Facile synthesis of MOF-808/RGO-based 3D macroscopic aerogel for enhanced photoreduction CO2.

Three-dimensional (3D) macroscopic aerogels have emerged as a critical component in the realm of photocatalysis. Maximizing the integration of materials can result in enhanced efficiency and selectivity in photocatalytic processes. In this investigation, we fabricated MOF-808/reduced graphene oxide (RGO) 3D macroscopic aerogel composite materials employing the techniques of hydrothermal synthesis and freeze-drying. The results revealed that the macroscopic aerogel material exhibited the highest performance in CO2 reduction to CO, particularly when the concentration of RGO was maintained at 5 mg mL-1. In addition, we synthesized powder materials of MR-5 composite photocatalysts and conducted a comparative analysis in terms of photocatalytic CO2 reduction performance and electron transfer efficiency. The results showthat the macroscopic aerogel material boasts a high specific surface area, an abundant internal pore structure, and increased active sites. These attributes collectively enhance light energy utilization, and electron transfer rates, thereby, improving photothermal and photoelectric conversion efficiencies. Furthermore, we conducted in-situ FT-IR measurements and found that the M/R-5 aerogel exhibited the best CO2 adsorption capacity under a CO2 flow rate of 10 mL min-1. The density functional theory results demonstrate the correlation between the formation pathway of the product and the charge transfer pathway. This study provides useful ideas for realizing photocatalytic CO2 reduction of macroscopic aerogel materials in gas-solid reaction mode.

The growth and nutrient removal properties of heterotrophic microalgae Chlorella sorokiniana in simulated wastewater containing volatile fatty acids.

To reduce the high cost of organic carbon sources in waste resource utilization in the cultivation of microalgae, volatile fatty acids (VFAs) derived from activated sludge were used as the sole carbon source to culture Chlorella sorokiniana under the heterotrophic cultivation. The addition of VFAs in the heterotrophic condition enhanced the total nitrogen (TN) and phosphorus (TP) removal of C. sorokiniana, which proved the advantageous microalgae in using VFAs in the heterotrophic culture after screening in the previous study. To discover the possible mechanism of nitrogen and phosphorus adsorption in heterotrophic conditions by microalgae, the effect of different ratios of VFAs (acetic acid (AA): propionic acid (PA): butyric acid (BA)) on the nutrient removal and growth properties of C. sorokiniana was studied. In the 8:1:1 group, the highest efficiency (77.19%) of VFAs assimilation, the highest biomass (0.80 g L-1) and lipid content (31.35%) were achieved, with the highest TN and TP removal efficiencies of 97.44 % and 91.02 %, respectively. Moreover, an aerobic denitrifying bacterium, Pseudomonas, was determined to be the dominant genus under this heterotrophic condition. This suggested that besides nitrate uptake and utilization by C. sorokiniana under the heterotrophy, the conduct of the denitrification process was also the main reason for obtaining high nitrogen removal efficiency.

Efficient Delivery of Lomitapide using Hybrid Membrane-Coated Tetrahedral DNA Nanostructures for Glioblastoma Therapy.

Glioblastoma (GBM) is the most aggressive and prevalent primary malignant tumor of the central nervous system. Traditional chemotherapy has poor therapeutic effects and significant side effects due to drug resistance, the natural blood-brain barrier (BBB), and nonspecific distribution, leading to a lack of clinically effective therapeutic drugs. Here, 1430 small molecule compounds are screened based on a high-throughput drug screening platform and a novel anti-GBM drug, lomitapide (LMP) is obtained. Furthermore, a bionic nanodrug delivery system (RFA NPs) actively targeting GBM is constructed, which mainly consists of tetrahedral DNA nanocages (tFNA NPs) loaded with LMP as the core and a folate-modified erythrocyte-cancer cell-macrophage hybrid membrane (FRUR) as the shell. FRUR camouflage conferred unique features on tFNA NPs, including excellent biocompatibility, improved pharmacokinetic profile, efficient BBB permeability, and tumor targeting ability. The results show that the LMP RFA NPs exhibited superior and specific anti-GBM activities, reduced off-target drug delivery, prolonged lifespan, and has negligible side effects in tumor-bearing mice. This study combines high-throughput drug screening with biomimetic nanodrug delivery system technology to provide a theoretical and practical basis for drug development and the optimization of clinical treatment strategies for GBM treatment.

Plant-Based Dietary Fibers and Polysaccharides as Modulators of Gut Microbiota in Intestinal and Lung Inflammation: Current State and Challenges.

Recent research has underscored the significant role of gut microbiota in managing various diseases, including intestinal and lung inflammation. It is now well established that diet plays a crucial role in shaping the composition of the microbiota, leading to changes in metabolite production. Consequently, dietary interventions have emerged as promising preventive and therapeutic approaches for managing these diseases. Plant-based dietary fibers, particularly polysaccharides and oligosaccharides, have attracted attention as potential therapeutic agents for modulating gut microbiota and alleviating intestinal and lung inflammation. This comprehensive review aims to provide an in-depth overview of the current state of research in this field, emphasizing the challenges and limitations associated with the use of plant-based dietary fibers and polysaccharides in managing intestinal and lung inflammation. By shedding light on existing issues and limitations, this review seeks to stimulate further research and development in this promising area of therapeutic intervention.

The effects of carbon nitrogen ratio and salinity on the treatment of swine digestion effluent simultaneously producing bioenergy by microalgae biofilm.

In order to remove high concentrations of ammonia nitrogen (NH4+-N) and refractory sulfamethazine (SM2) from swine digestion effluent, different carbon/nitrogen (C/N) ratios and salinity were used to determine the effects of pollutants removal in the microalgae biofilm system. Microalgae biofilm treatment under optimal environmental conditions in synthetic swine digestion effluent were C/N ratio of 20 and salinity of 140 mM. In order to make the actual swine digestion effluent discharge up to the standard, three different two-cycle treatments (suspended microalgae, microalgae biofilm, microalgae biofilm under the optimal conditions) were studied. The results showed that after two-cycle treatment with microalgae biofilm under the optimal conditions, the actual swine digestion effluent levels of total nitrogen (TN), NH4+-N, total phosphorus (TP), chemical oxygen demand (COD), SM2 were 22.65, 9.32, 4.11, 367.28, and 0.99 mg L-1, respectively, which could satisfy the discharge standards for livestock and poultry wastewater in China. At the same time, first-order kinetic simulation equations suggested a degradation half-life of 4.85 d for SM2 under optimal conditions in microalgae biofilm, and microbial community analysis indicated that the dominant genus was Halomonas. Furthermore, 35.66% of lipid, 32.56% of protein and 18.44% of polysaccharides were harvested after two-cycle in microalgae biofilm treatment under optimal environmental conditions. These results indicated that the regulation of C/N and salinity in microalgae biofilm for the treatment of swine digestion effluent was a high-efficiency strategy to simultaneously achieve wastewater treatment and bioenergy production.

The growth and lipid accumulation of Scenedesmus quadricauda under nitrogen starvation stress during xylose mixotrophic/heterotrophic cultivation.

In order to conquer the block of high cost and low yields which limit to realize the commercialization of microalgal biodiesel, the mixotrophic and heterotrophic cultivation of Scenedesmus quadricauda FACHB-1297 fed on xylose was separately studied employing six forms of media: phosphorus sufficient, phosphorus restricted, and phosphorus starvation were combined with nitrogen sufficient and nitrogen starvation conditions. The maximum lipid content (about 41% of dry weight) was obtained on the 5th day (heterotrophic cultivation) and 8th day (mixotrophic cultivation) under the nitrogen starved and phosphorus sufficient (N0&P) conditions, which was about twofold in comparison to the final lipid content on the sufficient nitrogen condition (control). Under mixotrophic and heterotrophic modes, the highest lipid production was achieved in the N0&P trial, with the value of 274.96 mg/L and 193.77 mg/L, respectively. Xylose utilization rate of 30-96% under heterotrophic modes was apparently higher than that of 20-50% in mixotrophic modes. In contrast, phosphorus uptake rate of 100% under mixotrophic cultivation was significantly more than that of 60-90% in heterotrophic cultivation. Furthermore, under the condition of heterotrophic cultivation using xylose as a carbon source, the phosphorus had a positive impact on microalgae cell synthesis and the lipid content enhanced with the augmentation in phosphorus concentrations. We suggested that sufficient phosphorus should be supplied for obtaining higher microalgal lipid production in the lack of nitrogen under xylose heterotrophic/mixotrophic condition. This was a highly effective way to obtain efficient microalgae lipid production.

Biomimetic nanoparticles for tumor immunotherapy.

Currently, tumor treatment research still focuses on the cancer cells themselves, but the fact that the immune system plays an important role in inhibiting tumor development cannot be ignored. The activation of the immune system depends on the difference between self and non-self. Unfortunately, cancer is characterized by genetic changes in the host cells that lead to uncontrolled cell proliferation and evade immune surveillance. Cancer immunotherapy aims to coordinate a patient's immune system to target, fight, and destroy cancer cells without destroying the normal cells. Nevertheless, antitumor immunity driven by the autoimmune system alone may be inadequate for treatment. The development of drug delivery systems (DDS) based on nanoparticles can not only promote immunotherapy but also improve the immunosuppressive tumor microenvironment (ITM), which provides promising strategies for cancer treatment. However, conventional nano drug delivery systems (NDDS) are subject to several limitations in clinical transformation, such as immunogenicity and the potential toxicity risks of the carrier materials, premature drug leakage at off-target sites during circulation and drug load content. In order to address these limitations, this paper reviews the trends and progress of biomimetic NDDS and discusses the applications of each biomimetic system in tumor immunotherapy. Furthermore, we review the various combination immunotherapies based on biomimetic NDDS and key considerations for clinical transformation.

Enhancement of nutrients removal and biomass accumulation of algal-bacterial symbiosis system by optimizing the concentration and type of carbon source in the treatment of swine digestion effluent.

The algae-bacteria symbiosis system (ABS) is used to effectively solve the problems of low carbon/nitrogen (C/N) ratio, low biodegradability and high ammonia toxicity in swine digestion effluent. This study examined the effects of the concentration and type of carbon source on ABS in the pollutants removal especially ammonia. When C/N ratio was 30:1 and carbon source was sodium acetate, the ABS was most conducive to the removal of nitrogen, phosphorus and COD, and to the accumulation of biomass and lipids. To make the wastewater discharge meet the relevant standard, the ABS + mono-cultivation of algae reprocessing system (MAS), was applied to actual swine digestion effluent. Through adjusting the C/N ratio in ABS to 30:1, the biomass concentration was 2.06 times higher than that of raw wastewater, and the removal efficiencies of NH4+-N, TN, TP and COD increased by 1.43, 1.46, 1.95 and 1.28 times, respectively. The final concentrations of NH4+-N, TN, TP and COD after the treatment of ABS (C/N ratio of 30:1) + MAS, were 16.98 ± 1.07 mg L-1, 18.72 ± 1.81 mg L-1, 0.48 ± 0.01 mg L-1 and 263.49 ± 11.89 mg L-1, respectively, reached the Chinese discharge standards for livestock and poultry wastewater. Bacterial community analysis showed that the dominant species of the ABS (C/N ratio of 30:1) was Corynebacterium (genus level). This study revealed that adjusting the concentration and type of carbon source was helpful to the nutrient cycling and resource utilization of ABS, indicating a feasible technique for treating high ammonia nitrogen digestate.

Screening of the heterotrophic microalgae strain for the reclamation of acid producing wastewater.

For the sustainable development of the environment, to reduce the high cost and low productivity of microalgae biofuel, nine microalgae strains were screened to study the growh and nutrient removal properties under heterotrophic culture by using the waste carbon source of volatile fatty acids (VFAs). Chlorella sorokiniana (C.sorokiniana) was selected as the best strain with the highest biomass concentration of 0.77 g L-1, specific growth rate of 0.25 d-1, biomass productivity of 91.43 mg L-1 d-1, total nitrogen removal efficiency of 95.96% and total phosphorus removal efficiency of 93.42%. To study the utilization potential of acid-producing wastewater by heterotrophic microalgae, actual acid-producing wastewater was recycled three times for the utilization of C.sorokiniana. After the three utilization cultivation, the removal rates of COD, total nitrogen, ammonia nitrogen, and total phosphorus were 74.44%, 88.05%, 79.08%, and 82.69%, respectively. The total utilization rates of acetic acid, propionic acid, and butyric acid were 58.99%, 70.54%, and 81.52%, respectively. In addition, the highest lipid content of 39.15% and protein content of 42.43% achieved at the third cultivation. After the first cultivation, the composition and diversity of the microbial community structure changed dramatically, with Protebacteria, Bacteroidota, Hydrogenophaga, and Algoriphagus becoming enriched. These results showed a promising way of coupling wastewater treatment with biomass production for long-term sustainability of microalgae lipid production.

CircCLTH promotes skeletal muscle development and regeneration.

Buffalo holds an excellent potential for beef production, and circRNA plays an important role in regulating myogenesis. However, the regulatory mechanism of circRNAs during buffalo skeletal muscle development has not been fully explored. In this study, circRNA expression profiles during the proliferation and differentiation stages of buffalo myoblasts were analysed by RNA-seq. Here, a total of 3,142 circRNAs candidates were identified, and 110 of them were found to be differentially expressed in the proliferation and differentiation stages of buffalo myoblast libraries. We focused on a 347 nt circRNA subsequently named circCLTH. It consists of three exons and is expressed specifically in muscle tissues. It is a highly conserved non-coding RNA with about 95% homology to both the human and the mouse circRNAs. The results of cell experiments and RNA pull-down assays indicated that circCLTH may capture PLEC protein, promote the proliferation and differentiation of myoblasts as well as inhibit apoptosis. Overexpression of circCLTH in vivo suggests that circCLTH is involved in the stimulation of skeletal muscle regeneration. In conclusion, we identified a novel noncoding regulator, circCLTH, that promotes proliferation and differentiation of myoblasts and skeletal muscles.

A new highly conserved circRNA was identified during muscle developmentCircCLTH promotes proliferation and differentiation of myoblastsCircCLTH promoted muscle damage repair in miceCircCLTH may target the PLEC protein.

Determination of isotope abundance for deuterium-labeled compounds by quantitative 1 H NMR + 2 H NMR.

Deuterated reagents have been used in many research fields. Isotope abundance, as the feature parameter of deuterated reagents, the precise quantification, is of great importance. Based on quantitative nuclear magnetic resonance technology, a novel method that combines 1 H NMR + 2 H NMR was systematically established to determine the isotopic abundance of deuterated reagents. The results showed that the isotopic abundance of partially labeled and fully labeled compounds calculated by this new method was even more accurate than that calculated by classical 1 H NMR and mass spectrometry (MS) methods. In brief, this new method is a robust strategy for the determination of isotope abundance in large-scale deuterated reagents.

Erythrocyte-biomimetic nanosystems to improve antitumor effects of paclitaxel on epithelial cancers.

Chemotherapy is a difficult treatment for cancer patients because of the low effective accumulation of chemo-drugs and their detrimental side effects. Nanoparticles have shown promise as a solution to these problems. However, the known differences in the porosity and vascularization of tumor vessels, and other factors, including the potential formation of a "protein crown," the short half-life time in circulation, and the low drug distribution, often limit their application. To address these problems, biomimetic nanoparticles coated with cell membranes have been developed and shown to have advantages such as prolonged circulation, high biocompatibility, and enhanced targeting abilities in drugs and nanoparticles, thus exhibiting good application prospects in cancer therapy for liver, lung, and melanoma cancers. Accordingly, we designed a PH-sensitive biomimetic nanodrug delivery system with a delicate "core-shell" structure based on red blood cell membranes. Briefly, core nanoparticles were synthesized by the self-assembly of natural amphoteric polymers, including hydrophilic carboxymethylcellulose sodium and hydrophobic stearic acid. For the shell structure, red blood cell membranes were modified using folic acid by a lipid tether (1,2-distearoyl-sn-glycero-3-phosphoethanolamine) to increase tumor-targeting ability, whereas polyethylene glycol was inserted to decrease lipid tether modification-induced potential sequestration by either the mononuclear phagocyte system or the reticuloendothelial system. Via a series of formulation optimizations, paclitaxel was packaged into the red blood membrane-based core-shell nanoparticles with an average size of 226.9 ± 2.75 nm and a negative Zeta potential of -14.5 ± 0.3 mV. More importantly, the examinations focusing on CD47, a representative red blood cell membrane protein, revealed not only the successful establishment of the membrane shell but also the right-side-out membrane orientation on our core-shell nanoparticles. Our nanodrug delivery system showed good biocompatibility and sensitivity to acidic tumor microenvironments while effectively prolonging the circulation time of paclitaxel and further enhancing its antitumor effects on epithelial malignancies, including liver, lung, and melanoma cancers. In particular, our nanodrug delivery system significantly alleviated paclitaxel-induced renal toxicity. Taken together, our findings highlight that the red blood membrane-based core-shell nanoparticle is a promising biomimetic nanodrug delivery system for functionally delivering chemotherapeutic drugs, and it has promise in clinical applications.

Micropollutant abatement by the UV/chloramine process in potable water reuse: A review.

The need in using reclaimed water increased significantly to address the water shortage and its continuing quality deterioration in sustaining societal development. Degrading micropollutants in wastewater treatment plant effluents is one of the most important tasks in supplying safe drinking water, which is often achieved by full advanced treatment technologies (FATs), including reverse osmosis (RO) and the UV-based advanced oxidation process (AOP). As an emerging AOP, UV/chloramine process shows many noteworthy advantages in the scenario of potable water reuse, including membrane biological fouling control by chloramine, producing highly reactive radicals (e.g., Cl•, HO•, Cl2•-, and reactive nitrogen-containing species) to degrade the RO permeated pollutants, and acting as long-lasting disinfectant in the potable water distribution system. In addition, chloramine is often designedly produced by taking advantage of the ammonia in source. Thus, UV/chloramine processes gather much attention from researcher and published papers on UV/chloramine process have drastically increased since 2016, which were thoroughly reviewed in this paper. The fundamentals of chloramine photolysis, including the photolysis kinetics, the quantum yield, the generation and transformation of radicals and the final products, were scrutinized. Further, the impacts of reaction conditions such as pH, chloramine dosage and water matrix on the degradation of micropollutants by the UV/chloramine process are discussed. Moreover, the formation potential of disinfection by-products is debated. The opportunity of application of the UV/chloramine process in real-world practice is also presented, emphasizing the need for extensive efforts to remove currently prevalent knowledge roadblocks.

Artificial intelligence applied in neoantigen identification facilitates personalized cancer immunotherapy.

The field of cancer neoantigen investigation has developed swiftly in the past decade. Predicting novel and true neoantigens derived from large multi-omics data became difficult but critical challenges. The rise of Artificial Intelligence (AI) or Machine Learning (ML) in biomedicine application has brought benefits to strengthen the current computational pipeline for neoantigen prediction. ML algorithms offer powerful tools to recognize the multidimensional nature of the omics data and therefore extract the key neoantigen features enabling a successful discovery of new neoantigens. The present review aims to outline the significant technology progress of machine learning approaches, especially the newly deep learning tools and pipelines, that were recently applied in neoantigen prediction. In this review article, we summarize the current state-of-the-art tools developed to predict neoantigens. The standard workflow includes calling genetic variants in paired tumor and blood samples, and rating the binding affinity between mutated peptide, MHC (I and II) and T cell receptor (TCR), followed by characterizing the immunogenicity of tumor epitopes. More specifically, we highlight the outstanding feature extraction tools and multi-layer neural network architectures in typical ML models. It is noted that more integrated neoantigen-predicting pipelines are constructed with hybrid or combined ML algorithms instead of conventional machine learning models. In addition, the trends and challenges in further optimizing and integrating the existing pipelines are discussed.

Remedial repair of extensive distal muscle secondary necrosis due to high level crush injury of the upper thighs: a case report.

Extensive necrosis of lower extremity muscles through the clinical practice of limb salvage after a case of high level crushing injury. A case of car accident injury complicated with necrotizing fasciitis, myositis, and septic shock was admitted to our hospital. The pathogenic factors, clinical characteristics, and surgical repair of this case were analyzed. Septic shock, pulmonary infection and atelectasis, and skin and soft tissue injury of lower limbs were all effectively treated, and limbs were saved successfully. After wound healing, the patient was discharged from hospital and entered the follow-up rehabilitation treatment. Although there is no direct trauma to the distal extremity below the cross-section of both lower extremities, there are still hypoxic ischemic changes, which can easily be ignored in the early stage. If not treated in time, myofascial and osteofascial compartment syndrome, necrotizing fasciitis, myositis, and sepsis are often secondary in the later stage, which should be warned against. During surgical debridement, attention should be paid to the protection of the source artery, and debridement and surgical exploration should be carried out according to the trend of blood vessels. The interecological muscle tissue between the intersections should be kept as far as possible, and the main nerves, blood vessels, and musculocutaneous perforators should be kept to ensure the blood supply of the skin flap.

MMP-12 siRNA improves the homeostasis of the small intestine and metabolic dysfunction in high-fat diet feeding-induced obese mice.

The changes of small intestinal homeostasis have been recognized to contribute essentially to the obese development. However, the core small intestinal regulator which mediates over-nutrient impacts on the homeostasis of the small intestines remains elusive. Here, we identify the MMP-12 as such a responsive factor in mouse small intestines. Taking advantages of the nano delivery system, we demonstrate that small intestine-specific MMP-12 knockdown alleviates high-fat diet feeding-induced metabolic disorders and improves intestinal homeostasis in mice, including a significant decrease in lipid transportation, bile acid reabsorption, and inflammation. In parallel, the small intestinal integrity is recovered and the gut microbiota composition is reversed towards that under normal diet feeding. Mechanistically, MMP-12, differing from its traditional elastolytic function, acts as a transcriptional factor to activate Fabp4 transcription through epigenetic modification. In translational medicine, clinical applications of our nanosystem and therapeutic interventions targeting MMP-12 will benefit patients with obesity and associated diseases.

Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy.

Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic strategies. The emergence of nanotechnology has had a profound impact on general clinical treatment. The application of nanotechnology has facilitated the development of nano-drug delivery systems (NDDSs) that are highly tumor selective and allow for the slow release of active anticancer drugs. In recent years, vehicles such as liposomes, dendrimers and polymer nanomaterials have been considered promising carriers for tumor-specific drug delivery, reducing toxicity and improving biocompatibility. Among them, polymer nanoparticles (NPs) are one of the most innovative methods of non-invasive drug delivery. Here, we review the application of polymer NPs in drug delivery, gene therapy, and early diagnostics for cancer therapy.

The effect of volatile fatty acids on the growth and lipid properties of two microalgae strains during batch heterotrophic cultivation.

To overcome the bottlenecks of waste resource utilization and energy shortage that restrict the commercial production of microalgae biodiesel, volatile fatty acids (VFAs) derived from activated sludge were used as the sole carbon source to culture oleaginous microalgae Chlorella pyrenoidosa FACHB-1216 and Scenedesmus quadricauda FACHB-1297 under the mixotrophic and heterotrophic cultivation. Four VFAs ratios (acetic acids (AA): propionic acids (PA): butyric acids (BA)) were tested to determine the effects and mechanisms of the VFAs on the two microalgae. The highest lipid content (29.54%) and lipid production (71.10 mg L-1) were achieved by S. quadricauda at the VFAs ratio of 6: 1: 3 under heterotrophic condition, with 46.27% and 67.52% removal efficiencies of total nitrogen and phosphorus, respectively. The assimilation efficiency of AA was the highest at 73.37%, followed by that of PA and BA. For C. pyrenoidosa, VFAs promoted the rapid reproduction within 2 days under the heterotrophic condition at different initial inoculation densities. At the optimal VFA ratio, algae achieved the highest biomass concentration (0.14 ± 0.02 g L-1), with a specific growth rate of 0.91 d-1 and biomass productivity of 125.17 mg L-1 d-1. The removal rates of total nitrogen and phosphorus were 47.03% and 74.40%, respectively, and the assimilation efficiency of AA was the best (61.06%). High AA assimilation efficiency under the heterotrophic condition was beneficial for the algal growth and lipid accumulation. These results simultaneously produced microalgae-based bioenergy and recycled VFAs in anaerobically digested effluent.

[Neutrophils mediate T lymphocyte function in septic mice via the CD80/cytotoxic T lymphocyte antigen-4 signaling pathway].

OBJECTIVE: To investigate the effect of neutrophils on T lymphocyte function in septic mice and the role of CD80/cytotoxic T lymphocyte antigen-4 (CTLA-4) signaling pathway in this modulated effects. METHODS: (1) In vivo experiment: 6-8 weeks old male C57BL/6 mice were divided into sham operation group (Sham group, n = 20), Sham+CTLA-4 antibody treatment group (Sham+aCTLA-4 group, n = 20), cecum ligation and perforation (CLP) induced sepsis model group (CLP group, n = 30) and CLP+CTLA-4 antibody treatment group (CLP+aCTLA-4 group, n = 30) according to the random number table. CLP was used to reproduce mouse sepsis model. The mice in the Sham group were treated identically but their cecums were neither punctured nor ligated. In CTLA-4 antibody treatment groups, 50 µg CTLA-4 antibody was injected intraperitoneally 6 hours and 24 hours after the operation. Forty-eight hours after operation, 6 mice in Sham group and Sham+aCTLA-4 group, 14 mice in CLP group and CLP+aCTLA-4 group were randomly selected to detect the expression of CD69 in spleen. At the same time, spleen, bone marrow and peripheral blood were collected, and the expression of CD80 on neutrophils was detected by flow cytometry. The expression of CTLA-4 on the surface of T lymphocytes in spleen was detected by immunofluorescence and flow cytometry. The remaining mice in each group were used to observe the 96-hour survival after operation. (2) In vitro experiment 1: neutrophils were extracted from bone marrow of healthy mice and stimulated with LPS (1 mg/L) for 4, 8 and 12 hours respectively. The control group was added with the same amount of phosphate buffer saline (PBS) at each time point, and the expression of CD80 was detected at each time point. (3) In vitro experiment 2: splenic T lymphocytes of healthy mice were extracted and divided into PBS control group, LPS group (final concentration of LPS 1 mg/L), neutrophil group and neutrophil+LPS group. In the latter two groups, the co-culture model of neutrophils and T lymphocytes was established, and then the corresponding treatment was given to detect the expression of CTLA-4 on the surface of T lymphocytes. With the above four groups as controls, CTLA-4 antibody treatment groups (final concentration of CTLA-4 antibody 50 mg/L) were set up respectively. After 48 hours, the level of interleukin-2 (IL-2) in the cell supernatant was detected by enzyme linked immunosorbent assay (ELISA). RESULTS: (1) Results of in vivo experiment: compared with Sham group, the expression of CD80 on neutrophils in spleen, bone marrow and peripheral blood was significantly up-regulated, while the expression of CTLA-4 on the surface of T lymphocytes was significantly increased [(9.98±0.84)% vs. (3.48±0.64)%, P < 0.05]. It suggested that neutrophils may affect T lymphocytes function through CD80/CTLA-4 pathway in sepsis. Compared with CLP group, CTLA-4 antibody could significantly improve the 96-hour cumulative survival rate of CLP mice (56.25% vs. 18.75%, P < 0.05), and increase the expression of CD69 on the surface of T lymphocytes. It suggested that CTLA-4 antibodies might increase T lymphocytes activation in sepsis and improve survival. (2) Results of in vitro experiment: with the prolongation of LPS stimulation, the expression of CD80 on neutrophils gradually increased in time-dependent manner as compared with PBS control group [4 hours: (6.35±0.40)% vs. (3.41±0.40)%, 8 hours: (8.57±0.64)% vs. (3.09±0.27)%, 12 hours: (19.83±1.06)% vs. (5.16±0.36)%, all P < 0.05]. Compared with PBS control group, the expression of CTLA-4 on CD4+/CD8+ T lymphocytes was not significantly affected by LPS stimulation alone, but CTLA-4 was increased after co-culture with neutrophils [CD4+: (4.92±0.30)% vs. (3.33±0.25)%, CD8+: (4.26±0.21)% vs. (2.53±0.66)%, both P < 0.05], and the increased trend of CTLA-4 was more obvious after co-culture with LPS-stimulated neutrophils [CD4+: (6.34±0.50)% vs. (3.33±0.25)%, CD8+: (6.21±0.41)% vs. (2.53±0.66)%, both P < 0.05]. In the PBS control group and LPS group, CTLA-4 antibody had no significant effect on IL-2 secretion of T lymphocytes. Compared with PBS control group, co-culture with neutrophils could inhibit the secretion of IL-2 by T lymphocytes (ng/L: 1 938.00±68.45 vs. 2 547.00±218.00, P < 0.05), and the inhibitory effect of neutrophils stimulated by LPS was more obvious (ng/L: 1 073.00±34.39 vs. 2 547.00±218.00, P < 0.05). CTLA-4 antibodies could partially restore IL-2 secretion. In conclusion, after promoting the expression of CTLA-4 on the surface of T lymphocytes, neutrophils might mediate the inhibition of T lymphocytes function by reducing the production of IL-2. CONCLUSIONS: Neutrophils mediate T lymphocytes dysfunction in sepsis, and the CD80/CTLA-4 pathway plays an important role. The CTLA-4 antibody improves survival and T lymphocytes function in sepsis mice, which may be a new method of immunotherapy for sepsis.