ortho-Alkynyl Benzyl Alcohols as C6 Synthons in Regioselective Construction of Polysubstituted Naphthalenes.

A straightforward methodology for the assembly of polysubstituted naphthalenes from ortho-alkynyl benzyl alcohols, enabled by using catalytic amounts of Tf2O, has been developed. This transformation not only features transition-metal free and without using other bases and additives but also provides a new synthetic application for ortho-alkynyl benzyl alcohols, i.e., as C6 synthons for the construction of PAHs.

Enhanced methane production from source-separated human feces (brown water) by single phase anaerobic co-digestion: Effects of different co-substrates.

Based on the concept of source separation of brown water (BW, human feces with flushing water) and yellow water (urine) in rural area, anaerobic co-digestion of BW with agricultural waste is a promising and effective method for rural waste treatment and resource recovery. The purpose of this study was to investigate the performance of different agricultural wastes (peanut straw (PST), peanut shell (PSH), swine wastewater acting as co-substrate for anaerobic co-digestion with BW, and the relative mechanisms were explored. When the mixed ratio was uniformly set as 1:1 (mass ratio, measured by volatile solid (VS)) and initial VS load as 20 g/L, the maximum cumulative methane production obtained by co-digestion (21 days) of BW and PST was 688 mL/g-VS, which performed better than the individual substrates (341 mL/g-VS), as well as the average of the sole BW and sole PST groups (531.2 mL/g-VS). The most impactful advantage was ascribed to the promotion of hydrolytic and acidogenic enzyme activities. The addition of PST also reduced the production of endogenous humus, which is difficult for biodegradation. Microbial community analysis showed that different co-substrates would affect the microbial community composition in the reactor. The relative abundance of hydrolytic acidogens in the PST and PSH co-digestion groups were higher than that in the SW co-digestion and sole BW groups, and the methanogenic archaea were dominated by the acetate-trophic Methanotrichaceae. The overall results suggest that anaerobic co-digestion is a feasible method, and co-digestion of BW and PST can improve methane production potential.

Controllable Thrombolysis Using a Nanobubble-Imaging-Guided rtPA Targeted Delivery Strategy.

Objective: The objective of this work is to design and fabricate a novel multifunctional nanocarrier combining thrombus-targeted imaging and ultrasound-mediated drug delivery for the theranostics of thrombotic diseases. Impact Statement: This study develops a new technology that can accurately visualize the thrombus and deliver drugs with controllable properties to diagnose and treat thrombotic diseases. Introduction: Thrombotic diseases are a serious threat to human life and health. The diagnosis and treatment of thrombotic diseases have always been a challenge. In recent years, nanomedicine has brought new ideas and new methods for the theranostics of thrombotic diseases. However, there are also many problems need to be solved, such as biosafety and stability of nanocarriers, early diagnosis, and timely treatment of thrombotic diseases, difficulty in clinical translation. Methods: The S1P@CD-PLGA-rtPA nanobubbles (NBs) were prepared by integrating sulfur hexafluoride (SF6)-loaded poly (D, L-lactide-co-glycolide) (PLGA) NBs, cyclodextrin (CD), sphingosine-1-phosphate (S1P), and recombinant tissue plasminogen activator (rtPA). Results: S1P@CD-PLGA-rtPA NBs had rapid and excellent thrombosis targeting imaging performance based on the specific interaction of S1P-S1PR1 (sphingosine-1-phosphate receptor 1). Furthermore, S1P@CD-PLGA-rtPA NBs that specifically targeting to the thrombosis regions could also respond to external ultrasound to achieve accurate and efficient delivery of rtPA to enhance the thrombolysis effectiveness and efficiency. Conclusion: This study proposes a new idea and strategy of targeting thrombus in rats via the specific interaction of S1P-S1PR1. On this basis, the acoustic response properties of bubble carriers could be fully utilized by combining thrombus-specific targeted imaging and ultrasound-mediated drug delivery for effective thrombolysis, which is expected to be applied in targeted diagnosis and treatment of thrombotic diseases in the future.

Leukemia inhibitory factor suppresses hepatic de novo lipogenesis and induces cachexia in mice.

Cancer cachexia is a systemic metabolic syndrome characterized by involuntary weight loss, and muscle and adipose tissue wasting. Mechanisms underlying cachexia remain poorly understood. Leukemia inhibitory factor (LIF), a multi-functional cytokine, has been suggested as a cachexia-inducing factor. In a transgenic mouse model with conditional LIF expression, systemic elevation of LIF induces cachexia. LIF overexpression decreases de novo lipogenesis and disrupts lipid homeostasis in the liver. Liver-specific LIF receptor knockout attenuates LIF-induced cachexia, suggesting that LIF-induced functional changes in the liver contribute to cachexia. Mechanistically, LIF overexpression activates STAT3 to downregulate PPARα, a master regulator of lipid metabolism, leading to the downregulation of a group of PPARα target genes involved in lipogenesis and decreased lipogenesis in the liver. Activating PPARα by fenofibrate, a PPARα agonist, restores lipid homeostasis in the liver and inhibits LIF-induced cachexia. These results provide valuable insights into cachexia, which may help develop strategies to treat cancer cachexia.

Advances in Aqueous Zinc Ion Batteries based on Conversion Mechanism: Challenges, Strategies, and Prospects.

Recently, aqueous zinc-ion batteries with conversion mechanisms have received wide attention in energy storage systems on account of excellent specific capacity, high power density, and energy density. Unfortunately, some characteristics of cathode material, zinc anode, and electrolyte still limit the development of aqueous zinc-ion batteries possessing conversion mechanism. Consequently, this paper provides a detailed summary of the development for numerous aqueous zinc-based batteries: zinc-sulfur (Zn-S) batteries, zinc-selenium (Zn-Se) batteries, zinc-tellurium (Zn-Te) batteries, zinc-iodine (Zn-I2 ) batteries, and zinc-bromine (Zn-Br2 ) batteries. Meanwhile, the reaction conversion mechanism of zinc-based batteries with conversion mechanism and the research progress in the investigation of composite cathode, zinc anode materials, and selection of electrolytes are systematically introduced. Finally, this review comprehensively describes the prospects and outlook of aqueous zinc-ion batteries with conversion mechanism, aiming to promote the rapid development of aqueous zinc-based batteries.

TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4+ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4+ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.

Case report outcome of cetuximab treatment in a metastatic colorectal cancer patient with novel KRAS P34R.

Cetuximab [the epidermal growth factor receptor (EGFR)-targeting mAb] improves clinical outcomes when added to standard chemotherapy used in the treatment of metastatic colorectal cancer. Patients with hotspot mutations in Kirsten rat sarcoma viral oncogene ( KRAS ) mutation in exon 2 were not recommended to be treated with cetuximab. However, there is still a lack of clinical data for those unreported non-hotspot KRAS mutations in exon 2 and their response to cetuximab. In this study, we reported a 35-year-old woman who was diagnosed with stage IVA CRC with liver metastases. An exceptionally uncommon KRASP34R mutation in KRAS exon 2 was detected in tumor specimens by next-generation sequencing. This patient obtained limited benefit from first-line chemotherapy and did not respond to cetuximab in the second-line course. In the third-line course, the patient also did not respond to the combination treatment of furaquitinib and cindilimab. The patient died 8 months after treatment initiation. In this study, we found amplification of the rare oncogenic KRASP34R was not only associated with an aggressive phenotype, but also supported cancer resistance to cetuximab, chemotherapy, and immunotherapy.

The physiological and biochemical responses to dark pericarp disease induced by excess manganese in litchi.

Dark pericarp disease (DPD), a physiological disorder induced by excess Manganese (Mn) in litchi, severely impacts the appearance and its economic value. To elucidate the underlying mechanisms of DPD, this study investigated the variations of phenolic compound, antioxidant defense system, subcellular structure, and transcriptome profiles in both normal fruit and dark pericarp fruit (DPF) at three developmental stages (green, turning, and maturity) of 'Guiwei' litchi. The results reveal that excess Mn in DPF pericarp resulted in a significant increase in reactive oxygen species, especially H2O2, and subsequent alterations in antioxidant enzyme activities. Notably, SOD (EC 1.15.1.1) activity at the green stage, along with POD (EC 1.11.1.7) and APX (EC 1.11.1.11) activities at the turning and the maturity stages, and GST (EC 2.5.1.18) activity during fruit development, were markedly higher in DPF. Cell injury was observed in pericarp, facilitating the formation of dark materials in DPF. Transcriptome profiling further reveals that genes involved in flavonoid and anthocyanin synthesis were up-regulated during the green stage but down-regulated during the turning and maturity stages. In contrast, PAL (EC 4.3.1.24), C4H (EC 1.14.14.91), 4CL (EC 6.2.1.12), CAD (EC 1.1.1.195), and particularly POD, were up-regulated, leading to reduced flavonoid and anthocyanin accumulation and increased lignin content in DPF pericarp. The above suggests that the antioxidant system and phenolic metabolism jointly resisted the oxidative stress induced by Mn stress. We speculate that phenols, terpenes, or their complexes might be the substrates of the dark substances in DPF pericarp, but more investigations are needed to identify them.

The Research Progress on Immortalization of Human B Cells.

Human B cell immortalization that maintains the constant growth characteristics and antibody expression of B cells in vitro is very critical for the development of antibody drugs and products for the diagnosis and bio-therapeutics of human diseases. Human B cell immortalization methods include Epstein-Barr virus (EBV) transformation, Simian virus 40 (SV40) virus infection, in vitro genetic modification, and activating CD40, etc. Immortalized human B cells produce monoclonal antibodies (mAbs) very efficiently, and the antibodies produced in this way can overcome the immune rejection caused by heterologous antibodies. It is an effective way to prepare mAbs and an important method for developing therapeutic monoclonal antibodies. Currently, the US FDA has approved more than 100 mAbs against a wide range of illnesses such as cancer, autoimmune diseases, infectious diseases, and neurological disorders. This paper reviews the research progress of human B cell immortalization, its methods, and future directions as it is a powerful tool for the development of monoclonal antibody preparation technology.

Interfacial assembled porous bismuthene/Ti3C2Tx MXene heterostructure for highly efficient capacitive deionization.

Capacitive deionization (CDI) is perceived as a promising technology for freshwater production owing to its environmentally friendly nature and low energy consumption. To date, the development of high-performance electrode materials represents the foremost challenge for CDI technology. In this work, the porous bismuthene/MXene (P-Bi-ene/MXene) heterostructure was synthesized using a simple interfacial self-assembly method with two-dimensional (2D) bismuthene and Ti3C2Tx MXene. Within the P-Bi-ene/MXene heterostructure, the porous structure can increase the active site and facilitate ion transport. Simultaneously, MXene effectively enhances the conductivity of the heterostructure, resulting in accelerating electron transport. Due to these attributes, the P-Bi-ene/MXene heterostructure demonstrates high desalination capacity (90.0 mg/g), fast desalination rate, and good cycling performance. The simple self-assembly strategy between 2D/2D materials described herein may offer inspirations for the synthesis of innovative electrode materials with high performance.

DNA Methylation-Based Testing in Peripheral Blood Mononuclear Cells Enables Accurate and Early Detection of Colorectal Cancer.

An effective blood-based method for the diagnosis of colorectal cancer has not yet been developed. Molecular alterations of immune cells occur early in tumorigenesis, providing the theoretical underpinning for early cancer diagnosis based on immune cell profiling. Therefore, we aimed to develop an effective detection method based on peripheral blood mononuclear cells (PBMC) to improve the diagnosis of colorectal cancer. Analysis of the genome-wide methylation landscape of PBMCs from patients with colorectal cancer and healthy controls by microarray, pyrosequencing, and targeted bisulfite sequencing revealed five DNA methylation markers for colorectal cancer diagnosis, especially early-stage colorectal cancer. A single-tube multiple methylation-specific quantitative PCR assay (multi-msqPCR) for simultaneous detection of five methylation markers was established, which allowed quantitative analysis of samples with as little as 0.1% PBMC DNA and had better discriminative performance than single-molecule detection. Then, a colorectal cancer diagnostic model (CDM) based on methylation markers and the multi-msqPCR method was constructed that achieved high accuracy for early-stage colorectal cancer (AUC = 0.91; sensitivity = 81.18%; specificity = 89.39%), which was improved compared with CEA (AUC = 0.79). The CDM also enabled a high degree of discrimination for advanced adenoma cases (AUC = 0.85; sensitivity = 63.04%). Follow-up data also demonstrated that the CDM could identify colorectal cancer potential up to 2 years before currently used diagnostic methods. In conclusion, the approach constructed in this study based on PBMC-derived DNA methylation markers and a multi-msqPCR method is a promising and easily implementable diagnostic method for early-stage colorectal cancer. SIGNIFICANCE: Development of a diagnostic model for early colorectal cancer based on epigenetic analysis of PBMCs supports the utility of altered DNA methylation in immune cells for cancer diagnosis.

A multiplex blood-based assay targeting DNA methylation in PBMCs enables early detection of breast cancer.

The immune system can monitor tumor development, and DNA methylation is involved in the body's immune response to tumors. In this work, we investigate whether DNA methylation alterations in peripheral blood mononuclear cells (PBMCs) could be used as markers for early detection of breast cancer (BC) from the perspective of tumor immune alterations. We identify four BC-specific methylation markers by combining Infinium 850 K BeadChips, pyrosequencing and targeted bisulfite sequencing. Based on the four methylation markers in PBMCs of BC, we develop an efficient and convenient multiplex methylation-specific quantitative PCR assay for the detection of BC and validate its diagnostic performance in a multicenter cohort. This assay was able to distinguish early-stage BC patients from normal controls, with an AUC of 0.940, sensitivity of 93.2%, and specificity of 90.4%. More importantly, this assay outperformed existing clinical diagnostic methods, especially in the detection of early-stage and minimal tumors.

Freestanding defective ammonium Vanadate@MXene hybrid films cathode for high performance aqueous zinc ion batteries.

Aqueous zinc ion batteries (AZIBs) have gained extensive attention due to the numerous advantages of zinc, such as low redox potential, high abundance, low cost as well as high theoretical specific capacity. However, the development of AZIBs is still hampered due to the lack of suitable cathodes. In this work, the freestanding defective ammonium vanadate@MXene (d-NVO@MXene) hybrid film was synthesized by simple vacuum filtration strategy. Due to the presence of the hierarchical freestanding structure, outstanding MXene conductive networks and abundant oxygen vacancy (in the d-NVO nanoribbons), the d-NVO@MXene hybrid film can not only expose more active sites but also possess outstanding conductivity and kinetics of charge transfer/ion diffusion. When the d-NVO@MXene hybrid film was directly used as the cathode, it displayed a high specific capacity of 498 mAh/g at 0.5 A/g and superior cycling stability performance with near 100 % coulomb efficiency. Furthermore, the corresponding storage mechanism was elucidated by ex situ various characterizations. This work provides new ideas for the development of freestanding vanadium-based cathode materials for AZIBs.

MoO2 Nanoclusters Embedded in Hierarchical Nitrogen Doped Carbon Nanoflower as Electrocatalytic Mediators in Aqueous Zinc-Tellurium Batteries: Enhancing Electrochemical Kinetics of Tellurium Redox Reaction.

Aqueous zinc-ion batteries (AZIBs) are considered to be one of the most promising devices for large-scale energy storage systems owing to their high theoretical capacity, environmental friendliness, and safety. However, the ionic intercalation or surface redox mechanisms in conventional cathode materials generally result in unsatisfactory capacities. Conversion-type aqueous zinc-tellurium (Zn-Te) batteries have recently gained widespread attention owing to their high theoretical specific capacities. However, it remains an enormous challenge to improve the slow kinetics of the aqueous Zn-Te batteries. Here, MoO2 nanoclusters embedded in hierarchical nitrogen-doped carbon nanoflower (MoO2 /NC) hosts are successfully synthesized and loaded with Te in aqueous Zn-Te batteries. Benefitting from the highly dispersed MoO2 nanoclusters and hierarchical nanoflower structure with a large specific surface area, the electrochemical kinetics of the Te redox reaction are significantly improved. As a result, the Te-MoO2 /NC electrode exhibits superior cycling stability and a high specific capacity of 493 mAh g-1 at 0.1 A g-1 . Meanwhile, the conversion mechanism is systematically explored using a variety of ex situ characterization methods. Therefore, this study provides a novel approach for enhancing the kinetics of the Te redox reaction in aqueous Zn-Te batteries.

Strong interface coupling boosting hierarchical bismuth embedded carbon hybrid for high-performance capacitive deionization.

Capacitive deionization (CDI) is regarded as a promising desalination technology owing to its low cost and environmental friendliness. However, the lack of high-performance electrode materials remains a challenge in CDI. Herein, the hierarchical bismuth-embedded carbon (Bi@C) hybrid with strong interface coupling was prepared through facile solvothermal and annealing strategy. The hierarchical structure with strong interface coupling between the bismuth and carbon matrix afforded abundant active sites for chloridion (Cl-) capture, improved electrons/ions transfer and the stability of the Bi@C hybrid. As a result of these advantages, the Bi@C hybrid showed a high salt adsorption capacity (75.3 mg/g under 1.2 V), salt adsorption rate and good stability, making it a promising electrode material for CDI. Furthermore, the desalination mechanism of the Bi@C hybrid was elucidated through various characterizations. Therefore, this work provides valuable insights for the design of high-performance bismuth-based electrode materials for CDI.

Albumin infusion may decrease the mortality of hypoalbuminemia patients with severe acute pancreatitis: a retrospective cohort study.

BACKGROUND: At present, the relationship between severe acute pancreatitis (SAP) and albumin infusion is not clear. We aimed to identify the impact of serum albumin on the prognosis of SAP and the association between albumin infusions and mortality for hypoalbuminemia patients. METHODS: This was a retrospective cohort study that analyzed 1000 patients with SAP who were admitted to the First Affiliated Hospital of Nanchang University between January 2010 and December 2021 using data from a prospectively maintained database. Multivariate logistic regression analysis was conducted to reveal the relationship between serum albumin within 1 week after admission and poor prognosis of SAP. Propensity score matching (PSM) analysis was adopted to evaluate the effect of albumin infusion for hypoalbuminemia patients with SAP. RESULTS: The prevalence of hypoalbuminemia (≤ 30 g/L) was 56.9% within 1 week after admission. Multivariate logistic regression identified that age (OR: 1.02; 95% CI: 1.00-1.04; P = 0.012), serum urea (OR: 1.08; 95% CI: 1.04-1.12; P < 0.001), serum calcium (OR: 0.27; 95% CI: 0.14-0.50; P < 0.001), lowest albumin level within 1 week after admission (OR: 0.93; 95% CI: 0.89-0.97; P = 0.002), and APACHE II score ≥ 15 (OR: 1.73; 95% CI: 1.19-2.51; P = 0.004) were independently associated with mortality. The PSM analysis demonstrated that mortality (OR: 0.52, 95% CI: 0.29-0.92, P = 0.023) was less common in albumin-infused than non-albumin-infused hypoalbuminemia patients. In subgroup analyses, doses > 100 g within 1 week after admission for hypoalbuminemia patients with albumin infusions was associated with lower mortality than doses ≤ 100 g (OR: 0.51, 95% CI: 0.28-0.90, P = 0.020). CONCLUSIONS: Hypoalbuminemia in early-stage SAP is significantly related to poor prognosis. However, albumin infusions could significantly decrease mortality in hypoalbuminemia patients with SAP. Additionally, infusing sufficient albumin within a week after admission may decrease mortality in hypoalbuminemia patients.

Hierarchical amorphous vanadium oxide and carbon nanotubes microspheres with strong interface interaction for Superior performance aqueous Zinc-ion batteries.

Aqueous zinc-ion batteries have attracted more and more attention due to their safety, environmental benignity and high theoretical capacity. However, the lack of appropriate cathode materials with high capacity and long cycle life have become an obstacle to the development of aqueous zinc-ion batteries. Herein, the hierarchical amorphous vanadium oxide and carbon nanotubes (a-V2O5@CNTs) microspheres with strong interface interaction were successfully prepared by combing facile spray drying technique with annealing treatment. Benefiting from the a-V2O5 amorphous characters, CNTs framework high conductivity and hierarchical microspheres with strong interface interaction, the a-V2O5@CNTs exhibited abundant active sites, fast reaction kinetics as well as eminent structure stability. As a promising electrode material, the a-V2O5@CNTs displayed high specific capacity (480 mAh g-1 at 0.5 A g-1), good rate capability and long-term stability under high current density (158 mAh g-1 at 30 A g-1 over 1000 cycles). Meanwhile, the corresponding mechanism was further illustrated through different characterizations. Furthermore, the as-assembled flexible pouch battery based on the a-V2O5@CNTs delivered outstanding flexibility and feasibility. Hence, this work provides a new idea for developing high performance cathode materials of aqueous zinc-ion batteries.

Peripheral changes in T cells predict efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer.

The application of programmed cell death protein 1 (PD-1) antibodies has brought great benefits to non-small cell lung cancer (NSCLC) patients. Nevertheless, not all patients respond to anti-PD-1 immunotherapy. This study aimed to find response markers to predict efficacy of anti-PD-1 immunotherapy in NSCLC patients. 80 patients with NSCLC who would accept anti-PD-1 immunotherapy were recruited, and peripheral blood was obtained before and after treatment. Flow cytometry was used to detect proportions of circulating cell subsets and expression of co-stimulatory molecules, co-inhibitory molecules and cytokines in T cells from pre- and post-treatment patients. Results showed that proportions of CD4+ and CD8+ T cells, NK, γδT and mucosal-associated invariant T (MAIT) cells were higher and regulatory T cells (Tregs) were lower in responders (n = 50) after treatment but no obvious difference was found in non-responders (n = 30). After treatment, responders showed an increase in the frequency of co-stimulatory and co-inhibitory molecules, as well as the production of cytokines in T cells. This study indicates that monitoring the alterations of immune markers in circulating cells from NSCLC patients may be helpful to discriminate responders and non-responders, which provides a potential novel way to assess efficacy of anti-PD-1 immunotherapy.

Facile and effective defect engineering strategy boosting ammonium vanadate nanoribbon for high performance aqueous zinc-ion batteries.

Vanadium-based oxides have gained widespread attention as promising cathode materials for aqueous zinc-ion batteries (AZIBs) due to their abundant valences, high theoretical capacity and low cost. However, the intrinsic sluggish kinetics and unsatisfactory conductivity have severely hampered their further development. Herein, a facile and effective defect engineering strategy was developed at room temperature to prepare the defective (NH4)2V10O25·8H2O (d-NHVO) nanoribbon with plenty of oxygen vacancies. Owing to the introduction of oxygen vacancies, the d-NHVO nanoribbon possessed more active sites, excellent electronic conductivity and fast ion diffusion kinetics. Benefiting from these advantages, the d-NHVO nanoribbon as an aqueous zinc-ion battery cathode material exhibited superior specific capacity (512 mAh g-1 at 0.3 A g-1), excellent rate capability and long-term cycle performance. Simultaneously, the storage mechanism of the d-NHVO nanoribbon was clarified via comprehensive characterizations. Furthermore, the pouch battery based on the d-NHVO nanoribbon was fabricated and presented eminent flexibility and feasibility. This work provides a novel thought for simple and efficient development of high- performance vanadium-based oxides cathode materials for AZIBs.

In Situ Nitric Oxide Gas Nanogenerator Reprograms Glioma Immunosuppressive Microenvironment.

Universal chemotherapy in glioblastoma patients causes chemoresistance and further limits immune cells by creating an immunosuppressive tumor microenvironment that are difficult to solve by single-drug therapeutic approaches. Here, this work designs hybrid drug-loaded nanoliposomes by co-loading the chemotherapeutic drug temozolomide (TMZ) and nitric oxide (NO) prodrug JS-K with sphingosine-1-phosphate molecules (S1P) on the surface. The S1P-S1P receptors axis endows nanoliposomes with rapid targeting and lysosomal escaping capability. Then, fine-tuned TMZ release and NO gas production following JS-K release in glioma microenvironment decrease chemoresistance and increase tumor immunogenicity through inhibiting the cellular autophagy as well as inducing mitochondrial dysfunction. RNA sequencing analysis demonstrates that the NO gas generation reprograms glioma microenvironment immune and inflammation-related pathways. The positive immune response in turn effectively activates the enhanced efficacy of chemotherapy. NO gas generated nanoliposomes thus have attractive paradigm-shifting applications in the treatment of "cold" tumors across a range of immunosuppressive indications.