A fibronectin gradient remodels mixed-phase mesoderm.

Physical processes ultimately shape tissue during development. Two emerging proposals are that cells migrate toward stiffer tissue (durotaxis) and that the extent of cell rearrangements reflects tissue phase, but it is unclear whether and how these concepts are related. Here, we identify fibronectin-dependent tissue stiffness as a control variable that underlies and unifies these phenomena in vivo. In murine limb bud mesoderm, cells are either caged, move directionally, or intercalate as a function of their location along a stiffness gradient. A modified Landau phase equation that incorporates tissue stiffness accurately predicts cell diffusivity upon loss or gain of fibronectin. Fibronectin is regulated by WNT5A-YAP feedback that controls cell movements, tissue shape, and skeletal pattern. The results identify a key determinant of phase transition and show how fibronectin-dependent directional cell movement emerges in a mixed-phase environment in vivo.

Greenhouse gas emissions from the growing season are regulated by precipitation events in conservation tillage farmland ecosystems of Northeast China.

Reducing greenhouse gas (GHG) emissions from agricultural ecosystems is vital to mitigate global warming. Conservation tillage is widely used in farmland management to improve soil quality; however, its effects on soil GHG emissions remain poorly understood, particularly in high-yield areas. Therefore, our study aimed to evaluate the effects of no-tillage (NT) combined with four straw-mulching levels (0 %, 33 %, 67 %, and 100 %) on GHG emission risk and the main influencing factors. We conducted in-situ observations of GHG emissions from soils under different management practices during the maize-growing season in Northeastern China. The results showed that NT0 (705.94 g m-2) reduced CO2 emissions by 18 % compared to ridge tillage (RT, 837.04 g m-2). Different straw mulching levels stimulated N2O emissions after rainfall, particularly under NT combined with 100 % straw mulching (2.89 kg ha-1), which was 45 % higher than that in any other treatments. The CH4 emissions flux among different treatments was nearly zero. Overall, straw mulching levels had no significant effect on the GHG emissions. During the growing season, soil NH4+-N (< 20 mg kg-1) remained low and decreased with the extension of growth stage, whereas soil NO3--N initially increased and then decreased. More importantly, the results of structural equation modeling indicate that: a) organic material input and soil moisture are key factors affecting CO2 emissions, b) nitrogen fertilizer and soil moisture promote N2O emissions, and c) climatic factors exert an inexorable influence on the GHG emissions process. Our conclusions emphasize the necessity of incorporating precipitation-response measures into farmland management to reduce the risk of GHG emissions.

Kaiser score diagnosis of breast MRI lesions: Factors associated with false-negative and false-positive results.

PURPOSE: We sought factors associated with false-negative and false-positive results in the diagnosis of breast lesions using the Kaiser score (KS) on breast magnetic resonance imaging (MRI). METHODS: We retrospectively analyzed 1058 patients with 1058 breast lesions who underwent preoperative breast MRI with successful histopathologic results. Two radiologists assessed each lesion according to KS criteria, and clinicopathologic features and MRI findings were analyzed. Multivariate regression analysis was conducted to identify factors associated with false-negative and false-positive KS results. RESULTS: Of the 1058 lesions, 859 were malignant and 199 were benign. Particularly high misdiagnosis rates were observed for intraductal papilloma, inflammatory lesion, and mucinous carcinoma. For breast cancer, KS yielded 821 (95.6 %) true-positive and 38 (4.4 %) false-negative results. Multivariate analysis showed that smaller lesion size (≤1 cm) (OR, 3.698; 95 %CI, 1.430-9.567; p = 0.007), absence of ipsilateral breast hypervascularity (OR, 3.029; 95 %CI, 1.370-6.693; p = 0.006), and presence of hyperintensity on T2WI (OR, 2.405; 95 %CI, 1.121-5.162; p = 0.024) were significantly associated with false-negative breast cancer results. For benign lesions, KS yielded 141 (70.9 %) true-negative and 58 (29.1 %) false-positive results. Multivariate regression analysis revealed that non-mass enhancement lesions (OR, 4.660; 95 %CI, 2.018-10.762; p＜0.001), moderate/high background parenchymal enhancement (OR, 2.402; 95 %CI, 1.180-4.892; p = 0.016), and the presence of hyperintensity on T2WI (OR, 2.986; 95 %CI, 1.386-6.433; p = 0.005) were significantly associated with false-positive KS results. CONCLUSION: Several clinicopathologic and MRI features influence the accuracy of KS diagnosis. Understanding these factors may facilitate appropriate use of KS and guide alternative diagnostic approaches, ultimately improving diagnostic accuracy in the evaluation of breast lesions.

Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls was performed, excluding patients previously treated with glucocorticoids. Several SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity of mineralocorticoids and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls, excluding those that affected adrenal function. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with those in SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with exacerbation of inflammation, differentiation and the presence of dual-ZG/ZF identity cells. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of adrenal axis and the corticosteroid sensitivity.

Dual-nodes bridged cobalt-modified Keggin-type polyoxometalate-based chains for highly efficient CO2 photoconversion.

The design of efficient catalysts for photocatalytic CO2 conversion is of great importance for the sustainable development of society. Herein, three polyoxometalate (POM)-based crystalline materials were formulated prepared by substituting transition metals and adjusting solvent acidity with 2-(2-pyridyl) benzimidazole (pyim) as the light-trapping ligand, namely {[SiW12O40][Co(pyim)2]2}·2C2H5OH (SiW12Co2), {[SiW12O40][Ni(pyim)2]2}·2C2H5OH (SiW12Ni2), and {[SiW12O40][Mn(pyim)2]2}·2C2H5OH (SiW12Mn2). X-ray crystallography diffraction analysis indicates that the three complexes exhibit isostructural properties, and form a stable one-dimensional chain structure stabilized by two [M(pyim)2]22+ (M = Co, Ni, and Mn) fragments serving as dual-nodes to the adjacent SiW12 units. A comprehensive analysis of the structural characterization and photocatalytic CO2 reduction properties is presented. Under light irradiation, SiW12Co2 exhibited a remarkable CO generation rate of 10 733 µmol g-1 h-1 with a turnover number of 328, outperforming most of the reported heterogeneous POM-based photocatalysts. Besides, cycling tests revealed that SiW12Co2 is an efficient and stable photocatalyst with great recyclability for at least four successive runs. This study proves that the successful incorporation of diverse transition metals into the POM anion could facilitate the development of highly efficient photocatalysts for the CO2RR.

Periostin predicts all-cause mortality in male but not female end-stage renal disease patients on hemodialysis.

BACKGROUND: Periostin is a matricellular protein. Elevated serum concentrations of periostin have been reported in patients with various cardiovascular diseases, including heart failure. Patients with end-stage renal disease have a substantially increased risk for cardiovascular diseases. However, there is a lack of clinical studies to clarify the prognostic significance of systemic periostin on all-cause mortality in patients with end-stage renal disease on hemodialysis. METHODS: 313 stable end-stage renal disease patients were recruited and followed for five years concerning all-cause mortality. At baseline, we collected blood samples and clinical data. Serum periostin concentrations were measured using a certified ELISA. RESULTS: The optimal cut-off value for serum periostin regarding all-cause mortality, calculated through ROC analysis, was 777.5 pmol/l. Kaplan-Meier survival analysis using this cut-off value demonstrated that higher periostin concentrations are linked to higher all-cause mortality (log-rank test: P = 0.002). Subgroup analysis revealed that serum periostin concentrations only affected all-cause mortality in male but not in female patients (P = 0.002 in male patients and P = 0.474 in female patients). Multivariate Cox regression analyses, adjusted for confounding factors, likewise showed that elevated serum periostin concentrations were positively associated with all-cause mortality in male (P = 0.028) but not in female patients on hemodialysis (P = 0.313). CONCLUSION: Baseline serum periostin is an independent risk factor for all-cause mortality in male patients with chronic renal disease on hemodialysis.

YTH domain family protein 3 accelerates non-small cell lung cancer immune evasion through targeting CD8+ T lymphocytes.

Immune evasion is one of the critical hallmarks of malignant tumors, especially non-small cell lung cancer (NSCLC). Emerging findings have illustrated the roles of N6-methyladenosine (m6A) on NSCLC immune evasion. Here, this study investigated the function and underlying mechanism of m6A reader YTH domain family protein 3 (YTHDF3) on NSCLC immune evasion. YTHDF3 was found to be highly expressed in NSCLC tissue and act as an independent prognostic factor for overall survival. Functionally, up-regulation of YTHDF3 impaired the CD8+ T antitumor activity to deteriorate NSCLC immune evasion, while YTHDF3 silencing recovered the CD8+ T antitumor activity to inhibit immune evasion. Besides, YTHDF3 up-regulation reduced the apoptosis of NSCLC cells. Mechanistically, PD-L1 acted as the downstream target for YTHDF3, and YTHDF3 could upregulate the transcription stability of PD-L1 mRNA. Overall, YTHDF3 targeted PD-L1 to promote NSCLC immune evasion partially through escaping effector cell cytotoxicity CD8+ T mediated killing and antitumor immunity. In summary, this study provides an essential insight for m6A modification on CD8+ T cell-mediated antitumor immunity in NSCLC, which might inspire an innovation for lung cancer tumor immunotherapy.

Progress in the Application of Hydrogels in Intervertebral Disc Repair: A Comprehensive Review.

PURPOSE OF REVIEW: Intervertebral disc degeneration (IVDD) is a common orthopaedic disease and an important cause of lower back pain, which seriously affects the work and life of patients and causes a large economic burden to society. The traditional treatment of IVDD mainly involves early pain relief and late surgical intervention, but it cannot reverse the pathological course of IVDD. Current studies suggest that IVDD is related to the imbalance between the anabolic and catabolic functions of the extracellular matrix (ECM). Anti-inflammatory drugs, bioactive substances, and stem cells have all been shown to improve ECM, but traditional injection methods face short half-life and leakage problems. RECENT FINDINGS: The good biocompatibility and slow-release function of polymer hydrogels are being noticed and explored to combine with drugs or bioactive substances to treat IVDD. This paper introduces the pathophysiological mechanism of IVDD, and discusses the advantages, disadvantages and development prospects of hydrogels for the treatment of IVDD, so as to provide guidance for future breakthroughs in the treatment of IVDD.

Direct Ethylene Purification from a Four-Component Gas Mixture by a Microporous MOF with Aromatic Pore Surface and Carboxylates.

The single-step purification of ethylene (C2H4) from a mixture of carbon dioxide (CO2), acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) was achieved through MOF Compound-1, where the aromatic pore surface and carboxylates selectively recognized C2H6 and CO2, respectively, resulting in a reversal of the adsorption orders for both gases (C2H6 > C2H4 and CO2 > C2H4). Breakthrough testing verified that the C2H4 purification ability could be enhanced 2.6 times after adding impure CO2. Grand Canonical Monte Carlo (GCMC) simulations demonstrate that there are interactions between CO2 and C2H6 molecules as well as between CO2 molecules themselves. These interactions contribute to the enhancement of the C2H4 purification ability upon the addition of CO2 and the increased adsorption of CO2.

Genetic causality and metabolite pathway identifying the relationship of blood metabolites and psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease that causes significant disability. However, little is known about the underlying metabolic mechanisms of psoriasis. Our study aims to investigate the causality of 975 blood metabolites with the risk of psoriasis. MATERIALS AND METHODS: We mainly applied genetic analysis to explore the possible associations between 975 blood metabolites and psoriasis. The inverse variance weighted (IVW) method was used as the primary analysis to assess the possible association of blood metabolites with psoriasis. Moreover, generalized summary-data-based Mendelian randomization (GSMR) was used as a supplementary analysis. In addition, linkage disequilibrium score regression (LDSC) was used to investigate their genetic correction further. Metabolic pathway analysis of the most suggested metabolites was also performed using MetaboAnalyst 5.0. RESULTS: In our primary analysis, 17 metabolites, including unsaturated fatty acids, phospholipids, and triglycerides traits, were selected as potential factors in psoriasis, with odd ratios (OR) ranging from 0.986 to 1.01. The GSMR method confirmed the above results (ß = 0.001, p < 0.05). LDSC analysis mainly suggested the genetic correlation of psoriasis with genetic correlations (rg) from 0.088 to 0.155. Based on the selected metabolites, metabolic pathway analysis suggested seven metabolic pathways including ketone body that may be prominent pathways for metabolites in psoriasis. CONCLUSION: Our study supports the causal role of unsaturated fatty acid properties and lipid traits with psoriasis. These properties may be regulated by the ketone body metabolic pathway.

Maternal linoleic acid-rich diet ameliorates bilirubin neurotoxicity in offspring mice.

Hyperbilirubinaemia is a prevalent condition during the neonatal period, and if not promptly and effectively managed, it can lead to severe bilirubin-induced neurotoxicity. Sunflower seeds are a nutrient-rich food source, particularly abundant in linoleic acid. Here, we provide compelling evidence that lactating maternal mice fed a sunflower seed diet experience enhanced neurological outcomes and increased survival rates in hyperbilirubinemic offspring. We assessed histomorphological indices, including cerebellar Nissl staining, and Calbindin staining, and hippocampal hematoxylin and eosin staining. Furthermore, we observed the transmission of linoleic acid, enriched in sunflower seeds, to offspring through lactation. The oral administration of linoleic acid-rich sunflower seed oil by lactating mothers significantly prolonged the survival time of hyperbilirubinemic offspring mice. Mechanistically, linoleic acid counteracts the bilirubin-induced accumulation of ubiquitinated proteins and neuronal cell death by activating autophagy. Collectively, these findings elucidate the novel role of a maternal linoleic acid-supplemented diet in promoting child health.

The Drosophila histone methyl-transferase SET1 coordinates multiple signaling pathways in regulating male germline stem cell maintenance and differentiation.

Many tissue-specific adult stem cell lineages maintain a balance between proliferation and differentiation. Here, we study how the H3K4me3 methyltransferase, Set1, regulates early-stage male germ cells in Drosophila. Early-stage germline-specific knockdown of set1 results in temporally progressed defects, arising as germ cell loss and developing into overpopulated early-stage germ cells. These germline defects also impact the niche architecture and cyst stem cell lineage non-cell-autonomously. Additionally, wild-type Set1, but not the catalytically inactive Set1, rescues the set1 knockdown phenotypes, highlighting the functional importance of the methyl-transferase activity of Set1. Further, RNA-seq experiments reveal key signaling pathway components, such as the JAK-STAT pathway stat92E and the BMP pathway mad genes that are upregulated upon set1 knockdown. Genetic interaction assays support the functional relationships between set1 and JAK-STAT or BMP pathways, as both stat92E and mad mutations suppress the set1 knockdown phenotypes. These findings enhance our understanding of the balance between proliferation and differentiation in an adult stem cell lineage. The germ cell loss followed by over-proliferation phenotype when inhibiting a histone methyl-transferase also raise concerns about using their inhibitors in cancer therapy.

Comparative efficacy and safety of systemic steroids, oral JAK inhibitors and Contact Immunotherapy in the Treatment of severe alopecia areata: a systematic review and network meta-analysis.

Severe alopecia areata (AA) is a nonscarring hair loss for immune disorder and SALT score ≥ 50%. The guidelines for managing patients with severe AA suggest treatments: systemic steroids, JAK inhibitors, and contact immunotherapy. However, there is a lack of evidence indicating the superiority of one treatment over another. Therefore, this study aimed to identify the most effective treatment for severe AA through network meta-analysis. Following the PRISMA guidelines, we conducted a network meta-analysis. The literature search was retrieved across four databases. The Cochrane 5.1 risk of bias assessment tool and ROBINS-I tool assessed quality of the included studies. Subsequently, efficacy and safety comparisons among the three treatments were conducted using Stata 14.0 on account of the frequency method. The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. As for safety, placebo(88.4%) > oral ritlecitinib (86.5%) > oral baricitinib (62.1%) > SADBE (37.0%) > oral dexamethasone(22.3%) > DPCP(3.8%) in the aspect of decreasing adverse events. Oral dexamethasone and DPCP showed superior efficacy compared to oral ritlecitinib and oral baricitinib. However, in terms of safety, oral ritlecitinib was preferable. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA.

Causal effects of autoimmune diseases on temporomandibular disorders and the mediating pathways: a Mendelian randomization study.

Background: The role of autoimmune diseases (ADs) in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder is destructive in TMDs. This Mendelian randomization (MR) study aims to estimate the causal effect of common ADs on TMDs. Methods: Genetic data from published genome-wide association studies for fourteen common ADs, specifically multiple sclerosis (MS, N = 15,283), ankylosing spondylitis (AS, N = 22,647), asthma (N = 408,422), celiac disease (N = 15,283), Graves' disease (N = 458,620), Hashimoto thyroiditis (N = 395,640), primary biliary cirrhosis (PBC, N = 11,375), primary sclerosing cholangitis (PSC, N = 14,890), psoriasis vulgaris (N = 483,174), rheumatoid arthritis (RA, N = 417,256), systemic lupus erythematosus (SLE, N = 23,210), Type 1 diabetes (T1D, N = 520,580), inflammatory bowel disease (IBD, N = 34,652), and Sjogren's syndrome (SS, N = 407,746) were collected. Additionally, the latest summary-level data for TMDs (N = 228,812) were extracted from the FinnGen database. The overall effects of each immune traits were assessed via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Finally, 731 immune cell phenotypes (N = 3,757) were analyzed for their mediating role in the significant causality. Results: Univariable MR analyses revealed that genetically predicted RA (IVW OR: 1.12, 95% CI: 1.05-1.19, p < 0.001) and MS (IVW OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were associated with increased risk of TMDs. Two out of 731 immune cell phenotypes were identified as causal mediators in the associations of RA with TMDs, including "CD25++ CD8+ T cell % CD8+ T cell" (mediation proportion: 6.2%) and "CD3 on activated CD4 regulatory T cell" (5.4%). Additionally, "CD127 on granulocyte" mediated 10.6% of the total effect of MS on TMDs. No reverse directions, heterogeneity, and pleiotropy were detected in the analyses (p > 0.05). Conclusion: This MR study provides new evidence regarding the causal impact of genetic predisposition to RA or MS on the increased risk of TMDs, potentially mediated by the modulation of immune cells. These findings highlight the importance for clinicians to pay more attention to patients with RA or MS when consulting for temporomandibular discomfort. The mediating role of specific immune cells is proposed but needs further investigation.

Oxalate regulates crystal-cell adhesion and macrophage metabolism via JPT2/PI3K/AKT signaling to promote the progression of kidney stones.

Oxalate is an organic dicarboxylic acid that is a common component of plant foods. The kidneys are essential organs for oxalate excretion, but excessive oxalates may induce kidney stones. Jupiter microtubule associated homolog 2 (JPT2) is a critical molecule in Ca2+ mobilization, and its intrinsic mechanism in oxalate exposure and kidney stones remains unclear. This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones. Genetic approaches were used to control JPT2 expression in cells and mice, and the JPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics. The results showed that oxalate exposure triggered the upregulation of JPT2, which is involved in nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated Ca2+ mobilization. Transcriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown, and these were dominated by phosphatidylinositol 3-kinase (PI3K)/AKT signaling, respectively. Untargeted metabolomics indicated that JPT2 knockdown inhibited the production of succinic acid semialdehyde (SSA) in macrophages. Furthermore, JPT2 deficiency in mice inhibited kidney stones mineralization. In conclusion, this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion, and modulating macrophage metabolism and inflammatory polarization via JPT2/PI3K/AKT signaling.

The Research on the Effect of Nutritional Stage-based Care Intervention in Elderly Patients with Severe Pneumonia.

Objective: To evaluate the efficacy of a nutritional stage-based care intervention in improving outcomes for elderly patients with severe pneumonia. Methods: A retrospective analysis of clinical data was conducted on 203 elderly patients with severe pneumonia admitted to our hospital from January 2022 to January 2023. All patients met the inclusion and exclusion criteria. Upon admission, all patients received relevant symptomatic treatment and basic care. Based on the nutritional care intervention received by the patients, they were divided into a control group (n=101) and an observation group (n=102). The control group received routine nutritional care intervention, while the observation group received nutritional stage-based care intervention. The study compared the levels of organ recovery indicators (mechanical ventilation time, ICU hospitalization time), nutritional status indicators [serum albumin (Alb), prealbumin (PAB), hemoglobin (Hb)], immune function indicators [immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM)], blood gas status indicators [arterial oxygen pressure (PaO2), arterial carbon dioxide pressure (PaCO2)], and the occurrence of complications between the two groups. Results: Organ Recovery Indicators: The observation group showed significantly lower mechanical ventilation time and ICU hospitalization time compared to the control group (P < .05). Nutritional Status Indicators: Before the intervention, there was no significant difference in albumin (Alb), prealbumin (PAB), and hemoglobin (Hb) levels between the two groups (P > .05). After the intervention, the Alb, PAB, and Hb levels in the observation group were significantly higher than the control group (P < .05). Immune Function Indicators: Before intervention, there was no significant difference in IgA, IgG, and IgM levels between the two groups (P > .05). After intervention, the levels of IgA, IgG, and IgM in the observation group were significantly higher than the control group (P < .05). Blood Gas Status Indicators: Before intervention, there was no significant difference in PaO2 and PaCO2 levels between the two groups (P > .05). After intervention, the PaO2 level in the observation group was significantly higher, while the PaCO2 level was significantly lower compared to the control group (P < .05). Complication Incidence: The complication incidence in the control group was 25.74%, while in the observation group it was 9.80%, which was significantly lower (P < .05). Conclusion: The application of nutritional stage-based care intervention in the management of elderly patients with severe pneumonia is shown to be highly beneficial. Compared to routine nutritional care, the nutritional stage-based approach significantly improved patients' nutritional status, immune function, blood gas conditions, and accelerated their organ recovery. Importantly, this intervention also led to a markedly lower incidence of complications. These findings suggest that incorporating nutritional stage-based care into standard treatment protocols for elderly patients with severe pneumonia may significantly enhance recovery rates and long-term health outcomes for this vulnerable patient population. Given the positive impact demonstrated in this study, the nutritional stage-based care intervention is worthy of broader clinical adoption and promotion.

Discrimination of relatedness drives rice flowering and reproduction in cultivar mixtures.

The improvement of performance and yield in both cultivar and species mixtures has been well established. Despite the clear benefits of crop mixtures to agriculture, identifying the critical mechanisms behind performance increases are largely lacking. We experimentally demonstrated that the benefits of rice cultivar mixtures were linked to relatedness-mediated intraspecific neighbour recognition and discrimination under both field and controlled conditions. We then tested biochemical mechanisms of responses in incubation experiments involving the addition of root exudates and a root-secreted signal, (-)-loliolide, followed by transcriptome analysis. We found that closely related cultivar mixtures increased grain yields by modifying root behaviour and accelerating flowering over distantly related mixtures. Importantly, these responses were accompanied by altered concentration of signalling (-)-loliolide that affected rice transcriptome profiling, directly regulating root growth and flowering gene expression. These findings suggest that beneficial crop combinations may be generated a-priori by manipulating neighbour genetic relatedness in rice cultivar mixtures and that root-secreted (-)-loliolide functions as a key mediator of genetic relatedness interactions. The ability of relatedness discrimination to regulate rice flowering and yield raises an intriguing possibility to increase crop production.

Colossal Zero-Field-Cooled Exchange Bias via Tuning Compensated Ferrimagnetic in Kagome Metals.

Exchange bias (EB) is a crucial property with widespread applications but particularly occurs by complex interfacial magnetic interactions after field cooling. To date, intrinsic zero-field-cooled EB (ZEB) has only emerged in a few bulk frustrated systems and their magnitudes remain small yet. Here, enabled by high temperature synthesis, we uncover a colossal ZEB field of 4.95 kOe via tuning compensated ferrimagnetism in a family of kagome metals, which is almost twice the magnitude of known materials. Atomic-scale structure, spin dynamics, and magnetic theory revealed that these compensated ferrimagnets originate from significant antiferromagnetic exchange interactions embedded in the holmium-iron ferrimagnetic matrix due to supersaturated preferential manganese doping. A random antiferromagnetic order of manganese sublattice sandwiched between ferromagnetic iron kagome bilayers accounts for such unconventional pinning. The outcome of the present study outlines disorder-induced giant bulk ZEB and coercivity in layered frustrated systems.

Decellularized Amnion Membrane Triggers Macrophage Polarization for Desired Host Immune Response.

Appropriate regulation of immunomodulatory responses, particularly acute inflammation involving macrophages, is crucial for the desired functionality of implants. Decellularized amnion membrane (DAM) is produced by removing cellular components and antigenicity, expected to reduce immunogenicity and the risk of inflammation. Despite the potential of DAM as biomaterial implants, few studies have investigated its specific effects on immunomodulation. Here, it is demonstrated that DAM can regulate macrophage-driven inflammatory response and potential mechanisms are investigated. In vitro results show that DAM significantly inhibits M1 polarization in LPS-induced macrophages by inhibiting Toll-like receptors (TLR) signaling pathway and TNF signaling pathway and promotes macrophage M2 polarization. Physical signals from the 3D micro-structure and the active protein, DCN, binding to key targets may play roles in the process. In the subcutaneous implant model in rats, DAM inhibits the persistence of inflammation and fibrous capsule formation, while promoting M2 macrophage polarization, thereby facilitating tissue regeneration. This study provides insights into DAM's effect and potential mechanisms on the balance of M1/M2 macrophage polarization in vitro and vivo, emphasizing the immunomodulation of ECM-based materials as promising implants.

Multimodal effects of an extracellular matrix on cellular morphology, dynamics and functionality.

Articular cartilage defects can lead to pain and even disability in patients and have significant socioeconomic loss. Repairing articular cartilage defects remains a long-term challenge in medicine owing to the limited ability of cartilage to regenerate. At present, the treatment methods adopted in clinical practice have many limitations, thereby necessitating the rapid development of biomaterials. Among them, decellularized biomaterials have been particularly prominent, with numerous breakthroughs in research progress and translational applications. Although many studies show that decellularized cartilage biomaterials promote tissue regeneration, any differences in cellular morphology, dynamics, and functionality among various biomaterials upon comparison have not been reported. In this study, we prepared cartilage-derived extracellular matrix (cdECM) biomaterials with different bioactive contents and various physical properties to compare their effects on the morphology, dynamics and functionality of chondrocytes. This cellular multimodal analysis of the characteristics of cdECM biomaterials provided a theoretical basis for understanding the interactions between biomaterials and cells, thus laying an experimental foundation for the translation and application of decellularized cartilage biomaterials in the treatment of cartilage defects.