Risk factors of prognosis for spontaneous cerebellar hemorrhage: a systematic review and meta-analysis.

BACKGROUND: The most deadly type of spontaneous intracerebral hemorrhage is spontaneous cerebellar hemorrhage (SCH). The purpose of this meta-analysis was to investigate risk factors for prognosis in SCH patients to provide a basis for taking preventive and therapeutic measures. METHODS: Seven electronic databases were searched from inception to May 2023 for randomized controlled trial, cohort study, case control study and cross-sectional study on prognosis of spontaneous cerebellar hemorrhage. The quality of the selected studies were assessed by the American Agency for Healthcare Research and Quality (AHRQ). To assess the impact of the included risk factors on the prognosis of spontaneous cerebellar hemorrhage, combined odds ratios (ORs) with matching 95% confidence intervals (CIs) were combined. RESULTS: Eight studies were included, including 539 participants. And a total of 31 potentially associated risk factors were identified. Ultimately, 6 risk factors were included in the meta-analysis after assessing. The factors supported by moderate evidence include the hydrocephalus (OR = 4.3, 95% CI: 2.33 to 7.91) and drug-induced coagulopathy (OR = 2.74, 95% CI: 1.23 to 6.09). The factors supported by limited evidence include the intraventricular bleeding(OR = 1.86, 95% CI: 1.13 to 3.07) and hematoma size>3 cm(OR = 3.18, 95% CI: 1.87 to 5.39). Meta-analysis revealed no association between hypertension, diabetes mellitus and SCH prognosis. CONCLUSION: The current meta-analysis revealed obvious risk factors for prognosis in spontaneous cerebellar hemorrhage patients, including hydrocephalus, drug-induced coagulopathy, intraventricular bleeding and hematoma size>3 cm.

Topological protection of dual-polarization biphoton states in photonic crystals.

Polarization control is a major issue in topological quantum optics that limits reliable generation and transmission of quantum states. This study presents what we believe to be a novel topological photonic crystal design that provides topological protection for biphoton pairs for both TE and TM polarization. By well-designed cell configurations within the lattice, two topological boundaries emerge that can accommodate TM and TE modes at the same time. By adjusting the dispersion curves, we can further design nonlinear four-wave mixing processes within the topological photonic crystals and provide theoretical explanations for the entanglement of the dual-polarization biphoton states. Numerical results confirm the robust transport of entangled photon pairs, even when subjected to sharp bending. Moreover, combining the dual-polarization topological photonic crystal with a polarization beam splitter enables the preparation of polarization-encoded maximally entangled states. Our work exhibits significant potential for applications in robust optical quantum information processing and quantum secure communication.

Genome-Wide Association Analysis of Yield-Related Traits and Candidate Genes in Vegetable Soybean.

Owing to the rising demand for vegetable soybean products, there is an increasing need for high-yield soybean varieties. However, the complex correlation patterns among quantitative traits with genetic architecture pose a challenge for improving vegetable soybean through breeding. Herein, a genome-wide association study (GWAS) was applied to 6 yield-related traits in 188 vegetable soybean accessions. Using a BLINK model, a total of 116 single nucleotide polymorphisms (SNPs) were identified for plant height, pod length, pod number, pod thickness, pod width, and fresh pod weight. Furthermore, a total of 220 genes were found in the 200 kb upstream and downstream regions of significant SNPs, including 11 genes encoding functional proteins. Among them, four candidate genes, Glyma.13G109100, Glyma.03G183200, Glyma.09G102200, and Glyma.09G102300 were analyzed for significant haplotype variations and to be in LD block, which encode MYB-related transcription factor, auxin-responsive protein, F-box protein, and CYP450, respectively. The relative expression of candidate genes in V030 and V071 vegetable soybean (for the plant height, pod number, and fresh pod weight of V030 were lower than those of the V071 strains) was significantly different, and these genes could be involved in plant growth and development via various pathways. Altogether, we identified four candidate genes for pod yield and plant height from vegetable soybean germplasm. This study provides insights into the genomic basis for improving soybean and crucial genomic resources that can facilitate genome-assisted high-yielding vegetable soybean breeding.

Reconstituted CD74+ NK cells trigger chronic graft versus host disease after allogeneic bone marrow transplantation.

Chronic graft-versus-host disease (cGVHD) is the most common long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients with pulmonary cGVHD in particular have a very poor prognosis. NK cells are the first reconstituted lymphocyte subset after allo-HSCT; however, the impact of reconstituted NK cells on cGVHD is unclear. Here, we found allogeneic recipients showed obvious pulmonary cGVHD. Surprisingly, deletion of reconstituted NK cells resulted in maximal relief of pulmonary cGVHD. Mechanistically, reconstituted NK cells with donor profiles modulated the pulmonary inflammatory microenvironment to trigger cGVHD. Reconstituted NK cells secreted IFN-γ and TNF-α to induce CXCL10 production by epithelial cells, which recruited macrophages and CD4+ T cells to the lungs. Then macrophages and CD4+ T cells were activated by the inflammatory microenvironment, thereby mediating lung injury. Through assessment of differences in cellular energy, we found that CD74+ NK cells with high mitochondrial potential and pro-inflammatory activity triggered pulmonary cGVHD. Furthermore, targeted elimination of CD74+ NK cells using the anti-CD74 antibody significantly alleviated pulmonary cGVHD but preserved the CD74- NK cells to exert graft-versus-leukemia (GVL) effects. Data from human samples corroborated our findings in mouse models. Collectively, our results reveal that reconstituted CD74+ NK cells trigger pulmonary cGVHD and suggest that administration of CD74 antibody was a potential therapeutic for patients with cGVHD.

Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.

Comparison of Novel 3D-printed Stepped Porous Metal Cones and Metaphyseal Sleeves for Reconstruction of Severe Knee Bone Defects: Short-term Clinical Outcomes.

OBJECTIVE: Both porous metal cones and metaphyseal sleeves are excellent implants for reconstructing severe bone defects in the knee joint, but they both exhibit design limitations. The porous metal cone, especially, has significant room for improvement in its shape design. The existing porous metal cones often feature a conical external surface with a relatively small taper, potentially compromising both rotational and axial stability. To improve both axial and rotational stability in porous metal cones, we developed a 3D-printed stepped porous metal cone. This study aimed to assess the short-term clinical outcome of the 3D-printed stepped porous metal cone and to compare it with the clinical outcome of patients who underwent revision total knee arthroplasty (rTKA) with the metaphyseal sleeves during the same period. METHOD: Patients who underwent total knee arthroplasty revision with metaphyseal bone defect reconstruction from 2019 to 2021 were retrospectively analyzed. A total of 61 patients were enrolled in the study, including 15 patients using 3D-printed stepped porous metal cones and 46 patients using metaphyseal metal sleeves. Thirty patients using metaphyseal sleeves were screened by propensity score matching method and compared with those using stepped cones. Analysis included the American Knee Society Score, the Hospital for Special Surgery knee score, the Western Ontario and McMaster Universities Arthritis index, the Short Form 12 (SF-12) health survey, and radiographic assessment with a mean follow-up of 28.5 ± 8.3 months. To conduct comparative analyses, unpaired Student's t-tests were employed for continuous variables, while categorical variables were analyzed using the appropriate Fisher exact or chi-squared test. RESULTS: In this study, the survival rates of both the stepped cone and metaphyseal sleeve were 100%. There was no statistically significant difference in postoperative knee function scores between the two groups (p > 0.05). However, patients in the cone group had significantly higher mental component summary scores on the SF-12 scale (p < 0.05) and higher increases in mean postoperative physical component summary scores than patients in the sleeve group (p < 0.05). In addition, patients in the cone group experienced fewer intraoperative and postoperative complications compared to the sleeve group. CONCLUSION: The 3D-printed stepped porous metal cone can effectively reconstruct bone defects in complex rTKA and provide satisfactory early clinical and radiographic results. The 3D-printed stepped cone provides a more stable structure similar to the sleeve while maintaining the original benefits of the cone making it a promising choice for rTKA.

Cytokine Storm Related to CD4+ T Cells in Influenza Virus-Associated Acute Necrotizing Encephalopathy.

Acute necrotizing encephalopathy (ANE) is a rare but deadly complication with an unclear pathogenesis. We aimed to elucidate the immune characteristics of H1N1 influenza virus-associated ANE (IANE) and provide a potential therapeutic approach for IANE. Seven pediatric cases from a concentrated outbreak of H1N1 influenza were included in this study. The patients' CD4+ T cells from peripheral blood decreased sharply in number but highly expressed Eomesodermin (Eomes), CD69 and PD-1, companied with extremely high levels of IL-6, IL-8 in the cerebrospinal fluid and plasma. Patient 2, who showed high fever and seizures and was admitted to the hospital very early in the disease course, received intravenous tocilizumab and subsequently showed a reduction in temperature and a stable conscious state 24 h later. In conclusion, a proinflammatory cytokine storm associated with activated CD4+ T cells may cause severe brain pathology in IANE. Tocilizumab may be helpful in treating IANE.

Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development.

Endometriosis, affecting 6%-10% of women, often leads to pain and infertility and its underlying inflammatory mechanisms are poorly understood. We established endometriosis models in wild-type and IL16KO mice, revealing the driver function of IL-16 in initiating endometriosis-related inflammation. Using an in vitro system, we confirmed iron overload-induced GSDME-mediated pyroptosis as a key trigger for IL-16 activation and release. In addition, our research led to the development of Z30702029, a compound inhibiting GSDME-NTD-mediated pyroptosis, which shows promise as a therapeutic intervention for endometriosis. Importantly, our findings extend beyond endometriosis, highlighting GSDME-mediated pyroptosis as a broader pathway for IL-16 release and offering insights into potential treatments for various inflammatory conditions.

Robotic-assisted total hip arthroplasty in patients with developmental dysplasia of the hip.

PURPOSES: Due to the morphological diversity of deformities, technical difficulties, improperly designed components, and so on, THA remains a challenging task in dysplastic hips, especially in highly dislocated hips. The purpose of this study was to comprehensively evaluate the clinical outcomes of robot-assisted THA in patients with DDH through a large cohort study, including the precision of acetabular cup positioning, indicators of inflammatory response, indicators of muscle damage, and complications. METHODS: We retrospectively analyzed patients with DDH who underwent THA in our prospectively constructed joint registry between August 2018 and August 2022. Finally, 147 manual THAs and 147 robotic-assisted THAs were included in the final analysis. Patient demographics, indicators of inflammation, indicators of muscle damage, operative time, Harris hip scores (HHS), and forgotten joint score (FJS) were recorded for analysis. The precision of the positioning of the acetabular component was assessed with plain radiographs. RESULTS: In the Crowe II/III groups, the reconstructed center of rotation (COR) in the robotic-assisted group was closer to the anatomical COR with less variation than the manual group (absolute horizontal distances of COR 3.5 ± 2.8 vs. 5.4 ± 4.9 mm, p < 0.05; absolute vertical distances of COR 6.4 ± 4.1 vs. 11.7 ± 8.2 mm, p = 0.001). For all Crowe subtypes, the robotic-assisted THA significantly increased the proportion of acetabular cups located in the safety zone within 5° (all p < 0.05). Interleukin-6 and creatine kinase levels were slightly lower and significantly different in the robotic-assisted group at three days postoperatively (all p < 0.05). CONCLUSIONS: Compared to the manual technique, the robot-assisted technique improved the precision and reproducibility of acetabular component positioning, particularly in DDH patients with Crowe types II/III. The robotic-assisted technique did not increase operative time, bleeding, complications, or revision rates, and had a slighter early inflammatory response and muscle damage.

Genome-Wide Identification and Comprehensive Analysis of the FtsH Gene Family in Soybean (Glycine max).

The filamentation temperature-sensitive H (FtsH) gene family is critical in regulating plant chloroplast development and photosynthesis. It plays a vital role in plant growth, development, and stress response. Although FtsH genes have been identified in a wide range of plants, there is no detailed study of the FtsH gene family in soybean (Glycine max). Here, we identified 34 GmFtsH genes, which could be categorized into eight groups, and GmFtsH genes in the same group had similar structures and conserved protein motifs. We also performed intraspecific and interspecific collinearity analysis and found that the GmFtsH family has large-scale gene duplication and is more closely related to Arabidopsis thaliana. Cis-acting elements analysis in the promoter region of the GmFtsH genes revealed that most genes contain developmental and stress response elements. Expression patterns based on transcriptome data and real-time reverse transcription quantitative PCR (qRT-PCR) showed that most of the GmFtsH genes were expressed at the highest levels in leaves. Then, GO enrichment analysis indicated that GmFtsH genes might function as a protein hydrolase. In addition, the GmFtsH13 protein was confirmed to be localized in chloroplasts by a transient expression experiment in tobacco. Taken together, the results of this study lay the foundation for the functional determination of GmFtsH genes and help researchers further understand the regulatory network in soybean leaf development.

Metaphyseal Metal Sleeves for Reconstruction of Severe Knee Bone Defects: Excellent Survival Rate at a Mean Follow-Up of 6.4 Years.

OBJECTIVE: Management of bone loss in complex primary and revision total knee arthroplasty is key to the surgeries. Metaphyseal metal sleeves have been increasingly used recently to reconstruct severe knee metaphyseal bone defects. This study aimed to investigate the outcomes of the metaphyseal sleeve reconstructing Anderson Orthopedic Research Institute (AORI) type II and type III bone defects of knee joint. METHODS: From 2014 to 2019, a total of 44 knees were enrolled in this clinical retrospective study after the screening, including seven cases of primary TKA and 37 cases of revision TKA. The types of bone defects involved in this study were AORI types II and III, and did not involve AORI type I bone defects. Patients' knee function preoperatively and postoperatively as well as quality of life were recorded and analyzed. Analysis included the American Knee Society Score (KSS), hospital for special surgery knee score (HSS), the Western Ontario and McMaster Universities (WOMAC) index, the Short Form 12 (SF-12) health survey, visual analogue scale score, and radiographic assessment with a mean follow-up of 6.4 years. Paired t-tests were used to determine the significance of changes in clinical scores and knee mobility. RESULTS: A mean follow-up of 77.2 (±17.6, standard deviation [SD]) months was performed, and none of the patients underwent knee revision for infection or aseptic loosening. At the last follow-up, the KSS knee score changed statistically from 37.1 (±19.7) preoperatively to 86.5 (±13.6, SD, p < 0.001) postoperatively and the KSS function score from 32.7 (±24.0) preoperatively to 78.3 (±15.6, SD, p < 0.001) postoperatively. The knee mobility improved from a mean of preoperative 72.61° (±33.42°, SD) to 108.52° (±24.15°, SD, p < 0.001). Postoperative radiographs showed that the host bone was tightly integrated with the metaphyseal metal sleeve, and there was no obvious translucent line formation around the sleeve. Of the patients, 86.4% had a postoperative satisfaction score ≥8 (10-point scale). CONCLUSION: At the mean follow-up of 6.4 years, the survival rate of the metaphyseal sleeves was 100%. Metaphyseal sleeves combined with cementless stems is an excellent and viable option for reconstruction of AORI type II and type III bone defects of the knee.

PH13 improves soybean shade traits and enhances yield for high-density planting at high latitudes.

Shading in combination with extended photoperiods can cause exaggerated stem elongation (ESE) in soybean, leading to lodging and reduced yields when planted at high-density in high-latitude regions. However, the genetic basis of plant height in adaptation to these regions remains unclear. Here, through a genome-wide association study, we identify a plant height regulating gene on chromosome 13 (PH13) encoding a WD40 protein with three main haplotypes in natural populations. We find that an insertion of a Ty1/Copia-like retrotransposon in the haplotype 3 leads to a truncated PH13H3 with reduced interaction with GmCOP1s, resulting in accumulation of STF1/2, and reduced plant height. In addition, PH13H3 allele has been strongly selected for genetic improvement at high latitudes. Deletion of both PH13 and its paralogue PHP can prevent shade-induced ESE and allow high-density planting. This study provides insights into the mechanism of shade-resistance and offers potential solutions for breeding high-yielding soybean cultivar for high-latitude regions.

A single-cell landscape of pre- and post-menopausal high-grade serous ovarian cancer ascites.

High-grade serous ovarian cancer (HGSOC) is a hormone-related cancer with high mortality and poor prognosis. Based on the transcriptome of 57,444 cells in ascites from 10 patients with HGSOC (including 5 pre-menopausal and 5 post-menopausal patients), we identified 14 cell clusters which were further classified into 6 cell types, including T cells, B cells, NK cells, myeloid cells, epithelial cells, and stromal cells. We discovered an increased proportion of epithelial cells and a decreased proportion of T cells in pre-menopausal ascites compared with post-menopausal ascites. GO analysis revealed the pre-menopausal tumor microenvironments (TME) are closely associated with viral infection, while the post-menopausal TME are mostly related to the IL-17 immune pathway. SPP1/CD44-mediated crosstalk between myeloid cells and B cells, NK cells, and stromal cells mainly present in the pre-menopausal group, while SPP1/PTGER4 -mediated crosstalk between myeloid cells and epithelial cells mostly present in the post-menopausal group.

Comparative Proteomic Analysis of Two Wild Soybean (Glycine soja) Genotypes Reveals Positive Regulation of Saline-Alkaline Stress Tolerance by Tonoplast Transporters.

Soil saline-alkalization is a significant constraint for soybean production. Owing to higher genetic diversity of wild soybean, we compared the proteomic landscape of saline-alkaline stress-tolerant (SWBY032) and stress-sensitive (SWLJ092) wild soybean (Glycine soja) strains under saline and saline-alkaline stress. Out of 346 differentially expressed proteins (DEPs) specifically involved in saline-alkaline stress, 159 and 133 DEPs were identified in only SWLJ092 and SWBY032, respectively. Functional annotations revealed that more ribosome proteins were downregulated in SWLJ092, whereas more membrane transporters were upregulated in SWBY032. Moreover, protein-protein interaction analysis of 133 DEPs revealed that 14 protein-synthesis- and 2 TCA-cycle-related DEPs might alter saline-alkaline tolerance by affecting protein synthesis and amino acid metabolism. Furthermore, we confirmed G. soja tonoplast intrinsic protein (GsTIP2-1 and GsTIP2-2), inositol transporter (GsINT1), sucrose transport protein (GsSUC4), and autoinhibited Ca2+-ATPase (GsACA11) as tonoplast transporters can synergistically improve saline-alkaline tolerance in soybean, possibly by relieving the inhibition of protein synthesis and amino acid metabolism. Overall, our findings provided a foundation for molecular breeding of a saline-alkaline stress-tolerant soybean.

Comprehensive tissue deconvolution of cell-free DNA by deep learning for disease diagnosis and monitoring.

Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.

Unfolding molecular switches for salt stress resilience in soybean: recent advances and prospects for salt-tolerant smart plant production.

The increasing sodium salts (NaCl, NaHCO3, NaSO4 etc.) in agricultural soil is a serious global concern for sustainable agricultural production and food security. Soybean is an important food crop, and their cultivation is severely challenged by high salt concentration in soils. Classical transgenic and innovative breeding technologies are immediately needed to engineer salt tolerant soybean plants. Additionally, unfolding the molecular switches and the key components of the soybean salt tolerance network are crucial for soybean salt tolerance improvement. Here we review our understandings of the core salt stress response mechanism in soybean. Recent findings described that salt stress sensing, signalling, ionic homeostasis (Na+/K+) and osmotic stress adjustment might be important in regulating the soybean salinity stress response. We also evaluated the importance of antiporters and transporters such as Arabidopsis K+ Transporter 1 (AKT1) potassium channel and the impact of epigenetic modification on soybean salt tolerance. We also review key phytohormones, and osmo-protectants and their role in salt tolerance in soybean. In addition, we discuss the progress of omics technologies for identifying salt stress responsive molecular switches and their targeted engineering for salt tolerance in soybean. This review summarizes recent progress in soybean salt stress functional genomics and way forward for molecular breeding for developing salt-tolerant soybean plant.

GmEID1 modulates light signaling through the Evening Complex to control flowering time and yield in soybean.

Soybean (Glycine max) morphogenesis and flowering time are accurately regulated by photoperiod, which determine the yield potential and limit soybean cultivars to a narrow latitudinal range. The E3 and E4 genes, which encode phytochrome A photoreceptors in soybean, promote the expression of the legume-specific flowering repressor E1 to delay floral transition under long-day (LD) conditions. However, the underlying molecular mechanism remains unclear. Here, we show that the diurnal expression pattern of GmEID1 is opposite to that of E1 and targeted mutations in the GmEID1 gene delay soybean flowering regardless of daylength. GmEID1 interacts with J, a key component of circadian Evening Complex (EC), to inhibit E1 transcription. Photoactivated E3/E4 interacts with GmEID1 to inhibit GmEID1-J interaction, promoting J degradation resulting in a negative correlation between daylength and the level of J protein. Notably, targeted mutations in GmEID1 improved soybean adaptability by enhancing yield per plant up to 55.3% compared to WT in field trials performed in a broad latitudinal span of more than 24°. Together, this study reveals a unique mechanism in which E3/E4-GmEID1-EC module controls flowering time and provides an effective strategy to improve soybean adaptability and production for molecular breeding.

Tumors evade immune cytotoxicity by altering the surface topology of NK cells.

The highly variable response rates to immunotherapies underscore our limited knowledge about how tumors can manipulate immune cells. Here the membrane topology of natural killer (NK) cells from patients with liver cancer showed that intratumoral NK cells have fewer membrane protrusions compared with liver NK cells outside tumors and with peripheral NK cells. Dysregulation of these protrusions prevented intratumoral NK cells from recognizing tumor cells, from forming lytic immunological synapses and from killing tumor cells. The membranes of intratumoral NK cells have altered sphingomyelin (SM) content and dysregulated serine metabolism in tumors contributed to the decrease in SM levels of intratumoral NK cells. Inhibition of SM biosynthesis in peripheral NK cells phenocopied the disrupted membrane topology and cytotoxicity of the intratumoral NK cells. Targeting sphingomyelinase confers powerful antitumor efficacy, both as a monotherapy and as a combination therapy with checkpoint blockade.

LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia.

BACKGROUND: Cancer cachexia is a deadly wasting syndrome that accompanies various diseases (including ~ 50% of cancers). Clinical studies have established that cachexia is not a nutritional deficiency and is linked to expression of certain proteins (e.g., interleukin-6 and C-reactive protein), but much remains unknown about this often fatal syndrome. METHODS: First, cachexia was created in experimental mouse models of lung cancer. Samples of human lung cancer were used to identify the association between the serum lipocalin 2 (LCN2) level and cachexia progression. Then, mouse models with LCN2 blockade or LCN2 overexpression were used to ascertain the role of LCN2 upon ferroptosis and cachexia. Furthermore, antibody depletion of tissue-infiltrating neutrophils (TI-Neu), as well as myeloid-specific-knockout of Lcn2, were undertaken to reveal if LCN2 secreted by TI-Neu caused cachexia. Finally, chemical inhibition of ferroptosis was conducted to illustrate the effect of ferroptosis upon tissue wasting. RESULTS: Protein expression of LCN2 was higher in the wasting adipose tissue and muscle tissues of experimental mouse models of lung cancer cachexia. Moreover, evaluation of lung cancer patients revealed an association between the serum LCN2 level and cachexia progression. Inhibition of LCN2 expression reduced cachexia symptoms significantly and inhibited tissue wasting in vivo. Strikingly, we discovered a significant increase in the number of TI-Neu in wasting tissues, and that these innate immune cells secreted high levels of LCN2. Antibody depletion of TI-Neu, as well as myeloid-specific-knockout of Lcn2, prevented ferroptosis and tissue wasting in experimental models of lung cancer cachexia. Chemical inhibition of ferroptosis alleviated tissue wasting significantly and also prolonged the survival of cachectic mice. CONCLUSIONS: Our study provides new insights into how LCN2-induced ferroptosis functionally impacts tissue wasting. We identified LCN2 as a potential target in the treatment of cancer cachexia.