Platelet-Mimicking Nanosponges for Functional Reversal of Antiplatelet Agents.

BACKGROUND: During long-term antiplatelet agents (APAs) administration, patients with thrombotic diseases take a fairly high risk of life-threatening bleeding, especially when in need of urgent surgery. Rapid functional reversal of APAs remains an issue yet to be efficiently resolved by far due to the lack of any specific reversal agent in the clinic, which greatly restricts the use of APAs. METHODS: Flow cytometry analysis was first applied to assess the dose-dependent reversal activity of platelet-mimicking perfluorocarbon-based nanosponges (PLT-PFCs) toward ticagrelor. The tail bleeding time of mice treated with APAs followed by PLT-PFCs was recorded at different time points, along with corresponding pharmacokinetic analysis of ticagrelor and tirofiban. A hemorrhagic transformation model was established in experimental stroke mice with thrombolytic/antiplatelet therapy. Magnetic resonance imaging was subsequently applied to observe hemorrhage and thrombosis in vivo. Further evaluation of the spontaneous clot formation activity of PLT-PFCs was achieved by clot retraction assay in vitro. RESULTS: PLT-PFCs potently reversed the antiplatelet effect of APAs by competitively binding with APAs. PLT-PFCs showed high binding affinity comparable to fresh platelets in vitro with first-line APAs, ticagrelor and tirofiban, and efficiently reversed their function in both tail bleeding and postischemic-reperfusion models. Moreover, the deficiency of platelet intrinsic thrombotic activity diminished the risk of thrombogenesis. CONCLUSIONS: This study demonstrated the safety and effectiveness of platelet-mimicking nanosponges in ameliorating the bleeding risk of different APAs, which offers a promising strategy for the management of bleeding complications induced by antiplatelet therapy.

Application of robot navigation system for insertion of femoral neck system in the treatment of femoral neck fracture.

PURPOSE: To evaluate the short-term clinical efficacy and advantages of surgery robot positioning system for insertion of Femoral Neck System (FNS) in the treatment of femoral neck fractures. METHODS: The clinical data of 52 patients with Femoral neck fracture (FNF) who had been treated with FNS between June 2020 and September 2021 were retrospectively analyzed. Among them, 26 patients were treated with traditional FNS (control group), while 26 additional patients were treated with FNS assisted by an orthopaedic robot positioning system (study group). The operation duration, frequency of key-guide needle placement, intraoperative blood loss, incision length, fracture healing rate, fracture healing time, and the Harris scores at the last follow-up were calculated and compared between the 2 groups. RESULTS: The study group had shorter operation duration, fewer numbers of placing the key-guide needle, less intraoperative blood loss, and smaller surgical incisions than the control group (all, P < 0.05). There was no significant difference in the rate of fracture healing rate between the 2 groups (P = 0.47), while the fracture healing duration of the study group was shorter than that of the control group (P = 0.03). At the last follow-up, compared with the control group, the Harris score and the number of excellent and good ratings were significantly higher in the study group (all, P < 0.05). CONCLUSIONS: Using orthopaedic surgery robot positioning system-assisted FNS in the treatment of FNFs can effectively improve the efficiency of surgery, shorten operation time, and reduce the number of placing the key-guide needle, intraoperative blood loss, and operative trauma. Simultaneously, it shortens the duration of fracture healing and improves the recovery of hip function.

Acromioclavicular joint dislocation with loop double endobutton fixation assisted by orthopaedic surgery robot positioning system.

OBJECTIVE: Acute acromioclavicular (AC) joint dislocation is a common orthopedic injury that can significantly impair shoulder function and reduce quality of life. Effective treatment methods are essential to restore function and alleviate pain. To investigate the short-term clinical efficacy of the minimally invasive closed-loop double endobutton fixation assisted by orthopaedic surgery robot positioning system (TiRobot) in the treatment of AC joint dislocation, and to evaluate its feasibility and safety. METHODS: The clinical data of 19 patients with AC joint dislocation who underwent treatment with closed-loop double Endobutton fixation assisted by TiRobot between May 2020 and December 2022 were retrospectively analyzed. Visual Analog Scale (VAS) pain scores, the Constant Murley Score (CMS), and shoulder abduction range of motion were assessed and compared preoperatively and at the last follow-up. Computed tomography (CT) parameters of the acromioclavicular joint, including acromioclavicular distance (ACD), the distance between the upper and lower Endobutton (DED), the horizontal distance between the anterior edge of the distal clavicle and the anterior edge of the acromion (DACC), the diameter of the clavicular tunnel (DCT), and coracoid tunnel diameter (DC), were compared at 2 days, and 1 month after surgery, as well as at the last follow-up, along with the evaluation of intraoperative and postoperative complications. RESULTS: The postoperative VAS, CMS, and shoulder-abduction range of motion were significantly improved compared with the preoperative (all, P<0.05). The statistical analysis showed no significant difference in the CT image parameters of the acromioclavicular joint at 2 days and 1 month after surgery(all, P>0.05). Comparisons of DCT and DC revealed statistically significant differences between the last follow-up and 1 month after surgery (P<0.05), and no statistically significant difference was found in ACD, DED, and DACC(all, P>0.05). There were no complications such as infection or vascular or neurological damage, no cases of rostral or clavicle fractures, loss of reduction, heterotopic ossification, shoulder stiffness, and no loosening or breaking of internal fixations. CONCLUSION: Closed-loop double endobutton internal fixation assisted by TiRobot is an ideal method for the treatment of acute acromioclavicular (AC) joint dislocation. This method has the advantages of relatively simple operation, more accurate localization of bone tunnel during operation, less surgical trauma, and good recovery of shoulder function.

Luminescence and Mechanism of Mn2+ Substitution in Cs7Cd3Br13 with Two Types of Coordination Number.

Cadmium-based perovskite materials as promising optoelectronic materials have been widely explored, but there are still some special microscopic interaction-dependent properties not fully understood. Here, we successfully synthesized Cs7(Cd1-XMnX)3Br13 crystal by a simple hydrothermal method. In Cs7Cd3Br13 crystals with their intrinsic self-trapped exciton (STE) emission, Cd2+ ions stay in both different coordination sites, and partial replacement of Cd2+ with Mn2+ can modify their luminescence properties significantly. The luminescence peak position of the doped sample was adjusted from 610 nm in the undoped sample to 577 nm in the doped one by the combination of STE and Mn d-d transition, with enhanced photoluminescence quantum yield (PLQY) of ∼50% at a Mn precursor ratio of 40%. Their magnetic responses occur from the coexisting ferromagnetic (FM) and antiferromagnetic (AFM) coupling of Mn pairs in four and six coordination sites, modifying its whole emission profile. This material is valuable for studying the structure-optical properties and finding applications in optoelectronic devices.

Hounsfield units predicts the occurrence but not the patterns of proximal humerus fracture in the elderly patients.

BACKGROUND: Increased incidence of fragility fractures of the proximal humerus has been reported. Proximal humerus Hounsfield unit (HU) measurements based on computed tomography (CT) scans of the shoulder can be used to evaluate bone mineral density (BMD). It is unknown whether HU values can predict the risk of proximal humerus osteoporotic fracture and /or fracture patterns. Therefore, the objectives of this study were to identify whether the HU value is associated with proximal humeral osteoporotic fracture risk, and whether or not it has an impact on the complexity of the fracture. METHODS: We identified 60 + years old patients' CT scans between 2019 and 2021 according to the inclusion and exclusion criteria. All patients were divided into two groups based on the presence or lack of a fracture in the proximal humerus, meanwhile, patients with fractures were stratified into simple and comminuted fractures based on the Neer classification. HU values were calculated within the proximal humerus and compared between groups using the Student t-test, and receiver operating characteristic (ROC) curve analysis was used to determine the ability of HU values to predict fracture. RESULTS: A total of 138 patients with proximal humerus fracture (PHF) including 62 simple PHFs and 76 complex PHFs and 138 non-fracture patients were enrolled in the study. The HU values decreased as age increased among all patients. Both male and female patients with PHF had significantly lower HU values compared with non-fracture patients, the area under the curve (AUC) of the ROC curve for males and females was 0.8 and 0.723 respectively. Nevertheless, no significant differences were found between simple and complex fractures of the proximal humerus in the HU values. CONCLUSION: Decreasing HU values on CT may be an early warning sign of fracture potential, however, it was not a predictive factor for comminuted fracture of the proximal humerus.

Quantitative fragmented QRS has a good diagnostic value on myocardial fibrosis in hypertrophic obstructive cardiomyopathy based on clinical-pathological study.

BACKGROUND: To investigate the relationship between fragmented QRS (fQRS) quantified by a new method and myocardial fibrosis (MF) and the diagnostic value of quantitative fQRS (Q-fQRS) to detect MF in hypertrophic obstructive cardiomyopathy (HOCM) patients based on histological validation. METHODS: We performed a retrospective study that included 69 patients with HOCM who underwent ventricular septal surgery. Nine individuals who died from accidents were studied as a control reference for the histological parameters. Septal myocardium samples were subjected to Masson's trichrome staining to quantify the collagen volume fraction (CVF). An fQRS pattern was defined as the presence of additional R waves or RSR', evidenced by notched R or S wave on electrocardiography (ECG). The Q-fQRS was quantified as the total amount of deflections in the QRS complex in all 12 routine ECG leads together. Cardiac magnetic resonance imaging was conducted, and late gadolinium enhancement (LGE) was measured at 2, 4, 6 and 8 standard deviations (SDs). RESULTS: Of the 69 patients, fQRS was documented in 38 (55.1%) patients, the mean number of leads with fQRS was 3.7 ± 1.6, and the mean Q-fQRS was 17 ± 7.2. Compared with HOCM patients without fQRS, HOCM patients with fQRS had a higher CVF and more LGE at 6 SD (P < 0.001; P = 0.040). Q-fQRS was correlated with CVF (r = 0.640, P < 0.001), and Q-fQRS showed the best correlation with LGE measured at 8 SD (r = 0.379, P = 0.002). Multivariate regression analyses revealed that Q-fQRS was independently associated with the extent of CVF in HOCM patients after adjusting for age, sex, body surface area and the extent of LGE at 6 SD (P < 0.001). When the patients were divided into subgroups with normal CVF or high CVF according to the CVF in controls, Q-fQRS and LGE at 6SD showed similar diagnostic value in detecting patients with high CVF, with sensitivities of 66.7% vs 68.6%, specificities of 76.7% vs 72.4%, and accuracies of 71% vs 70.3%. CONCLUSIONS: HOCM patients with fQRS showed more extensive MF. Q-fQRS was an independent predictor for MF and had a good diagnostic value, with a sensitivity of 66.7% and specificity of 76.7%, in identifying patients with higher fibrotic burden.

Elevated lymphatic vessel density measured by Lyve-1 expression in areas of replacement fibrosis in the ventricular septum of patients with hypertrophic obstructive cardiomyopathy (HOCM).

Lymphatic microvessel density (LMVD) contributes to fibrosis in patients with myocardial infarction. However, the role of LMVD in the process of myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) patients is unclear. We studied LMVD in ventricular septal (VS) samples from 52 individuals (42 was HOCM patients who underwent a transaortic extended septal myectomy, and 10 traffic accident victims), and examined the relationships between the LMVD stained immunohistochemically with lymphatic vessel endothelial hyaluronan receptor (LYVE-1) antibodies, collagen volume fraction (CVF), and clinical characteristics. Compared with traffic accident victims, LMVD was significantly increased in VS of HOCM patients (132.0 ± 49.0 VS 57.8 ± 48.8/mm2, p = 0.000). HOCM patients with syncope had higher level of LMVD than without syncope [166.7 (131.0-201.1) VS 116.4 (80.7-152.1)/mm2, p = 0.017], and LMVD were positively correlated with Log (CVF) (r = 0.431, p = 0.004). On multiple variables regression analysis, LMVD was independently associated with Log (CVF) (r = 0.379, p = 0.009) and syncope (r = 0.335, p = 0.020). In conclusions, the LYVE-1-positive lymphatics have close associations with VS fibrosis in HOCM patients.

Optimal sequence of surgical procedures for hemodynamically unstable patients with pelvic fracture: A network meta-analysis.

BACKGROUND: The mortality rate of patients with hemodynamic instability due to severe pelvic fracture remains substantial and massive transfusion happens frequently. Angio-embolization, external fixation and preperitoneal pelvic packing of the pelvis are the main managements used to control bleeding in these patients. In this paper, we aimed at characterizing the rationale of these surgical managements, and placed them in optimal management algorithm to compose a new guideline. METHODS: We selected controlled trials, assessing safety of management for the intervention of hemorrhagic shock from mortality data, and assessing efficacy from volume of first 24 h blood transfusion following hospitalization. Six single and combined managements were extracted as comparison. A pairwise meta-analysis was conducted using a random effect model, and then the analysis was extended to a network meta-analysis. Pooled effect sizes were ranked and demonstrated the probability of being the best treatments for safety and efficacy. RESULTS: 13 clinical trials and 24,396 participants were identified for this analysis. The assessment of rank probability indicated that pelvic packing presented the greatest likelihood of improving safety, while external fixation was indicated most efficient among the interventions for controlling hemorrhage. CONCLUSIONS: Clinical protocols for guidelines of hemodynamically unstable pelvic fracture patients have been multidirectionally developed. We strongly support the initial application of an external fixator. Provided that patients remain hemodynamically unstable after application of an external fixation, pelvic packing is the next procedure to consider. Angio-embolization is the complementary but not alternative method of choice subsequently.

Microvascular Rarefaction and Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is a myocardial disease characterized by fibrosis and microvascular ischemia. Microvessels play a critical role in myocardial fibrosis in HOCM. However, it remains unclear whether or not myocardial fibrosis is associated with microvascular density (MVD) changes. OBJECTIVE: The aim of the present study was to investigate whether a reduction in MVD is related to myocardial fibrosis in HOCM cardiac samples. METHODS: We analyzed MVD and fibrosis in myectomy left ventricular (LV) septal wall specimens from 53 HOCM patients. Control myocardium from the LV septal wall was collected at autopsy of 9 individuals who died of noncardiac causes. RESULTS: The fibrosis ratio (% area) in HOCM was higher and the MVD was lower than that in control subjects (i.e., 12.7 ± 10.0 vs. 4.0 ± 1.4%, p = 0.012, and 480.9 ± 206.7 vs. 1,425 ± 221/mm2, p < 0.001). Patients with mild fibrosis had a higher MVD than patients with moderate fibrosis (i.e., 568.2 ± 214.8 vs. 403.2 ± 167.8/mm2, p = 0.006) and patients with severe fibrosis (i.e., 568.2 ± 214.8 vs. 378.6 ± 154.0/mm2, p = 0.024). Furthermore, a significant negative correlation was found between myocardial fibrosis and MVD in HOCM patients (r = -0.40, p = 0.003), which was also found in mild fibrosis (r = -0.40, p = 0.043), moderate fibrosis (r = -0.50, p = 0.024), and severe fibrosis (r = -0.24, p = 0.61), although no significant differences were observed in severe fibrosis. Additionally, we demonstrated that late gadolinium enhancement was negatively correlated with MVD (r = -0.37, p = 0.03) and positively correlated with fibrosis (r = 0.44, p = 0.01). CONCLUSION: HOCM patients had a higher myocardial fibrosis ratio and a lower MVD. The severity of myocardial fibrosis was negatively correlated with MVD in HOCM. These findings showed that a reduced MVD may contribute to myocardial fibrosis in HOCM.

Left ventricular remodeling in hypertrophic cardiomyopathy patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common complication in hypertrophic cardiomyopathy (HCM). The mechanisms of AF is associated with left atrial (LA) structural remodeling in HCM patients. However, the impact of left ventricular (LV) remodeling on the presence of AF in HCM patients has not been evaluated yet. We sought to investigate effect of LV remodeling on the presence of AF assessed by cardiovascular magnetic resonance (CMR) in HCM patients. METHODS: A total of 394 HCM patients were enrolled into this study, including HOCM patients (n = 293) and NOHCM patients (n = 101). Patients were divided into HCM with AF (50) and HCM without AF (n = 344). Data were collected from hospital records. RESULTS: LA diameter and LV remodeling index (LVRI) were significantly higher in HCM patients with AF than that of HCM patients without AF (46.6 ± 7.4 mm versus 39.9 ± 8.0 mm, p < 0.001, and 1.46 ± 0.6 versus 1.2 ± 0.4, p = 0.002, respectively). HCM patients with AF were older than HCM patients without AF (53.6 ± 11.7 years versus 47.7 ± 13.6 years, p = 0.002). Additionally, LVRI positively correlated to LA size (r = 0.12, p = 0.02). In a multivariable logistic regression analysis, when adjusting for age and LV end diastolic mass index, LVRI and LA size remained an independent determinant of AF in HCM patients (OR = 4.7, p = 0.001 and OR = 1.13, P < 0.001). CONCLUSION: HCM patients with AF showed significantly more LA diameter, LVRI and age than HCM patients without AF. LVRI and LA size were strong independent predictor of AF in HCM, suggesting LV remodeling may contribute to the occurrence of AF in HCM patients.

Polyethylene-glycol-coated gold nanoparticles improve cardiac function after myocardial infarction in mice.

Gold nanoparticles (AuNPs) are widely used for drug delivery because of their unique biological properties, such as their safety and ability to prolong drug action. Some studies have demonstrated that AuNPs accumulate in the heart, especially during pathological processes. Therefore, it is very important to understand the effect of AuNPs on the heart. Myocardial infarction (MI) is a major cause of morbidity and mortality; however, the effect of AuNPs on MI remains unclear. In the present study, we carried out a comprehensive evaluation of AuNPs on acute MI. The results showed that AuNPs accumulated in infarcted hearts, decreased infarction size, improved systolic function, and inhibited cardiac fibrosis and TNF-α accumulation. Our work indicated that AuNPs have cardioprotective effects and can be used in drug delivery systems for the treatment of cardiac diseases.

Vascular Endothelial Cells Activate Peripheral Natural Killer T Cells and Participate in Regulation of Downstream Immune Cascades in Patients with Sepsis.

BACKGROUND This study investigated the effect of supernatant of endothelial cells stimulated by peripheral blood serum from sepsis patients on phenotype and function of peripheral NKT cells. MATERIAL AND METHODS Twenty-one patients with sepsis and 21 healthy subjects were included. Peripheral blood (5 ml) was collected from all patients and healthy subjects. To isolate peripheral blood mononuclear cells (PBMCs), Ficoll lymphocyte separation solution was used. Flow cytometry was carried out to determine NKT cell ratio, activity, and cytokine secretion. Human umbilical vein endothelial cells were cultured with serum from sepsis patients for 48 h before changing to fresh medium, and supernatant was collected. The supernatant was used to co-culture PBMCs before analyzing NKT activity and cytokines. RESULTS The ratios of CD3-CD56+NK cells and CD3+CD56+NKT cells were increased in peripheral blood from sepsis patients. Surface receptors p30, G2D, and p44 of CD3+CD56+NKT cells were elevated, while inhibitory receptors NKG2A and 158b were decreased. CD4+ NKT cells in peripheral blood from sepsis patients were enhanced. GranB, IFN-γ, IL-4, and IL-17 in NKT cells from sepsis patients were up-regulated. After co-culture with vascular endothelial cells treated with sepsis serum, expression of p30 and G2D in NKT cells was upregulated, and number of TCRVa24-positive cells was increased. In addition, ratio of CD4+NKT cells was increased, and intracellular expression of IL-4 and IFN-γ was elevated. CONCLUSIONS The study demonstrates that the level of NKT cells in peripheral blood from sepsis patients is increased, and their activity is enhanced. In addition, vascular endothelial cells from sepsis patients can regulate the activity of NKT cells.

Gender-related differences in ß-adrenergic receptor-mediated cardiac remodeling.

Cardiac remodeling is the pathological basis of various cardiovascular diseases. In this study, we found gender-related differences in ß-adrenergic receptor (AR)-mediated pathological cardiac remodeling. Cardiac remodeling model was established by subcutaneous injection of isoprenaline (ISO) for 14 days. Heart rate (HR), mean arterial pressure (MAP), and echocardiography were obtained on 7th and 14th days during ISO administration. Myocardial cross-sectional area and the ratio of heart mass to tibia length (HM/TL) were detected to assess cardiac hypertrophy. Picro-Sirius red staining (picric acid + Sirius red F3B) was used to evaluate cardiac fibrosis. Myocardial capillary density was assessed by immunohistochemistry for von Willebrand factor. Further, real-time PCR was used to measure the expression of ß1-AR and ß2-AR. Results showed that ISO induced cardiac remodeling, the extent of which was different between female and male mice. The extent of increase in cardiac wall thickness, myocardial cross-sectional area, and collagen deposition in females was less than that in males. However, no gender-related difference was observed in HR, MAP, cardiac function, and myocardial capillary density. The distinctive decrease of ß2-AR expression, rather than a decrease of ß1-AR expression, seemed to result in gender-related differences in cardiac remodeling.

Prevalence of Balantidium coli infection in sows in Hunan province, subtropical China.

Balantidium coli is a cosmopolitan parasitic-opportunistic pathogen that can be found throughout the world. However, little information is available about prevalence of B. coli in pigs in China. In the present study, the prevalence of B. coli in pigs was investigated in Hunan province, subtropical China, between January 2012 and August 2014. A total of 3925 diarrheic fecal samples from nine representative administrative regions in Hunan province, subtropical China, were examined for the presence of B. coli cysts and/or trophozoites using microscopy after sedimentation with water. The overall prevalence of B. coli in pigs was 36.9 % (1450/3925). The present survey revealed high circulation of B. coli in pigs in Hunan province, subtropical China, which poses potential threats to human health. The results of the present investigation have important implications for the control of B. coli infections in pigs in Hunan province, subtropical China. To our knowledge, this is the first comprehensive report of B. coli prevalence in sows in Hunan province, subtropical China.

Danshensu inhibits ß-adrenergic receptors-mediated cardiac fibrosis by ROS/p38 MAPK axis.

Danshensu, the effective ingredient of the plant Salvia miltiorrhiza (Danshen), has been widely used for treatment of cardiovascular diseases. Cardiac fibrosis is an important process in pathological cardiac remodeling and leads to heart failure. We investigated the effect of Danshensu on ß-adrenergic receptor (ß-AR)-mediated cardiac fibrosis and the involved signaling transduction. Danshensu inhibited cardiofibroblast proliferation and collagen I synthesis induced by isoproterenol (ISO), a selective ß-AR agonist. Phosphorylation of p38 mitogen-activated protein kinase (MAPK), which mediates ISO-induced cardiac fibrosis, was negatively regulated in this process. The negative regulation depended on the ISO inhibition of reactive oxygen species (ROS) production. Taken together, Danshensu may inhibit ß-AR-mediated cardiac fibrosis by negative regulation of ROS-p38 MAPK signaling.

Sb3+-Doped Indium-Based Metal Halide (Gua)3InCl6 with Efficient Yellow Emission.

In recent years, low-dimensional organic-inorganic hybrid metal halides (OIHMHs) have shown excellent photophysical properties due to their quantum structure, adjustable energy levels, and energy transfer between inorganic and organic components, which have attracted extensive attention from researchers. Herein, we synthesize a zero-dimensional (0D) OIHMH, Sb3+:(Gua)3InCl6, by introducing Sb3+ into (Gua)3InCl6, which undergoes a significant enhancement of the emission peak at 580 nm with the photoluminescence quantum yield (PLQY) boosted from 17.86 to 95.72% when excited at 340 nm. This boost in photoluminescence of the doped sample was studied by combining ultrafast femtosecond transient absorption, temperature-dependent photoluminescence (PL) spectra, and density functional theory (DFT) calculation, revealing the process of self-trapped exciton (STE) recombination to emit light at both Sb and In sites in this 0D structure simultaneously. This material with the lowest dark STE level at the In site for emission in the undoped sample can amazingly yield very strong emission in the doped sample, which has never been observed before. Finally, we tested its application in a photoelectric device. This work not only helps to gain a deeper understanding of the formation of STEs in In-based halides but also plays a certain guiding role in the design of new luminescent materials.

Taxifolin Inhibits the Growth of Non-Small-Cell Lung Cancer via Downregulating Genes Displaying Novel and Robust Associations with Immune Evasion Factors.

Using an LL2 cell-based syngeneic mouse LC model, taxifolin suppressed allografts along with the appearance of 578 differentially expressed genes (DEGs). These DEGs were associated with enhancement of processes related to the extracellular matrix and lymphocyte chemotaxis as well as the reduction in pathways relevant to cell proliferation. From these DEGs, we formulated 12-gene (TxflSig) and 7-gene (TxflSig1) panels; both predicted response to ICB (immune checkpoint blockade) therapy more effectively in non-small-cell lung cancer (NSCLC) than numerous well-established ICB biomarkers, including PD-L1. In both panels, the mouse counterparts of ITGAL, ITGAX, and TMEM119 genes were downregulated by taxifolin. They were strongly associated with immune suppression in LC, evidenced by their robust correlations with the major immunosuppressive cell types (MDSC, Treg, and macrophage) and multiple immune checkpoints in NSCLC and across multiple human cancer types. ITGAL, ITGAX, and IIT (ITGAL-ITGAX-TMEM119) effectively predicted NSCLC's response to ICB therapy; IIT stratified the mortality risk of NSCLC. The stromal expressions of ITGAL and ITGAX, together with tumor expression of TMEM119 in NSCLC, were demonstrated. Collectively, we report multiple novel ICB biomarkers-TxflSig, TxflSig1, IIT, ITGAL, and ITGAX-and taxifolin-derived attenuation of immunosuppressive activities in NSCLC, suggesting the inclusion of taxifolin in ICB therapies for NSCLC.

Nickel(II)-Doped Lead-Free Halide Crystals Exhibiting Highly Efficient Tunable Blue-Emitting out of Antiferromagnetic Ni-Ni Coupling.

Metal halide crystals are widely used in optoelectronic fields due to their excellent optical properties. The hunt for a lead-free halide semiconductor with superior optical performance is a particularly fascinating topic in order to avoid the toxicity of lead. Here, we incorporate Ni2+ into a series of halide nanocrystals (NCs) through solution-phase synthesis. By modifying the A-site and varying the halide compositions, we successfully achieved significant tunability of the blue emission of the Ni2+-doped AX (A = K+, Rb+, NH2CH = NH2+ (FA), CH3NH3+ (MA); X = Br, I) NCs, ranging from 375 to 490 nm, due to the antiferromagnetic polaron (AMP), which is in contrast with the excitonic magnetic polarons (EMP) from those with ferromagnetic (FM) coupling between transition metal ions in similar compounds. This work shows that Ni2+-doped halide crystals could become a typical example providing AMP excitation as the optional emission centers for use in light emitting devices.

Taxifolin Inhibits Breast Cancer Growth by Facilitating CD8+ T Cell Infiltration and Inducing a Novel Set of Genes including Potential Tumor Suppressor Genes in 1q21.3.

Taxifolin inhibits breast cancer (BC) via novel mechanisms. In a syngeneic mouse BC model, taxifolin suppressed 4T-1 cell-derived allografts. RNA-seq of 4T-1 tumors identified 36 differentially expressed genes (DEGs) upregulated by taxifolin. Among their human homologues, 19, 7, and 2 genes were downregulated in BCs, high-proliferative BCs, and BCs with high-fatality risks, respectively. Three genes were established as tumor suppressors and eight were novel to BC, including HNRN, KPRP, CRCT1, and FLG2. These four genes exhibit tumor suppressive actions and reside in 1q21.3, a locus amplified in 70% recurrent BCs, revealing a unique vulnerability of primary and recurrent BCs with 1q21.3 amplification with respect to taxifolin. Furthermore, the 36 DEGs formed a multiple gene panel (DEG36) that effectively stratified the fatality risk in luminal, HER2+, and triple-negative (TN) equivalent BCs in two large cohorts: the METABRIC and TCGA datasets. 4T-1 cells model human TNBC cells. The DEG36 most robustly predicted the poor prognosis of TNBCs and associated it with the infiltration of CD8+ T, NK, macrophages, and Th2 cells. Of note, taxifolin increased the CD8+ T cell content in 4T-1 tumors. The DEG36 is a novel and effective prognostic biomarker of BCs, particularly TNBCs, and can be used to assess the BC-associated immunosuppressive microenvironment.