Responsive and traceless assembly of iron nanoparticles and 131I labeled radiopharmaceuticals for ferroptosis enhanced radio-immunotherapy.

Ferroptosis is an iron-dependent form of programmed cell death with the potential to reverse traditional cancer therapy resistance. The combination of ferroptosis with chemotherapy, photodynamic therapy and X-ray therapy has demonstrated remarkably improved therapeutic efficiency. Radiopharmaceutical therapy (RPT) is an emerging approach that achieves precise radiation to diseased tissues via radionuclide delivery. However, insufficient accumulation and retention of therapeutic radiopharmaceuticals in tumor region as well as cancer radioresistance impact treatment efficacy. Here, a nanoassembly of renal clearable ultrasmall iron nanoparticles (USINPs) and 131I-aPD-L1 is prepared via the affinity of fluorophenylboronic acid modified on the USINPs with 131I-aPD-L1. The 150 nm USINAs(131I-aPD-L1) nanoassembly is stable in blood circulation, effectively targets to the tumor and disassembles in the presence of ATP in the tumor microenvironment. Both in vitro and in vivo experiments prove that USINPs-induced ferroptosis boosted the tumor radiosensitization to 131I while 131I-mediated RPT further enhanced ferroptosis. Meanwhile, the immunogenic cell death caused by RPT and ferroptosis combined with PD-L1 immune checkpoint blockade therapy exhibits a strong antitumor immunity. This study provides a novel way to improve the tumor accumulation of ferroptosis inducer and radiopharmaceuticals, insights into the interaction between RPT and ferroptosis and an effective SPECT-guided ferroptosis-enhanced radio-immunotherapy.

iNAP 2.0: Harnessing metabolic complementarity in microbial network analysis.

With the widespread adoption of metagenomic sequencing, new perspectives have emerged for studying microbial ecological networks, yielding metabolic evidence of interspecies interactions that traditional co-occurrence networks cannot infer. This protocol introduces the integrated Network Analysis Pipeline 2.0 (iNAP 2.0), which features an innovative metabolic complementarity network for microbial studies from metagenomics sequencing data. iNAP 2.0 sets up a four-module process for metabolic interaction analysis, namely: (I) Prepare genome-scale metabolic models; (II) Infer pairwise interactions of genome-scale metabolic models; (III) Construct metabolic interaction networks; and (IV) Analyze metabolic interaction networks. Starting from metagenome-assembled or complete genomes, iNAP 2.0 offers a variety of methods to quantify the potential and trends of metabolic complementarity between models, including the PhyloMint pipeline based on phylogenetic distance-adjusted metabolic complementarity, the SMETANA (species metabolic interaction analysis) approach based on cross-feeding substrate exchange prediction, and metabolic distance calculation based on parsimonious flux balance analysis (pFBA). Notably, iNAP 2.0 integrates the random matrix theory (RMT) approach to find the suitable threshold for metabolic interaction network construction. Finally, the metabolic interaction networks can proceed to analysis using topological feature analysis such as hub node determination. In addition, a key feature of iNAP 2.0 is the identification of potentially transferable metabolites between species, presented as intermediate nodes that connect microbial nodes in the metabolic complementarity network. To illustrate these new features, we use a set of metagenome-assembled genomes as an example to comprehensively document the usage of the tools. iNAP 2.0 is available at https://inap.denglab.org.cn for all users to register and use for free.

Increased serum phenylalanine/tyrosine ratio associated with the psychiatric symptom of anti-NMDAR encephalitis.

Background: Encephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) results in a distinctive neuro-psychiatric syndrome. It has been reported that the serum phenylalanine-tyrosine (Phe/Tyr) ratio increases during infection. However, the connection between phenylalanine-tyrosine metabolism and psychiatric symptoms remains unclear. Methods: We enrolled 24 individuals with anti-NMDAR encephalitis and 18 individuals with non-inflammatory neurological diseases (OND). Chromatography was used to measure serum levels of phenylalanine and tyrosine. Serum and cerebrospinal fluid (CSF) TNF-α levels were obtained from the clinical database. The modified Rankin Scale (mRS) score and Glasgow Coma Scale (GCS) score were recorded during the acute phase. The area under the curve (AUC) of the receiver operating characteristic curve was used to assess prediction efficacy. Results: In NMDAR patients, levels of serum Phe and the ratio of serum Phe/Tyr were higher compared to OND patients. The serum Phe/Tyr ratio was also elevated in NMDAR patients with psychiatric syndrome. Furthermore, serum Phe and Tyr levels were correlated with inflammatory indexes. Conclusion: The serum Phe/Tyr ratio is elevated in NMDAR patients with psychiatric syndrome and is associated with severity. Therefore, the serum Phe/Tyr ratio may serve as a potential prognostic biomarker.

Stand age-related effects of mangrove on archaeal methanogenesis in sediments: Community assembly and co-occurrence patterns.

Mangrove sediment is a key source of methane emissions; however, archaea community structure dynamics and methanogenesis activities during long-term mangrove restoration remain unclear. In this study, microcosm incubations revealed a substantial reduction in microbial-mediated methane production potential from mangrove sediments with increasing stand age; methane production rates decreased from 0.42 ng g-1 d-1 in 6-year-old stands to 0.23 ng g-1 d-1 in 64-year-old stands. High-throughput sequencing revealed a reduction in community diversity because of specific microorganism colonization and species loss, notably a decline in the relative abundance of Bathyarchaeia in sediments of 64-year-old stands. In addition, mangrove sediments, especially those in older stands (20- and 64-year-old), had more complex and stable co-occurrence microbial networks than mudflats. Furthermore, archaea community assembly in older stands was dominated by stochastic processes wherein dispersal limitation was prominent, and that in younger stands (6- and 12-year-old) was driven by deterministic processes. The proportion of dispersal limitation of Bathyarchaeia and traditional methanogens in sediment decreased with an increase in stand age. Quantitative polymerase chain reaction analysis confirmed a decrease in Bathyarchaeia (from 3.50 to 0.54 copies g-1) and mcrA gene (from 3.83 to 0.25 copies g-1) abundance in mangrove sediments with an increase in stand age. These findings demonstrate the critical role of Bathyarchaeia in methanogenesis; the decline in microbial interactions and abundance, and the reduced proportion of dispersal limitation of Bathyarchaeia and traditional methanogens collectively contributed to the mitigation of microbial-mediated methane production potential in older mangrove stands.

ESC-sEVs alleviate non-early-stage osteoarthritis progression by rejuvenating senescent chondrocytes via FOXO1A-autophagy axis but not inducing apoptosis.

Osteoarthritis (OA) is a common joint degenerative disease which currently lacks satisfactory disease-modifying treatments. Oxidative stress-mediated senescent chondrocytes accumulation is closely associated with OA progression, which abrogates cartilage metabolism homeostasis by secreting senescence-associated secretory phenotype (SASP) factors. Numerous studies suggested mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) have been regarded as promising candidates for OA therapy. However, MSC-sEVs were applied before the occurrence of cartilage degeneration or at early-stage OA, while in clinical practice, most OA patients who present with pain are already in non-early-stage. Recently, embryonic stem cells-derived sEVs (ESC-sEVs) have been reported to possess powerful anti-aging effects. However, whether ESC-sEVs could attenuate non-early-stage OA progression remains unknown. In this study, we demonstrated ESC-sEVs ameliorated senescent phenotype and cartilage destruction in both mechanical stress-induced non-early-stage posttraumatic OA and naturally aged mice. More importantly, we found ESC-sEVs alleviated senescent phenotype by rejuvenating aged chondrocytes but not inducing apoptosis. We also provided evidence that the FOXO1A-autophagy axis played an important role in the anti-aging effects of ESC-sEVs. To promote clinical translation, we confirmed ESC-sEVs reversed senescent phenotype in ex-vivo cultured human end-stage OA cartilage explants. Collectively, our findings reveal that ESC-sEVs-based therapy is of high translational value in non-early-stage OA treatment.

Unveiling the deterministic dynamics of microbial meta-metabolism: a multi-omics investigation of anaerobic biodegradation.

BACKGROUND: Microbial anaerobic metabolism is a key driver of biogeochemical cycles, influencing ecosystem function and health of both natural and engineered environments. However, the temporal dynamics of the intricate interactions between microorganisms and the organic metabolites are still poorly understood. Leveraging metagenomic and metabolomic approaches, we unveiled the principles governing microbial metabolism during a 96-day anaerobic bioreactor experiment. RESULTS: During the turnover and assembly of metabolites, homogeneous selection was predominant, peaking at 84.05% on day 12. Consistent dynamic coordination between microbes and metabolites was observed regarding their composition and assembly processes. Our findings suggested that microbes drove deterministic metabolite turnover, leading to consistent molecular conversions across parallel reactors. Moreover, due to the more favorable thermodynamics of N-containing organic biotransformations, microbes preferentially carried out sequential degradations from N-containing to S-containing compounds. Similarly, the metabolic strategy of C18 lipid-like molecules could switch from synthesis to degradation due to nutrient exhaustion and thermodynamical disadvantage. This indicated that community biotransformation thermodynamics emerged as a key regulator of both catabolic and synthetic metabolisms, shaping metabolic strategy shifts at the community level. Furthermore, the co-occurrence network of microbes-metabolites was structured around microbial metabolic functions centered on methanogenesis, with CH4 as a network hub, connecting with 62.15% of total nodes as 1st and 2nd neighbors. Microbes aggregate molecules with different molecular traits and are modularized depending on their metabolic abilities. They established increasingly positive relationships with high-molecular-weight molecules, facilitating resource acquisition and energy utilization. This metabolic complementarity and substance exchange further underscored the cooperative nature of microbial interactions. CONCLUSIONS: All results revealed three key rules governing microbial anaerobic degradation. These rules indicate that microbes adapt to environmental conditions according to their community-level metabolic trade-offs and synergistic metabolic functions, further driving the deterministic dynamics of molecular composition. This research offers valuable insights for enhancing the prediction and regulation of microbial activities and carbon flow in anaerobic environments. Video Abstract.

Allelopathic effects of Borreria latifolia on weed germination and identification of allelochemicals.

BACKGROUND: Borreria latifolia (Aubl.) K. Schum (Rubiaceae) is an annual weed with a strong allelopathic inhibitory effect on malignant weeds in orchards in southern China. This study was carried out to investigate its allelopathic potential and to identify allelochemicals present in B. latifolia. RESULTS: Aqueous extracts of B. latifolia inhibited the germination and radicle growth of Eleusine indica and the radicle growth of Bidens alba in a dose-dependent manner. However, only the high-concentration treatment at 50 mg mL-1 delayed the germination of B. alba and Digitaria sanguinalis. Among the root, stem, and leaf aqueous extracts of B. latifolia, the leaf extract had the strongest inhibitory effects on the germination and seedling growth of E. indica, followed by stem extract and then root extract. A total of 47 published allelochemicals, including coumarin, 4-hydroxybenzoate, salicylic acid, 4-hydroxycinnamic acid, and vanillic acid, were identified in the leaf extract. Among the five allelochemicals, coumarin was found to be present in the highest concentration in the leaf extract. Furthermore, coumarin exhibited a significantly greater inhibitory effect on E. indica (EC50 = 36.87 mg L-1) than did the other allelochemicals (EC50 = 100.87-156.30 mg L-1). CONCLUSION: This study indicates that the leaf extracts of B. latifolia and their allelochemicals have excellent potential as bioherbicides and that coumarin is one of the key allelochemicals in B. latifolia. © 2024 Society of Chemical Industry.

Deep insights into the assembly mechanisms, co-occurrence patterns, and functional roles of microbial community in wastewater treatment plants.

The understanding of activated sludge microbial status and roles is imperative for improving and enhancing the performance of wastewater treatment plants (WWTPs). In this study, we conducted a deep analysis of activated sludge microbial communities across five compartments (inflow, effluent, and aerobic, anoxic, anaerobic tanks) over temporal scales, employing high-throughput sequencing of 16S rRNA amplicons and metagenome data. Clearly discernible seasonal patterns, exhibiting cyclic variations, were observed in microbial diversity, assembly, co-occurrence network, and metabolic functions. Notably, summer samples exhibited higher α-diversity and were distinctly separated from winter samples. Our analysis revealed that microbial community assembly is influenced by both stochastic processes (66%) and deterministic processes (34%), with winter samples demonstrating more random assembly compared to summer. Co-occurrence patterns were predominantly mutualistic, with over 96% positive correlations, and summer networks were more organized than those in winter. These variations were significantly correlated with temperature, total phosphorus and sludge volume index. However, no significant differences were found among microbial community across five compartments in terms of ß diversity. A core community of keystone taxa was identified, playing key roles in eight nitrogen and eleven phosphorus cycling pathways. Understanding the assembly mechanisms, co-occurrence patterns, and functional roles of microbial communities is essential for the design and optimization of biotechnological treatment processes in WWTPs.

Metabolic interdependencies in thermophilic communities are revealed using co-occurrence and complementarity networks.

Microbial communities exhibit intricate interactions underpinned by metabolic dependencies. To elucidate these dependencies, we present a workflow utilizing random matrix theory on metagenome-assembled genomes to construct co-occurrence and metabolic complementarity networks. We apply this approach to a temperature gradient hot spring, unraveling the interplay between thermal stress and metabolic cooperation. Our analysis reveals an increase in the frequency of metabolic interactions with rising temperatures. Amino acids, coenzyme A derivatives, and carbohydrates emerge as key exchange metabolites, forming the foundation for syntrophic dependencies, in which commensalistic interactions take a greater proportion than mutualistic ones. These metabolic exchanges are most prevalent between phylogenetically distant species, especially archaea-bacteria collaborations, as a crucial adaptation to harsh environments. Furthermore, we identify a significant positive correlation between basal metabolite exchange and genome size disparity, potentially signifying a means for streamlined genomes to leverage cooperation with metabolically richer partners. This phenomenon is also confirmed by another composting system which has a similar wide range of temperature fluctuations. Our workflow provides a feasible way to decipher the metabolic complementarity mechanisms underlying microbial interactions, and our findings suggested environmental stress regulates the cooperative strategies of thermophiles, while these dependencies have been potentially hardwired into their genomes during co-evolutions.

Latent profile analysis on the decent work of Chinese employees: applying the Psychology of Working theory.

Background: This study used a person-centered approach to identify the specific performance of decent work in various groups to determine the heterogeneity of its five dimensions. Method: The Decent Work Scale, Work Need Satisfaction Scale, Socioeconomic Status Scale, Job Satisfaction Scale, and Life Well-being Scale were used to conduct a network survey of organizations in various industries in Mainland China. A total of 1,000 questionnaires were distributed, and 780 valid responses were obtained. Results: The results showed that the decent work of participants could be divided into three types: low salary, low free time, and high decent work. The results showed no significant difference in age among the groups, whereas the differences in socioeconomic status were significant. Welch's test was used to determine differences in the positive outcomes of the three potential types of decent work, and the results showed significant differences in work need satisfaction, job satisfaction, and life well-being among all groups. Conclusion: This study examined the characteristics of decent work more realistically, showing that decent work is not an all-or-nothing structure and that its intrinsic components should be flexibly combined according to the research background and purpose.

Clinical and Prognostic Characteristics of Acute BAD-Related Stroke: A Multicenter MRI-Based Prospective Study.

BACKGROUND: Branch atheromatous disease (BAD)-related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke. METHODS: The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0-2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0-1) during 90-day follow-up. RESULTS: We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53-68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2-6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22-62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes. CONCLUSIONS: With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.

Anti-Corrosion Flocking Surface with Enhanced Wettability and Evaporation.

The corrosion protection of tool steel surfaces is of significant importance for ensuring cutting precision and cost savings. However, conventional surface protection measures usually rely on toxic organic solvents, posing threats to the environment and human health. In this regard, an integrated process of laser texturing and electrostatic flocking is introduced as a green anti-corrosion method on a high-speed steel (HSS) surface. Drawing from the principles of textured surface energy barrier reduction and fiber array capillary water evaporation enhancement, a flocking surface with a synergistic optimization of surface wettability and evaporation performance was achieved. Then, contact corrosion tests using 0.1 mol/L of NaCl droplets were performed. Contact angles representing wettability and change in droplet mass representing evaporation properties were collected. The elements and chemical bonds presented on the corroded surfaces were characterized by X-ray photoelectron spectroscopy (XPS). The results revealed that the flocking surface exhibited the lowest degree of corrosion when compared with smooth and textured surfaces. Corrosion resistance of the flocking surface was achieved through the rapid spread and evaporation of droplets, which reduced the reaction time and mitigated electrochemical corrosion. This innovative flocking surface holds promise as an effective treatment in anti-corrosion strategies for cutting tools.

The novel peptide PEP-Z-2 potentially treats renal fibrosis in vivo and in vitro by regulating TGF-ß/Smad/AKT/MAPK signaling.

Renal fibrosis is a process in which excessive deposition of extracellular matrix leads to an increase in tissue hardness and gradual destruction of the renal parenchyma. Chronic kidney disease (CKD) commonly progresses to end-stage renal disease (ESRD), ultimately leading to renal failure. This disease has high incidence and mortality rates, but to date, effective treatment options are lacking. PEP-Z-2 is a collagen peptide isolated from redlip croaker scales and may have potential fibroprotective activity. In this study, PEP-Z-2 was found to alleviate unilateral ureteral obstruction (UUO)- and folic acid (FA)-induced kidney injury in a mouse model, reduce collagen deposition in tissues, normalize renal function, reduce the expression of fibrosis markers, reduce reactive oxygen species (ROS) production, and restore the balance of the oxidant/antioxidant system. In vitro experiments also demonstrated that PEP-Z-2 inhibits the TGF-ß-induced differentiation of fibroblasts and renal tubular epithelial cells into myofibroblasts and reduces the production of extracellular matrix (ECM) proteins such as fibronectin, Col I, and α-SMA, demonstrating notable therapeutic effects on renal fibrosis. This effect is achieved by regulating the TGF-ß/Smad/AKT/MAPK pathway. Our research suggested that PEP-Z-2 is a potential therapeutic drug for renal fibrosis, and peptides from aquatic organisms may constitute a new class of candidate drugs for the treatment of renal fibrosis and even other types of organ fibrosis.

Life history strategies predict responses of lacustrine fish communities to eutrophication.

The demographic traits of an organism are key components of its fitness and life history theory aims at identifying the environmental drivers underlying the evolution of life history strategies. For fishes, the equilibrium species, those investing into larval survival (large eggs, parental care) rather than into absolute fecundity, are hypothesized to have evolved in stable and predictable environments with high biotic pressure. Human induced nutrient enrichment in many lakes around the world makes them increasingly subjected to perturbations such as anoxia and toxic algal blooms. We hypothesized that eutrophication results in lakes becoming more unstable, unpredictable and less resource-limited, in turn less favorable to equilibrium species. Another hypothesis states that lacustrine environment stability increases with ecosystem size. This study presents the first attempt to compare the two hypotheses in a group of 26 lakes. We found that the population abundance of equilibrium species was negatively related to increasing eutrophication. Long-lived and highly fecund periodic species responded more positively to eutrophication than short lived opportunistic species, with no parental care. This result could be demonstrated by seasonality in primary productivity which favors periodic species, disconnection from the river which prevents good colonist (i.e., opportunistic) species to (re)-establish after perturbation events, and predation by periodic species on opportunistic species. In contrast, we found no support for the ecosystem size hypothesis. Overall, we showed that human driven eutrophication affected species according to their life history strategies, reinforcing the usefulness of life history theory as a framework for assessing fish community response to a large array of human perturbations. More generally, our study emphasizes the importance of species traits to assess, explain, and predict community responses to human and natural perturbations.

Microbial necromass contribution to soil carbon storage via community assembly processes.

Soil organic matter has been well acknowledged as a natural solution to mitigate climate change and to maintain agricultural productivity. Microbial necromass is an important contributor to soil organic carbon (SOC) storage, and serves as a resource pool for microbial utilization. The trade-off between microbial births/deaths and resource acquisition might influence the fate of microbial necromass in the SOC pool, which remains poorly understood. We coupled soil microbial assembly with microbial necromass contribution to SOC on a long-term, no-till (NT) farm that received maize (Zea mays L.) stover mulching in amounts of 0 %, 33 %, 67 %, and 100 % for 8 y. We characterized soil microbial assembly using the Infer Community Assembly Mechanisms by Phylogenetic-bin-based null model (iCAMP), and microbial necromass using its biomarker amino sugars. We found that 100 % maize stover mulching (NT100) was associated with significantly lower amino sugars (66.4 mg g-1 SOC) than the other treatments (>70 mg g-1 SOC). Bacterial and fungal communities responded divergently to maize stover mulching: bacterial communities were positive for phylogenetic diversity, while fungal communities were positive for taxonomic richness. Soil bacterial communities influenced microbial necromass contribution to SOC through determinism on certain phylogenetic groups and bacterial bin composition, while fungal communities impacted SOC accumulation through taxonomic richness, which is enhanced by the positive contribution of dispersal limitation-dominated saprotrophic guilds. The prevalence of homogeneous selection and dispersal limitation on microbial cell wall-degrading bacteria, specifically Chitinophagaceae, along with increased soil fungal richness and interactions, might induce the decreased microbial necromass contribution to SOC under NT100. Our findings shed new light on the role of microbial assembly in shaping the dynamics of microbial necromass and SOC storage. This advances our understanding of the biological mechanisms that underpin microbial necromass associated with SOC storage, with implications for sustainable agriculture and mitigation of climate change.

Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism.

Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving "immune cell-gut microbes-bile acid metabolites" contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD.

Transcriptome analysis of the diseased intervertebral disc tissue in patients with spinal tuberculosis.

OBJECTIVE: To investigate the differential expression genes (DEGs) in spinal tuberculosis using transcriptomics, with the aim of identifying novel therapeutic targets and prognostic indicators for the clinical management of spinal tuberculosis. METHODS: Patients who visited the Department of Orthopedics at the Second Hospital, Lanzhou University from January 2021 to May 2023 were enrolled. Based on the inclusion and exclusion criteria, there were 5 patients in the test group and 5 patients in the control group. Total RNA was extracted and paired-end sequencing was conducted on the sequencing platform. After processing the sequencing data with clean reads and annotating the reference genome, FPKM normalization and differential expression analysis were performed. The DEGs and long non-coding RNAs (LncRNAs) were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. The cis-regulation of differentially expressed mRNAs (DE mRNAs) by LncRNAs was predicted and analyzed to establish a co-expression network. RESULTS: This study identified 2366 DEGs, with 974 genes significantly upregulated and 1392 genes significantly downregulated. The upregulated genes are associated with cytokine-cytokine receptor interactions, tuberculosis, and TNF-α signaling pathways, primarily enriched in biological processes such as immunity and inflammation. The downregulated genes are related to muscle development, contraction, fungal defense response, and collagen metabolism processes. Analysis of LncRNAs from bone tuberculosis RNA-seq data detected a total of 3652 LncRNAs, with 356 significantly upregulated and 184 significantly downregulated. Further analysis identified 311 significantly different LncRNAs that could cis-regulate 777 target genes, enriched in pathways such as muscle contraction, inflammatory response, and immune response, closely related to bone tuberculosis. There are 51 genes enriched in the immune response pathway regulated by cis-acting LncRNAs. LncRNAs that regulate immune response-related genes, such as upregulated RP11-451G4.2, RP11-701P16.5, AC079767.4, AC017002.1, LINC01094, CTA-384D8.35, and AC092484.1, as well as downregulated RP11-2C24.7, may serve as potential prognostic and therapeutic targets. CONCLUSION: The DE mRNAs and LncRNAs in spinal tuberculosis are both associated with immune regulatory pathways. These pathways promote or inhibit the tuberculosis infection and development at the mechanistic level and play an important role in the process of tuberculosis transferring to bone tissue.

The efficacy and safety of Radiofrequency ablation combined with Lenvatinib plus Sintilimab in Unresectable Hepatocellular Carcinoma: a real-world study.

BACKGROUND: The combination of targeted therapy and immunotherapy has improved the clinical outcomes of unresectable hepatocellular Carcinoma (HCC). However, the overall prognosis remains suboptimal. This study aims to evaluate the efficacy and safety of a novel combination of radiofrequency ablation (RFA) with lenvatinib plus sintilimab in unresectable HCC. METHODS: In this retrospective study, patients diagnosed with unresectable HCC were included and divided into two cohorts: RFA combined with lenvatinib plus sintilimab (R-L-S group) and lenvatinib plus sintilimab (L-S group). The primary efficacy endpoints were objective response rate (ORR) and progression free survival (PFS). Adverse events were analyzed to assess the safety profiles. RESULTS: The median follow-up periods for the entire cohort were 14.0 months. The R-L-S group (n = 60) had a significantly higher ORR than those with L-S alone (n = 62) (40.0% vs. 20.9%; p = 0.022). Moreover, patients in the R-L-S group had improved median PFS (12 vs. 8 months; p = 0.013) and median overall survival (24 vs. 18 months; p = 0.037), as compared with lenvatinib and sintilimab alone. No significant difference in treatment related adverse event (TRAE) of any grade between the two groups. The most common TRAEs of grade ≥ 3 were fatigue 10.0% (6/60) and hand-foot skin reaction 10.0% (6/60) in the R-L-S group and hand-foot skin reaction 11.3% (7/62) in the L-S group. CONCLUSION: In unresectable HCC patients, the incorporation of RFA to lenvatinib plus sintilimab demonstrated improved efficacy without compromising safety compared with lenvatinib plus sintilimab alone.

An Identification Method for Road Hypnosis Based on Human EEG Data.

The driver in road hypnosis has not only some external characteristics, but also some internal characteristics. External features have obvious manifestations and can be directly observed. Internal features do not have obvious manifestations and cannot be directly observed. They need to be measured with specific instruments. Electroencephalography (EEG), as an internal feature of drivers, is the golden parameter for drivers' life identification. EEG is of great significance for the identification of road hypnosis. An identification method for road hypnosis based on human EEG data is proposed in this paper. EEG data on drivers in road hypnosis can be collected through vehicle driving experiments and virtual driving experiments. The collected data are preprocessed with the PSD (power spectral density) method, and EEG characteristics are extracted. The neural networks EEGNet, RNN, and LSTM are used to train the road hypnosis identification model. It is shown from the results that the model based on EEGNet has the best performance in terms of identification for road hypnosis, with an accuracy of 93.01%. The effectiveness and accuracy of the identification for road hypnosis are improved in this study. The essential characteristics for road hypnosis are also revealed. This is of great significance for improving the safety level of intelligent vehicles and reducing the number of traffic accidents caused by road hypnosis.