Label-free detection of kidney stones urine combined with SERS and multivariate statistical algorithm.

Kidney stones are a common urological disease with an increasing incidence worldwide. Traditional diagnostic methods for kidney stones are relatively complex and time-consuming, thus necessitating the development of a quicker and simpler diagnostic approach. This study investigates the clinical screening of kidney stones using Surface-Enhanced Raman Scattering (SERS) technology combined with multivariate statistical algorithms, comparing the classification performance of three algorithms (PCA-LDA, PCA-LR, PCA-SVM). Urine samples from 32 kidney stone patients, 30 patients with other urinary stones, and 36 healthy individuals were analyzed. SERS spectra data were collected in the range of 450-1800 cm-1 and analyzed. The results showed that the PCA-SVM algorithm had the highest classification accuracy, with 92.9 % for distinguishing kidney stone patients from healthy individuals and 92 % for distinguishing kidney stone patients from those with other urinary stones. In comparison, the classification accuracy of PCA-LR and PCA-LDA was slightly lower. The findings indicate that SERS combined with PCA-SVM demonstrates excellent performance in the clinical screening of kidney stones and has potential for practical clinical application. Future research can further optimize SERS technology and algorithms to enhance their stability and accuracy, and expand the sample size to verify their applicability across different populations. Overall, this study provides a new method for the rapid diagnosis of kidney stones, which is expected to play an important role in clinical diagnostics.

Chirality-Mediated 1D-to-2D Phase Transition in Hybrid Lead Halide Perovskites.

Dimensionality engineering plays a pivotal role in optimizing the performance, ensuring long-term stability, and expanding the versatile applications of lead halide perovskites (LHPs). Currently, the manipulation of LHP dimensions primarily occurs during the synthesis stage, a procedure hampered by constraints, including synthetic complexity and irreversibility. This investigation successfully achieved a transition from one-dimensional (1D) to two-dimensional (2D) structures in chiral LHPs by applying hydrostatic pressure. Remarkably, this pressure-induced transition in dimensionality is absent in the racemic analogue due to the staggered arrangement of inorganic chains and the elevated steric hindrance posed by the organic cations. Notably, the hydrogen bonding between organic cations and the inorganic framework adopts a symmetrical arrangement in the racemic system but a helical configuration along the 1D chain direction in the chiral counterparts. This distinct helical arrangement induces a consequential distortion in the inorganic moiety, resulting in the emergence of a spin-polarized Rashba-Dresselhaus texture that explains the chirality's electronic spin origin. Furthermore, both experimental and density functional theory calculation results demonstrate that the 1D-to-2D phase transition in chiral halide perovskites can induce significant modifications in the electronic structures and associated optical emissions. In summary, the findings unveil novel avenues for manipulating optoelectronic properties in chiral perovskites through dimensionality engineering.

Apoptotic vesicles (apoVs) derived from fibroblast-converted hepatocyte-like cells effectively ameliorate liver fibrosis.

Liver fibrosis is a serious global health issue for which effective treatment remains elusive. Chemical-induced hepatocyte-like cells (ciHeps) have emerged as an appealing source for cell transplantation therapy, although they present several challenges such as the risk of lung thromboembolism or hemorrhage. Apoptotic vesicles (apoVs), small membrane vesicles generated during the apoptosis process, have gained attention for their role in regulating various physiological and pathological processes. In this study, we generated ciHep-derived apoVs (ciHep-apoVs) and investigated their therapeutic potential in alleviating liver fibrosis. Our findings revealed that ciHep-apoVs induced the transformation of macrophages into an anti-inflammatory phenotype, effectively suppressed the activity of activated hepatic stellate cells (aHSCs), and enhanced the survival of hepatocytes. When intravenously administered to mice with liver fibrosis, ciHep-apoVs were primarily engulfed by macrophages and myofibroblasts, leading to a reduction in liver inflammation and fibrosis. Proteomic and miRNA analyses showed that ciHep-apoVs were enriched in various functional molecules that modulate crucial cellular processes, including metabolism, signaling transduction, and ECM-receptor interactions. ciHep-apoVs effectively suppressed aHSCs activity through the synergistic inhibition of glycolysis, the PI3K/AKT/mTOR pathway, and epithelial-to-mesenchymal transition (EMT) cascades. These findings highlight the potential of ciHep-apoVs as multifunctional nanotherapeutics for liver fibrosis and provide insights into the treatment of other liver diseases and fibrosis in other organs.

A Janus hydrogel that enables wet tissue adhesion and resists abdominal adhesions.

Hydrogels have indeed achieved significant advancements, yet their clinical translation has been hampered by their inherent limitations in wet adhesion properties. Furthermore, the design of adhesive hydrogels that can resist postoperative adhesions remains an intricate challenge. In this study, we introduce a Janus hydrogel (JGP) that offers a novel approach to address these challenges. The JGP hydrogel has two asymmetrical sides, consisting of an adhesion layer (AL) and an anti-adhesion layer (AAL). Specifically, the AL incorporates three key components: N-[tris(hydroxymethyl)methyl]acrylamide (THMA), acrylic acid (AAc), and the acrylic acid N-hydroxysuccinimide ester (AAc-NHS). By drying the AL, it has a rapid water absorption capability. The abundance of hydroxyl and carboxyl groups in the AL enables the formation of robust hydrogen bonds with tissues, thereby achieving superior adhesive properties. Additionally, the synergistic effect of THMA's tridentate hydrogen bonding and the covalent bonding formed by AAc-NHS with tissue ensures long-lasting wet adhesion. To realize the anti-adhesion function, one side of the AL was immersed in a solution of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), which undergoes crosslinking to form the AAL. A comprehensive series of tests have confirmed that the JGP hydrogel exhibits exceptional mechanical properties, efficient and enduring adhesion, excellent biocompatibility, and degradability. Moreover, it possesses remarkable hemostatic properties and robust anti-abdominal adhesion characteristics.

Elucidation on Abnormal Capacity Increase in SiO2@C Core-Shell Nanospheres Anode for Lithium-Ion Battery.

An abnormal capacity increase stage has been observed in nanostructured SiO2 after the initial capacity drop stage. To investigate the Li+ storage kinetic mechanism for each stage, SiO2@C core-shell nanospheres with a total diameter of ∼108 to 170 nm but an adjustable C shell thickness of ∼4 to 31 nm have been fabricated. First, the existence form and specific content of SiO2 nanoparticles with a size of ∼6-10 nm, which are embedded in the outer C shell of SiO2@C core-shell nanospheres, were confirmed by SEM, TEM, BET, and TGA, respectively. It was found that the initial stage for capacity drop happens at 15-43 cycles and is followed by an enhancement stage, which presents an increase of ∼120 to 180% in capacity relative to the lowest capacity value during cycling. Among them, the sample of P-1 with a diameter of 109 nm for the SiO2 core and thickness of 31 nm for the C shell delivers the highest specific capacity of 1060 mAh/g at 100 mA/g and a capacity increase rate of ∼180% through 300 cycles. XPS analysis for the delithiation process indicates that the capacity drop and increase stage involves the partial oxidation of Li silicate, which is correlated to the formation of Li2Si2O5. Our study can be used to explain the mechanism of the abnormal capacity increase phenomenon for the SiO2 anode and provide a high-capacity anode material for LIB application.

Achieving optical transparency in live animals with absorbing molecules.

Optical imaging plays a central role in biology and medicine but is hindered by light scattering in live tissue. We report the counterintuitive observation that strongly absorbing molecules can achieve optical transparency in live animals. We explored the physics behind this observation and found that when strongly absorbing molecules dissolve in water, they can modify the refractive index of the aqueous medium through the Kramers-Kronig relations to match that of high-index tissue components such as lipids. We have demonstrated that our straightforward approach can reversibly render a live mouse body transparent to allow visualization of a wide range of deep-seated structures and activities. This work suggests that the search for high-performance optical clearing agents should focus on strongly absorbing molecules.

Integrative analysis of bulk and single-cell RNA sequencing reveals sphingolipid metabolism and immune landscape in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is characterized by its aggressive behavior and complex molecular heterogeneity, posing significant challenges for treatment and prognostication. This study offers a comprehensive analysis of ccRCC by leveraging both bulk and single-cell RNA sequencing data, with a specific aim to unravel the complexities of sphingolipid metabolism and the intricate dynamics within the tumor microenvironment (TME). By examining ccRCC samples sourced from public databases, our investigation delves deep into the genetic and transcriptomic landscape of this cancer type. Employing advanced analytical techniques, we have identified pivotal patterns in gene expression and cellular heterogeneity, with a special focus on the roles and interactions of various immune cells within the TME. Significantly, our research has unearthed insights into the dynamics of sphingolipid metabolism in ccRCC, shedding light on its potential implications for tumor progression and strategies for immune evasion. A novel aspect of this study is the development of a risk score model designed to enhance prognostic predictions for ccRCC patients, which is currently pending external validation to ascertain its clinical utility. Despite its contributions, the study is mindful of its limitations, including a reliance on observational data from public sources and a primary focus on RNA sequencing data, which may constrain the depth and generalizability of the findings. The study does not encompass critical aspects, such as protein expression, posttranslational modifications, and comprehensive metabolic profiles. Moreover, its retrospective design underscores the necessity for future prospective studies to solidify these preliminary conclusions. Our findings illuminate the intricate interplay between genetic alterations, sphingolipid metabolism, and immune responses in ccRCC. This research not only enhances our understanding of the molecular foundations of ccRCC but also paves the way for the development of targeted therapies and personalized treatment modalities. The study underlines the importance of cautious interpretation of results and champions ongoing research using diverse methodologies to thoroughly comprehend and effectively combat this formidable cancer type.

In-situ induced formation of Fe-OM association in soil: Theory and practice of remediation of cadmium contaminated paddy fields in high cadmium geological background areas.

Cadmium (Cd) pollution in rice paddies, attributable to high geological Cd backgrounds, has emerged as a global concern. This study leverages the passivation mechanism of bioavailable Cd by iron-organic matter associations (Fe-OM) to explore a novel strategy for Cd immobilization. We examined the adsorptive capacity and removal efficiency of Cd by laccase-mediated Fe-OM association and assessed their natural stability using 57Fe isotopic tracing. Additionally, we conducted in-situ remediation trials in a Cd-enriched paddy soil. Our results indicate that the theoretical maximum adsorption capacity for Cd by the laccase-mediated Fe-OM is 100.0 mg/g, which is a 15% improvement over the common Fe-OM and a 150% enhancement over inorganic iron oxides (ferrihydrite). The 57Fe isotope tracing test showed that the affinity of laccase-modified organic matter for iron increased by 55.6%, and it exhibited better stability than common Fe-OM under anaerobic conditions. The field-scale remediation, predicated on the in situ synthesis of Fe-OM association, effectively reduced the bioavailable Cd concentration in the soil from 0.91 mg/kg to 0.40 mg/kg. Concurrently, the Cd concentration in rice grains was lowered from 0.63 mg/kg to 0.15 mg/kg, thus falling beneath the national safety threshold. This study represents a significant advancement in the safe reclamation and utilization of agricultural soils with elevated geological Cd burdens.

The correlation between the level of cellular classification in bronchoalveolar lavage fluid of children with severe Mycoplasma pneumoniae and clinical characteristics.

Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infection disease in children. To date, there have been few studies on the relationship between cytological changes in bronchoalveolar lavage fluid (BALF) and clinical features. The objective of this study is to investigate the correlation between changes in the proportion of cell classifications in BALF and the clinical features in children with severe MPP (SMPP). In total, the study included 64 children with SMPP requiring bronchoalveolar lavage who were admitted to our hospital between March and September 2022 (study group) and 11 children with bronchial foreign bodies without co-infection (control group), who were admitted during the same period. The proportion of cell classifications in BALF was determined by microscopic examination after performing Wright-Giemsa staining. Patients were grouped according to different clinical characteristics, and between-group comparisons were made regarding the variations in the proportion of cell classifications in BALF. The levels of blood routine neutrophil percentage (GRA%), C-reactive protein, D-dimer and lactate dehydrogenase in the study group were higher than those in the control group (P < 0.05). There were differences in the GRA% and macrophage percentage in the BALF between the two groups (P < 0.05). The GRA% and blood lymphocyte percentage were associated with pleural effusion. Multiple indicators correlated with extrapulmonary manifestations (P < 0.05). Moreover, the percentage of lymphocytes in the BALF correlated with pleural effusion, extrapulmonary manifestations and refractory MPP (RMPP) (P < 0.05). Logistic regression showed that BALF lymphocytes were protective factors for RMPP, while serum amyloid A and extrapulmonary manifestations were risk factors (P < 0.05). CONCLUSION: The BALF of children with SMPP is predominantly neutrophilic. A lower percentage of lymphocytes is related to a higher incidence of pleural effusion, extrapulmonary manifestations and progression to RMPP, as well as a longer length of hospitalisation. WHAT IS KNOWN: • Mycoplasma pneumonia in children is relatively common in clinical practice. Bronchoalveolar lavage (BAL) is a routine clinical procedure. WHAT IS NEW: However, there are relatively few studies focusing on the cytomorphological analysis of cells in BAL fluid.

Toxoplasma gondii infection is associated with schizophrenia from the perspectives of seroepidemiology and serum metabolomics in Hunan Province, China.

Toxoplasma gondii (T.gondii) can influence the host's neurotransmission, central immune responses, and brain structure, potentially impacting the onset and development of various psychiatric disorders such as schizophrenia. We employed Electrochemiluminescence Immunoassay (ECLIA) to measure anti-Toxoplasma antibodies in 451 schizophrenic patients and 478 individuals from the general population in Hunan, China. The incidence rate of T.gondii infection in schizophrenic patients (8.87 %) was higher than that in the general population (3.77 %). A significant difference was observed among females, but not in males. Age-stratified analysis revealed significant differences in the 21-40 and 41-60 age groups. The two populations had no significant difference in the antibody titer for T. gondii infection. Additionally, the profile of circulating metabolites in the serum of schizophrenic patients with or without T. gondii infection was examined using non-targeted metabolomics assay. A total of 68 metabolites were differentially expressed between Toxoplasma-positive and Toxoplasma-negative groups, potentially mediating the connection between T. gondii infection and schizophrenia. Our research suggests that schizophrenic patients are susceptible to T. gondii infection with distinct metabolic program.

Prognostic Value and Immune Landscapes of Four Types of RNA Modification Writer-Related LncRNAs Signature in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the predominant pathological subtype of non-small cell lung cancer (NSCLC). The four primary forms of RNA adenosine modifications, N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA) and adenosine-to-inosine (A-to-I) RNA editing, play a critical role in tumor progression. However, the clinical significance of RNA modification writer-related long non-coding RNAs (lncRNAs) in LUAD remains unclear. Methods: The Cancer Genome Atlas (TCGA) database was used to obtain transcriptomic and clinicopathological data. Univariate Cox regression analysis, consensus cluster analysis, and least absolute shrinkage and selection operator (LASSO) Cox regression were used to establish the molecular subtypes and prognostic signatures of LUAD based on the expression levels of lncRNAs. ESTIMATE, CIBERSORT, ssGSEA, and TIDE algorithms were used to investigate immune cell infiltration and immunotherapy. In addition, IC50 of chemotherapeutic agents were calculated for different risk subgroups using the "pRRophetic" R package. Finally, the expression of prognosis-associated lncRNAs in lung cancer tissues was verified using qPCR. Results: A prognostic risk signature containing seven lncRNAs associated with four types of RNA modification writers was established. The high-risk group had a poorer prognosis and higher clinicopathological grade. Most immune checkpoint genes and immune cell infiltration differed significantly between the two risk groups. The high-risk group had a higher tumor mutation burden (TMB), lower TIDE score, and was more sensitive to immunotherapy. Conclusion: We developed an RNA modification writer-related seven-lncRNA signature prognostic model that was associated with prognosis, tumor microenvironment, and response to immunotherapy in LUAD patients. Among them, LINC01352, AC024075.1, AC005070.3, AL133445.2, AC005856.1, and LINC00968 were downregulated in LUAD, whereas AC092168.2 was upregulated. This model may be a valuable tool for personalized LUAD therapies.

Anisotropy of Additively Manufactured Metallic Materials.

Additive manufacturing (AM) is a technology that builds parts layer by layer. Over the past decade, metal additive manufacturing (AM) technology has developed rapidly to form a complete industry chain. AM metal parts are employed in a multitude of industries, including biomedical, aerospace, automotive, marine, and offshore. The design of components can be improved to a greater extent than is possible with existing manufacturing processes, which can result in a significant enhancement of performance. Studies on the anisotropy of additively manufactured metallic materials have been reported, and they describe the advantages and disadvantages of preparing different metallic materials using additive manufacturing processes; however, there are few in-depth and comprehensive studies that summarize the microstructural and mechanical properties of different types of additively manufactured metallic materials in the same article. This paper begins by outlining the intricate relationship between the additive manufacturing process, microstructure, and metal properties. It then explains the fundamental principles of powder bed fusion (PBF) and directed energy deposition (DED). It goes on to describe the molten pool and heat-affected zone in the additive manufacturing process and analyzes their effects on the microstructure of the formed parts. Subsequently, the mechanical properties and typical microstructures of additively manufactured titanium alloys, stainless steel, magnesium-aluminum alloys, and high-temperature alloys, along with their anisotropy, are summarized and presented. The summary indicates that the factors leading to the anisotropy of the mechanical properties of metallic AM parts are either their unique microstructural features or manufacturing defects. This anisotropy can be improved by post-heat treatment. Finally, the most recent research on the subject of metal AM anisotropy is presented.

Mesoporous NiMoO4 nanorod electrode materials for flexible and asymmetric energy storage devices.

Recently, ternary metal oxides as cathode materials have been the focus of research into supercapacitors owing to their high power density and cost-efficient features. The development of excellent electrode materials is the key to improving supercapacitor total performance. Herein, we report several kinds of NiMoO4 nanostructures grown on nickel foam using a simple hydrothermal strategy. The assembled hybrid devices show an energy density of 35.9 W h kg-1 at a power density of 2708 W kg-1. After repeated charging and discharging cycling and bending tests, they show excellent durability performance and mechanical stability performance.

Bacterial image analysis using multi-task deep learning approaches for clinical microscopy.

Background: Bacterial image analysis plays a vital role in various fields, providing valuable information and insights for studying bacterial structural biology, diagnosing and treating infectious diseases caused by pathogenic bacteria, discovering and developing drugs that can combat bacterial infections, etc. As a result, it has prompted efforts to automate bacterial image analysis tasks. By automating analysis tasks and leveraging more advanced computational techniques, such as deep learning (DL) algorithms, bacterial image analysis can contribute to rapid, more accurate, efficient, reliable, and standardised analysis, leading to enhanced understanding, diagnosis, and control of bacterial-related phenomena. Methods: Three object detection networks of DL algorithms, namely SSD-MobileNetV2, EfficientDet, and YOLOv4, were developed to automatically detect Escherichia coli (E. coli) bacteria from microscopic images. The multi-task DL framework is developed to classify the bacteria according to their respective growth stages, which include rod-shaped cells, dividing cells, and microcolonies. Data preprocessing steps were carried out before training the object detection models, including image augmentation, image annotation, and data splitting. The performance of the DL techniques is evaluated using the quantitative assessment method based on mean average precision (mAP), precision, recall, and F1-score. The performance metrics of the models were compared and analysed. The best DL model was then selected to perform multi-task object detections in identifying rod-shaped cells, dividing cells, and microcolonies. Results: The output of the test images generated from the three proposed DL models displayed high detection accuracy, with YOLOv4 achieving the highest confidence score range of detection and being able to create different coloured bounding boxes for different growth stages of E. coli bacteria. In terms of statistical analysis, among the three proposed models, YOLOv4 demonstrates superior performance, achieving the highest mAP of 98% with the highest precision, recall, and F1-score of 86%, 97%, and 91%, respectively. Conclusions: This study has demonstrated the effectiveness, potential, and applicability of DL approaches in multi-task bacterial image analysis, focusing on automating the detection and classification of bacteria from microscopic images. The proposed models can output images with bounding boxes surrounding each detected E. coli bacteria, labelled with their growth stage and confidence level of detection. All proposed object detection models have achieved promising results, with YOLOv4 outperforming the other models.

Cerebral-Cerebellar Cortical Activity and Connectivity Underlying Sensory Trick in Cervical Dystonia.

OBJECTIVE: The objective of this study was to investigate the activity and connectivity of cerebral and cerebellar cortices underlying the sensory trick (ST) effects in patients with cervical dystonia (CD), using electroencephalography (EEG). METHODS: We recruited 15 CD patients who exhibited clinically effective ST and 15 healthy controls (HCs) who mimicked the ST maneuver. EEG signals and multiple-channel electromyography (EMG) were recorded simultaneously during resting and acting stages. EEG source analysis and functional connectivity were performed. To account for the effects of sensory processing, we calculated relative power changes as the difference in power spectral density between resting and the maneuver execution. RESULTS: ST induced a decrease in low gamma (30-50 Hz) spectral power in the primary sensory and cerebellar cortices, which remained lower than in HCs during the maintenance period. Compared with HCs, patients exhibited consistently strengthened connectivity within the sensorimotor network during the maintenance period, particularly in the primary sensory-sensorimotor cerebellum connection. INTERPRETATION: The application of ST resulted in altered cortical excitability and functional connectivity regulated by gamma oscillation in CD patients, suggesting that this effect cannot be solely attributed to motor components. The cerebellum may play important roles in mediating the ST effects.

Prognostic Impact of Neoadjuvant Chemotherapy in Localized or Locoregionally Advanced Gallbladder Cancer: A Population-Based and Propensity Score Matched SEER Analysis.

BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis. METHODS: Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT. RESULTS: Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups. CONCLUSIONS: NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.

Programmed cell death in hepatocellular carcinoma: mechanisms and therapeutic prospects.

Hepatocellular Carcinoma (HCC), the most common primary liver cancer, ranks as the third most common cause of cancer-related deaths globally. A deeper understanding of the cell death mechanisms in HCC is essential for developing more effective treatment strategies. This review explores programmed cell death (PCD) pathways involved in HCC, including apoptosis, necroptosis, pyroptosis, ferroptosis, and immunogenic cell death (ICD). These mechanisms trigger specific cell death cascades that influence the development and progression of HCC. Although multiple PCD pathways are involved in HCC, shared cellular factors suggest a possible interplay between the different forms of cell death. However, the exact roles of different cell death pathways in HCC and which cell death pathway plays a major role remain unclear. This review also highlights how disruptions in cell death pathways are related to drug resistance in cancer therapy, promoting a combined approach of cell death induction and anti-tumor treatment to enhance therapeutic efficacy. Further research is required to unravel the complex interplay between cell death modalities in HCC, which may lead to innovative therapeutic breakthroughs.

PTBP3 Mediates IL-18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer.

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA-seq analysis, it is found high expression of the splicing factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping of interleukin-18 (IL-18), resulting in the expression of ΔIL-18, an isoform specifically expressed in tumors. That ΔIL-18 promotes GBC immune escape by down-regulating FBXO38 transcription levels in CD8+T cells to reduce PD-1 ubiquitin-mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL-18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL-18 production displayed anti-tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL-18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL-18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL-18 pre-mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.

A nationwide study of heavy metal(loid)s in agricultural soils and the soil-grown black morel Morchella sextelata in China.

The accumulation of heavy metal(loid)s (HMs) in soil-grown mushrooms poses potential health risks. Morchella sextelata (black morel) is a typical soil-grown mushroom with a rapidly expanding cultivation area. This study investigated the distribution of arsenic, cadmium, chromium, copper, mercury, nickel, lead, and zinc in 213 pairs of soil and morel samples collected from 29 provincial administrative regions in China, together with the nutritional contents in the morel samples. The HM contents in the arable soils used to cultivate morels were 2.4-33.1 times higher than those in desert soils, while the HM contents in arable-soil morels were 2.9-155.9 times higher than desert morels. The HM contents of morels and their cultivation soils were significantly correlated (0.465 ≤ R ≤ 0.778, P < 0.001). Furthermore, the enrichment factors of most HMs were higher in arable soils than in desert soils (P < 0.05), except Hg. A considerable proportion of the arable soils produced morels with HMs exceeding the risk control standards (RCSs) for food and the health-risk thresholds of dietary intake. In comparison, HMs in morels from desert soils were far below the RCSs and health-risk thresholds. In addition, desert morels contained higher contents of crude proteins, total polysaccharides, and free amino acids (P < 0.001). These findings indicate that growing morels in desert soils is a way of green production that provides mushroom products with improved safety and nutrition.