Manhattan Vision Screening and Follow-up Study (NYC-SIGHT): a nested cross-sectional assessment of falls risk within a cluster randomised trial.

BACKGROUND: To investigate the feasibility of using the Stopping Elderly Accidents, Deaths and Injuries (STEADI) Falls Risk Tool Kit during community-based eye health screenings to assess falls risk of participants enrolled in the Manhattan Vision Screening and Follow-Up Study (NYC-SIGHT). METHODS: Cross-sectional analysis of data from a 5-year prospective, cluster-randomised clinical trial conducted in affordable housing developments in New York City in adults age 40 years and older. Prescreening questions determined whether participants were at risk of falling. STEADI tests classified participants at low, moderate or high risk of falling. Multivariate logistic regression determined odds of falls risk of all enrolled participants. RESULTS: 708 participants completed the eye health screening; 351 (49.6%) performed STEADI tests; mean age: 71.0 years (SD±11.3); 72.1% female; 53.6% Black, non-Hispanic, 37.6% Hispanic/Latino. Level of falls risk: 32 (9.1%) low, 188 (53.6%) moderate and 131 (37.3%) high. Individuals age >80 (OR 5.921, 95% CI (2.383 to 14.708), p=0.000), had blurry vision (OR 1.978, 95% CI (1.186 to 3.300), p=0.009), high blood pressure (OR 2.131, 95% CI (1.252 to 3.628), p=0.005), arthritis (OR 2.29876, 95% CI (1.362 to 3.875), p=0.002) or foot problems (OR 5.239, 95% CI (2.947 to 9.314), p=0.000) had significantly higher odds of falling, emergency department visits or hospitalisation due to falling. CONCLUSION: This study detected a significant amount of falls risk in an underserved population. The STEADI Falls Risk screening questions were easy for eye care providers to ask, were highly predictive of falls risk and may be adequate for referral to occupational health and/or physical therapy.

A correlated ferromagnetic polar metal by design.

Polar metals have recently garnered increasing interest because of their promising functionalities. Here we report the experimental realization of an intrinsic coexisting ferromagnetism, polar distortion and metallicity in quasi-two-dimensional Ca3Co3O8. This material crystallizes with alternating stacking of oxygen tetrahedral CoO4 monolayers and octahedral CoO6 bilayers. The ferromagnetic metallic state is confined within the quasi-two-dimensional CoO6 layers, and the broken inversion symmetry arises simultaneously from the Co displacements. The breaking of both spatial-inversion and time-reversal symmetries, along with their strong coupling, gives rise to an intrinsic magnetochiral anisotropy with exotic magnetic field-free non-reciprocal electrical resistivity. An extraordinarily robust topological Hall effect persists over a broad temperature-magnetic field phase space, arising from dipole-induced Rashba spin-orbit coupling. Our work not only provides a rich platform to explore the coupling between polarity and magnetism in a metallic system, with extensive potential applications, but also defines a novel design strategy to access exotic correlated electronic states.

An antiviral oligomerized linear thiopeptide with a nitrile group from soil-derived Streptomyces sp. CPCC 203702.

A new linear thiopeptide, bernitrilecin (1), was isolated from Streptomyces sp. CPCC 203702. Compound 1 is the first example of a nitrile-bearing thiopeptide. Its structure and absolute configuration were elucidated by extensive analysis of spectroscopic data and Marfey's method. The biosynthesis of the nitrile unit for 1 was proposed to be through oxidations, decarboxylation, and dehydration. Compound 1 exhibited significant anti-influenza A virus activity with the IC50 value of 16.7 µM.

Exploration of the Clinical Effect of Different Autotransfusion Methods on Patients With Femoral Shaft Fracture Surgery.

OBJECTIVE: To explore the clinical effect of predeposit, salvage, and hemodilution autotransfusion on patients with femoral shaft fracture (FSF) surgery. METHODS: Selected patients with FSF were randomly divided into three groups: intraoperative blood salvage autotransfusion, preoperative hemodilution autohemotransfusion, and predeposit autotransfusion. Five days after the operation, the body temperature, heart rate, blood platelet (PLT), and hemoglobin (Hb) of patients were determined. The concentrations of EPO and GM-CSF in the three groups were calculated by ELISA. The content of CD14+ monocytes was calculated by FCM assay. The growth time and condition of the patient's callus were determined at the 30th, 45th, and 60th day after operation. Cox regression analysis was used to analyze the correlation between EPO, GM-CSF, CD14+ mononuclear content, callus growth, and autotransfusion methods. RESULTS: There were no statistically significant differences in body temperature and heart rate between the three groups (p > 0.05). PLT and Hb in the Predeposit group were markedly increased compared with that in the Salvage and Hemodilution groups. The concentrations of EPO and GM-CSF in the Predeposit group were markedly increased compared with that in the Salvage and Hemodilution groups. The content of CD14+ monocytes in the Predeposit group was significantly higher than that in the Salvage and Hemodilution groups. Predeposit autotransfusion promotes callus growth more quickly. CONCLUSION: Predeposit autotransfusion promoted the recovery of patients with FSF after the operation more quickly than salvage autotransfusion and hemodilution autotransfusion.

Bioinformatics analysis characterizes immune infiltration landscape and identifies potential blood biomarkers for heart transplantation.

BACKGROUND: Cardiac allograft rejection (AR) remains a significant complication following heart transplantation. The primary objective of our study is to gain a comprehensive understanding of the fundamental mechanisms involved in AR and identify possible therapeutic targets. METHODS: We acquired the GSE87301 dataset from the Gene Expression Omnibus database. In GSE87301, a comparison was conducted on blood samples from patients with and without cardiac allograft rejection (AR and NAR) to detect differentially expressed genes (DEGs). Enrichment analysis was conducted to identify the pathways that show significant enrichment during AR. Machine learning techniques, including the least absolute shrinkage and selection operator regression (LASSO) and random forest (RF) algorithms, were employed to identify potential genes for the diagnosis of AR. The diagnostic value was evaluated using a nomogram and receiver operating characteristic (ROC) curve. Additionally, immune cell infiltration was analyzed to explore any dysregulation of immune cells in AR. RESULTS: A total of 114 DEGs were identified from the GSE87301 dataset. These DEGs were mainly found to be enriched in pathways related to the immune system. To identify the signature genes, the LASSO and RF algorithms were used, and four genes, namely ALAS2, HBD, EPB42, and FECH, were identified. The performance of these signature genes was evaluated using the receiver operating characteristic curve (ROC) analysis, which showed that the area under the curve (AUC) values for ALAS2, HBD, EPB42, and FECH were 0.906, 0.881, 0.900, and 0.856, respectively. These findings were further confirmed in the independent datasets and clinical samples. The selection of these specific genes was made to construct a nomogram, which demonstrated excellent diagnostic ability. Additionally, the results of the single-sample gene set enrichment analysis (ssGSEA) revealed that these genes may be involved in immune cell infiltration. CONCLUSION: We identified four signature genes (ALAS2, HBD, EPB42, and FECH) as potential peripheral blood diagnostic candidates for AR diagnosis. Additionally, a nomogram was constructed to aid in the diagnosis of heart transplantation. This study offers valuable insights into the identification of candidate genes for heart transplantation using peripheral blood samples.

Analysis of four hereditary protein C deficiencies associated with vascular thromboembolism.

OBJECTIVE: To analyze the clinical features and gene mutations in four families with hereditary protein C (PC) deficiency and explore their association with vascular thromboembolism. METHODS: The clinical data of four patients with PC deficiency were retrospectively analyzed. Venous blood samples were collected from the four affected patients and their family members, and relevant coagulation indexes and thrombin production and inhibition tests were performed. PCR was used to amplify and directly sequence the PROC gene of the probands. Software analysis was conducted to assess the conservativeness and pathogenicity of the mutated loci. Protein models were constructed to analyze the spatial structure before and after the mutation. RESULTS: Thrombin generation and inhibition assays demonstrated impaired anticoagulation in all four probands. Proband 1 and 4 presented clinically with pulmonary embolism and lower extremity deep vein thrombosis (DVT), Proband 2 with cerebral infarction, and Proband 3 with DVT. Genetic analysis revealed the presence of the following mutations: c.541T > G heterozygous missense mutation, c.577-579delAAG heterozygous deletion mutation, c.247-248insCT heterozygous insertion mutation, c.659G > A heterozygous missense mutation, and a new variant locus c.1146_1146delT heterozygous deletion mutation in the four probands, respectively. In particular, c.1146_1146delT heterozygous deletion mutations not reported previously. Conservativeness and pathogenicity analyses confirmed that most of these amino acid residues were conserved, and all the mutations were found to be pathogenic. Analysis of protein modeling revealed that these mutations induced structural alterations in the protein or led to the formation of truncated proteins. According to the American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants, c.1146_1146delT was rated as pathogenic (PVS1 + M2 + PM4 + PP1 + PP3 + PP4). CONCLUSION: The identified mutations are likely associated with decreased PC levels in each of the four families. The clinical manifestations of hereditary PC deficiency exhibit considerable diversity.

Large Polarization Near 50 µC/cm2 in a Single Unit Cell Layer SrTiO3.

The generally nonpolar SrTiO3 has attracted more attention recently because of its possibly induced novel polar states and related paraelectric-ferroelectric phase transitions. By using controlled pulsed laser deposition, high-quality, ultrathin, and strained SrTiO3 layers were obtained. Here, transmission electron microscopy and theoretical simulations have unveiled highly polar states in SrTiO3 films even down to one unit cell at room temperature, which were stabilized in the PbTiO3/SrTiO3/PbTiO3 sandwich structures by in-plane tensile strain and interfacial coupling, as evidenced by large tetragonality (∼1.05), notable polar ion displacement (0.019 nm), and thus ultrahigh spontaneous polarization (up to ∼50 µC/cm2). These values are nearly comparable to those of the strong ferroelectrics as the PbZrxTi1-xO3 family. Our findings provide an effective and practical approach for integrating large strain states into oxide films and inducing polarization in nonpolar materials, which may broaden the functionality of nonpolar oxides and pave the way for the discovery of new electronic materials.

Plasma metabolomics identifies S-adenosylmethionine as a biomarker and potential therapeutic target for vascular aging in older adult males.

Brachial-ankle pulse wave velocity (baPWV) is a noninvasive index of vascular aging. However, the metabolic profile underlying vascular aging has not yet been fully elucidated. The current study aimed to identify circulating markers of vascular aging as assessed by baPWV and to elucidate its mechanism from a metabolomic perspective in older adults. A total of 60 and 61 Chinese male participants aged ≥80 years were recruited to the metabolome and validation cohorts, respectively. The baPWV of participants was measured using an automatic waveform analyzer. Plasma metabolic profile was investigated using ultra-performance liquid chromatography coupled with triple quadrupole linear ion trap tandem mass spectrometry. Orthogonal partial least squares (OPLS) regression modeling established the association between metabolic profile and baPWV to determine important metabolites predictive of vascular aging. Additionally, an enzyme-linked immunosorbent assay was employed to validate the metabolites in plasma and culture media of vascular smooth muscle cells in vitro. OPLS modeling identified 14 and 22 metabolites inversely and positively associated with baPWV, respectively. These 36 biomarkers were significantly enriched in seven metabolite sets, especially in cysteine and methionine metabolism (p <0.05). Notably, among metabolites involved in cysteine and methionine metabolism, S-adenosylmethionine (SAM) level was inversely related to baPWV, with a significant correlation coefficient in the OPLS model (p <0.05). Furthermore, the relationship between SAM and vascular aging was reconfirmed in an independent cohort and at the cellular level in vitro. SAM was independently associated with baPWV after adjustments for clinical covariates (ß = -0.448, p <0.001) in the validation cohort. In summary, plasma metabolomics identified an inverse correlation between SAM and baPWV in older males. SAM has the potential to be a novel biomarker and therapeutic target for vascular aging.

Association of Psychosocial Factors with Activation Among Patients with Glaucoma.

OBJECTIVE: To investigate the association of psychosocial factors with health self-management behaviors and beliefs among patients with primary open-angle glaucoma (POAG). DESIGN: Prospective cross-sectional cohort study. PARTICIPANTS: Patients (n = 202) with mild, moderate, or advanced bilateral POAG. METHODS: Patients (N = 1164) were identified from electronic medical records at a single academic medical center. Letters soliciting participation were mailed to 591 randomly selected potential participants. Psychometric measures and a social determinants of health questionnaire were administered by phone to 202 study participants. MAIN OUTCOME MEASURES: The National Eye Institute Visual Function Questionnaire-8 (NEI-VFQ), the Multidimensional Health Locus of Control (MHLC), the Perceived Medical Condition Self-Management Scale-4, the Patient Health Questionnaire-9 (PHQ), the Patient Activation Measure-13 (PAM), a health literacy question, and a social determinants of health questionnaire. RESULTS: For each increase in level of POAG severity, there was a decrease in mean NEI-VFQ score (P < 0.001). For each unit increase in NEI-VFQ item 1, self-rated vision, mean PAM score increased (R2 = 5.3%; P = 0.001; 95% confidence interval [CI], 0.077-0.276). For each unit increase in "Internal" on the MHLC, mean PAM score increased (R2 = 19.3%; 95% CI, 0.649-1.166; P < 0.001). For each unit increase in "Doctors" on the MHLC, mean PAM score increased (R2 = 11.0%; 95% CI, 1.555-3.606; P < 0.001). For each unit increase in "Chance" on the MHLC, mean PAM score decreased (R2 = 2.6%; 95% CI, -0.664 to -0.051; P = 0.023). On multivariate analysis, adjusting for age, sex and race, for each unit increase in PHQ, mean PAM score decreased (95% CI, 0.061-1.35; P = 0.032); for each unit increase in MHLC "Doctors", mean PAM score increased (95% CI, -1.448 to 3.453; P < 0.001); for each unit increase in MHLC "Internal", mean PAM score increased (95% CI, 0.639-1.137; P < 0.001); for each unit increase in MHLC "Chance", mean PAM score decreased (95% CI, -0.685 to -0.098; P = 0.009). CONCLUSIONS: We identified modifiable behavioral factors that could increase patients' self-perceived ability and confidence to manage their own eye care. Locus of control (MHLC), level of depression (PHQ), and self-rated functional vision (NEI-VFQ) were each associated with patient behaviors, attitudes, and beliefs needed for health self-management (activation, assessed by the PAM) and may be important determinants of adherence behaviors. Targeting change in patients' care beliefs and behaviors may improve activation and treatment outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

An assessment system for clinical and biological interpretability in ulcerative colitis.

Ulcerative colitis (UC) is a serious inflammatory bowel disease (IBD) with high morbidity and mortality worldwide. As the traditional diagnostic techniques have various limitations in the practice and diagnosis of early ulcerative colitis, it is necessary to develop new diagnostic models from molecular biology to supplement the existing methods. In this study, we developed a machine learning-based synthesis to construct an artificial intelligence diagnostic model for ulcerative colitis, and the correctness of the model is verified using an external independent dataset. According to the significantly expressed genes related to the occurrence of UC in the model, an unsupervised quantitative ulcerative colitis related score (UCRScore) based on principal coordinate analysis was established. The UCRScore is not only highly generalizable across UC bulk cohorts at different stages, but also highly generalizable across single-cell datasets, with the same effect in terms of cell numbers, activation pathways and mechanisms. As an important role of screening genes in disease occurrence, based on connectivity map analysis, 5 potential targeting molecular compounds were identified, which can be used as an additional supplement to the therapeutic of UC. Overall, this study provides a potential tool for differential diagnosis and assessment of bio-pathological changes in UC at the macroscopic level, providing an opportunity to optimize the diagnosis and treatment of UC.

Cluster of Differentiation-44-Targeting Prussian Blue Nanoparticles Onloaded with Colchicine for Atherosclerotic Plaque Regression in a Mice Model.

Atherosclerosis management heavily relies on the suppression of the inflammatory response of macrophages. Colchicine's potent anti-inflammatory properties make it a promising candidate for secondary prevention against cardiovascular disease. However, its high toxicity and numerous adverse effects limit its clinical use. To address this, there is an urgent need for specific drug delivery systems to boost the level of accumulation of colchicine within atherosclerotic plaques. In this study, the cluster of differentiation-44 receptor was verified to be overexpressed in inflammatory macrophages within plaques both in vitro and in vivo. Subsequently, a Prussian blue-based nanomedical loading system with hyaluronic acid (HA) coating was constructed, and its effects were observed on the atherosclerosis regression. Colchicine and Cy5.5 were encapsulated within Prussian blue nanoparticles through self-assembly, followed by conjugation with hyaluronic acid to create col@PBNP@HA. The formulated col@PBNP@HA displayed a cubic shape and scattered distribution. Importantly, col@PBNP@HA demonstrated specific cellular uptake into lipopolysaccharide-stimulated macrophages. In vitro experiments showed that col@PBNP@HA more effectively inhibited expression of inflammatory factors and scavenged reactive oxygen species compared with the control group, which were treated with colchicine. Furthermore, col@PBNP@HA exhibited its specific and higher accumulation in aortic plaque analysis via fluorescence imaging of aortas. After 4 weeks, administration of col@PBNP@HA resulted in significant atherosclerosis regression in the mice model, with therapeutic effects superior to those of free colchicine. Similar to colchicine, col@PBNP@HA inhibited the secretion of inflammation factors and scavenged ROS through the regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa-B (NF-κB) and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) signaling pathway. In summary, col@PBNP@HA demonstrated specific targeting ability to inflammatory plaques and exerted beneficial effects on atherosclerosis regression through TLR4/Myd88/NF-κB and PGC-1α modulation.

A biomimetic orthogonal flow sensor based on an asymmetric optical fiber sensory structure for marine sensing.

With increasing attention on the world's oceans, a significant amount of research has been focused on the sensing of marine-related parameters in recent years. In this paper, a bioinspired flow sensor with corrosion resistance, anti-interference capability, a portable design structure, easy integration, and directional sensing ability is presented to realize flow speed sensing in open water. The sensor is realized by a flexible artificial cupula that seals one side of an optical fiber acting as an artificial kinocilium. Below the artificial kinocilium, an encapsulated s-tapered optical fiber mimics the fish neuromast sensory mechanism and is supported by a 3D-printed structure that acts as the artificial supporting cell. To characterize the sensor, the optical transmission spectra of the sensory fiber under a set of water flow velocities and four orthogonal directions were monitored. The sensor's peak intensity responses were found to demonstrate flow sensing ability for velocity and direction, proving that this biomimetic portable sensing structure is a promising candidate for flow sensing in marine environments.

Autologous transplantation of P63+ lung progenitor cells for chronic obstructive pulmonary disease therapy.

Adult lung resident stem/progenitor cells, including P63+ progenitor cells, have demonstrated the capacity for regeneration of lung epithelium in preclinical models. Here, we report a clinical trial of intrapulmonary P63+ progenitor cell transplantation in 28 participants with stage II to IV chronic obstructive pulmonary disease (COPD). Autologous P63+ progenitor cells were isolated from the airway basal layer of participants in the intervention group via bronchoscopic brushing, cultured for 3 to 5 weeks, and then transplanted back into the lungs via bronchoscopy at 0.7 × 106 to 5.2 × 106 cells per kilogram of body weight. Twenty patients were evaluable at the end of the study (intervention group, n = 17; control group, n = 3). No grade 3 to 5 adverse events (AEs) or serious AEs occurred. Although bronchoscopy-associated AEs were recorded in participants in the intervention group, other AEs were not substantial different between groups. Twenty-four weeks after transplantation, participants in the intervention group displayed improvement in gas transfer capacity [diffusing capacity of the lung for carbon monoxide (DLCO) change from baseline: +18.2%], whereas the control group experienced a decrease (DLCO change from baseline: -17.4%; P = 0.008). Furthermore, participants in the intervention group showed >30-meter increase in walking distance within 6 minutes. Transcriptomic analysis of progenitor cells isolated from responding and nonresponding individuals in the intervention group showed that higher expression of P63 was associated with treatment efficacy. In conclusion, transplantation of cultured P63+ lung progenitor cells was safe and might represent a potential therapeutic strategy for COPD.

Relationship between bullous pemphigoid and malignancy: A Mendelian randomization study.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease, which primarily affects the elderly. However, the relationship between BP and malignancy remains controversial in traditional observational studies. The aim of this study, which included only European populations, was to assess the potential causative link between BP and 13 types of malignant tumors in a two-sample Mendelian randomization (MR) study. BP was not associated with an increased risk of developing 13 types of malignant tumors. This study did not find a causal relationship between BP and malignant tumors. However, further research is warranted to examine the generalizability of this conclusion in non-European populations.

Pharmacological inhibition of MYC to mitigate chemoresistance in preclinical models of squamous cell carcinoma.

Rationale: Cisplatin-based chemotherapy is the first-line treatment for late-stage head and neck squamous cell carcinoma (HNSCC). However, resistance to cisplatin has become a major obstacle for effective therapy. Cancer stem cells (CSCs) are critical for tumor initiation, growth, metastasis, and chemoresistance. How to effectively eliminate CSCs and overcome chemoresistance remains a key challenge. Herein, we confirmed that MYC plays critical roles in chemoresistance, and explored targeting MYC to overcome cisplatin resistance in preclinical models. Methods: The roles of MYC in HNSCC cisplatin resistance and cancer stemness were tested in vitro and in vivo. The combined therapeutic efficiency of MYC targeting using the small molecule MYC inhibitor MYCi975 and cisplatin was assessed in a 4­nitroquinoline 1-oxide-induced model and in a patient-derived xenograft model. Results: MYC was highly-expressed in cisplatin-resistant HNSCC. Targeting MYC using MYCi975 eliminated CSCs, prevented metastasis, and overcame cisplatin resistance. MYCi975 also induced tumor cell-intrinsic immune responses, and promoted CD8+ T cell infiltration. Mechanistically, MYCi975 induced the DNA damage response and activated the cGAS-STING-IRF3 signaling pathway to increase CD8+ T cell-recruiting chemokines. Conclusions: Our findings suggested that targeting MYC might eliminate CSCs, prevent metastasis, and activate antitumor immunity to overcome cisplatin resistance in HNSCC.

Potential Interaction between WNT16 and Vitamin D on Bone Qualities in Adolescent Idiopathic Scoliosis Patients and Healthy Controls.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that is associated with low bone mineral density (BMD). Vitamin D (Vit-D) supplementation has been suggested to improve BMD in AIS, and its outcomes may be related to genetic factors. The present study aimed to (a) investigate the synergistic effect between a low BMD-related gene (wingless-related integration site 16, WNT16) and two important Vit-D pathway genes (Vit-D receptor, VDR, and Vit-D binding protein, VDBP) on serum Vit-D and bone qualities in Chinese AIS patients and healthy adolescents, and (b) to further investigate the effect of ablating Wnt16 on the cortical bone quality and whether diets with different dosages of Vit-D would further influence bone quality during the rapid growth phase in mice in the absence of Wnt16. A total of 519 girls (318 AIS vs. 201 controls) were recruited, and three selected single-nucleotide polymorphisms (SNPs) (WNT16 rs3801387, VDBP rs2282679, and VDR rs2228570) were genotyped. The serum 25(OH)Vit-D level was significantly associated with VDBP rs2282679 alleles (OR = -4.844; 95% CI, -7.521 to -2.167, p < 0.001). Significant multi-locus models were identified by generalized multifactor dimensionality reduction (GMDR) analyses on the serum 25(OH)Vit-D level (p = 0.006) and trabecular area (p = 0.044). In the gene-edited animal study, Wnt16 global knockout (KO) and wildtype (WT) male mice were provided with different Vit-D diets (control chow (1000 IU/Kg) vs. Vit-D-deficient chow (Nil in Vit-D) vs. high-dose Vit-D chow (20,000 IU/Kg)) from 4 weeks to 10 weeks old. Wnt16 global KO mice had significantly lower serum 25(OH)Vit-D levels and higher liver Vdbp mRNA expression levels than WT mice. In addition, Wnt16 global KO mice showed a decrease in bone density, cortical thickness and cortical area compared with WT mice. Interestingly, high-dose Vit-D chow led to lower bone density, cortical thickness, and cortical area in WT mice, which were less obvious in Wnt16 global KO mice. In conclusion, WNT16 may regulate the serum 25(OH)Vit-D level and bone qualities, which might be associated with VDBP expression. Further investigations with a larger sample size and wider spectrum of scoliosis severity are required to validate our findings regarding the interaction between WNT16 and Vit-D status in patients with AIS.

Replacing cholesterol with asiatic acid to prolong circulation and enhance anti-metastatic effects of non-PEGylated liposomes.

Cholesterol is an indispensable component of most liposomes, heavily influencing their physical and surface properties. In this study, cholesterol in non-PEGylated liposomes was replaced by its analog, asiatic acid (AA), to generate liposomes with an alternative composition. These AA liposomes are generally smaller and more rigid than conventional liposomes, circulate longer in the body, and accumulate more in primary tumors and lung metastases in vivo. On the other hand, as an active ingredient, AA can decrease TGF-ß secretion to inhibit the epithelial-mesenchymal transition (EMT) process, increase the sensitivity of tumor cells to doxorubicin (DOX), and synergize with DOX to enhance the immune response, thus improving their antitumor and anti-metastasis efficiency. Based on this rationale, DOX-loaded AA liposomes were fabricated and tested against triple-negative breast cancer (TNBC). Results showed that compared with conventional liposomes, the DOX-AALip provided approximately 28.4% higher tumor volume reduction with almost no metastatic nodules in the mouse model. Our data demonstrate that AA liposomes are safe, simple, and efficient, and thus in many situations may be used instead of conventional liposomes, having good potential for further clinical translational development.

GSDMD and GSDME synergy in the transition of acute kidney injury to chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Acute kidney injury (AKI) could progress to chronic kidney disease (CKD) and the AKI-CKD transition has major clinical significance. A growing body of evidence has unveiled the role of pyroptosis in kidney injury. We postulate that GSDMD and GSDME exert cumulative effects on the AKI-CKD transition by modulating different cellular responses. METHODS: We established an AKI-CKD transition model induced by folic acid in wildtype (WT), Gsdmd-/-, Gsdme-/-, and Gsdmd-/-Gsdme-/- mice. Tubular injury, renal fibrosis and inflammatory responses were evaluated. In vitro studies were conducted to investigate the interplay among tubular cells, neutrophils, and macrophages. RESULTS: Double deletion of Gsdmd and Gsdme conferred heightened protection against AKI, mitigating inflammatory responses, including the formation of neutrophil extracellular traps (NETs), macrophage polarization and differentiation, and ultimately renal fibrosis, compared with wildtype mice and mice with single deletion of either Gsdmd or Gsdme. Gsdme, but not Gsdmd deficiency, shielded tubular cells from pyroptosis. GSDME-dependent tubular cell death stimulated NETs formation and prompted macrophage polarization towards a pro-inflammatory phenotype. Gsdmd deficiency suppressed NETs formation and subsequently hindered NETs-induced macrophage-to-myofibroblast transition (MMT). CONCLUSION: GSDMD and GSDME collaborate to contribute to AKI and subsequent renal fibrosis induced by folic acid. Synchronous inhibition of GSDMD and GSDME could be an innovative therapeutic strategy for mitigating the AKI-CKD transition.

Protein corona, influence on drug delivery system and its improvement strategy: A review.

Nano drug delivery systems offer several benefits, including enhancing drug solubility, regulating drug release, prolonging drug circulation time, and minimized toxicity and side effects. However, upon entering the bloodstream, nanoparticles (NPs) encounter a complex biological environment and get absorbed by various biological components, primarily proteins, leading to the formation of a 'Protein Corona'. The formation of the protein corona is affected by the characteristics of NPs, the physiological environment, and experimental design, which in turn affects of the immunotoxicity, specific recognition, cell uptake, and drug release of NPs. To improve the abundance of a specific protein on NPs, researchers have explored pre-coating, modifying, or wrapping NPs with the cell membrane to reduce protein adsorption. This paper, we have reviewed studies of the protein corona in recent years, summarized the formation and detection methods of the protein corona, the effect of the protein corona composition on the fate of NPs, and the design of new drug delivery systems based on the optimization of protein corona to provide a reference for further study of the protein corona and a theoretical basis for the clinical transformation of NPs.