Involvement of the Laboratory Department in MDT Discussion for the Diagnosis of Unexplained Leukocytosis.

BACKGROUND: This paper reports the diagnostic process of a case involving an 86-year-old male patient who was admitted with cough, sputum, and fever, accompanied by persistent leukocytosis. METHODS: Through a multidisciplinary team (MDT) discussion, the laboratory department identified elevated ferritin levels, prompting clinical consideration of potential malignancy. RESULTS: Further investigations confirmed the diagnosis of thyroid cancer with multiple lung metastases. CONCLUSIONS: This case highlights the potential value of ferritin in tumor diagnosis, offering new insights into the etiology of abnormal leukocyte elevation. Additionally, the active involvement of the laboratory department in MDT discussions proves to be crucial for diagnosing challenging cases.

Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis.

BACKGROUND: Cholestasis is a common yet severe complication that occurs during the advancement of liver metastasis. However, how cholestasis impacts the development, treatment, and tumor microenvironment (TME) of liver metastasis remains to be elucidated. METHODS: Extrahepatic and intrahepatic cholestatic mouse models with liver metastasis were established to detect the differential expression levels of genes, infiltration of immune cells and change in bile acid-associated metabolites by using RNA-Sequencing, flowcytometry, and liquid chromatography and mass spectrometry. Western blot was applied to neutrophils under the stimulation of primary bile acids (BAs) in vitro to study the mechanism of phenotypic alteration. In vitro coculture of BA-treated neutrophils with CD8+ T cells were performed to study the immune-suppressive effect of phenotypic-altered neutrophils. Clinical samples collected from colorectal cancer patients with liver metastasis and cholestasis were applied to RNA-Seq. RESULTS: Compared to non-cholestatic mice, the progression of liver metastasis of cholestatic mice was significantly accelerated, which was associated with increased neutrophil infiltration and T-cell exclusion. Both neutrophils and T cells expressed higher immunosuppressive markers in the cholestatic mouse model, further indicating that an immunosuppressive tumor microenvironment was induced during cholestasis. Although neutrophils deletion via anti-Ly6G antibody partially hindered liver metastasis progression, it reduced the overall survival of mice. Tauro-ß-muricholic acid (Tß-MCA) and Glycocholic acid (GCA), the two most abundant cholestasis-associated primary BAs, remarkably promoted the expression of Arg1 and iNOS on neutrophils via p38 MAPK signaling pathway. In addition, BAs-pretreated neutrophils significantly suppressed the activation and cytotoxic effects of CD8+ T cells, indicating that the immunosuppressive phenotype of neutrophils was directly induced by BAs. Importantly, targeting BA anabolism with Obeticholic acid (OCA) under cholestasis effectively suppressed liver metastasis progression, enhanced the efficacy of immune checkpoint blockade, and prolonged survival of mice. CONCLUSIONS: Our study reveals the TME of cholestasis-associated liver metastasis and proposes a new strategy for such patients by targeting bile acid anabolism.

Huanglian Wendan Decoction Improves Insomnia in Rats by Regulating BDNF/TrkB Signaling Pathway Through Gut Microbiota-Mediated SCFAs and Affecting Microglia Polarization.

Insomnia is a typical type of sleep disorder. Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) with the effects of regulating Qi, drying dampness and resolving phlegm, calming the mind, and relieving irritation. This study aims to investigate the effect of HWD on insomnia in rats and its mechanism. Para-chlorophenylalanine (PCPA)-induced insomnia in rats was used for in vivo experiments and then treated with HWD. Behavioral tests, Western blot, real-time PCR, immunofluorescent staining, 16S rRNA sequencing were conducted. The content of SCFAs was determined by GC-MS. Acetic acid-pretreated rat hippocampal nerve cells were used for in vitro experiments. The results showed that HWD significantly improved the learning memory ability, decreased sleep latency, and prolonged sleep duration in insomniac rats. HWD reduced TNF-α and IL-6 levels and increased IL-10 and Foxp3 levels. HWD also promoted the polarization of macrophages from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. In addition, HWD increased the expression levels of BDNF and TrkB in the hippocampus. Administration of the TrkB receptor agonist 7,8-dihydroxyflavone (7,8-DHF) confirmed the mechanism by which HWD activates BDNF/TrkB signaling to ameliorate insomnia. Furthermore, HWD restored gut microbiota richness and diversity and promoted short-chain fatty acid (SCFA) production in insomniac rats. In vitro experiments confirmed that the acetic acid-treated SCFA group could activate the BDNF/TrkB signaling pathway in neuronal cells, further promoting neuronal cell growth. In conclusion, HWD alleviated insomnia by maintaining gut microbiota homeostasis, promoting SCFA production, reducing neuroinflammatory response and microglia activation, and activating BDNF/TrkB signaling pathway.

Treatment of posterolateral tibial plateau fractures: a narrative review and therapeutic strategy.

The posterolateral tibial plateau is crucial for maintaining knee stability during flexion, and fractures in this area often involve ligament and meniscus injuries, necessitating effective management. However, treating posterolateral tibial plateau fractures (PLF) poses significant challenges due to the complex anatomy. Therefore, this review aims to explore contemporary concepts of PLF, from identification to fixation, and proposes a comprehensive treatment strategy. In this article, the authors detail the injury mechanisms, fracture morphology, PLF classification systems, surgical approaches, and techniques for open reduction and internal fixation (ORIF) as well as arthroscopic-assisted internal fixation (ARIF). The findings indicate that PLF is typically caused by flexion-valgus forces, resulting in depression or split-depression patterns. For isolated PLF, the supra-fibular head approach is often preferable, whereas posterior approaches are more suitable for combined fractures. Additionally, innovative plates, particularly the horizontal belt plate, have shown satisfactory outcomes in treating PLF. Currently, the 'bicondylar four-quadrant' concept is widely used for assessing and managing the tibial plateau fractures involving PLF, forming the cornerstone of the comprehensive treatment strategy. Despite challenges in surgical exposure and implant placement, ORIF remains the mainstream treatment for PLF, benefiting significantly from the supra-fibular head approach and the horizontal belt plate. Furthermore, ARIF has proven effective by providing enhanced visualization and surgical precision in managing PLF, emerging as a promising technique.

Learning Virtual View Selection for 3D Scene Semantic Segmentation.

2D-3D joint learning is essential and effective for fundamental 3D vision tasks, such as 3D semantic segmentation, due to the complementary information these two visual modalities contain. Most current 3D scene semantic segmentation methods process 2D images "as they are", i.e., only real captured 2D images are used. However, such captured 2D images may be redundant, with abundant occlusion and/or limited field of view (FoV), leading to poor performance for the current methods involving 2D inputs. In this paper, we propose a general learning framework for joint 2D-3D scene understanding by selecting informative virtual 2D views of the underlying 3D scene. We then feed both the 3D geometry and the generated virtual 2D views into any joint 2D-3D-input or pure 3D-input based deep neural models for improving 3D scene understanding. Specifically, we generate virtual 2D views based on an information score map learned from the current 3D scene semantic segmentation results. To achieve this, we formalize the learning of the information score map as a deep reinforcement learning process, which rewards good predictions using a deep neural network. To obtain a compact set of virtual 2D views that jointly cover informative surfaces of the 3D scene as much as possible, we further propose an efficient greedy virtual view coverage strategy in the normal-sensitive 6D space, including 3-dimensional point coordinates and 3-dimensional normal. We have validated our proposed framework for various joint 2D-3D-input or pure 3D-input based deep neural models on two real-world 3D scene datasets, i.e., ScanNet v2 and S3DIS, and the results demonstrate that our method obtains a consistent gain over baseline models and achieves new top accuracy for joint 2D and 3D scene semantic segmentation. Code is available at https://github.com/smy-THU/VirtualViewSelection.

[Tumor-Like Primary Central Nervous System Vasculitis With Spina Involvement:Report of One Case].

Primary central nervous system vasculitis (PACNS) is a vasculitic disorder affecting small to medium-sized blood vessels primarily in the central nervous system,involving the brain,spinal cord,and meninges.Tumor-like PNCAS,a rare subtype of PACNS,is often misdiagnosed as intracranial malignancy,and that with spinal cord involvement is even more uncommon.The lack of specific clinical symptoms and imaging manifestations poses a challenge to the diagnosis of PACNS.This report presents a case of tumor-like PACNS with spinal cord involvement based on the pathological evidence,aiming to enrich the knowledge about this condition.

Clinicopathologic Features and Outcomes of Acute Leukemia Harboring PICALM::MLLT10 Fusion.

The PICALM::MLLT10 fusion is a rare but recurrent cytogenetic abnormality in acute leukemia, with limited clinicopathologic and outcome data available. Herein, we analyzed 156 acute leukemia patients with PICALM::MLLT10 fusion, including 12 patients from our institutions and 144 patients from the literature. The PICALM::MLLT10 fusion preferentially manifested in pediatric and young adult patients, with a median age of 24 years. T-lymphoblastic leukemia/lymphoma (T-ALL) constituted 65% of cases, acute myeloid leukemia (AML) 27%, and acute leukemia of ambiguous lineage (ALAL) 8%. About half of T-ALL were classified as an early T-precursor (ETP)-ALL. In our institutions' cohort, mediastinum was the most common extramedullary site of involvement. Eight of 12 patients were diagnosed with T-ALL exhibiting a pro-/pre-T stage phenotype (CD4/CD8-double negative, CD7-positive), and frequent CD79a expression. NGS revealed pathogenic mutations in 5 of 6 tested cases, including NOTCH1, and genes in RAS and JAK-STAT pathways and epigenetic modifiers. Of 138 cases with follow-up, pediatric patients (<18 years) had 5-year overall survival (OS) of 71%, significantly better than adults at 33%. The 5-year OS for AML patients was 25%, notably shorter than T-ALL patients at 54%; this distinction was observed in both pediatric and adult populations. Furthermore, adult but not pediatric ETP-ALL patients demonstrated inferior survival compared to non-ETP-ALL patients. Neither karyotype complexity nor transplant status had a discernible impact on OS. In conclusion, PICALM::MLLT10 fusion is most commonly seen in T-ALL patients, particularly those with an ETP phenotype. AML and adult ETP-ALL patients had adverse prognosis. PICALM::MLTT10 fusion testing should be considered in T-ALL, AML, and ALAL patients.

Visible-Light-Mediated Activation of Remote C(sp3)-H Bonds by Carbon-Centered Biradical via Intramolecular 1,5- or 1,6-Hydrogen Atom Transfer.

In this study, we introduce a novel intramolecular hydrogen atom transfer (HAT) reaction that efficiently yields azetidine, oxetane, and indoline derivatives through a mechanism resembling the carbon analogue of the Norrish-Yang reaction. This process is facilitated by excited triplet-state carbon-centered biradicals, enabling the 1,5-HAT reaction by suppressing the critical 1,4-biradical intermediates from undergoing the Norrish Type II cleavage reaction, and pioneering unprecedented 1,6-HAT reactions initiated by excited triplet-state alkenes. We demonstrate the synthetic utility and compatibility of this method across various functional groups, validated through scope evaluation, large-scale synthesis, and derivatization. Our findings are supported by control experiments, deuterium labeling, kinetic studies, cyclic voltammetry, Stern-Volmer experiments, and density functional theory (DFT) calculations.

Performance evaluation of the MAGLUMI Hepatitis B virus surface antigen chemiluminescence immunoassay.

A highly sensitive and reliable Hepatitis B virus surface antigen (HBsAg) measurement is essential to universal screening, timely diagnosis, and management of Hepatitis B virus (HBV) infection. This study aimed to evaluate the performance of MAGLUMI HBsAg chemiluminescence immunoassay (CLIA). MAGLUMI HBsAg (CLIA) was compared against ARCHITECT HBsAg. 411 HBsAg positive samples, including different stages of infection, genotypes, subtypes, mutants, and 30 seroconversion panels were tested to evaluate diagnostic sensitivity. Diagnostic specificity was evaluated by testing 205 hospitalized samples and 5101 blood donor samples. Precision, limit of blank (LoB), limit of detection (LoD), and linearity were also verified. The diagnostic sensitivity of the MAGLUMI HBsAg (CLIA) was 100% with better seroconversion sensitivity than ARCHITECT HBsAg. The MAGLUMI HBsAg (CLIA) has optimal detection efficacy for HBV subgenotypes samples. The analytical sensitivity is 0.039 IU/mL. The initial diagnostic specificity is 99.63% on blood donors and 96.59% on hospitalized samples. The verification data demonstrated high repeatability, a LoB of 0.02 IU/mL, LoD of 0.05 IU/mL and an excellent linearity of 0.050-250 IU/mL (R2 = 0.9946). The MAGLUMI HBsAg (CLIA) is proved a highly sensitive and reliable assay with optimal subgenotype detection efficacy.

Mechanistic insights into phosphoactivation of SLAC1 in guard cell signaling.

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli.

CD151-enriched migrasomes mediate hepatocellular carcinoma invasion by conditioning cancer cells and promoting angiogenesis.

BACKGROUND: The tetraspanin family plays a pivotal role in the genesis of migrasomes, and Tetraspanin CD151 is also implicated in neovascularization within tumorous contexts. Nevertheless, research pertaining to the involvement of CD151 in hepatocellular carcinoma (HCC) neovascularization and its association with migrasomes remains inadequate. METHODS: To investigate the correlation between CD151 and migrasome marker TSPAN4 in liver cancer, we conducted database analysis using clinical data from HCC patients. Expression levels of CD151 were assessed in HCC tissues and correlated with patient survival outcomes. In vitro experiments were performed using HCC cell lines to evaluate the impact of CD151 expression on migrasome formation and cellular invasiveness. Cell lines with altered CD151 expression levels were utilized to study migrasome generation and in vitro invasion capabilities. Additionally, migrasome function was explored through cellular aggregation assays and phagocytosis studies. Subsequent VEGF level analysis and tissue chip experiments further confirmed the role of CD151 in mediating migrasome involvement in angiogenesis and cellular signal transduction. RESULTS: Our study revealed a significant correlation between CD151 expression and migrasome marker TSPAN4 in liver cancer, based on database analysis of clinical samples. High expression levels of CD151 were closely associated with poor survival outcomes in HCC patients. Experimentally, decreased CD151 expression led to reduced migrasome generation and diminished in vitro invasion capabilities, resulting in attenuated in vivo metastatic potential. Migrasomes were demonstrated to facilitate cellular aggregation and phagocytosis, thereby promoting cellular invasiveness. Furthermore, VEGF-enriched migrasomes were implicated in signaling and angiogenesis, accelerating HCC progression. CONCLUSIONS: In summary, our findings support the notion that elevated CD151 expression promotes migrasome formation, and migrasomes play a pivotal role in the invasiveness and angiogenesis of liver cancer cells, thereby facilitating HCC progression. This finding implies that migrasomes generated by elevated CD151 expression may constitute a promising high-priority target for anti-angiogenic therapy in HCC, offering crucial insights for the in-depth exploration of migrasome function and a renewed comprehension of the mechanism underlying liver cancer metastasis.

Mechanisms of well iron clogging in groundwater heat pump systems: Insights from video imaging, hydrogeochemical analysis, and geochemical modeling.

Groundwater heat pump (GWHP) systems are increasingly popular as low-carbon and environmentally friendly technologies, but well clogging induced by iron remains a significant issue. This study investigated the clogging characteristics and biogeochemistry of three typical wells (pumping, injection, and observation wells) in an operating GWHP system using video imaging, sampling, and analysis of hydrogeochemical and microbial data. The results revealed that iron-induced well clogging is a complex process involving physical, chemical, and microbial factors. Pumping wells experience clogging due to water mixing with varying redox conditions, resulting in hematite-based iron oxide deposits. Injection wells exhibit higher clogging severity, with transformed oxidation and accumulation of reduced iron minerals at the solid-liquid interface, resulting in darker colored clogs with magnetite. Clogging in both extraction and injection wells is closely related to iron-rich aquifer sections, where severe clogging occurs. Shallow clogging due to iron oxide is limited and attributed to the oxidation of zero-valent iron in well casing material. Iron-oxidizing bacteria and iron-reducing bacteria were detected in the consolidated deposits of clogged wells, indicating their involvement in the clogging formation process. Moreover, a strong correlation was observed between the presence of nitrate-reducing bacteria in the water phase and the severity of clogging, suggesting a possible link between iron oxidation and nitrate reduction in the system. Geochemical modeling results further supported the observed clogging severity in GWHP systems and confirmed varying clogging mechanisms in different wells and depths. These findings contribute to the understanding of clogging in GWHP operations, aiding in robust water utilization and energy-saving efforts, and supporting global carbon reduction initiatives.

Psychological Outcomes in Families of PICU Survivors: A Meta-Analysis.

BACKGROUND: Pediatric critical illness exposes family members to stressful experiences that may lead to subsequent psychological repercussions. OBJECTIVE: To systematically review psychological outcomes among PICU survivors' family members. DATA SOURCES: Four medical databases (PubMed, Embase, CINAHL and PsycInfo) were searched from inception till October 2023. STUDY SELECTION: Studies reporting psychological disorders in family members of PICU patients with at least 3 months follow-up were included. Family members of nonsurvivors and palliative care patients were excluded. DATA EXTRACTION: Screening and data extraction was performed according to PRISMA guidelines. Data were pooled using a random-effects model. RESULTS: Of 5360 articles identified, 4 randomized controlled trials, 16 cohort studies, and 2 cross-sectional studies were included (total patients = 55 597; total family members = 97 506). Psychological distress was reported in 35.2% to 64.3% and 40.9% to 53% of family members 3 to 6 months and 1 year after their child's PICU admission, respectively. Post-traumatic stress disorder was diagnosed in 10% to 48% of parents 3 to 9 months later. Parents that experienced moderate to severe anxiety and depression 3 to 6 months later was 20.9% to 42% and 6.1% to 42.6%, respectively. Uptake of mental counseling among parents was disproportionately low at 0.7% to 29%. Risk factors for psychiatric morbidity include mothers, parents of younger children, and longer duration of PICU stay. LIMITATIONS: The majority of studies were on parents with limited data on siblings and second degree relatives. CONCLUSIONS: There is a high burden of psychological sequelae in family members of PICU survivors. Risk stratification to identify high-risk groups and early interventions are needed.

The Impact of Prone Position Ventilation on the Prognosis of Patients with Pulmonary Infections in Intensive Care Units.

Objective: This retrospective study aimed to analyze the impact of prone position ventilation compared to supine position ventilation on the prognosis of patients with pulmonary infections in the intensive care unit (ICU). Prone position ventilation has been suggested to enhance oxygenation, reduce ventilation-perfusion mismatch, and alleviate lung compression, which may contribute to improved respiratory mechanics and better outcomes in patients with pulmonary infections. By comparing these two ventilation positions, we sought to evaluate their respective effects on patient prognosis and shed light on the potential advantages of prone position ventilation in the ICU setting. Methods: A total of 160 critically ill patients with pulmonary infections were included in the study and divided into two groups: the prone position ventilation group (n=80) and the supine position ventilation group (n=80). Inclusion criteria for patient selection in this study included individuals between the ages of 18 and 75 who were critically ill with pulmonary infections and receiving treatment in the Intensive Care Unit (ICU). Basic vital sign monitoring, airway pathogen examinations, multidrug-resistant bacterial detection rates analysis, and prognosis assessments were conducted. Results: The prone position ventilation group demonstrated several advantages compared to the supine position ventilation group. The positive rate of airway pathogen examinations in the prone position ventilation group was 55%, significantly lower than the 75% in the supine position ventilation group (P = .005). The detection rate of multidrug-resistant bacteria was 20%, significantly lower than the 43.75% in the supine position group (P = .002). Furthermore, the prone position ventilation group showed shorter mechanical ventilation duration, intubation time, and ICU length of stay. Specifically, the duration of mechanical ventilation in the prone position ventilation group was 12.34±3.45 days, compared to 13.89±4.12 days in the supine position ventilation group. The intubation time was 10.56±2.78 days in the prone position group and 11.67±3.01 days in the supine position group. The ICU length of stay was 16.45±4.56 days in the prone position group and 18.67±5.34 days in the supine position group (P < .05). The two groups had no significant differences in total hospital stay and survival rate. Conclusion: Compared to supine position ventilation, prone position ventilation significantly improved airway pathogen examination results and reduced the detection rate of multidrug-resistant bacteria in patients with pulmonary infections in the ICU. Additionally, it decreased the duration of mechanical ventilation and ICU stay, although it did not significantly impact the survival rate. Further validation through larger-scale, multicenter studies is warranted. ICU practices may consider incorporating prone position ventilation as a standard intervention for patients with severe pulmonary infections. This could involve developing guidelines and protocols for the appropriate selection and implementation of prone position ventilation, as well as providing training to healthcare providers on its safe and effective use.

Surgical repositioning with omentalisation of an exposed subcutaneous ureteral bypass shunting port in a cat.

Case summary: A 9-year-old, spayed, female domestic shorthair cat presented with an open wound approximately 1 cm in size with exposure of the left subcutaneous ureteral bypass (SUB) shunting port that was placed approximately 11 months before presentation. Primary closures were attempted twice before local wound management with omentalisation and repositioning of the port. The exposed port was lavaged topically with a polyhexanide and propylbetaine wound irrigation solution before omentalisation and repositioning, resulting in successful retention of the implant. Five months after revision and omentalisation, there was complete coverage and healing of the wound. Relevance and novel information: Adequate topical treatment, repositioning and omentalisation could be a successful treatment option for the uncommon complication of SUB shunting port extrusion secondary to resistant local infection originating from the urinary tract.

Palladium-catalyzed selective C-C bond cleavage of keto-vinylidenecyclopropanes: construction of structurally rich dihydrofurans and tetrahydrofurans.

Palladium-catalyzed selective cleavage of the distal C-C bond and proximal C-C bond of keto-vinylidenecyclopropanes by altering the sterically bulky phosphine ligands has been realized. The proximal C-C bond cleavage can be achieved by using dtbpf as a phosphine ligand, affording bicyclic products containing dihydrofuran skeletons in good yields along with broad substrate scope. In proximal C-C bond cleavage reactions, the eight-membered cyclic palladium intermediate plays a key role in the reaction. The [3 + 2] cycloaddition of keto-vinylidenecyclopropanes through the distal C-C bond cleavage can be effectively accomplished with t BuXPhos as a phosphine ligand and ZnCl2 as an additive, delivering bicyclic products containing tetrahydrofuran skeletons in good yields. The further transformation of these bicyclic products has been demonstrated, and the reaction mechanisms of two different C-C bond cleavage reactions have been investigated by control experiments and DFT calculations.

Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer.

Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic "face-off" mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8+ T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8+ T cell cytotoxicity and the anti-PD-1 response in gastric cancer.