Successful use of Palbociclib combined with Venetoclax and Azacitidine in an adult with refractory/relapsed therapy-related acute myeloid leukemia.

BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) is considered high risk as it related to prior exposure to cytotoxic chemotherapy agents for solid tumors or hematologic malignancies. Compared with de novo AML, t-AML is associated with lower remission rates, inferior overall survival (OS) and higher relapse rates. Many efforts have been devoted to improving the overall but with limited success, and novel strategy is thus highly needed. CASE DESCRIPTION: We reported one patient with refractory/relapsed t-AML was successfully treated with Palbociclib combined with Venetoclax and Azacytidine (AZA). In this case, a 47-year-old patient with t-AML recurred during Venetoclax in combination with AZA therapy. However, the patient achieved morphological, immunophenotypic and molecular complete remission again after Palbociclib combined with Venetoclax and AZA. CONCLUSIONS: Although only one successful case is presented here, three-drug combination regimens should be considered as another treatment option for t-AML in the future.

Prediction of Treatment Effect of SLE-ITP Patients Based on Cost-Sensitive Neural Network and Variational Autoencoder.

OBJECTIVE: The aim of the study was to examine the factors influencing the therapeutic effect of patients with systemic lupus erythematosus combined with immune thrombocytopenia (SLE-ITP) and develop a prediction model to predict the therapeutic effect of SLE-ITP. METHODS: Three hundred twenty-four SLE-ITP patients were retrieved from the electronic health record database of SLE patients in Jiangsu Province according to the latest treatment response criteria for ITP. We adopted the Cox model based on the least absolute shrinkage and selection operator to explore the impact factors affecting patient therapeutic effect, and we developed neural network model to predict therapeutic effect, and in prediction model, cost-sensitivity was introduced to address data category imbalance, and variational autoencoder was used to achieve data augmentation. The performance of each model was evaluated by accuracy and the area under the receiver operator curve. RESULTS: The results showed that B-lymphocyte count, H-cholesterol level, complement-3 level, anticardiolipin antibody, and so on could be used as predictors of SLE-ITP curative effect, and abnormal levels of alanine transaminase, immunoglobulin A, and apolipoprotein B predicted adverse treatment response. The neural network treatment effect prediction model based on cost-sensitivity and variational autoencoder was better than the traditional classifiers, with an overall accuracy rate closed to 0.9 and a specificity of more than 0.9, which was useful for clinical practice to identify patients at risk of ineffective treatment response and to achieve better individualized management. CONCLUSIONS: By predicting the curative effect of SLE-ITP, the severity of patients can be determined, and then the best treatment strategy can be planned to avoid ineffective treatment.

Promoting C-F bond activation via proton donor for CF4 decomposition.

Tetrafluoromethane (CF4), the simplest perfluorocarbons, is a permanently potent greenhouse gas due to its powerful infrared radiation adsorption capacity. The highly symmetric and robust C-F bond structure makes its activation a great challenge. Herein, we presented an innovated approach that efficiently activates C-F bond utilizing protonated sulfate (-HSO4) modified Al2O3@ZrO2 (S-Al2O3@ZrO2) catalyst, resulting in highly efficient CF4 decomposition. By combining in situ infrared spectroscopy tests and density function theory simulations, we demonstrate that the introduced -HSO4 proton donor has a stronger interaction on the C-F bond than the hydroxyl (-OH) proton donor, which can effectively stretch the C-F bond for its activation. Consequently, the obtained S-Al2O3@ZrO2 catalyst achieved a stable 100% CF4 decomposition at a record low temperature of 580 °C with a turnover frequency value of ~8.3 times higher than the Al2O3@ZrO2 catalyst without -HSO4 modification, outperforming the previously reported results. This work paves a new way for achieving efficient C-F bond activation to decompose CF4 at a low temperature.

Ultrahighly Alkali-Tolerant NOx Reduction over Self-Adaptive CePO4/FePO4 Catalysts.

Catalyst deactivation caused by alkali metal poisoning has long been a key bottleneck in the application of selective catalytic reduction of NOx with NH3 (NH3-SCR), limiting the service life of the catalyst and increasing the cost of environmental protection. Despite great efforts, continuous accumulation of alkali metal deposition makes the resistance capacity of 2 wt % K2O difficult to enhance via merely loading acid sites on the surface, resulting in rapid deactivation and frequent replacement of the NH3-SCR catalyst. To further improve the resistance of alkali metals, encapsulating alkali metals into the bulk phase could be a promising strategy. The bottleneck of 2 wt % K2O tolerance has been solved by virtue of ultrahigh potassium storage capacity in the amorphous FePO4 bulk phase. Amorphous FePO4 as a support of the NH3-SCR catalyst exhibited a self-adaptive alkali-tolerance mechanism, where potassium ions spontaneously migrated into the bulk phase of amorphous FePO4 and were anchored by PO43- with the generation of Fe2O3 at the NH3-SCR reaction temperature. This ingenious potassium storage mechanism could boost the K2O resistance capacity to 6 wt % while maintaining approximately 81% NOx conversion. Besides, amorphous FePO4 also exhibited excellent resistance to individual and coexistence of alkali (K2O and Na2O), alkali earth (CaO), and heavy metals (PbO and CdO), providing long durability for CePO4/FePO4 catalysts in flue gas with multipollutants. The cheap and accessible amorphous FePO4 paves the way for the development and implementation of poisoning-resistant NOx abatement.

Deep-penetration functionalized cuttlefish ink nanoparticles for combating wound infections with synergetic photothermal-immunologic therapy.

The challenge of wound infections post-surgery and open trauma caused by multidrug-resistant bacteria poses a constant threat to clinical treatment. As a promising antimicrobial treatment, photothermal therapy can effectively resolve the problem of drug resistance in conventional antibiotic antimicrobial therapy. Here, we report a deep-penetration functionalized cuttlefish ink nanoparticle (CINP) for photothermal and immunological therapy of wound infections. CINP is decorated with zwitterionic polymer (ZP, namely sulfobetaine methacrylate-methacrylate copolymer) to form CINP@ZP nanoparticles. Natural CINP is found to not only exhibit photothermal destruction of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), but also trigger macrophages-related innate immunity and enhance their antibacterial functions. The ZP coating on the surface of CINP enables nanoparticles to penetrate into deeply infected wound environment. In addition, CINP@ZP is further integrated into the thermosensitive Pluronic F127 gel (CINP@ZP-F127). After in situ spraying gel, CINP@ZP-F127 is also documented notable antibacterial effects in mice wound models infected with MRSA and E. coli. Collectively, this approach combining of photothermal therapy with immunotherapy can promote delivery efficiency of nanoparticles to the deep foci of infective wounds, and effectively eliminate wound infections.

Revealing the Dynamic Behavior of Active Sites on Acid-Functionalized CeO2 Catalysts for NOx Reduction.

Unraveling the dynamics of the active sites upon CeO2-based catalysts in selective catalytic reduction of nitrogen oxides by ammonia (NH3-SCR) is challenging. In this work, we prepared tungsten-acidified and sulfated CeO2 catalysts and used operando spectroscopy to reveal the dynamics of acid sites and redox sites on catalysts during NH3-SCR reaction. We found that both Lewis and Brønsted acid sites are needed to participate in the catalytic reaction. Notably, Brønsted acid sites are the main active sites after a tungsten-acidified or sulfated treatment, and the change of Brønsted acid sites significantly affects the NOx removal. Moreover, acid functionalization promotes the cerium species cycle between Ce4+ and Ce3+ for the NOx reduction. This work is critical to deeply understanding the natural properties of active sites, and it also provides new insights into the mechanism for NH3-SCR over CeO2-based catalysts.

Atomically Local Electric Field Induced Interface Water Reorientation for Alkaline Hydrogen Evolution Reaction.

The slow water dissociation process in alkaline electrolyte severely limits the kinetics of HER. The orientation of H2 O is well known to affect the dissociation process, but H2 O orientation is hard to control because of its random distribution. Herein, an atomically asymmetric local electric field was designed by IrRu dizygotic single-atom sites (IrRu DSACs) to tune the H2 O adsorption configuration and orientation, thus optimizing its dissociation process. The electric field intensity of IrRu DSACs is over 4.00×1010  N/C. The ab initio molecular dynamics simulations combined with in situ Raman spectroscopy analysis on the adsorption behavior of H2 O show that the M-H bond length (M=active site) is shortened at the interface due to the strong local electric field gradient and the optimized water orientation promotes the dissociation process of interfacial water. This work provides a new way to explore the role of single atomic sites in alkaline hydrogen evolution reaction.

Development and Verify of Survival Analysis Models for Chinese Patients With Systemic Lupus Erythematosus.

Background: The aim of this study is to develop survival analysis models of hospitalized systemic lupus erythematosus (h-SLE) patients in Jiangsu province using data mining techniques to predict patient survival outcomes and survival status. Methods: In this study, based on 1999-2009 survival data of 2453 hospitalized SLE (h-SLE) patients in Jiangsu Province, we not only used the Cox proportional hazards model to analyze patients' survival factors, but also used neural network models to predict survival outcomes. We used semi-supervised learning to label the censored data and introduced cost-sensitivity to achieve data augmentation, addressing category imbalance and pseudo label credibility. In addition, the risk score model was developed by logistic regression. Results: The overall accuracy of the survival outcome prediction model exceeded 0.7, and the sensitivity was close to 0.8, and through the comparative analysis of multiple indicators, our model outperformed traditional classifiers. The developed survival risk assessment model based on logistic regression found that there was a clear threshold, i.e., a survival threshold indicating the survival risk of patients, and cardiopulmonary and neuropsychiatric involvement, abnormal blood urea nitrogen levels and alanine aminotransferase level had the greatest impact on patient survival time. In addition, the study developed a graphical user interface (GUI) integrating survival analysis models to assist physicians in diagnosis and treatment. Conclusions: The proposed survival analysis scheme identifies disease-related pathogenic and prognosis factors, and has the potential to improve the effectiveness of clinical interventions.

Coking- and Sintering-Resistant Ni Nanocatalysts Confined by Active BN Edges for Methane Dry Reforming.

Methane dry reforming (MDR) has attracted significant attention for effectively consuming greenhouse gases and producing valuable syngas. The development of coking- and sintering-resistant catalysts is still a challenge. Herein, highly active Ni nanocatalysts confined by the active edges of boron nitride have been originally developed, and the coking- and sintering-resistant MDR mechanism has also been unraveled. The active edges of boron nitride consisted of boundary BOx species interact with Ni nanoparticles (NPs), which can contribute to the activation of both CH4 and CO2. The etching of BN is restrained under the buffer of boundary BOx species. Operando spectra reveal that the formation and conversion of active bicarbonate species is accelerated by the boundary BOx species. The complete decomposition of CH4 is suppressed, and thus the coke formation is restricted. The functional groups of active BN edges are confirmed to stabilize the Ni NPs and facilitate the MDR reaction. This work provides a novel approach for the development of coking- and sintering-resistant catalysts for MDR.

NOx Reduction over Smart Catalysts with Self-Created Targeted Antipoisoning Sites.

Selective catalytic reduction of NOx in the presence of alkali (earth) metals and heavy metals is still a challenge due to the easy deactivation of catalysts. Herein, NOx reduction over smart catalysts with self-created targeted antipoisoning sites is originally demonstrated. The smart catalyst consisted of TiO2 pillared montmorillonite with abundant cation exchange sites to anchor poisoning substances and active components to catalyze NOx into N2. It was not deactivated during the NOx reduction process in the presence of alkali (earth) metals and heavy metals. The enhanced surface acidity, reducible active species, and active chemisorbed oxygen species of the smart catalyst accounted for the remarkable NOx reduction efficiency. More importantly, the self-created targeted antipoisoning sites expressed specific anchoring effects on poisoning substances and protected the active components from poisoning. It was demonstrated that the tetrahedrally coordinated aluminum species of the smart catalyst mainly acted as self-created targeted antipoisoning sites to stabilize the poisoning substances into the interlayers of montmorillonite. This work paves a new way for efficient reduction of NOx from the complex flue gas in practical applications.

Stemness Subtypes and Scoring System Predict Prognosis and Efficacy of Immunotherapy in Soft Tissue Sarcoma.

Tumor stemness has been reported to play important roles in cancers. However, a comprehensive analysis of tumor stemness remains to be performed to investigate the specific mechanisms and practical values of stemness in soft tissue sarcomas (STS). Here, we applied machine learning to muti-omic data of patients from TCGA-SARC and GSE21050 cohorts to reveal important roles of stemness in STS. We demonstrated limited roles of existing mRNAsi in clinical application. Therefore, based on stemness-related signatures (SRSs), we identified three stemness subtypes with distinct stemness, immune, and metabolic characteristics using consensus clustering. The low-stemness subtype had better prognosis, activated innate and adaptive immunity (e.g., infiltrating B, DC, Th1, CD8+ T, activated NK, gamma delta T cells, and M1 macrophages), more enrichment of metabolic pathways, more sites with higher methylation level, higher gene mutations, CNA burdens, and immunogenicity indicators. Furthermore, the 16 SRS-based stemness prognostic index (SPi) was developed, and we found that low-SPi patients with low stemness had better prognosis and other characteristics similar to those in the low-stemness subtype. Besides, low-stemness subtype and low-SPi patients could benefit from immunotherapy. The predictive value of SPi in immunotherapy was more accurate after the addition of MSI into SPi. MSIlowSPilow patients might be more sensitive to immunotherapy. In conclusion, we highlighted mechanisms and practical values of the stemness in STS. We also recommended the combination of MSI and SPi which is a promising tool to predict prognosis and achieve precise treatments of immunotherapy in STS.

Prediction of diagnosis results of rheumatoid arthritis patients based on autoantibodies and cost-sensitive neural network.

OBJECTIVES: To analyze and evaluate the effectiveness of the detection of single autoantibody and combined autoantibodies in patients with rheumatoid arthritis (RA) and related autoimmune diseases and establish a machine learning model to predict the disease of RA. METHODS: A total of 309 patients with joint pain as the first symptom were retrieved from the database. The effectiveness of single and combined antibodies tests was analyzed and evaluated in patients with RA, a cost-sensitive neural network (CSNN) model was used to integrate multiple autoantibodies and patient symptoms to predict the diagnosis of RA, and the ROC curve was used to analyze the diagnosis performance and calculate the optimal cutoff value. RESULTS: There are differences in the seropositive rate of autoimmune diseases, the sensitivity and specificity of single or multiple autoantibody tests were insufficient, and anti-CCP performed best in RA diagnosis and had high diagnostic value. The cost-sensitive neural network prediction model had a sensitivity of up to 0.90 and specificity of up to 0.86, which was better than a single antibody and combined multiple antibody detection. CONCLUSION: In-depth analysis of autoantibodies and reliable early diagnosis based on the neural network could guide specialized physicians to develop different treatment plans to prevent deterioration and enable early treatment with antirheumatic drugs for remission. Key Points • There are differences in the seropositive rate of autoimmune diseases. • This is the first study to use a cost-sensitive neural network model to diagnose RA disease in patients. • The diagnosis effect of the cost-sensitive neural network model is better than a single antibody and combined multiple antibody detection.

Synergistic Catalytic Elimination of NOx and Chlorinated Organics: Cooperation of Acid Sites.

The synergistic catalytic removal of NOx and chlorinated volatile organic compounds under low temperatures is still a big challenge. Generally, degradation of chlorinated organics demands sufficient redox ability, which leads to low N2 selectivity in the selective catalytic reduction of NOx by NH3 (NH3-SCR). Herein, mediating acid sites via introducing the CePO4 component into MnO2/TiO2 NH3-SCR catalysts was found to be an effective approach for promoting chlorobenzene degradation. The observation of in situ diffuse reflectance infrared Fourier transform (in situ DRIFT) and Raman spectra reflected that the Lewis acid sites over CePO4 promoted the nucleophilic substitution process of chlorobenzene over MnO2 by weakening the bond between Cl and benzene ring. Meanwhile, MnO2 provided adequate Brønsted acid sites and redox sites. Under the cooperation of Lewis and Brønsted acid sites, relying on the rational redox ability, chlorobenzene degradation was promoted with synergistically improved NH3-SCR activity and selectivity. This work offers a distinct pathway for promoting the combination of chlorobenzene catalytic oxidation and NH3-SCR, and is expected to provide a novel strategy for synergistic catalytic elimination of NOx and chlorinated volatile organic compounds.

The relationship of polluted air and drinking water sources with the prevalence of systemic lupus erythematosus: a provincial population-based study.

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.

Pseudo in situ construction of high-performance thermoelectric composites with a dioxothiopyrone-based D-A polymer coating on SWCNTs.

Organic polymer/inorganic particle composites with thermoelectric (TE) properties have witnessed rapid progress in recent years. Nevertheless, both development of novel polymers and optimization of compositing methods remain highly desirable. In this study, we first demonstrated a simulated in situ coagulation strategy for construction of high-performance thermoelectric materials by utilizing single-walled carbon nanotubes (SWCNTs) and a new D-A polymer TPO-TTP12 that was synthesized via incorporating dioxothiopyrone subunit into a polymeric chain. It was proven that the preparation methods have a significant influence on thermoelectric properties of the TPO-TTP12/SWCNT composites. The in situ prepared composite films tend to achieve much better thermoelectric performances than those prepared by simply mixing the corresponding polymer with SWCNTs. As a result, the in situ compositing obtains the highest Seebeck coefficient of 66.10 ± 0.05 µV K-1 at the TPO-TTP12-to-SWCNT mass ratio of 1/2, and the best electrical conductivity of up to 500.5 ± 53.3 S cm-1 at the polymer/SWCNT mass ratio of 1/20, respectively; moreover, the power factor for the in situ prepared composites reaches a maximum value of 141.94 ± 1.47 µW m-1 K-2, far higher than that of 104.68 ± 0.86 µW m-1 K-2 for the by-mixing produced composites. This indicates that the dioxothiopyrone moiety is a promising building block for constructing thermoelectric polymers, and the simulated in situ compositing strategy is a promising way to improve TE properties of composite materials.

Delocalization Effect Promoted the Indoor Air Purification via Directly Unlocking the Ring-Opening Pathway of Toluene.

The ring-opening process was generally considered as the rate-determining step for aromatic volatile organic compound photocatalytic degradation. A sophisticated and intensive degradation pathway is critical to the poor removal efficiency and low mineralization. In the present contribution, we successfully tailored and identified the ring-opening pathway of toluene elimination by electron delocalization in a borocarbonitride photocatalyst. By means of modulation of the dopant coordination configuration and electron geometry in the catalyst, the lone electrons of carbon transform into delocalized counterparts, sequentially elevating the interaction between the toluene molecules and photocatalyst. The aromatic ring of toluene can be attacked directly in the effect of electron delocalization without engendering additional intermediate species, significantly facilitating the removal and mineralization of toluene. This unprecedented route-control strategy alters the aromatic-ring-based reaction behavior from toluene to CO2 and paves a way to purify the refractory pollutants from the top design.

Three-Stage Masquelet Technique and One-Stage Reconstruction to Treat Foot and Ankle Tuberculosis.

BACKGROUND: The purpose of this article was to report the feasibility and effectiveness of 3-stage Masquelet technique and 1-stage operation for different stages of foot and ankle tuberculosis (TB). METHODS: Ten consecutive patients with foot and ankle TB were retrospectively analyzed between January 2014 and December 2018. Five patients were treated with the 3-stage Masquelet technique, including thorough debridement with vacuum sealing drainage, implantation of antibiotic cement spacer, and subsequent reconstruction. Five patients were treated with a 1-stage reconstruction. The American Orthopaedic Foot & Ankle Society (AOFAS) and visual analog scale (VAS) pain scores were recorded at the last follow-up. The follow-up was 30.3 ± 17.8 months. RESULTS: No reactivation of TB was observed in any patients. For the 3-stage operation group, 1 patient developed a distal tibia fracture. The duration of anti-TB therapy was 12.0 ± 0.8 months. The AOFAS score increased from 39.5 ± 9.9 preoperatively to 75.3 ± 7.0 postoperatively (P < .05). The VAS pain score decreased from 6.3 ± 1.9 to 1.5 ± 1.3 (P < .05). For the 1-stage operation, 1 patient had wound necrosis. The duration of anti-TB therapy was 13.8 ± 1.1 months. The AOFAS score increased from 51.8 ± 15.0 to 81.8 ± 6.3 (P < .05). The VAS pain score decreased from 5.4 ± 1.1 to 1.0 ± 0.7 (P < .05). CONCLUSION: Three-stage operation was effective for foot and ankle TB with stage IV, sinus tracts or other infections, and 1-stage reconstruction was effective for early-stage TBs. LEVEL OF EVIDENCE: Level IV, case series.

Preparation of porous semi-IPN temperature-sensitive hydrogel-supported nZVI and its application in the reduction of nitrophenol.

Nanoscale zero-valent iron (nZVI) particles supported on a porous, semi-interpenetrating (semi-IPN), temperature-sensitive composite hydrogel (PNIPAm-PHEMA). nZVI@PNIPAm-PHEMA, was successfully synthesized and characterized by FT-IR, SEM, EDS, XRD and the weighing method. The loading of nZVI was 0.1548 ±â€¯0.0015 g/g and the particle size was 30-100 nm. NZVI was uniformly dispersed on the pore walls inside the PNIPAm-PHEMA. Because of the well-dispersed nZVI, the highly porous structure, and the synergistic effect of PNIPAm-PHEMA, nZVI@PNIPAm-PHEMA showed excellent reductive activity and wide pH applicability. 95% of 4-NP in 100 mL of 400 mg/L 4-NP solution with initial pH 3.0-9.0 could be completely reduced into 4-AP by about 0.0548 g of fresh supported nZVI at 18-25 °C under stirring (110 r/min) within 45 min reaction time. A greater than 99% 4-NP degradation ratio was obtained when the initial pH was 5.0-9.0. The reduction of 4-NP by nZVI@PNIPAm-PHEMA was in agreement with the pseudo-first-order kinetics model with Kobs values of 0.0885-0.101 min-1. NZVI@PNIPAm-PHEMA was able to be recycled, and about 85% degradation ratio of 4-NP was obtained after its sixth reuse cycle. According to the temperature sensitivity of PNIPAm-PHEMA, nZVI@PNIPAm-PHEMA exhibited very good storage stability, and about 88.9% degradation ratio of 4-NP was obtained after its storage for 30 days. The hybrid reducer was highly efficient for the reduction of 2-NP, 3-NP, 2-chloro-4-nitrophenol and 2-chloro-4-nitrophenol. Our results suggest that PNIPAm-PHEMA could be a good potential carrier, with nZVI@PNIPAm-PHEMA having potential value in the application of reductive degradation of nitrophenol pollutants.