of tumor oxygenation and caused efficient production of reactive oxygen species (ROS) upon radiation. M-FDH + X ray treatment resulted in notable DNA damages, over 90% elimination of cancer-associated fibroblasts (CAFs) and major components of extracellular matrix, significant enhancement of tumoricidal CD3+CD8+ T cells, and profound elimination of suppressive immune cells in 4T1 tumors. The therapeutic benefits of M-FDH + X ray on suppressing tumor growth were confirmed in two murine tumor models. Therefore, this study provides an encouraging microvesicle-inspired strategy to target cancer cells and CAFs in tumors and synergize radiotherapy for effective cancer treatment.

ROS-Responsive Nanocomplex of aPD-L1 and Cabazitaxel Improves Intratumor Delivery and Potentiates Radiation-Mediated Antitumor Immunity.

Despite the promising benefits of immune checkpoint inhibitors (ICIs) in clinical cancer treatments, the therapeutic efficacy is largely restricted by low antitumor immunity and limited intratumor delivery in solid tumors. Herein, we designed a reactive oxygen species (ROS)-responsive albumin nanocomplex of antiprogrammed cell death receptor ligand 1 (aPD-L1) and cabazitaxel (RAN-PC), which exhibited prominent tumor accumulation and intratumor permeation in 4T1 tumors. Compared with the negative control, the RAN-PC + radiation treatment (RAN-PC+X) produced a 3.61- and 5.10-fold enhancement in CD3+CD8+ T cells and the interferon (IFN)-γ-expressing subtype, respectively, and notably reduced versatile immunosuppressive cells. Moreover, RAN-PC+X treatment resulted in notable retardation of tumor growth, with a 78.97% inhibition in a 4T1 breast tumor model and a 90.30% suppression in a CT-26 colon tumor model. Therefore, the ROS-responsive albumin nanocomplex offers an encouraging platform for ICIs with prominent intratumor delivery capacity for cancer immunotherapy.

Supplementary benefits of CT-guided transthoracic lung aspiration biopsy for core needle biopsy.

Objective: This study aimed to investigate the diagnostic efficacy of computed tomography (CT)-guided transthoracic lung core needle biopsy combined with aspiration biopsy and the clinical value of this combined routine microbial detection. Materials and methods: We retrospectively collected the electronic medical records, CT images, pathology, and other data of 1085 patients with sequential core needle biopsy and aspiration biopsy of the same lung lesion under CT guidance in the First Affiliated Hospital of Wenzhou Medical University from January 2016 to January 2021. GenXpert MTB/RIF detection and BD BACTEC™ Mycobacterium/fungus culture were applied to identifying the microbiological results of these patients. We then compared the positive diagnostic rate, false negative rate, and diagnostic sensitivity rate of three methods including core needle biopsy alone, aspiration biopsy alone, and both core needle biopsy and aspiration biopsy. Results: The pathological results of cutting histopathology and aspiration of cell wax were examined for 1085 patients. The diagnostic rates of cutting and aspiration pathology were 90.1% (978/1085) and 86.3% (937/1085), respectively, with no significant difference (P > 0.05). Considering both cutting and aspiration pathologies, the diagnostic rate was significantly improved, up to 98% (1063/1085) (P < 0.001). A total of 803 malignant lesions were finally diagnosed (803/1085, 74.0%). The false negative rate by cutting pathology was 11.8% (95/803), which was significantly lower than that by aspiration biopsy [31.1% (250/803), P < 0.001]. Compared with core needle biopsy alone, the false negative rate of malignant lesions decreased to 5.6% (45/803) (P < 0.05). Next, the aspirates of the malignant lesions highly suspected of corresponding infection were cultured. The results showed that 16 cases (3.1%, 16/511) were infected with Mycobacterium tuberculosis complex, Aspergillus niger, and Acinetobacter baumannii, which required clinical treatment. 803 malignant tumors were excluded and 282 cases of benign lesions were diagnosed, including 232 cases of infectious lesions (82.3%, 232/282). The diagnostic rate of Mycobacterium/fungus culture for infectious lesions by aspiration biopsy (47.4%) was significantly higher than that by lung core needle biopsy (22.8%; P < 0.001). The diagnostic rate of aspiration biopsy combined with core needle biopsy was 56% (130/232). The parallel diagnostic rate of aspirated biopsy for GenXpert detection and Mycobacterium/fungal culture combined with core needle biopsy was 64.7% (150/232), which was significantly higher than that of lung core needle biopsy alone (P < 0.001). Finally, pulmonary tuberculosis was diagnosed in 90 cases (38.8%) of infectious lesions. Compared with the sensitivity of core needle biopsy to detect tuberculosis (27.8%, 25/90), the sensitivity of aspirating biopsy for GenXpert detection and Mycobacterium/fungal culture was significantly higher, at 70% (63/90) and 56.7% (51/90), respectively. Although there was no significant difference in the sensitivity of aspirated biopsy for GenXpert and Mycobacterium/fungal culture to detect pulmonary tuberculosis, the sensitivity was significantly increased to 83.3% (P < 0.05) when the two tests were combined. Moreover, when aspirated biopsies were combined with GenXpert detection, Mycobacterium/fungus culture, and core needle biopsy, the sensitivity was as high as 90% (81/90). Conclusion: CT-guided lung aspiration biopsy has a significant supplementary effect on core needle biopsies, which is indispensable in clinical application. Additionally, the combination of aspiration biopsy and core needle biopsy can significantly improve the diagnostic rate of benign and malignant lesions. Aspiration biopsy showed that pulmonary malignant lesions are complicated with pulmonary tuberculosis, aspergillus, and other infections. Finally, the diagnostic ability of lung puncture core needle biopsy and aspiration biopsy combined with routine microbial detection under CT positioning in the diagnosis of pulmonary infectious diseases was significantly improved.

Effects of cadmium and flooding on the formation of iron plaques, the rhizosphere bacterial community structure, and root exudates in Kandelia obovata seedlings.

In the rhizosphere, plant root exudates (REs) serve as a bridge between plant and soil functional microorganisms, which play a key role in the redox cycle of iron (Fe). This study examined the effects of periodic flooding and cadmium (Cd) on plant REs, the rhizosphere bacterial community structure, and the formation of root Fe plaques in the typical mangrove plant Kandelia obovata, as well as the relationship between REs and Fe redox cycling bacteria. Based on two-way analysis of variance, flooding and Cd had a considerable effect on the REs of K. obovata. DOC, NH4+-N, NO3--N, dissolved inorganic phosphorus, acetic acid, and malonic acid concentrations in REs of K. obovata increased considerably with the increase of Cd concentration under 5 and 10 h flooding conditions. Fe plaque development in the plant root was stimulated by flooding and Cd, although flooding was more effective. After Cd treatment, the ways in which Fe-oxidizing bacteria (FeOB) and Fe-reducing bacteria (FeRB) were enriched in the rhizosphere and rhizoplane of plants were different. Thiobacillus and Sideroxydans (dominant FeOB) were more abundant in the plant rhizosphere, whereas Acinetobacter (dominant FeRB) was more abundant in the rhizoplane. Cd considerably decreased the relative abundance of unclassified_f_Gallionellaceae in the rhizosphere and rhizoplane but dramatically enhanced the relative abundance of Thiobacillus, Shewanella, and unclassified_f_Geobacteraceae. Unclassified_f_Geobacteraceae and Thiobacillus exhibited substantial positive correlations with citric acid and DOC in REs in the rhizosphere and rhizoplane but strong negative correlations with Sideroxydans. The findings indicate that Cd and flooding treatments may play a role in the production and breakdown of Fe plaque in K. obovata roots by affecting the relative abundance of Fe redox cycling bacteria in the rhizosphere and rhizoplane.

Single-cell multiomics reveals heterogeneous cell states linked to metastatic potential in liver cancer cell lines.

Hepatocellular carcinoma (HCC) is the most common liver cancer with a high rate of metastasis. However, the molecular mechanisms that drive metastasis remain unclear. We combined single-cell transcriptomic, proteomic, and chromatin accessibility data to investigate how heterogeneous phenotypes contribute to metastatic potential in five HCC cell lines. We confirmed that the prevalence of a mesenchymal state and levels of cell proliferation are linked to the metastatic potential. We also identified a rare hypoxic subtype that has a higher capacity for glycolysis and exhibits dormant, invasive, and malignant characteristics. This subtype has increased metastatic potential. We further identified a robust 14-gene panel representing this hypoxia signature and this hypoxia signature could serve as a prognostic index. Our data provide a valuable data resource, facilitate a deeper understanding of metastatic mechanisms, and may help diagnosis of metastatic potential in individual patients, thus supporting personalized medicine.

Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells.

Ex vivo-expanded mesenchymal stem cells (MSCs) have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative, multipotential, and immunomodulatory capacities. However, the exact characteristics of MSCs remain largely unknown. By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton's jelly, we revealed five distinct subpopulations. The developmental trajectory of these five MSC subpopulations was mapped, revealing a differentiation path from stem-like active proliferative cells (APCs) to multipotent progenitor cells, followed by branching into two paths: 1) unipotent preadipocytes or 2) bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondrocytes. The stem-like APCs, expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES, uniquely exhibited strong proliferation and stemness signatures. Remarkably, the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to suppress activated CD3+ T cell proliferation in vitro, supporting the role of this population in immunoregulation. In summary, our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation. Our findings advance the definition of MSCs by identifying the specific functions of their heterogeneous cellular composition, allowing for more specific and effective MSC application through the purification of their functional subpopulations.

Cardioprotective effects of corilagin on doxorubicin induced cardiotoxicity via P13K/Akt and NF-κB signaling pathways in a rat model.

Even though doxorubicin (DOX) is a potential chemotherapeutic drug, its usage is restricted due to its ability to induce cardiac damage. In order to prevent this damage, a potent cardioprotective agent should be associated with DOX treatment. Corilagin is a natural polyphenol tannic acid which unveils enormous pharmacological activities predominantly as an antitumor agent. Hence, the current work is designed to study the precise mechanisms of corilagin upon administration in doxorubicin induced cardiotoxicity in experimental rats. DOX treated rats showed diminished level of blood pressures and heart rate, whereas corilagin along with DOX treatment improved the status. Cardiotoxicity enzymes and biomarkers were found to be increased in the serum of DOX induced rats. Upon treatment, corilagin could reduce the cardiotoxicity enzymes and biomarkers in serum. Histopathological examination of cardiac tissue also revealed the anti-toxic effects of corilagin in contrast to DOX. Injection of DOX in rats showed inflammatory cells infiltration, necrosis and fragmented myofibrils. Corilagin treatment reverted the cardiac histology to near normal. Inflammatory mediators and P13K, Akt, and NF-κB were upregulated in DOX administered rats. Corilagin repressed the levels of P13K, Akt, and NF-κB in DOX induced rats. In the present investigations, corilagin improved cardiac function via reducing injury, inflammation and promoting apoptosis thereby suggesting that corilagin would be recommended for DOX-induced cardiotoxicity.