Heparin prevents caspase-11-dependent septic lethality independent of anticoagulant properties.

Heparin, a mammalian polysaccharide, is a widely used anticoagulant medicine to treat thrombotic disorders. It is also known to improve outcomes in sepsis, a leading cause of mortality resulted from infection-induced immune dysfunction. Whereas it is relatively clear how heparin exerts its anticoagulant effect, the immunomodulatory mechanisms enabled by heparin remain enigmatic. Here, we show that heparin prevented caspase-11-dependent immune responses and lethality in sepsis independent of its anticoagulant properties. Heparin or a chemically modified form of heparin without anticoagulant function inhibited the alarmin HMGB1-lipopolysaccharide (LPS) interaction and prevented the macrophage glycocalyx degradation by heparanase. These events blocked the cytosolic delivery of LPS in macrophages and the activation of caspase-11, a cytosolic LPS receptor that mediates lethality in sepsis. Survival was higher in septic patients treated with heparin than those without heparin treatment. The identification of this previously unrecognized heparin function establishes a link between innate immune responses and coagulation.

A long-duration gamma-ray burst with a peculiar origin.

It is generally believed that long-duration gamma-ray bursts (GRBs) are associated with massive star core collapse1, whereas short-duration GRBs are associated with mergers of compact star binaries2. However, growing observations3-6 have suggested that oddball GRBs do exist, and several criteria (prompt emission properties, supernova/kilonova associations and host galaxy properties) rather than burst duration only are needed to classify GRBs physically7. A previously reported long-duration burst, GRB 060614 (ref. 3), could be viewed as a short GRB with extended emission if it were observed at a larger distance8 and was associated with a kilonova-like feature9. As a result, it belongs to the type I (compact star merger) GRB category and is probably of binary neutron star (NS) merger origin. Here we report a peculiar long-duration burst, GRB 211211A, whose prompt emission properties in many aspects differ from all known type I GRBs, yet its multiband observations suggest a non-massive-star origin. In particular, substantial excess emission in both optical and near-infrared wavelengths has been discovered (see also ref. 10), which resembles kilonova emission, as observed in some type I GRBs. These observations point towards a new progenitor type of GRBs. A scenario invoking a white dwarf (WD)-NS merger with a post-merger magnetar engine provides a self-consistent interpretation for all the observations, including prompt gamma rays, early X-ray afterglow, as well as the engine-fed11,12 kilonova emission.

The Endotoxin Delivery Protein HMGB1 Mediates Caspase-11-Dependent Lethality in Sepsis.

Caspase-11, a cytosolic endotoxin (lipopolysaccharide: LPS) receptor, mediates pyroptosis, a lytic form of cell death. Caspase-11-dependent pyroptosis mediates lethality in endotoxemia, but it is unclear how LPS is delivered into the cytosol for the activation of caspase-11. Here we discovered that hepatocyte-released high mobility group box 1 (HMGB1) was required for caspase-11-dependent pyroptosis and lethality in endotoxemia and bacterial sepsis. Mechanistically, hepatocyte-released HMGB1 bound LPS and targeted its internalization into the lysosomes of macrophages and endothelial cells via the receptor for advanced glycation end-products (RAGE). Subsequently, HMGB1 permeabilized the phospholipid bilayer in the acidic environment of lysosomes. This resulted in LPS leakage into the cytosol and caspase-11 activation. Depletion of hepatocyte HMGB1, inhibition of hepatocyte HMGB1 release, neutralizing extracellular HMGB1, or RAGE deficiency prevented caspase-11-dependent pyroptosis and death in endotoxemia and bacterial sepsis. These findings indicate that HMGB1 interacts with LPS to mediate caspase-11-dependent pyroptosis in lethal sepsis.

Nuclear VCP drives colorectal cancer progression by promoting fatty acid oxidation.

Fatty acid oxidation (FAO) fuels many cancers. However, knowledge of pathways that drive FAO in cancer remains unclear. Here, we revealed that valosin-containing protein (VCP) upregulates FAO to promote colorectal cancer growth. Mechanistically, nuclear VCP binds to histone deacetylase 1 (HDAC1) and facilitates its degradation, thus promoting the transcription of FAO genes, including the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). FAO is an alternative fuel for cancer cells in environments exhibiting limited glucose availability. We observed that a VCP inhibitor blocked the upregulation of FAO activity and CPT1A expression triggered by metformin in colorectal cancer (CRC) cells. Combined VCP inhibitor and metformin prove more effective than either agent alone in culture and in vivo. Our study illustrates the molecular mechanism underlying the regulation of FAO by nuclear VCP and demonstrates the potential therapeutic utility of VCP inhibitor and metformin combination treatment for colorectal cancer.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) restores immune regulatory functions of airway macrophages of patients with asthma.

Allergic asthma is characterized by the polarization of Th2 cells and impaired immune regulation. Macrophages occupy the largest proportion of airway immune cells. This study aims to discover the mechanism that hinders the immune regulatory functions of airway macrophages. In this study, macrophages were isolated from cells in bronchoalveolar lavage fluids (BALF) collected from asthma patients and normal control (NC) subjects. The results indicated that macrophages occupied the largest portion of the cellular components in BALF. The frequency of IL-10+ macrophage was significantly lower in asthma patients than in NC subjects. The expression of IL-10 in macrophages of BALF was associated with the levels of asthma-related parameters. The immune-suppressive functions of BALF M0 cells were defective in asthma patients. The inducibility of IL-10 expression was impaired in BALF macrophages of asthma patients, which could be restored by exposing to CpG. In conclusion, the induction of IL-10 in macrophages of BALF in asthma patients was impaired, and it could be restored by exposure to CpG.

Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses.

Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines.

The Key Role of Tumor Budding in Predicting the Status of Lymph Node Involvement in Early Gastric Cancer Patients: A Clinical Multicenter Validation in China.

BACKGROUND: Accurate preoperative prediction of lymph node (LN) involvement is essential for the management of early gastric cancer (EGC). Our objective was to formulate a potent nomogram for predicting LN involvement in EGC by leveraging an innovative predictor of tumor budding. METHODS: We assembled a cohort of EGC patients who underwent radical surgery at two tertiary cancer centers. Tumor budding was stratified by using an optimal cutoff value and integrated with other clinicopathological variables to ascertain the risk factors associated with LN involvement. A nomogram was developed and its predictive performance was assessed by using receiver operating characteristic (ROC) curves and calibration plots. In addition, we conducted decision curve analysis to evaluate its clinical utility. Finally, an external validation was conducted by using an independent cohort. RESULTS: Finally, 307 eligible patients (215 in the primary cohort and 92 in the validation cohort) were included. Tumor budding, categorized by a count of two, exhibited a robust association with LN involvement (OR 14.12, p = 0.012). Other significant risk factors include lymphovascular invasion, depth of tumor invasion, ulceration, and tumor differentiation. Notably, the nomogram demonstrated exceptional discriminative power (area under the ROC curve, 0.872 in the primary cohort and 0.885 in the validation cohort) and precise predictive capabilities. Furthermore, the nomogram showed notable clinical applicability through decision curve analysis, particularly in endoscopic curability C-2, by mitigating the risk of overtreatment. CONCLUSIONS: Tumor budding is a robust predictor of LN involvement in EGC. The incorporation of tumor budding into a nomogram is an effective strategy, thereby informing and enhancing clinical decision-making.

Experimental Realization of Self-Contained Quantum Refrigeration.

A fundamental challenge in quantum thermodynamics is the exploration of inherent dimensional constraints in thermodynamic machines. In the context of two-level systems, the most compact refrigerator necessitates the involvement of three entities, operating under self-contained conditions that preclude the use of external work sources. Here, we build such a smallest refrigerator using a nuclear spin system, where three distinct two-level carbon-13 nuclei in the same molecule are involved to facilitate the refrigeration process. The self-contained feature enables it to operate without relying on net external work, and the unique mechanism sets this refrigerator apart from its classical counterparts. We evaluate its performance under varying conditions and systematically scrutinize the cooling constraints across a spectrum of scenarios, which sheds light on the interplay between quantum information and thermodynamics.

Recent progress in chimeric antigen receptor therapy for acute myeloid leukemia.

Although CAR-T cell therapy has been particularly successful as a treatment for B cell malignancies, effectively treating acute myeloid leukemia with CAR remains a greater challenge. Multiple preclinical studies and clinical trials are underway, including on AML-related surface markers that CAR-T cells can target, such as CD123, CD33, NKG2D, CLL1, CD7, FLT3, Lewis Y and CD70, all of which provide opportunities for developing CAR-T therapies with improved specificity and efficacy. We also explored specific strategies for CAR-T cell treatment of AML, including immune checkpoints, suicide genes, dual targeting, genomic tools and the potential for universal CAR. In addition, CAR-T cell therapy for AML still has certain risks and challenges, including cytokine release syndrome (CRS) and haematotoxicity. Despite these challenges, as a new targeting method for AML treatment, CAR-T cell therapy still has great prospects. Ongoing research aims to further optimize this treatment mode.

Tandem bispecific CD123/CLL-1 CAR-T cells exhibit specific cytolytic effector functions against human acute myeloid leukaemia.

OBJECTIVES: The treatment of refractory and recurrent acute myeloid leukaemia (AML) is still a challenge with poor response rates and short survival times. In an attempt to solve this problem, we constructed a tandem bispecific chimeric antigen receptor (CAR) targeting CD123 and C-type lectin-like molecule 1 (CLL-1), two different AML antigens, and verified its cytotoxic effects in vitro. METHODS: We established and cultured K562 cell lines expressing both CD123 and CLL1 antigens. Single-target CAR-T cells specific to CD123 and CLL1 were engineered, alongside tandem CD123/CLL1 bispecific CAR-T cells. Flow cytometry was used to determine cell phenotypes, transfection efficiencies, cytokine release, and CAR-T-cell proliferation, and an lactate dehydrogenase assay was used to detect the cytotoxicity of CD123/CLL-1 bispecific tandem CAR-T cells in vitro. RESULTS: Two types of tandem CAR-T cells exhibited significant killing effects on CLL-1 + CD123+ leukaemia cell lines and primary AML tumour cells. The killing efficiency of tandem CAR-T cells in the case of single antigen expression is comparable to that of single target CAR-T cells. When faced with dual target tumour cells, dual target CAR-T cells significantly surpass single target CAR-T cells. CD123/CLL-1 CAR-T cells in tandem targeted and killed CD123- and CLL-1-positive leukaemia cell lines and released a large number of cytokines. CONCLUSIONS: CD123/CLL-1 CAR-T cells in tandem can simultaneously target CD123 and CLL-1 on AML cells, demonstrating a significant ability to kill single antigens and multi-target tumour cells. This suggests that CD123/CLL-1 CAR-T cells exhibit significant advantages in the expression of multiple antigens in a wide range of target cells, which may help overcome the challenges posed by tumour heterogeneity and evasion mechanisms.

The Role of Seed Users in Nurturing an Online Health Community for Smoking Cessation Among People With HIV/AIDS.

BACKGROUND: To nurture a new online community for health behavior change, a fruitful strategy is to recruit "seed users" to create content and encourage participation. PURPOSE: This study evaluated the impact of support from seed users in an online community for smoking cessation among people living with HIV/AIDS and explored the linguistic characteristics of their interactions. METHODS: These secondary analyses examined data from a randomized trial of a smoking cessation intervention for HIV+ smokers delivered via an online health community (OHC). The analytic sample comprised n = 188 participants randomized to the intervention arm who participated in the community. Independent variables were OHC interactions categorized by participant interlocutor type (study participant, seed user) and interaction type (active, passive). The primary outcome was biochemically verified 7-day abstinence from cigarettes measured 3 months post-randomization; 30-day abstinence was examined for robustness. RESULTS: Logistic regression models showed that participants' interactions with seed users were a positive predictor of abstinence but interactions with other study participants were not. Specifically, the odds of abstinence increased as the number of posts received from seed users increased. Exploratory linguistic analyses revealed that seed users wrote longer comments which included more frequent use of "we" and "you" pronouns and that study participants users used more first-person singular pronouns ("I"). CONCLUSIONS: Seeding a community at its inception and nurturing its growth through seed users may be a scalable way to foster behavior change among OHC members. These findings have implications for the design and management of an OHC capable of promoting smoking cessation.

Online health communities (OHCs) are a popular means for people with similar health concerns to exchange information and support. The success of OHCs depends on members' active participation and on the formation of meaningful relationships. Jumpstarting a new OHC with active members (seed users) can promote engagement and foster its growth. Using data from a multisite randomized controlled trial of a web-based smoking cessation intervention developed specifically for people living with HIV/AIDS (PLWH), we examined whether support provided by seed users in the OHC was a stronger predictor of abstinence from smoking compared with support from other tobacco users who are also trying to quit. These secondary analyses focused on 188 urban, predominantly Black PLWH who smoked that were randomized to the intervention arm and participated in the online community. The primary outcome was biochemically verified 7-day abstinence from cigarettes measured 3 months following study enrollment. Receiving support from seed users was a positive predictor of abstinence among smokers in the trial whereas interactions with other study participants did not relate to abstinence. These findings suggest that for a new OHC, seed users can be critical for generating engagement and promoting health behavior change.

Mo4+-Doped CuS Nanosheet-Assembled Hollow Spheres for CO2 Electroreduction to Ethanol in a Flow Cell.

Electrocatalytic CO2 reduction reaction (CO2RR) to ethanol has been widely researched for potential commercial application. However, it still faces limited selectivity at a large current density. Herein, Mo4+-doped CuS nanosheet-assembled hollow spheres are constructed to address this issue. Mo4+ ion doping modifies the local electronic environments and diversifies the binding sites of CuS, which increases the coverage of linear *COL and produces bridge *COB for subsequent *COL-*COH coupling toward ethanol production. The optimal Mo9.0%-CuS can electrocatalyze CO2 to ethanol with a faradaic efficiency of 67.5% and a partial current density of 186.5 mA cm-2 at -0.6 V in a flow cell. This work clarifies that doping high valence transition metal ions into Cu-based sulfides can regulate the coverage and configuration of related intermediates for ethanol production during the CO2RR in a flow cell.

Amino Functionality Enables Aqueous Synthesis of Carboxylic Acid-Based MOFs at Room Temperature by Biomimetic Crystallization.

Enzyme immobilization within metal-organic frameworks (MOFs) is a promising solution to avoid denaturation and thereby utilize the desirable properties of enzymes outside of their native environments. The biomimetic mineralization strategy employs biomacromolecules as nucleation agents to promote the crystallization of MOFs in water at room temperature, thus overcoming pore size limitations presented by traditional postassembly encapsulation. Most biomimetic crystallization studies reported to date have employed zeolitic imidazole frameworks (ZIFs). Herein, we expand the library of MOFs suitable for biomimetic mineralization to include zinc(II) MOFs incorporating functionalized terephthalic acid linkers and study the catalytic performance of the enzyme@MOFs. Amine functionalization of terephthalic acids is shown to accelerate the formation of crystalline MOFs enabling new enzyme@MOFs to be synthesized. The structure and morphology of the enzyme@MOFs were characterized by PXRD, FTIR, and SEM-EDX, and the catalytic potential was evaluated. Increasing the linker length while retaining the amino moiety gave rise to a family of linkers; however, MOFs generated with the 2,2'-aminoterephthalic acid linker displayed the best catalytic performance. Our data also illustrate that the pH of the reaction mixture affects the crystal structure of the MOF and that this structural transformation impacts the catalytic performance of the enzyme@MOF.

Development and validation of a novel colonoscopy withdrawal time indicator based on YOLOv5.

BACKGROUND AND AIM: The study aims to introduce a novel indicator, effective withdrawal time (WTS), which measures the time spent actively searching for suspicious lesions during colonoscopy and to compare WTS and the conventional withdrawal time (WT). METHODS: Colonoscopy video data from 472 patients across two hospitals were retrospectively analyzed. WTS was computed through a combination of artificial intelligence (AI) and manual verification. The results obtained through WTS were compared with those generated by the AI system. Patients were categorized into four groups based on the presence of polyps and whether resections or biopsies were performed. Bland Altman plots were utilized to compare AI-computed WTS with manually verified WTS. Scatterplots were used to illustrate WTS within the four groups, among different hospitals, and across various physicians. A parallel box plot was employed to depict the proportions of WTS relative to WT within each of the four groups. RESULTS: The study included 472 patients, with a median age of 55 years, and 57.8% were male. A significant correlation with manually verified WTS (r = 0.918) was observed in AI-computed WTS. Significant differences in WTS/WT among the four groups were revealed by the parallel box plot (P < 0.001). The group with no detected polyps had the highest WTS/WT, with a median of 0.69 (interquartile range: 0.40, 0.97). WTS patterns were found to be varied between the two hospitals and among senior and junior physicians. CONCLUSIONS: A promising alternative to traditional WT for quality control and training assessment in colonoscopy is offered by AI-assisted computation of WTS.

Z-scheme Fe@Fe2O3/BiOBr heterojunction with efficient carrier separation for enhanced heterogeneous photo-Fenton activity of tetracycline degradation: Fe2+ regeneration, mechanism insight and toxicity evaluation.

The recombination of photogenerated carrier leads to inefficient Fe2+ regeneration, which limits the extensive application of heterogeneous photo-Fenton. Here, a novel Fe@Fe2O3/BiOBr catalyst with Z-scheme heterojunction structure is designed, and the establishment of the Z-scheme heterojunction facilitates the separation and transfer of photogenerated carrier and maintains the superior redox capability of the system. As-prepared Fe@Fe2O3/BiOBr catalyst exhibits outstanding catalytic performance and stability, especially for the optimum composite FFB-3, its degradation efficiency of tetracycline (TC) achieves 98.22% and the mineralization degree reaches 59.48% within 90 min under natural pH. The preeminent catalytic efficiency benefited from the synergistic of heterogeneous photo-Fenton and Z-scheme carriers transfer mechanism, where Fe2+ regeneration was achieved by photogenerated electrons, and increased hydroxyl radicals were produced with the participation of H2O2 in-situ generated. The results of free-radical scavenging experiment and ESR illustrated that •OH, •O2-, 1O2 and h+ were active species participating in TC degradation. Furthermore, the TC degradation paths were proposed according to LC-MS, and the toxicity evaluation result showed that the toxicity of TC solutions was markedly decreased after degradation. This study provides an innovative strategy for heterogeneous photo-Fenton degradation of antibiotic contaminations by constructing Z-scheme heterojunctions.

Synergetic effect of green synthesized NZVI@Chitin-modified ZSM-5 for efficient oxidative degradation of tetracycline.

The aggregation and limited activity of nanoscale zero-valent iron (NZVI) in aqueous media hinder its practical application. In this study, a cost-effective, environmentally friendly, robust, and efficient synthesis method for NZVI-based composite was developed. NZVI@Chitin-modified ZSM-5 (NZVI@C-ZSM) composite was facilely and greenly synthesized by loading NZVI into alkali-modified ZSM-5 molecular sieves after modifying with chitin as a surfactant and binder. NZVI@C-ZSM exhibited remarkable efficacy in TC removal, achieving a removal efficiency of 97.72% within 60 min. Compared with pristine NZVI, NZVI@C-ZSM demonstrated twice the removal efficiency, indicating that NZVI@C-ZSM effectively improved the dispersion and stability of NZVI. This enhancement provided more reactive sites for generating reactive oxygen species (ROS), significantly boosting catalytic activity and durability while reducing the potential risk of secondary pollution. An improved two-parameter pseudo-first-order kinetic model was used to effectively characterize the reaction kinetics. The mechanism for TC removal primarily involved an adsorption process and chemical oxidation-reduction reactions induced by hydroxyl radicals (•OH) and superoxide radicals (•O2-). Three potential degradation pathways for TC were suggested. Furthermore, NZVI@C-ZSM exhibited good resistance to interference, suggesting its broad potential for practical applications in complex environmental conditions. This study offers a viable material and method for addressing the issue of antibiotic-contaminated water, with potential applications in water resource management.

Associations between patterns of blood heavy metal exposure and health outcomes: insights from NHANES 2011-2016.

BACKGROUND: Extensive research has explored the association between heavy metal exposure and various health outcomes, including malignant neoplasms, hypertension, diabetes, and heart diseases. This study aimed to investigate the relationship between patterns of exposure to a mixture of seven heavy metals and these health outcomes. METHODS: Blood samples from 7,236 adults in the NHANES 2011-2016 studies were analyzed for levels of cadmium, manganese, lead, mercury, selenium, copper, and zinc. Cluster analysis and logistic regression identified three distinct patterns of mixed heavy metal exposure, and their associations with health outcomes were evaluated. RESULTS: Pattern 1 exhibited higher odds ratios (ORs) for malignancy during NHANES 2011-2012 (OR = 1.33) and 2015-2016 (OR = 1.29) compared to pattern 2. Pattern 3 showed a lower OR for malignancy during NHANES 2013-2014 (OR = 0.62). For hypertension, pattern 1 displayed higher ORs than pattern 2 for NHANES 2011-2012 (OR = 1.26), 2013-2014 (OR = 1.31), and 2015-2016 (OR = 1.41). Pattern 3 had lower ORs for hypertension during NHANES 2013-2014 (OR = 0.72) and 2015-2016 (OR = 0.67). In terms of heart diseases, pattern 1 exhibited higher ORs than pattern 2 for NHANES 2011-2012 (OR = 1.34), 2013-2014 (OR = 1.76), and 2015-2016 (OR = 1.68). Pattern 3 had lower ORs for heart diseases during NHANES 2013-2014 (OR = 0.59) and 2015-2016 (OR = 0.52). However, no significant trend was observed for diabetes. All three patterns showed the strongest association with hypertension among the health outcomes studied. CONCLUSIONS: The identified patterns of seven-metal mixtures in NHANES 2011-2016 were robust. Pattern 1 exhibited higher correlations with hypertension, heart disease, and malignancy compared to pattern 2, suggesting an interaction between these metals. Particularly, the identified patterns could offer valuable insights into the management of hypertension in healthy populations.

A novel classification for guiding the surgical approach for cranio-orbital lesions: a single institution case series of 45 cases and a literature review.

We aim to share our experience of the removal of cranio-orbital lesions (COLs) and propose a novel classification to guide the tailored approach selection. We retrospectively reviewed 45 consecutive patients with COLs who underwent surgery performed by the same neurosurgeon between November 2010 and November 2022. The surgical approach was selected according to the anatomical region classification of the COLs. For lesions limited to space A (lateral superior orbital fissure, SOF), the pterion or extended pterion approach (PA or EPA) was used. For lesions limited to space B (extraconal compartment medial SOF, and cavernous sinus CS) and C (intraconal compartment, medial SOF, and CS), the pretemporal transcavernous approach (PTCA) was used. For lesions limited to space D (intraconal compartment and optic canals), the subfrontal approach (SA) was used. For lesions extending into the infratemporal fossa (ITF), the cranio-orbito-zygomatic approach (COZA) was used. For lesions involving pterygopalatine fossa (PPF), the endoscopic transnasal approach (ETNA) was used. We analyzed the clinical manifestations, imaging data, surgical approaches, surgical outcomes, neurological outcomes, and follow-up data. Gross total resection was performed in 35 patients (35/45, 77.8%). SA, PA, EPA, PTCA, COZA, and ETNA were performed in 9, 9, 10, 10, 6, and 1 case(s), respectively. Progression of the residual tumor was observed in 6 cases (1 adenoid cystic carcinoma and 5 meningiomas). Surgical approach selection plays a vital role in patient prognosis. This novel classification based on the involvement of anatomic space could help surgeons select an appropriate approach to remove the COLs.

Single-cell transcriptome analysis upon ECM-remodeling meningioma cells.

Meningiomas are the most common tumours that primarily arise in the central nervous system, but their intratumoural heterogeneity has not yet been thoroughly studied. We aimed to investigate the transcriptome characteristics and biological properties of ECM-remodeling meningioma cells. Single-cell RNA sequencing (ScRNA-seq) data from meningioma samples were acquired and used for analyses. We conducted comprehensive bioinformatics analyses, including screening for differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) term enrichment analyses, Gene Set Enrichment Analysis (GSEA), protein-protein interaction (PPI) analysis, and copy number variation (CNV) analysis on single-cell sequencing data from meningiomas. Eighteen cell types, including six meningioma subtypes, were identified in the data. ECM-remodeling meningioma cells (MGCs) were mainly distributed in brain-tumour interface tissues. KEGG and GO enrichment analyses revealed that 908 DEGs were mainly related to cell adhesion, extracellular matrix organization, and ECM-receptor interaction. GSEA analysis demonstrated that homophilic cell adhesion via plasma membrane adhesion molecules was significantly enriched (NES = 2.375, P < 0.001). CNV analysis suggested that ECM-remodeling MGCs showed considerably lower average CNV scores. ECM-remodeling MGCs predominantly localized at the brain-tumour interface area and adhere stably to the basement membrane with a lower degree of malignancy. This study provides novel insights into the malignancy of meningiomas.

Thyroid transcriptomic profiling reveals the differential regulation of lncRNA and mRNA related to prolificacy in Small Tail Han sheep with FecB++ genotype.

The thyroid gland is an important endocrine gland in animals, which mainly secretes thyroid hormones and acts on various organs of the body. Long-chain non-coding RNA (lncRNA) plays an important role in animal reproduction. However, there is still a lack of understanding of their expression patterns and potential roles in the thyroid of Small Tail Han (STH) sheep. In this study, RNA-seq was used to examine the transcriptome expression patterns of lncRNAs and mRNAs in the follicular phase (ww_FT) and luteal phase (ww_LT) in FecB++ genotype STH Sheep. A total of 17,217 lncRNAs and 39,112 mRNAs were identified including 96 differentially expressed lncRNAs (DELs) and 1054 differentially expressed mRNAs (DEGs). Functional analysis of genes with significant differences in expression level showed that these genes could be enriched in Ras signalling pathway, hedgehog (HH) signalling pathway, ATP-binding cassette (ABC) transporters and other signalling pathways related to animal reproduction. In addition, through correlation analysis for lncRNA-mRNA co-expression and network construction, we found that LNC_009115 and LNC_005796 trans target NIK-related kinase (NRK) and poly(A)-specific ribonuclease (PARN). LNC_007189 and LNC_002045 trans target progesterone-induced blocking factor 1 (PIBF1), LNC_009013 trans targets small mothers against decapentaplegic (SMAD1) are related to animal reproduction. These genes add new resources for elucidating the regulatory mechanisms of reproduction in sheep with different reproductive cycles of the FecB++ genotype STH sheep.