A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy.

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

Scalable Preparation of Ultraselective and Highly Permeable Fully Aromatic Polyamide Nanofiltration Membranes for Antibiotic Desalination.

Membranes are important in the pharmaceutical industry for the separation of antibiotics and salts. However, its widespread adoption has been hindered by limited control of the membrane microstructure (pore architecture and free-volume elements), separation threshold, scalability, and operational stability. In this study, 4,4',4'',4'''-methanetetrayltetrakis(benzene-1,2-diamine) (MTLB) as prepared as a molecular building block for fabricating thin-film composite membranes (TFCMs) via interfacial polymerization. The relatively large molecular size and rigid molecular structure of MTLB, along with its non-coplanar and distorted conformation, produced thin and defect-free selective layers (~27 nm) with ideal microporosities for antibiotic desalination. These structural advantages yielded an unprecedented high performance with a water permeance of 45.2 L m-2 h-1 bar-1 and efficient antibiotic desalination (NaCl/adriamycin selectivity of 422). We demonstrated the feasibility of the industrial scaling of the membrane into a spiral-wound module (with an effective area of 2.0 m2). This module exhibited long-term stability and performance that surpassed those of state-of-the-art membranes used for antibiotic desalination. This study provides a scientific reference for the development of high-performance TFCMs for water purification and desalination in the pharmaceutical industry.

Characteristics and literature review of ETV6::ABL1 fusion gene-positive acute myeloid leukemia.

OBJECTIVE: To describe the features of ETV6::ABL1 AML as well as the clinical treatment and outcomes. METHODS: Clinical data were collected from three patients diagnosed with ETV6::ABL1 AML at Hebei Yanda Lu Daopei Hospital and Beijing Lu Daopei Hospital. Their clinical and laboratory features were analyzed, and the treatment process and outcomes were described. Ten reported cases of ETV6::ABL1 AML from the literature were also included for analysis. RESULTS: The median age of the patients was 34 years, and 2 patients were male. No patient had a history of blood disorders before diagnosis. After relapse, they were referred to our hospital, where the ETV6::ABL1 gene was detected. Unfortunately, Patient 1 died rapidly after leukemia relapse due to severe infection. Patients 2 and 3 received salvage therapy with a dasatinib-containing regimen, followed by allo-HSCT, and are currently alive and disease-free. CONCLUSION: ETV6::ABL1 is a rare but recurrent genetic aberration in AML, and the combined use of fluorescence in situ hybridization and PCR can better identify this fusion gene. Patients carrying ETV6::ABL1 have a high relapse rate and a poor prognosis. TKIs are a reasonable treatment option for this group, and allo-HSCT may be curative.

Medical waste incineration fly ash-based magnesium potassium phosphate cement: Calcium-reinforced chlorine solidification/stabilization mechanism and optimized carbon reduction process strategy.

The traditional solidification/stabilization (S/S) technology, Ordinary Portland Cement (OPC), has been widely criticized due to its poor resistance to chloride and significant carbon emissions. Herein, a S/S strategy based on magnesium potassium phosphate cement (MKPC) was developed for the medical waste incineration fly ash (MFA) disposal, which harmonized the chlorine stabilization rate and potential carbon emissions. The in-situ XRD results indicated that the Cl- was efficiently immobilized in the MKPC system with coexisting Ca2+ by the formation of stable Ca5(PO4)3Cl through direct precipitation or intermediate transformation (the Cl- immobilization rate was up to 77.29%). Additionally, the MFA-based MKPC also demonstrated a compressive strength of up to 39.6 MPa, along with an immobilization rate exceeding 90% for heavy metals. Notably, despite the deterioration of the aforementioned S/S performances with increasing MFA incorporation, the potential carbon emissions associated with the entire S/S process were significantly reduced. According to the Life Cycle Assessment, the potential carbon emissions decreased to 8.35 × 102 kg CO2-eq when the MFA reached the blending equilibrium point (17.68 wt.%), while the Cl- immobilization rate still remained above 65%, achieving an acceptable equilibrium. This work proposes a low-carbon preparation strategy for MKPC that realizes chlorine stabilization, which is instructive for the design of S/S materials.

Investigating the network structure and causal relationships among bridge symptoms of comorbid depression and anxiety: A Bayesian network analysis.

BACKGROUND: The network analysis method emphasizes the interaction between individual symptoms to identify shared or bridging symptoms between depression and anxiety to understand comorbidity. However, the network analysis and community detection approach have limitations in identifying causal relationships among symptoms. This study aims to address this gap by applying Bayesian network (BN) analysis to investigate potential causal relationships. METHOD: Data were collected from a sample of newly enrolled college students. The network structure of depression and anxiety was estimated using the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) Scale measures, respectively. Shared symptoms between depression and anxiety were identified through network analysis and clique percolation (CP) method. The causal relationships among symptoms were estimated using BN. RESULTS: The strongest bridge symptoms, as indicated by bridge strength, include sad mood (PHQ2), motor (PHQ8), suicide (PHQ9), restlessness (GAD5), and irritability (GAD6). These bridge symptoms formed a distinct community using the CP algorithm. Sad mood (PHQ2) played an activating role, influencing other symptoms. Meanwhile, restlessness (GAD5) played a mediating role with reciprocal influences on both anxiety and depression symptoms. Motor (PHQ8), suicide (PHQ9), and irritability (GAD6) assumed recipient positions. CONCLUSION: BN analysis presents a valuable approach for investigating the complex interplay between symptoms in the context of comorbid depression and anxiety. It identifies two activating symptoms (i.e., sadness and worry), which serve to underscore the fundamental differences between these two disorders. Additionally, psychomotor symptoms and suicidal ideations are recognized as recipient roles, being influenced by other symptoms within the network.

Lily LlHSFC2 coordinates with HSFAs to balance heat stress response and improve thermotolerance.

Heat stress transcription factors (HSFs) are core regulators of plant heat stress response. Much research has focused on class A and B HSFs, leaving those of class C relatively understudied. Here, we reported a lily (Lilium longiflorum) heat-inducible HSFC2 homology involved in thermotolerance. LlHSFC2 was located in the nucleus and cytoplasm and exhibited a repression ability by binding heat stress element. Overexpression of LlHSFC2 in Arabidopsis, tobacco (Nicotiana benthamiana), and lily, all increased the thermotolerance. Conversely, silencing of LlHSFC2 in lily reduced its thermotolerance. LlHSFC2 could interact with itself, or interact with LlHSFA1, LlHSFA2, LlHSFA3A, and LlHSFA3B of lily, AtHSFA1e and AtHSFA2 of Arabidopsis, and NbHSFA2 of tobacco. LlHSFC2 interacted with HSFAs to accelerate their transactivation ability and act as a transcriptional coactivator. Notably, compared with the separate LlHSFA3A overexpression, co-overexpression of LlHSFC2/LlHSFA3A further enhanced thermotolerance of transgenic plants. In addition, after suffering HS, the homologous interaction of LlHSFC2 was repressed, but its heterologous interaction with the heat-inducible HSFAs was promoted, enabling it to exert its co-activation effect for thermotolerance establishment and maintenance. Taken together, we identified that LlHSFC2 plays an active role in the general balance and maintenance of heat stress response by cooperating with HSFAs, and provided an important candidate for the enhanced thermotolerance breeding of crops and horticulture plants.

A LlWRKY33-LlHSFA4-LlCAT2 module confers resistance to Botrytis cinerea in lily.

Gray mold caused by Botrytis cinerea is one of the major threats in lily production. However, limited information is available about the underlying defense mechanism against B. cinerea in lily. Here, we characterized a nuclear-localized class A heat stress transcription factor (HSF)-LlHSFA4 from lily (Lilium longiflorum), which positively regulated the response to B. cinerea infection. LlHSFA4 transcript and its promoter activity were increased by B. cinerea infection in lily, indicating its involvement in the response to B. cinerea. Virus-induced gene silencing (VIGS) of LlHSFA4 impaired the resistance of lily to B. cinerea. Consistent with its role in lily, overexpression of LlHSFA4 in Arabidopsis (Arabidopsis thaliana) enhanced the resistance of transgenic Arabidopsis to B. cinerea infection. Further analysis showed that LlWRKY33 directly activated LlHSFA4 expression. We also found that both LlHSFA4 and LlWRKY33 positively regulated plant response to B. cinerea through reducing cell death and H2O2 accumulation and activating the expression of the reactive oxygen species (ROS) scavenging enzyme gene LlCAT2 (Catalase 2) by binding its prompter, which might contribute to reducing H2O2 accumulation in the infected area. Taken together, our data suggested that there may be a LlWRKY33-LlHSFA4-LlCAT2 regulatory module which confers B. cinerea resistance via reducing cell death and the ROS accumulation.

Photosynthesis of Benzonitriles on BiOBr Nanosheets Promoted by Vacancy Associates.

Photocatalytic organic functionalization reactions represent a green, cost-effective, and sustainable synthesis route for value-added chemicals. However, heterogeneous photocatalysis is inefficient in directly activating ammonia molecules for the production of high-value-added nitrogenous organic products when compared with oxygen activation in the formation of related oxygenated compounds. In this study, we report the heterogeneous photosynthesis of benzonitriles by the ammoxidation of benzyl alcohols (99 % conversion, 93 % selectivity) promoted using BiOBr nanosheets with surface vacancy associates. In contrast, the main reaction of catalysts with other types of vacancy sites is the oxidation of benzyl alcohol to benzaldehyde or benzoic acid. Experimental measurements and theoretical calculations have demonstrated a specificity of vacancy type with respect to product selectivity, which arises from the adsorption and activation of NH3 and O2 that is required to promote subsequent C-N coupling and oxidation to nitrile. This study provides a better understanding of the role of vacancies as catalytic sites in heterogeneous photocatalysis.

Pregnancy characteristics and adverse outcomes in offspring of women with epilepsy: a prospective registry study from Mainland China.

Objective: This study aimed to explore the influencing factors of adverse outcomes in the offspring of women with epilepsy (WWE) and to analyze the changes brought about by the epilepsy knowledge popularization campaign in China (EKPCIC). Methods: This nested case-control study focused on WWE and their offspring from a female epilepsy cohort in mainland China. From January 2009 to August 2022, WWE was prospectively enrolled in 32 study centers. This study aimed to observe the health outcomes of their offspring within 1 year of age. The main outcome measure assessed the health status of the offspring within their first year of age. We aimed to analyze the effects of seizures, anti-seizure medicines (ASMs), and a lack of folic acid supplementation on adverse outcomes in the offspring of WWE and to explore the changes in perinatal management and adverse outcomes of the offspring after dissemination of the EKPCIC in 2015. Additionally, subgroup analyses were conducted to compare seizure control during pregnancy between the valproate and non-valproate groups. Results: In total, 781 pregnancies in 695 WWE were included, of which 186 (23.69%) had adverse outcomes. The National Hospital Epilepsy Severity Scale score, number of seizures, status epilepticus, ASM type, and valproate and folic acid doses were associated with a high risk of adverse outcomes. After the EKPCIC, the use of ASMs (P = 0.013) and folic acid (P < 0.001), the seizure-free rate during pregnancy (P = 0.013), and the breastfeeding rate (P < 0.001) increased, whereas the incidence of complications during pregnancy decreased (P = 0.013). However, there was no significant difference in the incidence of adverse outcomes between the analyzed offspring pre-/post-EKPCIC. Additionally, there was no association between the frequency of seizures at different time points during pregnancy and the use of valproate (F = 1.514, P = 0.221). Conclusion: Possible factors influencing adverse outcomes in the offspring of WWE include seizures, type and number of ASM usage, and a lack of folic acid supplementation. Although the management of WWE during pregnancy is now more standardized, further efforts are needed to reduce adverse outcomes in offspring.

Analysis benefits of a second Allo-HSCT after CAR-T cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia who relapsed after transplant.

Background: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated high initial complete remission (CR) rates in B-cell acute lymphoblastic leukemia (B-ALL) patients, including those who relapsed after transplant. However, the duration of remission requires improvements. Whether bridging to a second allogeneic hematopoietic stem cell transplant (allo-HSCT) after CAR-T therapy can improve long-term survival remains controversial. We retrospectively analyzed long-term follow-up data of B-ALL patients who relapsed post-transplant and received CAR-T therapy followed by consolidation second allo-HSCT to investigate whether such a treatment sequence could improve long-term survival. Methods: A single-center, retrospective study was performed between October 2017 and March 2022, involving 95 patients who received a consolidation second transplant after achieving CR from CAR-T therapy. Results: The median age of patients was 22.8 years (range: 3.3-52.8) at the second transplant. After the first transplant, 71 patients (74.7%) experienced bone marrow relapse, 16 patients (16.8%) had extramedullary relapse, 5 patients (5.3%) had both bone marrow and extramedullary relapse and 3/95 patients (3.2%) had positive minimal residual disease (MRD) only. Patients received autologous (n=57, 60.0%) or allogeneic (n=28, 29.5%) CAR-T cells, while 10 patients (10.5%) were unknown. All patients achieved CR after CAR-T therapy. Before second HSCT, 86 patients (90.5%) were MRD-negative, and 9 (9.5%) were MRD-positive. All second transplant donors were different from the first transplant donors. The median follow-up time was 623 days (range: 33-1901) after the second HSCT. The 3-year overall survival (OS) and leukemia-free survival (LFS) were 55.3% (95%CI, 44.3-66.1%) and 49.8% (95%CI, 38.7-60.9%), respectively. The 3-year relapse incidence (RI) and non-relapse mortality (NRM) were 10.5% (95%CI, 5.6-19.6%) and 43.6% (95%CI, 33.9-56.2%), respectively. In multivariate analysis, the interval from CAR-T to second HSCT ≤90 days was associated with superior LFS(HR, 4.10, 95%CI,1.64-10.24; p=0.003) and OS(HR, 2.67, 95%CI, 1.24-5.74, p=0.012), as well as reduced NRM (HR, 2.45, 95%CI, 1.14-5.24, p=0.021). Conclusions: Our study indicated that CAR-T therapy followed by consolidation second transplant could significantly improve long-term survival in B-ALL patients who relapsed post-transplant. The second transplant should be considered in suitable patients and is recommended to be performed within 90 days after CAR-T treatment.

Highly Efficient Biomass Upgrading by a Ni-Cu Electrocatalyst Featuring Passivation of Water Oxidation Activity.

Electricity-driven organo-oxidations have shown an increasing potential recently. However, oxygen evolution reaction (OER) is the primary competitive reaction, especially under high current densities, which leads to low Faradaic efficiency (FE) of the product and catalyst detachment from the electrode. Here, we report a bimetallic Ni-Cu electrocatalyst supported on Ni foam (Ni-Cu/NF) to passivate the OER process while the oxidation of 5-hydroxymethylfurfural (HMF) is significantly enhanced. A current density of 1000 mA cm-2 can be achieved at 1.50 V vs. reversible hydrogen electrode, and both FE and yield keep close to 100 % over a wide range of potentials. Both experimental results and theoretical calculations reveal that Cu doping impedes the OH* deprotonation to O* and hereby OER process is greatly passivated. Those instructive results provide a new approach to realizing highly efficient biomass upgrading by regulating the OER activity.

Enhancing heat stress tolerance in Lanzhou lily (Lilium davidii var. unicolor) with Trichokonins isolated from Trichoderma longibrachiatum SMF2.

Lanzhou lily (Lilium davidii var. unicolor) is a renowned edible crop produced in China and relatively sensitive to high temperature (HT). Trichokonins (TKs) are antimicrobial peptaibols secreted from Trichoderma longibrachiatum strain SMF2. Here, we report that TKs application improves the thermotolerance of Lanzhou lily. The activity of the antioxidant enzyme system (SOD, CAT, and POD), the level of heat-resistance-associated phytohormones (ABA, SA, and JA), the relative water content (RWC), the content of chlorophyll (Chl), and the net photosynthetic rate (P n) were promoted by TKs treatment in Lanzhou lily plants subjected to heat stress (HS). TKs treatment also mitigated cell injury as shown by a lower accumulation of malondialdehyde (MDA) and relative electrolyte leakage (REL) under HS conditions. RNA-seq data analysis showed that more than 4.5 times differentially expressed genes (DEGs) responded to TKs treatment under HS compared to non-HS, and TKs treatment reduced protein folding and enhanced cellular repair function under HS conditions. The analyses of DEGs involved in hormone (ABA, SA and JA) synthesis and signaling pathways suggested that TKs might improve Lanzhou lily heat tolerance by promoting ABA synthesis and signal transduction. TKs highly induced DEGs of the HSF-HSP pathway under HS, in which HSFA2 accounted for most of the HSF family. Furthermore, TKs treatment resulted in the upregulation of heat-protective genes LzDREB2B, LzHsfA2a, LzMBF1c, LzHsp90, and LzHsp70 involved in HSF-HSP signal pathway after long-term HS. LzHsfA2a-1 likely plays a key role in acquisition of TKs-induced thermotolerance of Lanzhou lily as evidenced by the sustained response to HS, the enhanced response to TKs treatment under long-term HS, and the high sequence similarity to LlHsfA2a which is a key regulator for the improvement of heat tolerance in Lilium longiflorum. Our results reveal the underlying mechanisms of TKs-mediated thermotolerance in Lanzhou lily and highlight an attractive approach to protecting crop plants from damage caused by HS in a global warming future.

[Removal Performance and Mechanism of Potassium Permanganate Modified Coconut Shell Biochar for Cd(â ¡) and Ni(â ¡) in Aquatic Environment].

In this study, coconut shell biochar modified by KMnO4 (MCBC) was used as the adsorbent, and its removal performance and mechanism for Cd(Ⅱ) and Ni(Ⅱ) were discussed. When the initial pH and MCBC dosage were separately 5 and 3.0 g·L-1, respectively, the removal efficiencies of Cd(Ⅱ) and Ni(Ⅱ) were both higher than 99%. The removal of Cd(Ⅱ) and Ni(Ⅱ) was more in line with the pseudo-second-order kinetic model, indicating that their removal was dominated by chemisorption. The rate-controlling step for Cd(Ⅱ) and Ni(Ⅱ) removal was the fast removal stage, for which the rate depended on the liquid film diffusion and intraparticle diffusion (surface diffusion). Cd(Ⅱ) and Ni(Ⅱ) were mainly attached to the MCBC via surface adsorption and pore filling, in which the contribution of surface adsorption was greater. The maximum adsorption amounts of Cd(Ⅱ) and Ni(Ⅱ) by MCBC were individually 57.18 mg·g-1 and 23.29 mg·g-1, which were approximately 5.74 and 6.97 times that of the precursor (coconut shell biochar), respectively. The removal of Cd(Ⅱ) and Zn(Ⅱ) was spontaneous and endothermic and had obvious thermodynamic characteristics of chemisorption. Cd(Ⅱ) was attached to MCBC through ion exchange, co-precipitation, complexation reaction, and cation-π interaction, whereas Ni(Ⅱ) was removed by MCBC via ion exchange, co-precipitation, complexation reaction, and redox. Among them, co-precipitation and complexation were the main modes of surface adsorption of Cd(Ⅱ) and Ni(Ⅱ). Additionally, the proportion of amorphous Mn-O-Cd or Mn-O-Ni in the complex may have been higher. These research results will provide important technical support and theoretical basis for the practical application of commercial biochar in the treatment of heavy metal wastewater.

Transcutaneous auricular vagus nerve stimulation improves gait and cortical activity in Parkinson's disease: A pilot randomized study.

OBJECTIVE: In this randomized, double-blind, sham-controlled trial, we explored the effect of 20 Hz transcutaneous auricular vagus nerve stimulation (taVNS) on gait impairments in Parkinson's disease (PD) patients and investigated the underlying neural mechanism. METHODS: In total, 22 PD patients and 14 healthy controls were enrolled. PD patients were randomized (1:1) to receive active or sham taVNS (same position as active taVNS group but without releasing current) twice a day for 1 week. Meanwhile, all subjects were measured activation in the bilateral frontal and sensorimotor cortex during usual walking by functional near-infrared spectroscopy. RESULTS: PD patients showed instable gait with insufficient range of motion during usual walking. Active taVNS improved gait characteristics including step length, stride velocity, stride length, and step length variability compared with sham taVNS after completion of the 7-day therapy. No difference was found in the Unified Parkinson's Disease Rating Scale III, Timed Up and Go, Tinetti Balance, and Gait scores. Moreover, PD patients had higher relative change of oxyhemoglobin in the left dorsolateral prefrontal cortex, pre-motor area, supplementary motor area, primary motor cortex, and primary somatosensory cortex than HCs group during usual walking. Hemodynamic responses in the left primary somatosensory cortex were significantly decreased after taVNS therapy. CONCLUSION: taVNS can relieve gait impairments and remodel sensorimotor integration in PD patients.

Preparation of magnesium potassium phosphate cement from municipal solid waste incineration fly ash and lead slag co-blended: Ca-induced crystal reconstruction process and Pb-Cl synergistic solidification mechanism.

Higher chlorine (Cl) content than lead (Pb) content in municipal solid waste incineration fly ash (MSWIFA) impeded the practical application of Pb5(PO4)3Cl-derived magnesium potassium phosphate cement (MKPC) preparation strategy. Herein, Pb/Ca-rich lead slag (LS) was co-blended with MSWIFA to prepare MKPC for the synergistic treatment of both two solid wastes and the Pb-Cl solidification. The results showed that the resulting 15-15 (15 wt% MSWIFA and 15 wt% LS incorporation) sample achieved 25.44 MPa compressive strength, and Pb and Cl leaching toxicity was reduced by 99.18 % and 92.80 %, respectively. The X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses showed that Pb2+, Ca2+, phosphate and Cl- formed PbxCa5-x(PO4)3Cl in samples. The formation of PbxCa5-x(PO4)3Cl was also demonstrated by the high-angle annular dark field scanning transmission electron microscope (HAADF-STEM), while differences in the lattice characteristics of PbxCa5-x(PO4)3Cl and Pb5(PO4)3Cl were found. In-situ XRD indicated that Ca2+ accelerated the transformation of Pb2+ to Pb5(PO4)3Cl. After co-precipitating with Ca2+ to form PbxCa5-x(PO4)3Cl, Pb2+ continuously substituted Ca2+ to eventually transform to Pb5(PO4)3Cl. This work informs the synergistic treatment of MSWIFA and LS and offers new insights into the reaction mechanism between Pb2+, phosphate and Cl- under Ca2+ induction.

Robust, Flame-Retardant, and Anti-Corrosive Waterborne Polyurethane Enabled by a PN Synergistic Flame-Retardant Containing Benzimidazole and Phosphinate Groups.

Waterborne polyurethanes (WPUs) have attracted great interest owing to their environmentally friendly properties, and are wildly applied in production and daily life. However, waterborne polyurethanes are flammable. Up to now, the challenge remains to prepare WPUs with excellent flame resistance, high emulsion stability, and outstanding mechanical properties. Herein, a novel flame-retardant additive, 2-hydroxyethan-1-aminium (2-(1H-benzo[d]imidazol-2-yl)ethyl)(phenyl)phosphinate (BIEP-ETA) has been synthesized and applied to improve the flame resistance of WPUs, which has both phosphorus nitrogen synergistic effect and the ability to form hydrogen bonds with WPUs. The WPU blends (WPU/FRs) exhibited a positive fire-retardant effect in both the vapor and condensed phases, with significantly improved self-extinguishing performance and reduced heat release value. Interestingly, thanks to the good compatibility between BIEP-ETA and WPUs, WPU/FRs not only have higher emulsion stability, but also have better mechanical properties with synchronously improved tensile strength and toughness. Moreover, WPU/FRs also exhibit excellent potential as a corrosion-resistant coating.

Accumulated biomechanical effects of mandibular molar mesialization using clear aligners with auxiliary devices: an iterative finite element analysis.

BACKGROUND: The biomechanics generated by the clear aligner (CA) material changes continuously during orthodontic tooth movement, but this factor remains unknown during the computer-aid design process and the predictability of molars movement is not as expected. Therefore, the purpose of this study was to propose an iterative finite element method to simulate the long-term biomechanical effects of mandibular molar mesialization (MM) in CA therapy under dual-mechanical systems. METHODS: Three groups including CA alone, CA with a button, and CA with a modified lever arm (MLA) were created. Material properties of CA were obtained by in vitro mechanical experiments. MM was conducted by the rebound force exerted by CA material and the mesial elastic force (2N, 30° to the occlusal plane) applied to the auxiliary devices. Stress intensity and distribution on periodontal ligament (PDL), attachment, button and MLA, and displacement of the second molar (M2) during the iterations were recorded. RESULTS: There was a significant difference between the initial and cumulative long-term displacement. Specifically, compared to the beginning, the maximum stress of PDL decreased by 90% on average in the intermediate and final steps. The aligner was the main mechanical system at first, and then, the additional system exerted by the button and MLA dominated gradually. The stress of attachments and auxiliary devices is mainly concentrated on their interfaces with the tooth. Additionally, MLA provided a distal tipping and extrusive moment, which was the only group that manifested a total mesial displacement of the root. CONCLUSIONS: The innovatively designed MLA was more effective in reducing undesigned mesial tipping and rotation of M2 than the traditional button and CA alone, which provided a therapeutic method for MM. The proposed iterative method simulated tooth movement by considering the mechanical characteristic of CA and its long-term mechanical force changes, which will facilitate better movement prediction and minimize the failure rate.

Biomechanical effects of clear aligners with different thicknesses and gingival-margin morphology for appliance design optimization.

INTRODUCTION: The objectives of this study were to investigate the biomechanical effects of clear aligners (CAs) with various thermoplastic material thicknesses and gingival-margin designs for space closure in extraction treatment and to propose a computer-aided procedure to optimize CA design. METHODS: The radiologic and intraoral scanning technology, in vitro mechanical experiment, viscoelastic modeling, and finite element analysis (FEA) were integrated to establish an orthodontic simulation model. Twelve FEA models of CA were created, comprising combinations of 2 kinds of thicknesses (0.75 and 0.50 mm), 2 forms of gingival-margin shape (scalloped and straight), and 3 types of margin height (-2, 0, and 2 mm). In vitro testing was carried out to determine the actual properties of material thickness. RESULTS: A 0.75-mm-thick aligner resulted in greater periodontal ligament (PDL) stress than 0.50 mm, and there was no clear correlation between the control ability of tooth movement and the thickness. For different margin designs, PDL stress at -2 mm height was significantly lower than those with a higher border. Aligners with straight margins had higher stress than the scalloped aligners, whereas the differences were unnoticeable at 2 mm height. The optimized aligner with differential margin designs was recommended on the basis of biomechanical calculations, which facilitated the efficiency and control of tooth movement for multiple teeth. CONCLUSIONS: The effect of material thickness and margin design of CA on the force and movement differed in different teeth. Preferable CA designs of each tooth during different movement stages should be presented personalized under the guidance of precise biomechanics instead of pure morphologic analysis.

The Impact of Concomitant Proton Pump Inhibitors Therapy on Clinical Outcome of Cancer Patients Treated With Immune Checkpoint Inhibitors: A Meta-analysis.

BACKGROUND: In patients with advanced cancer receiving immune checkpoint inhibitors (ICIs) therapy, there are conflict perspectives about the influence of concomitant use of proton pump inhibitors (PPIs). We are aimed at exploring the influence of concomitant PPIs exposure on clinical outcome among cancer patients receiving ICIs treatment. METHODS: We searched relevant literatures in PubMed, EMBASE, and the Cochrane Library without language restrictions. We extracted the data from selected studies and calculated the pooled hazard ratios (HRs) with 95% CIs through professional software for overall survival and progression-free survival among cancer patients undergoing ICIs therapy exposed to PPIs. RESULTS: Fourteen studies including 6716 advanced cancer patients receiving ICIs treatment were appropriate for analysis judging by pre-set inclusion and exclusion criteria. The result indicated that concomitant PPIs exposure was significantly related to shorter overall survival (HR=1.388; 95% CI: 1.278-1.498, P <0.001) and progression-free survival (HR=1.285; 95% CI: 1.193-1.384, P <0.001) among multiple cancer patients receiving ICIs therapy. CONCLUSIONS: Our meta-analysis showed that concomitant PPIs exposure had an adverse impact on clinical outcome among patients receiving ICIs therapy. Clinical oncologists must be cautious of PPIs delivery during ICIs treatment.

Bisphosphonate-Modified Functional Supramolecular Hydrogel Promotes Periodontal Bone Regeneration by Osteoclast Inhibition.

Regeneration of periodontal tissue remains a challenge. Under periodontitis, osteoclasts are overactivated and bone loss occurs. We incorporated sodium alendronate (Alen), a medication commonly used to treat osteoporosis, into a supramolecular hydrogel system in order to create a novel biomaterial that would promote periodontal bone regeneration by inhibiting osteoclast overactivation. The Nap-Gly-Phe-Phe (NapGFF) peptide chain was modified to synthesize the functional Nap-Alen gelator. Afterward, the Nap-Alen/HAP supramolecular hydrogel composite with a suitable hydroxyapatite (HAP) ratio was constructed, which has outstanding mechanical properties and 3D structure. In addition to its good biocompatibility, it can inhibit the proliferation of bone marrow-derived macrophages (BMDMs) and differentiation of osteoclasts. Due to the simultaneous introduction of porous HAP, the hydrogel with a nanofiber structure was formed into a 3D mesh-like sparse porous composite hydrogel. While enhancing the mechanical properties of the gel, the porous structure facilitated the attachment and migration of bone regeneration-related cells. Therefore, it can effectively promote the regeneration of periodontal bone. In the future, by modifying the biophysical properties and loading stem cells or cytokines, this supramolecular hydrogel composite constructed in this study may provide a new strategy for tissue regeneration engineering and provide a preliminary experimental basis for relevant clinical translational studies.