Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial).

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Poor pretransplantation minimal residual disease clearance as an independent prognostic risk factor for survival in myelodysplastic syndrome with excess blasts: A multicenter, retrospective cohort study.

BACKGROUND: Minimal residual disease (MRD) is an important prognostic factor for survival in adults with acute leukemia. The role of pretransplantation MRD status in myelodysplastic syndrome with excess blasts (MDS-EB) is unknown. This study retrospectively analyzed the relationship between pretransplantation MRD status and long-term survival. MATERIALS AND METHODS: Patients with MDS-EB who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from March 5, 2005, to November 8, 2020, were included. The relationship between pretransplantation MRD status and long-term survival was analyzed using univariate and multivariate logistic regression models. RESULTS: Of 220 patients with MDS-EB who underwent allo-HSCT, 198 were eligible for inclusion in this multicenter, retrospective cohort study. Complete remission was attained in 121 (61.1%) patients, and 103 patients underwent detection of MRD pretransplantation, with 67 patients being MRD-positive and 36 patients being MRD-negative. The median follow-up time was 16 months, the median age was 41 years (6-65 years), and 58% of the patients were men. The 3-year disease-free survival (DFS) and overall survival (OS) probabilities for all patients were 70.1% and 72.9%, respectively. For patients in complete remission, the 3-year DFS and OS probabilities were 72.2% and 74.8%, respectively. Further analysis found that the 3-year DFS rates of MRD-negative and MRD-positive patients were 85.6% and 66.5% (p = .045), respectively, whereas the 3-year OS rates were 91.3% and 66.4% (p = .035), respectively. Univariate and multivariate analyses showed that poor pretransplantation MRD clearance was an independent prognostic risk factor for DFS and OS. CONCLUSION: Poor pretransplantation MRD clearance is an independent prognostic risk factor for long-term survival after allo-HSCT for patients with MDS-EB. PLAIN LANGUAGE SUMMARY: Poor minimal residual disease clearance pretransplanation is an independent prognostic risk factor for long-term survival after allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome with excess blasts.

OsBAK2/OsSERK2 expression is repressed by OsBZR1 to modulate brassinosteroid response and grain length in rice.

Brassinosteroids (BRs) are a class of polyhydroxylated steroidal phytohormones that are essential for plant growth and development. Rice BRASSINOSTEROID-INSENSITIVE1 (BRI1)-ASSOCIATED RECEPTOR KINASES (OsBAKs) are plasma membrane-localized receptor kinases belonging to the subfamily of leucine-rich repeat receptor kinases. It has been found that in Arabidopsis, BRs induce the formation of a BRI1-BAK1 heterodimer complex and transmit the cascade signal to BRASSINAZOLE RESISTANT1/bri1-EMS-SUPPRESSOR1 (BZR1/BES1) to regulate BR signaling. Here, in rice (Oryza sativa ssp. japonica), we found that OsBZR1 binds directly to the promoter of OsBAK2, but not OsBAK1, and represses the expression of OsBAK2 to form a BR feedback inhibition loop. Additionally, the phosphorylation of OsBZR1 by OsGSK3 reduced its binding to the OsBAK2 promoter. The osbak2 mutant displays a typical BR-deficiency phenotype and negative modulates the accumulation of OsBZR1. Interestingly, the grain length of the osbak2 mutant was increased whereas in the cr-osbak2/cr-osbzr1 double mutant, the reduced grain length of the cr-osbzr1 mutant was restored, implying that the increased grain length of osbak2 may be due to the rice somatic embryogenesis receptor kinase-dependent pathway. Our study reveals a novel mechanism by which OsBAK2 and OsBZR1 engage in a negative feedback loop to maintain rice BR homeostasis, facilitating a deeper understanding of the BR signaling network and grain length regulation in rice.

Predicative factors and development of a nomogram for postoperative delayed neurocognitive recovery in elderly patients with gastric cancer.

BACKGROUND: Delayed neurocognitive recovery (DNR) is a common complication after radical gastrectomy and closely associated with poor outcomes. This study aimed to investigate predictors and develop a nomogram prediction model for DNR. METHODS: Elderly gastric cancer (GC) patients (≥ 65 years) undergoing elective laparoscopic radical gastrectomy between 2018 and 2022 were prospectively included in this study. DNR was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V, 2013). Independent risk factors for DNR were screened by the multivariate logistic regression analysis. Based on these factors, the nomogram model was established and validated by R. RESULTS: A total of 312 elderly GC patients were enrolled in the training set, with an incidence of DNR within postoperative 1 month of 23.4% (73/312). Multivariate logistic regression analysis indicated that age (OR: 1.207, 95%CI: 1.113-1.309, P < 0.001), nutritional risk screening 2002 (NRS2002) score (OR: 1.716, 95%CI: 1.211-2.433, P = 0.002), neutrophil-to-lymphocyte ratio (NLR) (OR: 1.976, 95%CI: 1.099-3.552, P = 0.023), albumin-to-fibrinogen ratio (AFR) (OR: 0.774, 95%CI: 0.620-0.966, P = 0.024), and prognostic nutritional index (PNI) (OR: 0.768, 95%CI: 0.706-0.835, P < 0.001) were five independent factors for DNR in elderly GC patients. The constructed nomogram model based on these five factors has a good predictive value for DNR with an area under the curve (AUC) of 0.863. CONCLUSIONS: In conclusions, the established nomogram model based on age, NRS-2002, NLR, AFR, and PNI has a well predictive value for postoperative DNR in elderly GC patients.

Performance evaluation of rural water environment governance based on AHP: a case study of the Beitang River Basin.

Rural water environment governance in China still lacks a systematic and comprehensive assessment protocol to help analyze and improve such governance performance. The Analytic Hierarchy Process (AHP) method was employed in this study to build a governance assessment system that integrates ecological conditions, water pollution control, and public satisfaction. To cover these topics, the assessment system is composed of an indicator layer that is customized to rural water environment governance in China. The Beitang River, located in the rural region of Hangzhou, Zhejiang, China, was presented as a case study. Field investigation provided raw data for this assessment. A questionnaire survey was conducted to interview local residents on the governance performance. An additional survey with executives who played major roles in the governance was performed to reconstruct a water environment assessment on the Beitang River prior to the governance, in order to highlight the effects of the governance through contrast. The results showed consistency in the questionnaire survey and the assessment system. The AHP assessment system was able to reflect the improvement in the water quality, river ecology, and residential welfare after the governance, and suggested limits and future directions in the following upgrade programs for the river basin.

[Effects of Xihuang Pills on proliferation and apoptosis of prostate cancer LNCaP cells based on AR/m TOR signaling pathway].

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.

[Xihuang Pills and its main components inhibit PI3K/Akt/mTOR signaling pathways and promote the apoptosis of prostate cancer cells in PC-3 tumor-bearing mice].

OBJECTIVE: To evaluate the effects of Xihuang Pills (XHP) and its main components on PI3K, AKT and mTOR signaling pathways and cell apoptosis of castration-resistant human PCa PC-3 cell subcutaneously transplanted tumors in nude mice. METHODS: We assigned 36 PC-3 tumor-bearing model mice to six groups of equal numbers to be treated with XHP, musk, calculus bovis (CB), musk + CB and docetaxel, respectively. After 14 days of intervention, we calculated the tumor-inhibition rate in different groups, observed the morphology of the tumor cells by HE staining, determined the levels of PI3K, Akt and mTOR mRNA by RT-qPCR, and determined the expressions of PI3K, Akt and mTOR signaling pathways and caspase-3 and caspase-9 proteins by Western blot. RESULTS: After 14 days of medication, the tumor-inhibition rates in the XHP, musk, CB, musk + CB and docetaxel groups were 29.67%, 5.52%, 7.26%, 12.88% and 6.26%, respectively. HE staining showed the formation of apoptotic bodies in the tumor tissues after intervention, especially in the XHP and musk + CB groups. The mRNA and phosphorylated protein expressions of PI3K, Akt and mTOR were significantly down-regulated (P < 0.01), and so were the expressions of caspase-3 and caspase-9 proteins in the XHP and musk + CB groups in comparison with the control (P < 0.01). CONCLUSIONS: Xihuang Pills, musk and calculus bovis can inhibit the growth of castration-resistant human PCa PC-3 cell subcutaneously transplanted tumors, which is associated with their effects of suppressing the abnormally activated PI3K, Akt and mTOR signaling pathways and promoting the apoptosis of PCa PC3 cells.

Immune recovery after in vivo T-cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta-thalassemia children.

BACKGROUND: The clinical outcome of hematopoietic stem cell transplantation (HSCT) in those with severe beta-thalassemia (ß-TM) is closely related to post-transplantation immune reconstitution (IR). However, the data on the IR in these settings are scarce. METHODS: A prospective analysis of the clinical outcome and IR in 47 children with severe ß-TM who underwent in vivo T-cell depletion myeloablative conditioning and matched sibling donor HSCT was performed. Immune reconstitution, including immune cell subset counts, as well as the generation of new T and B cells assays after HSCT, was measured. RESULTS: In the first year after HSCT, bacterial infections and cytomegalovirus (CMV) reactivation were observed in 70.2% and 36.2% of the patients, respectively. In the same period, poor CD4+ T-cell recovery was observed. The B cells recovered within 6 months. Natural killer (NK) cells recovered as early as 1 month, but their function was defective. Cord blood and bone marrow (CB + BM) group had slower T-cell recovery, and higher B cells and NK cells in comparison with peripheral blood and bone marrow (PB + BM) group. CONCLUSIONS: The high incidence of infection within 1 year after in vivo T-cell depletion myeloablative conditioning HSCT in severe ß-TM was consistent with poor IR.

In vitro and in vivo metabolic profiles of fasiglifam using ultrahigh-performance liquid chromatography combined with Q-Exactive Orbitrap tandem mass spectrometry.

RATIONALE: Fasiglifam is an orally available and selective partial agonist of hGPR40 receptor, which was unexpectedly terminated at phase III clinical trials due to its severe hepatotoxicity. To fully understand the mechanism of action of fasiglifam, it is necessary to investigate its in vitro and in vivo metabolic profiles. METHODS: For in vitro metabolism, fasiglifam was incubated with rat or human liver microsomes in the presence of ß-nicotinamide adenine dinucleotide phosphate tetrasodium salt, glutathione (GSH) and uridine diphosphate glucuronic acid trisodium salt for 60 min. For in vivo metabolism, fasiglifam was orally administered to rats at a single dose of 20 mg/kg and the bile was collected. In vitro and in vivo samples were analyzed by the developed ultrahigh-performance liquid chromatography combined with Q-Exactive Orbitrap tandem mass spectrometry. The structures of metabolites were proposed according to their accurate masses and fragment ions. RESULTS: A total of eight metabolites, including an acyl-GSH adduct, were detected and identified. M1 (acylglucuronide) and M5 (carboxylic acid derivative) were the major metabolites of fasiglifam. Metabolic pathways of fasiglifam involved oxygenation, oxidative dealkylation, dehydrogenation, glucuronidation and GSH conjugation. Fasiglifam may undergo metabolic bioactivation via acylglucuronide. CONCLUSIONS: Oxidative dealkylation and glucuronidation were the predominant metabolic pathways of fasiglifam in vitro and in vivo. Metabolic bioactivation via acylglucuronide may be the perpetrator of its hepatotoxicity. Our findings would be helpful in understanding the disposition of fasiglifam as well as its hepatotoxicity.

Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study.

Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10mg/kg/day. Mean actual dose±SD over 1year was 14.70±5.48mg/kg/day. At week 52, mean LIC±SD decreased significantly from 15.13±10.72mg Fe/g dw at baseline to 8.46±6.25mg Fe/g dw (absolute change from baseline, -6.68±7.02mg Fe/g dw [95% CI: -7.91, -5.45]; P<0.0001). Most common drug-related adverse events were gastrointestinal: abdominal discomfort, diarrhoea and nausea (n=6 each). There was one death (pneumonia, not considered drug related). With significant and clinically relevant reductions in iron burden alongside a safety profile similar to that in THALASSA, these data support earlier escalation with higher deferasirox doses in iron-overloaded non-transfusion-dependent anaemia patients.

Anion Effects on Lanthanide(III) Tetrazole-1-acetate Dinuclear Complexes Showing Slow Magnetic Relaxation and Photofluorescent Emission.

Three types of lanthanide complexes based on the tetrazole-1-acetic acid ligand and the 2,2'-bipyridine coligand were prepared and characterized by single-crystal X-ray diffraction, IR spectroscopy, and elemental analyses; the formulas of these complexes are [Ln2(1-tza)4(NO3)2(2,2'-bipy)2] (Ln = Sm (1), Eu (2), Gd (3), Tb (4), Dy (5)), [Dy2(1-tza)4Cl2(2,2'-bipy)2] (6), and [Yb2(1-tza)4(NO3)2(2,2'-bipy)2] (7) (1-tza = tetrazole-1-acetate and 2,2'-bipy = 2,2'-bipyridine). They are dinuclear complexes possessing similar structures but different lanthanide(III) ion coordination geometries because of the distinction of peripheral anions (such as NO3(-) and Cl(-)) and the effect of lanthanide contraction. The variable-temperature magnetic susceptibilities of 1-6 were measured. Both Dy(III) complexes (5 and 6) display field-induced single-molecule magnet behaviors. Ab initio calculations revealed that the Dy(III) complex 6 possesses a more anisotropic Dy(III) ion in comparison to that in 5. The room-temperature photoluminescence spectra of Sm(III) (1), Eu(III) (2), Tb(III) (4), and Dy(III) (5 and 6) complexes exhibit strong characteristic emissions in the visible region, whereas the Yb(III) (7) complex shows near-infrared (NIR) luminescence.

Plastic Crystals with Polar Halochromate Anion: Thermosensitive Dielectrics Based upon Plastic Transition and Dipole Rotation.

Plastic crystals functioning with rotatable components offer new opportunities in areas such as modern optoelectronic materials. Here, by taking advantage of controllable rotation of the polar component within the ion-pair plastic-crystal system, we present two such crystals, namely, (Et4N)(CrO3X) (X = Cl or Br), which are unusual examples exhibiting two-staged thermosensitive dielectric responses above room temperature. The frequency-dependent response in the first stage is due to the structural phase transitions, whereas that in the second stage is induced by dynamic rotation of the polar halochromate anions in their NaCl-type plastic-crystal phases. The intrinsic mechanisms were also explicated by molecular dynamics simulations, providing a direct insight into the dynamic characteristics of these two compounds. These studies show that ionic plastic crystals functioning with polar groups are an attractive candidate as sensitive thermoresponsive dielectric materials.

Favorable prognosis of biallelic CEBPA gene mutations in acute myeloid leukemia patients: a meta-analysis.

OBJECTIVES: Increasing number of studies suggested that biallelic CEBPA (bi CEBPA) mutations were associated with favorable prognosis in patients with acute myeloid leukemia (AML), but the results remain inconclusive. We therefore present a meta-analysis to evaluate the prognostic value of bi CEBPA mutations in patients with AML. METHODS: A comprehensive literature search was undertaken through August 2014 looking for eligible studies. Pooled hazard ratios (HRs) estimates and 95% confidence intervals (95% CIs) in overall survival (OS) and event-free survival (EFS) were used to calculate estimated effect. RESULTS: Ten studies covering a total of 6219 subjects were included in this analysis. Overall, bi CEBPA mutations were associated with favorable clinical outcome in patients with AML (HR for EFS: 0.41, 95% CI: 0.32-0.52; for OS: 0.37, 95% CI: 0.27-0.50), in cytogenetically normal (CN)-AML (HR for EFS: 0.38, 95% CI: 0.29-0.49; for OS: 0.32, 95% CI: 0.23-0.43). When took the cohort of monoallelic CEBPA (mo CEBPA) mutated and wild-type CEBPA (wt CEBPA) AML as a reference group, bi CEBPA mutated AML also shown beneficial outcomes (HR for OS: 0.52, 95% CI: 0.37-0.72). No significant difference was found between mo CEBPA mutation and wt CEBPA in patients with AML or CN-AML (P > 0.05). CONCLUSION: Bi CEBPA mutations in patients with AML are strongly associated with a favorable prognosis, which suggested that bi CEBPA mutations would potentially serve as a novel prognostic marker in AML.

Sustained improvements in myocardial T2* over 2 years in severely iron-overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine.

Long-term controlled studies are needed to inform on the clinical benefit of chelation therapy for myocardial iron removal in transfusion-dependent beta thalassemia patients. In a 1-year nonrandomized extension to the CORDELIA study, data collected from patients with myocardial siderosis provided additional information on deferasirox or deferoxamine (DFO) efficacy and safety. Myocardial (m)T2* increased from baseline 11.6 to 15.9 ms in patients receiving deferasirox for 24 months (n = 74; geometric mean [Gmean ] ratio of month 24/baseline 1.38 [95% confidence interval 1.28, 1.49]) and from 10.8 to 14.2 ms in those receiving DFO (n = 29; Gmean ratio 1.33 [1.13, 1.55]; P = 0.93 between groups). Improved mT2* with deferasirox was evident across all subgroups evaluated irrespective of baseline myocardial (mT2* < 10 vs. ≥ 10 ms) or liver (LIC <15 vs. ≥15 mg Fe/g dw) iron burden. Mean LVEF was stable and remained within normal limits with deferasirox or DFO. Liver iron concentration decreased from high baseline values of 30.6 ± 18.0 to 14.4 ± 16.6 mg Fe/g dw at month 24 in deferasirox patients and from 36.8 ± 15.6 to 11.0 ± 12.1 mg Fe/g dw in DFO patients. The long-term safety profile of deferasirox or DFO was consistent with previous reports; serious drug-related AEs were reported in 6.8% of deferasirox and 6.9% of DFO patients. Continued treatment of severely iron-overloaded beta thalassemia patients with deferasirox or DFO led to sustained improvements in myocardial iron irrespective of high or low baseline myocardial or liver iron burden, in parallel with substantial improvements in liver iron (Clinicaltrials.gov identifier: NCT00600938).

Epithelial-to-mesenchymal transition is involved in BCNU resistance in human glioma cells.

Chemotherapy has been considered as an effective treatment for malignant glioma; however, it becomes increasingly ineffective with tumor progression. Epithelial-to-mesenchymal transition (EMT) is a process whereby cells acquire morphologic and molecular alterations that facilitate tumor metastasis and progression. Emerging evidence associates chemoresistance with the acquisition of EMT in cancer. However, it is not clear whether this phenomenon is involved in glioma. We used the previously established human glioma cell lines SWOZ1, SWOZ2 and SWOZ2-BCNU to assess cellular morphology, molecular changes, migration and invasion. We found that BCNU-resistant cells showed multiple drug resistance and phenotypic changes consistent with EMT, including spindle-shaped morphology and enhanced pseudopodia formation. Decreased expression of the epithelial adhesion molecule E-cadherin and increased expression of the mesenchymal marker vimentin were observed in BCNU-resistant SWOZ1 and SWOZ2-BCNU cells compared to SWOZ2 cells. Migratory and metastatic potentials were markedly enhanced in SWOZ1 and SWOZ2-BCNU cells compared to SWOZ2 cells. These data suggest that there is a possible link between drug resistance and EMT induction in glioma cells. Gaining further insight into the mechanisms underlying chemoresistance and EMT may enable the restoration of chemosensitivity or suppression of metastasis.

[Effective endmembers based bilinear unmixing model].

An effective endmembers based bilinear unmixing algorithm is prompted in the present paper together with an end-member subset selection algorithm as well. Firstly, the endmembers are ranked according to their distance to the mixed pixel, involving the Euclidean distance and spectral angle. And then, an effective subset of the endmembers is abstracted considering both the ranking result and the change of error. The algorithm reduces the influence of endmembers which are not component of the mixed pixel, decrease the number of endmembers involved in unmixing and improve the accuracy of abundance. The test results for simulation image prove that the algorithm would provide a lower reconstructing error. And the analysis results of actual airborne hyperspectral oil spill image further illustrate its effectiveness.

Optimizing a five-factor cocktail to prepare reparative macrophages for wound healing.

The treatment of non-healing wounds, such as diabetic ulcers, remains a critical clinical challenge. Recent breakthroughs in cell therapy have shown great promise, with one primary focus on preparing cells with comprehensive reparative functions and foreseeable safety. In our previous study, we recapitulated the pro-regenerative and immunosuppressive functions of tumor-associated macrophages (TAMs) in non-tumor-derived macrophages, endowing the latter with characteristics for promoting diabetic wound healing - termed TAMs-educated macrophages (TAMEMs). To eliminate the use of tumor-derived sources and devise a more controllable method to prepare TAMEM-like cells, in this study, we identify a cocktail comprising five recombinant proteins as an essential condition to induce non-polarized macrophages (termed TAMEMs5) into therapeutic cells with pro-healing functions. The screened five factors are osteopontin (OPN), macrophage inflammatory protein (MIP)-2, chemokine (C-C motif) ligand 8 (CCL8), vascular endothelial growth factor (VEGF)-B, and macrophage colony-stimulating factor (M-CSF). We demonstrate the rationale for screening these factors and the phenotype of TAMEMs5 prepared from murine bone marrow-derived macrophages, which exhibit angiogenic and immunomodulatory effects in vitro. Then, we induce primary human monocytes from periphery blood into TAMEMs5, which show pro-healing effects in a human primary cell-based ex vivo model (T-SkinTM). Our study demonstrates a simple, effective, and controllable approach to induce primary macrophages to possess repairing activities, which may provide insights for developing cell-based therapeutics for non-healing wounds clinically.

Factors influencing recurrence and model development for recurrence of minimally invasive percutaneous transhepatic lithotripsy: a single-center retrospective study.

OBJECTIVE: To identify factors influencing recurrence after percutaneous transhepatic choledochoscopic lithotripsy (PTCSL) and to develop a predictive model. METHODS: We retrospectively analyzed clinical data from 354 patients with intrahepatic and extrahepatic bile duct stones treated with PTCSL at Qinzhou First People's Hospital between February 2018 and January 2020. Patients were followed for three years and categorized into non-recurrence and recurrence groups based on postoperative outcome. Univariate analysis identified possible predictors of stone recurrence. Data were split using the gradient boosting machine (GBM) algorithm, assigning 70% as the training set and 30% as the test set. The predictive performance of the GBM model was assessed using the receiver operating characteristic (ROC) curve and calibration curve, and compared with a logistic regression model. RESULTS: Six factors were identified as significant predictors of recurrence: age, diabetes, total bilirubin, biliary stricture, number of stones, and stone diameter. The GBM model, developed based on these factors, showed high predictive accuracy. The area under the ROC curve (AUC) was 0.763 (95% CI: 0.695-0.830) for the training set and 0.709 (95% CI: 0.596-0.822) for the test set. Optimal cutoff values were 0.286 and 0.264, with sensitivities of 62.30% and 66.70%, and specificities of 77.20% and 68.50%, respectively. Calibration curves indicated good agreement between predicted probabilities and observed recurrence rates in both sets. DeLong's test revealed no significant differences between the GBM and logistic regression models in predictive performance (training set: D = 0.003, P = 0.997 > 0.05; test set: D = 0.075, P = 0.940 > 0.05). CONCLUSION: Biliary stricture, stone diameter, diabetes, stone number, age, and total bilirubin significantly influence stone recurrence after PTCSL. The GBM model, based on these factors, demonstrates robust accuracy and discrimination. Both GBM and logistic regression models effectively predicted stone recurrence post-PTCSL.

Chemical Constituents and Pharmacological Properties of Frankincense: Implications for Anticancer Therapy.

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.