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Abstract Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). Here we present a new approach to treat MASH, termed “Fibrosis overexpression and retention (FORT)”. In this strategy, we design (1) retinoid-derivative lipid nanoparticle (LNP) to enable enhanced mRNA overexpression in fibrotic regions, and (2) mRNA modifications which facilitate anchoring of therapeutic proteins in ECM. LNPs containing carboxyl-retinoids, rather than alcohol- or ester-retinoids, effectively deliver mRNA with over 10-fold enhancement of protein expression in fibrotic livers. The carboxyl-retinoid rearrangement on the LNP surface improves protein binding and membrane fusion. Therapeutic proteins are then engineered with an endogenous collagen-binding domain. These fusion proteins exhibit increased retention in fibrotic lesions and reduced systemic toxicity. In vivo, fibrosis-targeting LNPs encoding fusion proteins demonstrate superior therapeutic efficacy in three clinically relevant male-animal MASH models. This approach holds promise in fibrotic diseases unsuited for protein injection.

Abstract The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen‐carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption‐caused insufficient hypoxia relief. Herein, a carrier‐free oxygen nano‐tank based on modular fluorination prodrug design and co‐assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano‐tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co‐assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on‐demand laser‐triggerable ATO release, closed‐loop tumor hypoxia relief, and significant enhancement to PPa‐mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention‐enhanced cancer therapy.

Large amounts of CO2 were discharged into the atmosphere, resulting in a severe greenhouse effect and inducing ecological environmental problems that threaten human survival. Integrated carbon dioxide capture and conversion (ICCC) with Dual Functional Materials (DFMs) was a promising process to capture CO2 emission in flue gas and convert it into value-added chemicals, reducing energy consumption and economic cost. The catalytic component of DFMs enhances hydrogen source activation and promotes carbonate hydrogenation to produce high value-added chemicals. The hydrogenation process achieved the regeneration of bifunctional materials, which is the key to realizing the ICCC process. This research focuses on DFMs development with different hydrogen sources (hydrogen or light alkanes) for the ICCC process in recent years. In addition, the reaction mechanism and catalytic components modification were discussed to improve the in-situ conversion activity of the ICCC process. Finally, future prospects were anticipated to guide the development and application scenarios of DFMs in the ICCC process.

Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery. However, prodrug activation remains a rate-limiting step for exerting therapeutic actions, which requires to quickly reach the minimum valid concentrations of free drugs. Fortunately, we find that a natural compound (BL-193) selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin (PPT) at ineffective dose concentrations. Based on this, we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT. Specifically, a redox-sensitive prodrug (PSSF) of PPT is synthesized by coupling 9-fluorenyl-methanol (Fmoc-OH) with PPT linked via disulfide bond. Intriguingly, PSSF with a π-conjugated structure readily co-assembles with BL-193 into stable nanoassembly. Significantly, BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic window for PPT. Moreover, prodrug design and precise hybrid nanoassembly well manage off-target toxicity. As expected, such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses. This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.

Background: This study compared the efficacy of oropharyngeal airways (OA) and nasopharyngeal airways (NA) in maintaining oxygenation during painless fiberoptic bronchoscopy (PFB) in patients sedated with remimazolam besylate. Methods: Two hundred and fifty-two patients were randomized to the OA or NA group. Remimazolam besylate was used for anesthesia induction and maintenance in both groups. We measured and recorded several physiological parameters, including mean arterial pressure, heart rate and oxygen saturation (SpO2), at various time points: before anesthesia (T1), after anesthesia induction (T2), immediately after the bronchoscope reached the trachea (T3), during the procedure (T4), and 5 min after transfer to the post-anesthesia care unit (T5). The incidence and frequency of hypoxemia, minimum SpO2 during the procedure and patient awakening time after flumazenil administration were also recorded. Additionally, the relationship between minimum SpO2 and body mass index (BMI) was investigated. Results: Patients in the NA group experienced a higher incidence of hypoxemia compared to the OA group. Patients in the OA group maintained higher SpO2 levels at T3 and had a higher minimum SpO2 during the procedure than the NA group. Furthermore, a significant negative correlation was observed between minimum SpO2 and BMI. Following flumazenil anesthesia reversal, nearly 97 % of patients awakened within 1 min. Conclusions: This study suggests that OA may provide a better safety profile than NA by preserving respiratory function during PFB.

The reaction of coal char is a unique feature of pulverized coal combustion, which is differed from that of gas or liquid fuels combustion. Since the heterogeneous reaction process accounts for about 90% of the entire time for pulverized coal combustion, it is very important for the efficient utilization of pulverized coal. In general, pulverized coal particles are carried into the furnace in the form of dense phase rather than sparse phase or single particle, and the interaction between particles will affect the heterogeneous reaction of coal char. Therefore, it is necessary to deepen the understandings on the heterogeneous reaction behavior of coal char particles for the efficient utilization of pulverized coal. This study carries out a two-dimensional numerical simulation with the pseudo-steady state approach to study the reaction characteristics of coal char particle group. Firstly, the reaction characteristics of coal char single particle and coal char particle group are analyzed by the comparison, compared with the single particle, the peak temperature of the particle group increases by about 300 K, the surface temperature of the particle decreases by about 100 K, and the carbon consumption rate decreases by 56%−65%, which indicates that the interaction between particles affects the combustion reaction process of coal char particles. Then, the combustion characteristics of the coal char particles dispersed with three typical modes are studied. With the increase of particle spacing, the proportion of coal char oxidation reaction in each dispersion mode increases by 0.22%−2.20%, and the carbon consumption rate increases by 9.8%−26.1%. A larger particle spacing is beneficial to the diffusion of O2 molecules between particles, and the oxidation reaction and carbon consumption are promoted. Finally, the reaction characteristics of coal char particles under different reaction atmospheres are explored. Compared with the air cases, the peak temperature of the particles under high CO2 and H2O concentration atmospheres increases by 4%−30%, and the surface temperature of the particles increases by 0.5%−3.7%, among which the carbon consumption rate under the condition of 30% O2/70% H2O is the largest, which is 80% higher than that under the air atmosphere. By comprehensive comparison, the order of carbon consumption rate of coal particles dispersed with three modes under the conditions of interaction between particles, particle spacing and reaction atmosphere is as follows: Mode C > Mode B > Mode A (Mode A: particle group is rectangular dispersed; Mode B: particle group is diamond dispersed; Mode C: particles are dispersed in a regular triangle). Thus, the disturbing effect between the particles and the air flow on the consumption of coal char cannot be ignored.

This paper considers the impact of setup time in production scheduling and proposes energy-aware distributed hybrid flow shop scheduling problem with sequence-dependent setup time (EADHFSP-ST) that simultaneously optimizes the makespan and the energy consumption. We develop a mixed integer linear programming model to describe this problem and present a two-stage adaptive memetic algorithm (TAMA) with a surprisingly popular mechanism. First, a hybrid initialization strategy is designed based on the two optimization objectives to ensure the convergence and diversity of solutions. Second, multiple population co-evolutionary approaches are proposed for global search to escape from traditional cross-randomization and to balance exploration and exploitation. Third, considering that the memetic algorithm (MA) framework is less efficient due to the randomness in the selection of local search operators, TAMA is proposed to balance the local and global searches. The first stage accumulates more experience for updating the surprisingly popular algorithm (SPA) model to guide the second stage operator selection and ensures population convergence. The second stage gets rid of local optimization and designs an elite archive to ensure population diversity. Fourth, five problem-specific operators are designed, and non-critical path deceleration and right-shift strategies are designed for energy efficiency. Finally, to evaluate the performance of the proposed algorithm, multiple experiments are performed on a benchmark with 45 instances. The experimental results show that the proposed TAMA can solve the problem effectively.

Abstract Purpose Radical surgery, the first‐line treatment for patients with hepatocellular cancer (HCC), faces the dilemma of high early recurrence rates and the inability to predict effectively. We aim to develop and validate a multimodal model combining clinical, radiomics, and pathomics features to predict the risk of early recurrence. Materials and Methods We recruited HCC patients who underwent radical surgery and collected their preoperative clinical information, enhanced computed tomography (CT) images, and whole slide images (WSI) of hematoxylin and eosin (H & E) stained biopsy sections. After feature screening analysis, independent clinical, radiomics, and pathomics features closely associated with early recurrence were identified. Next, we built 16 models using four combination data composed of three type features, four machine learning algorithms, and 5‐fold cross‐validation to assess the performance and predictive power of the comparative models. Results Between January 2016 and December 2020, we recruited 107 HCC patients, of whom 45.8% (49/107) experienced early recurrence. After analysis, we identified two clinical features, two radiomics features, and three pathomics features associated with early recurrence. Multimodal machine learning models showed better predictive performance than bimodal models. Moreover, the SVM algorithm showed the best prediction results among the multimodal models. The average area under the curve (AUC), accuracy (ACC), sensitivity, and specificity were 0.863, 0.784, 0.731, and 0.826, respectively. Finally, we constructed a comprehensive nomogram using clinical features, a radiomics score and a pathomics score to provide a reference for predicting the risk of early recurrence. Conclusions The multimodal models can be used as a primary tool for oncologists to predict the risk of early recurrence after radical HCC surgery, which will help optimize and personalize treatment strategies.

BackgroundThe utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated.MethodsFrom a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns.ResultsPreoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers.ConclusionsAFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

Abstract The incidence of prostate cancer (PCa), the most prevalent malignancy, is currently at the forefront. RNA modification is a subfield of the booming field of epigenetics. To date, more than 170 types of RNA modifications have been described, and N6-methyladenosine (m6A) is the most abundant and well-characterized internal modification of mRNAs involved in various aspects of cancer progression. METTL3, the first identified key methyltransferase, regulates human mRNA and non-coding RNA expression in an m6A-dependent manner. This review elucidates the biological function and role of METTL3 in PCa and discusses the implications of METTL3 as a potential therapeutic target for future research directions and clinical applications.

Abstract RNA modification is a post-transcriptional level of regulation that is widely distributed in all types of RNAs, including mRNA, tRNA, rRNA, miRNA, and lncRNA, where N6-methyladenine (m6A) is the most abundant mRNA methylation modification. Significant evidence has depicted that m6A modifications are closely related to human diseases, especially cancer, and play pivotal roles in RNA transcription, splicing, stabilization, and translation processes. The most common urological cancers include prostate, bladder, kidney, and testicular cancers, accounting for a certain proportion of human cancers, with an ever-increasing incidence and mortality. The recurrence, systemic metastasis, poor prognosis, and drug resistance of urologic tumors have prompted the identification of new therapeutic targets and mechanisms. Research on m6A modifications may provide new solutions to the current puzzles. In this review, we provide a comprehensive overview of the key roles played by RNA modifications, especially m6A modifications, in urologic cancers, as well as recent research advances in diagnostics and molecularly targeted therapies.

The interfacial structure of metal and oxide support plays a pivotal role in reverse water gas shift (RWGS). However, rare work investigated the factor of the metal-oxide interface during RWGS reaction. In this work, the interface of Cu/CeO2 catalysts was designed through the thermal treatment of copper nitrate salt on CeO2 with an H2 atmosphere under different temperatures, and CO2 hydrogenation performance was studied at 400 °C to investigate the effect of interfacial structure on RWGS reaction. Among these prepared catalysts, Cu/CeO2-400 catalysts achieved the best CO2 conversion activity (CO production rate 1.23 mol/gcat.h). Cu interacted with CeO2 to form Cu-O-Ce interface and induced more oxygen vacancy formation. The oxygen vacancy around the Cu-CeO2 interface enhanced CO2 adsorption and promoted CO2 conversion. CO2 reacted with active hydrogen to COOH, then COOH species dissociated into CO and OH adsorbed on the surface of Cu-CeO2. These results gave insights into the design of a highly effective catalyst for CO2 hydrogenation.

In the realm of customized manufacturing, production cycles are often compressed to capture market opportunities swiftly. The blanking system stands as the inaugural and pivotal phase in the realm of large equipment customized manufacturing. This study abstracts a novel problem from real-world blanking systems, as the distributed unrelated parallel machine scheduling with heterogeneous factories and order priorities (DUPMS-HP). The presented work formulates the bi-objective DUPMS-HP, aiming to minimize both the total weighted tardiness and the workload gap of each machine. A learning-based two-phase cooperative optimizer (LCTPO) is introduced to address this NP-hard problem, featuring: i) a cooperative evolutionary algorithm during the first stage for global search to ensure diversity; ii) the incorporation of five problem-specific local search strategies in the first stage to balance priority and due date constraints. Additionally, reinforcement learning is applied to learn and select the best neighborhood search operator for each elite solution, further enhancing diversity. The effectiveness of the proposed algorithm is validated through a comparative analysis with five state-of-the-art algorithms on 20 instances. Experimental results affirm that LCTPO is more adept at solving DUPMS-HP compared to the alternative algorithms.

China has put forward the ''Dual Carbon'' target, carbon peak by 2030 and carbon neutrality by 2060. It is necessary to study the current situation of carbon emissions, carbon reduction potential, and decarbonization paths of industrial cities in China. Taking Wuhan, a typical industrial city, as an object, anthropogenic carbon emissions and distribution in Wuhan in the last 20 years are analyzed. The extended STIRPAT and the gray relation models are adopted to construct a decomposition model for discerning the driving factors of carbon emissions in Wuhan. Besides, a scenario-driven carbon emission projection system with five development scenarios is established, where carbon sinks from the ecosystem and CCUS technology and the decoupling status of “CO2 emissions-GDP” are considered, to assess Wuhan's carbon emissions reduction potential and decarbonization pathways by 2060. The results show that Wuhan's carbon emissions mainly come from the industrial and transportation sectors and that the increase in the share of tertiary industry and the decrease in carbon intensity are the main factors curbing Wuhan's carbon emissions. To realize the “Dual Carbon” target, Wuhan's decarbonization development should start with the ISI (Industrial Structure improving) scenario and focus mainly on the development of tertiary industry between 2022 and 2035. Between 2035 and 2045, the decarbonization development transitions to the BID (Comprehensively improving) scenario, which requires simultaneous accelerating improvement of the city's economy and energy structure. Finally, carbon neutrality can be achieved between 2050 and 2060 through ecosystem carbon sinks and technology carbon sinks.

During oxy-fuel combustion, the NO emission can be inhibited by the strongly reductive atmosphere caused by the high proportion of gasification reaction, which is a unique feature that differs from air combustion. The alkali and alkaline earth metals (AAEMs) contained in coal ash can catalyze gasification reactions, promoting the homogeneous reduction process of NO. Besides, AAEMs also suppress NO emission through catalyzing the NO heterogeneous reduction by char (CNO). Both catalytic effects of AAEMs have been studied at relatively low temperatures (below 1000 °C) in a simple atmosphere (pure CO2). However, the catalytic effect of AAEMs on NO reduction is still unclear during oxy-fuel combustion due to the more complex reaction atmosphere, higher reaction temperatures, and the presence of gasification reactions. In this work, the effect of different factors on the catalytic effect of AAEMs under O2/CO2 atmosphere is investigated. Results show that the order of the catalytic effect of AAEMs on NO reduction is Na > K > Ca > Mg, with the highest NO reduction efficiency of 30 % for Na. The catalytic effect of Na on NO reduction weakened as the temperature increases. When the temperature increased from 1373 K to 1573 K, the NO reduction efficiency (ηNO) of Na decreased from 30 % to 6 %. While the catalytic effect of Na on NO reduction strengthened as the oxygen concentration increases. When the O2 concentrations increased from 10 vol.% to 30 vol.%, the ηNO values of Na increased from 27 % to 35 %. The K-Na binary additive is more effective in reducing NO emissions than K and Na alone, with NO reduction efficiency as high as 46.8 % at a K/ Na is 1:2. Besides, the Raman test results reveal that K contributed to the conversion of amorphous carbon into a regular graphite crystal structure. Na disrupted the graphite structure resulting in more defective points appearing in the graphite lattice. These results are expected to provide a theoretical reference and new insights for the reduction of NO emission during oxy-fuel combustion.

Abstract HER2-positive gastric cancer (GC) makes up 15–20% of all GC incidences, and targeted therapy with trastuzumab is the standard of treatment. However, the mechanisms of resistance to trastuzumab are still not fully understood and presents a significant challenge in clinical practice. In this study, whole exome sequencing (WES) was performed on paired tumor tissues before trastuzumab treatment (at baseline) and at progressive disease (PD) in 23 GC patients. Clinicopathological and molecular features that may be associated with primary and/or acquired resistance to trastuzumab were identified. Lauren classification of intestinal type was associated with a more prolonged progression-free survival (PFS) than diffuse type (HR = 0.29, P = 0.019). Patients with low tumor mutation burden (TMB) showed significantly worse PFS, while high chromosome instability (CIN) was correlated with prolonged OS (HR = 0.27; P = 0.044). Patients who responded to treatment had a higher CIN than nonresponders, and a positive trend towards increasing CIN was observed as response improved (P = 0.019). In our cohort, the most common genes to acquire mutations are AURKA, MYC, STK11, and LRP6 with four patients each. We also discovered an association between clonal branching pattern and survival, with an extensive clonal branching pattern being more closely related to a shorter PFS than other branching patterns (HR = 4.71; P = 0.008). We identified potential molecular and clinical factors that provide insight regarding potential association to trastuzumab resistance in advanced HER2-positive GC patients.

The time-fractional Cattaneo (TFC) equation is a practical tool for simulating anomalous dynamics in physical diffusive processes. The existing numerical solutions to the TFC equation generally deal with the Dirichlet boundary conditions. In this paper, we incorporate the absorbing boundary condition as a complex-frequency-shifted (CFS) perfectly matched layer (PML) into the TFC equation. Then, we develop an adaptive-coefficient (AC) finite-difference frequency-domain (FDFD) method for solving the TFC with CFS PML. The corresponding analytical solution for homogeneous TFC equation with a point source is proposed for validation. The effectiveness of the developed AC FDFD method is verified by the numerical examples of four typical TFC models, including the different orders of time-fractional derivatives for both the homogeneous model and the layered model. The numerical examples show that the developed AC FDFD method is more accurate than the traditional second-order FDFD method for solving the TFC equation with the CFS PML absorbing boundary condition, while requiring similar computational costs.

Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide but current drug therapeutics show important limitations. Here, the authors exploit a selfpropelling nano-penetrator with high fuel loading and controllable motion which is molecularly co-assembled using a photothermal photosensitizer and a photothermal-activable NO donor.

Photodynamic therapy (PDT) has been extensively investigated as a spatiotemporally noninvasive and controllable modality for cancer treatment. However, the intracellular antioxidant systems mainly consisting of thioredoxin (Trx) and glutathione (GSH) significantly counteract and prevent reactive oxygen species (ROS) accumulation, resulting in a serious loss of PDT efficiency. To address this challenge, we propose that PDT can be improved by precisely blocking antioxidant systems. After molecular engineering and synergistic cytotoxic optimization, a DSPE-PEG2K-modified dual-drug nanoassembly (PPa@GA/DSPE-PEG2K NPs) of pyropheophorbide a (PPa) and gambogic acid (GA) is successfully constructed. Interestingly, GA can effectively destroy intracellular antioxidant systems by simultaneously inhibiting Trx and GSH. Under laser irradiation, the cell-killing effects of PPa is significantly enhanced by GA-induced inhibition of the antioxidant systems. As expected, PPa@GA/DSPE-PEG2K nanoparticles demonstrate potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model. Such a carrier-free self-sensitized nanotherapeutic offers a novel co-delivery strategy for effective PDT.

Background Among B-cell lymphoma, multiple myeloma (MM) is an incurable malignancy. miR-140-3p was known to be an inhibitor in malignant tumors. However, the function of miR-140-3p in MM remains unclear. Methods qRT-PCR was performed to determine the expressions of miR-140-3p and BZW2 mRNA. The protein level of BZW2 was determined by the western blot. Cell viability or cell apoptosis was detected by the MTT assay or flow cytometry, respectively. Binding between miR-140-3p and BZW2 was validated using the dual luciferase assay. Xenograft model was applied to verify the results of in vitro study. Results The level of miR-140-3p was significantly downregulated in MM. Overpexression of miR-140-3p impaired the proliferation of MM cell lines and induced apoptosis in MM cells. miR-140-3p was validated to target BZW2 and inhibit the expression of BZW2. BZW2 was involved in the regulation of miR-140-3p on MM cell vitality and apoptosis. In vivo study revealed that miR-140-3p impeded tumorigenesis of MM cell line in nude mice. Conclusion Our present study revealed that miR-140-3p served as a suppressor in MM by negatively regulating BZW2. Thus, miR-140-3p could act as a new target for treating MM.

Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.

Urological tumors, such as prostate cancer, renal cell carcinoma, and bladder cancer, have shown a significant rise in prevalence in recent years and account for a significant proportion of malignant tumors. It has been established that metastasis to distant organs caused by urological tumors is the main cause of death, although the mechanisms underlying metastasis have not been fully elucidated. The fibronectin receptor integrin α5β1 reportedly plays an important role in distant metastasis and is closely related to tumor development. It is widely thought to be an important cancer mediator by interacting with different ligands, mediating tumor adhesion, invasion, and migration, and leading to immune escape. In this paper, we expound on the relationship and regulatory mechanisms of integrin α5β1 in these three cancers. In addition, the clinical applications of integrin α5β1 in these cancers, especially against treatment resistance, are discussed. Last but not least, the possibility of integrin α5β1 as a potential target for treatment is examined, with new ideas for future research being proposed.

Summary: Platelets have a great ability to modulate immune responses. Monocyte-platelet aggregates (MPAs) are associated with the pathogenesis of cardiac disease. Notably, a low preoperative platelet count often indicates poor postoperative recovery following acute aortic dissection (AAD). The functions of platelets and MPAs in AAD, however, remain poorly understood. We found that, despite decreased platelet counts, platelets were also activated in AAD patients, with significant alterations in immune-modulating mediators. Of interest, monocytes in AAD patients had a suppressed immune status, which was correlated with poor outcomes following surgery. Interestingly, platelets preferentially aggregated with monocytes, and the levels of MPAs were related to recovery after surgical repair in AAD patients. Platelets restored suppressed monocyte functions in AAD patients by forming aggregates and partly by secreting matrix metalloproteinase-9 (MMP-9). Thus, the results point to a previously unknown mechanism for platelets involving monocyte reprogramming, which may improve postoperative outcomes following complex cardiovascular surgery.

Abstract Purpose To explore the relationship between the genotype and renal phenotype in a Chinese cohort and guide clinical decision-making for treating tuberous sclerosis complex (TSC). Materials and methods We reviewed 173 patients with definite TSC at three centers in China from September 2014 to September 2020. All the patients underwent TSC1 and TSC2 genetic testing as well as renal phenotypic evaluation. All analyses were performed using the SPSS software, version 19.0, with a cut-off P value of 0.05 considered statistically significant. Results We identified variants in 93% (161/173) cases, including 16% TSC1 and 77% TSC2 variants. Analysis of the relationship between the genotype and renal phenotype, revealed that those with TSC2 variants were more likely to develop severe renal AML (> 4) (P = 0.044). In terms of treatment, TSC2 variants were more likely to undergo nephrectomy/partial nephrectomy (P = 0.036) and receive mTOR medication such as everolimus (P

Abstract Background Homologous recombination deficiency (HRD) is closely associated with patient prognosis and treatment options in prostate cancer (PCa). However, there is a lack of quantitative indicators related to HRD to predict the prognosis of PCa accurately. Methods We screened HRD-related genes based on the HRD scores and constructed an HRD cluster system to explore different clinicopathological, genomic, and immunogenomic patterns among the clusters. A risk signature, HRDscore, was established and evaluated by multivariate Cox regression analysis. We noticed that SLC26A4, a model gene, demonstrated unique potential to predict prognosis and HRD in PCa. Multi-omics analysis was conducted to explore its role in PCa, and the results were validated by qRT-PCR and immunohistochemistry. Results Three HRD clusters were identified with significant differences in patient prognosis, clinicopathological characteristics, biological pathways, immune infiltration characteristics, and regulation of immunomodulators. Further analyses revealed that the constructed HRDscore system was an independent prognostic factor of PCa patients with good stability. Finally, we identified a single gene, SLC26A4, which significantly correlated with prognosis in three independent cohorts. Importantly, SLC26A4 was confirmed to distinguish PCa (AUC for mRNA 0.845; AUC for immunohistochemistry score 0.769) and HRD (AUC for mRNA 0.911; AUC for immunohistochemistry score 0.689) at both RNA and protein levels in our cohort. Conclusion This study introduces HRDscore to quantify the HRD pattern of individual PCa patients. Meanwhile, SLC26A4 is a novel biomarker and can reasonably predict the prognosis and HRD in PCa.

Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs, whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable drug release still limits the development and application of this technology. Here, a simple and practical nanoassembly of DOX and DiR is constructed on basis of their co-assembly characteristics. Multiple interaction forces are found to drive the co-assembly process. Moreover, DOX release from the nanoassembly can be well controlled by the acidic tumor microenvironment and laser irradiation, resulting in favorable delivery efficiency of DiR and DOX in vitro and in vivo. As expected, the nanoassembly with high therapeutic safety completely eradicated the mice triple negative breast cancer cells (4T1) on BALB/c mice, owing to synergistic chemo-photothermal therapy. More interestingly, DiR and DOX synergistically induce immunogenic cell death (ICD) of tumor cells after treatment, enabling the mice to acquire immune memory against tumor growth and recurrence. Such a facile nanoassembly technique provides a novel multimodal cancer treatment platform of chemotherapy/phototherapy/immunotherapy.

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a type of leukemia with high malignant behaviors, which seriously threatens the health of people. It has been reported that circFBXW7 is downregulated in lymphoblastic leukemia. Nevertheless, the exact role of circFBXW7 in T-ALL remains elusive. MTT assay was used to assess the cell viability. Cell apoptosis was assessed by flow cytometry. In addition, mRNA expressions were assessed by RT-qPCR, and a western blot was applied to investigate the protein levels. Meanwhile, the correlation among circFBXW7, miR-494-3p, and SOX1 was explored by RNA pull-down and dual-luciferase reporter assays. Furthermore, a xenograft mice model was conducted to verify the function of circFBXW7 in T-ALL in vivo. CircFBXW7 was significantly downregulated in T-ALL, of which overexpression inhibited the cell viability and induced the apoptosis of Jurkat cells. Moreover, miR-494-3p was identified to be a functional downstream effector to be involved in circFBXW7-mediated T-ALL cell proliferation. Besides, SOX1 was a direct target of miR-494-3p, and the impact of miR-494-3p mimics on T-ALL cell growth was inhibited in the presence of SOX1 overexpression. Furthermore, overexpression of circFBXW7 dramatically inhibited T-ALL tumor growth. In summary, circFBXW7 attenuated the tumorigenesis of T-ALL through the mediation of the miR-494-3p/SOX1 axis, which might be novel targets for T-ALL treatment.

Background The imbalance of monocyte/macrophage polarization toward the preferential proinflammatory phenotype and a lack of normal inflammation resolution are present in acute myocardial infarction (AMI). Our previous study showed that upregulation of brain‐derived neurotrophic factor precursor (proBDNF) in M2‐like monocytes may contribute to the proinflammatory response in the Stanford type‐A acute aortic dissection. The present study aimed to investigate the role of proBDNF signaling in monocytes/macrophages in the progress of AMI. Methods and Results We observed the upregulation of proBDNF in the proinflammatory monocytes of patients with AMI. The upregulation of proBDNF was also observed in the circulating proinflammatory Ly6Chigh monocytes and cardiac F4/80+CD86+ macrophages 3 days after AMI in a mice model. To neutralize proBDNF, the mice subjected to AMI were injected intraperitoneally with a monoclonal anti‐proBDNF antibody. Echocardiography, 2,3,5‐triphenyltetrazolium chloride staining, and positron emission tomography/computed tomography results demonstrate that monoclonal anti‐proBDNF antibody treatment further impaired cardiac functions, increased infarct size, and exacerbated the proinflammatory state. Moreover, the level of proinflammatory Ly6Chigh in the blood and F4/80+CD86+ in the heart was further increased in monoclonal anti‐proBDNF antibody mice. RNA sequencing revealed that matrix metalloprotease‐9 protein level was dramatically increased, along with the activated proinflammatory‐related cytokines. Matrix metalloprotease‐9 inhibitor treatment attenuated the deteriorated effect of monoclonal anti‐proBDNF antibody on cardiac function and infarct areas. Conclusions Our study shows that endogenous proBDNF in monocytes/macrophages may exert protective roles in cardiac remodeling after AMI by regulating matrix metalloprotease‐9 activity.

Highlights Hyperactivation of mammalian target of rapamycin (mTOR) is essential in the pathogenesis of tuberous sclerosis complex (TSC) and can serve as a therapeutic target. mTOR inhibitors have shown considerable success in multiple clinical trials for the treatment of TSC, including neurological, pulmonary, cardiac, renal, and cutaneous phenotypes. mTOR inhibitors are associated with adverse events, which should be considered during the management of TSC. Indicators to predict mTOR inhibitor efficacy are required to select patients who are likely to benefit from such therapy.

Background: Exons are an important part of genes. However, there has been no molecular marker technique based on single primer amplification developed for exons region. Results: A novel molecular marker technique called exon based amplified polymorphism (EBAP) which used single primer to perform the PCR was developed. Single primers were designed based on the rich GC bases in the exon region of genes. The single primer consists of filling sequence, intermediate core region sequence and selective bases sequence. The filling sequence has a total of six bases, which can be 2A and 2T or 3A and 3T. The intermediate core region sequence consists of eight bases, all of which are G and C, but at least 2G or 2C are required. The first of the three selective bases must be either A or T, and the second and third are arbitrary bases. Due to the principle of primer design, these single primers should be universal. We applied it to the DNA polymorphisms detection of maize, sugarcane, potato, cassava, cabbage, and peanut. The results showed that it detected more abundant DNA polymorphisms in the first five crops, but not in the cultivated peanut. In addition, different band patterns were obtained by amplifying peanut cDNA with different single primers. Conclusions: We have developed a novel and universal molecular marker technique. It is simple, fast and efficient. It does not require genomic sequence information. It can be widely used in germplasm identification, genetic diversity analysis, and molecular fingerprinting. How to cite: Xiong F, Liu J, Tang R, et al. Exon based amplified polymorphism (EBAP): A novel and universal molecular marker for plants. Electron J Biotechnol 2022;56. https://doi.org/10.1016/j.ejbt.2022.01.001.

The limiter in grid-connected inverter control may cause sustained oscillation in the system. The large-signal impedance model is provided since the traditional small-signal impedance model cannot accurately describe the characteristics of the limiter. In this paper, there are three established large-signal impedance models of grid-connected inverters that take into account the limiter in the phase-locked loop (PLL), the limiter in the current control loop and the limiter in the pulse width modulation (PWM). Based on the established models, the influences of these different limiters on the output impedance characteristics of the grid-connected inverter are discussed. Furthermore, the stability of the system considering the influence of different limiters is analyzed and the oscillation frequency and amplitude of the system are predicted. The simulation verifies the accuracy of the large-signal impedance model and the predicted oscillation frequency and amplitude.

IntroductionImmune checkpoint inhibition (ICI) plus bevacizumab (BEV) is the standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of ICI plus bevacizumab and ICI plus receptor tyrosine kinase inhibitor (TKI) in this patient population.MethodsThis retrospective single-institution study enrolled 94 patients with uHCC who received ICI plus TKI or bevacizumab as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were used to evaluate treatment efficacy. RECIST v1.1 criteria were used to calculate the objective clinical response. Common Terminology Criteria for Adverse Events were used to report and categorize adverse events.ResultsBy the last follow-up interview on May 15, 2022, there were 57 deaths, and 19 patients did not develop disease progression. Thirty patients received sintilimab/atezolizumab plus bevacizumab (ICI + BEV group), and 64 received ICI plus TKI (ICI + TKI group). The median OS was 430 days (95% CI, 266-NA) in the ICI+TKI group and 498 days (95% CI, 349-NA) in the ICI+BEV group (HR, 1.20; 95% CI, 0.69-2.07; P = 0.52). There was no significant difference between the two groups in the median PFS (182 vs. 221 days, P=0.67). In the ICI+TKI group, the ORR and DCR were 28.1% and 67.2%, respectively. In the ICI+BEV group, the ORR and DCR were 26.7% and 66.7%, respectively. The overall incidence of adverse events was similar between the two groups. Palmar-plantar erythrodysesthesia syndrome (23[36%]) occurred only in the ICI + TKI group. Patients who received ICI+BEV were more prone to upper gastrointestinal bleeding (2 [7%]), with one patient with grade 4 requiring emergency DSA treatment.ConclusionThis study found that ICI+TKI and ICI+BEV as first-line treatments were similar in OS, PFS, and tumor response in uHCC. Different populations are suitable for different regimens because of the different adverse events.

Abstract After field cooling (FC) alternating current poling (ACP), we investigated the dielectric and piezoelectric properties of [001]pc-oriented 0.24Pb(In1/2Nb1/2)O3 (PIN)-0.46Pb(Mg1/3Nb2/3)O3 (PMN)-0.30PbTiO3 (PT) (PIMN-0.30PT) single crystals (SCs), which were manufactured by continuous-feeding Bridgman (CF BM) within morphotropic phase boundary (MPB) region. By ACP with 4 kVrms/cm from 100 to 70 °C, the PIMN-0.30PT SC attained high dielectric permittivity (ε33 T /ε0) of 8330, piezoelectric coefficient (d 33) of 2750 pC/N, bar mode electromechanical coupling factor k 33 of 0.96 with higher phase change temperature (T pc) of 103 °C, and high Curie temperature (T C ) of 180 °C. These values are the highest ever reported as PIMN-xPT SC system with T pc > 100 °C. The enhancement of these properties is attributed to the induced low symmetry multi-phase supported by phase analysis. This work indicates that FC ACP is a smart and promising method to enhance piezoelectric properties of relaxor-PT ferroelectric SCs including PIMN-xPT, and provides a route to a wide range of piezoelectric device applications.

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG2K) is utilized to achieve core-matched PEGylating modification via the π‒π stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG2K shell. Compared to PCL-PEG2K with similar molecular weight, PPa-PEG2K significantly increases the stability, prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly. As a result, PPa/PPa-PEG2K NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model. Together, such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.

To provide an overview of the current situation, challenges, and trends in online medical services from the perspective of andrology and promote the development of online medical services. Users of the Learning Alliance of Urology, who mainly worked in central regions of China, were invited to complete the questionnaire that included information on the participants and their institutions and their involvement in and concerns for online medical services. We received 875 complete responses. The percentage of online andrology patients at most institutions was less than 30%. The most common services were online appointment registration (92.7%) and online payment (81.8%). Online chat consultation (77.7%) was the most common form of consultation. Only 1 in 5 of the institutions had constructed their Internet hospital. Factors related to the percentage of online andrology patients included specialized andrology clinics and wards, sufficient time for doctors to provide online services, more diversified services, and online clinic training. The biggest challenge for online medical services was diagnosis and treatment safety. It is essential to raise awareness of online medical services for hospitals and patients and strengthen standardized management and training of online medical services, especially applicable to central regions of China. However, online medical services cannot wholly replace offline services due to insufficient diagnosis and treatment.

According to existing reports, mutations in the slow tropomyosin gene (TPM3) may lead to congenital fiber-type disproportion (CFTD), nemaline myopathy (NM) and cap myopathy (CD). They are all congenital myopathies and are associated with clinical, pathological and genetic heterogeneity. A ten-year-old girl with scoliosis was unable to wean from mechanical ventilation after total intravenous anesthesia. The girl has scoliosis, respiratory insufficiency, motion delay and muscle weakness; her younger brother has a similar physiology but does not have scoliosis or respiratory insufficiency, and her parents are healthy. We conducted genetic testing and found a c.502C > G (p.R168G) heterozygous mutation in the family. This mutation originated from the father and was autosomal dominant. Muscle biopsy results indicated that no special structures were present, and the type I fiber ratio was not notably high compared to previous reports. Although the family members have the same mutations, their clinical manifestations are quite different.

Abstract Background TERMINAL FLOWER 1 (TFL1) belongs to the phosphatidylethanolamine-binding protein (PEBP) family, which is involved in inflorescence meristem development and represses flowering in several plant species. In the present study, four TFL1 genes were cloned from the mango (Mangifera indica L.) variety ‘SiJiMi’ and named MiTFL1-1, MiTFL1-2, MiTFL1-3 and MiTFL1-4. Results Sequence analysis showed that the encoded MiTFL1 proteins contained a conserved PEBP domain and belonged to the TFL1 group. Expression analysis showed that the MiTFL1 genes were expressed in not only vegetative organs but also reproductive organs and that the expression levels were related to floral development. Overexpression of the four MiTFL1 genes delayed flowering in transgenic Arabidopsis. Additionally, MiTFL1-1 and MiTFL1-3 changed the flower morphology in some transgenic plants. Yeast two-hybrid (Y2H) analysis showed that several stress-related proteins interacted with MiTFL1 proteins. Conclusions The four MiTFL1 genes exhibited a similar expression pattern, and overexpression in Arabidopsis resulted in delayed flowering. Additionally, MiTFL1-1 and MiTFL1-3 overexpression affected floral organ development. Furthermore, the MiTFL1 proteins could interact with bHLH and 14-3-3 proteins. These results indicate that the MiTFL1 genes may play an important role in the flowering process in mango.

Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles (PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxel-fatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cis-trans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.

Abstract Background Photothermal therapy (PTT) has been extensively investigated as a tumor-localizing therapeutic modality for neoplastic disorders. However, the hyperthermia effect of PTT is greatly restricted by the thermoresistance of tumor cells. Particularly, the compensatory expression of heat shock protein 90 (HSP90) has been found to significantly accelerate the thermal tolerance of tumor cells. Thus, a combination of HSP90 inhibitor and photothermal photosensitizer is expected to significantly enhance antitumor efficacy of PTT through hyperthermia sensitization. However, it remains challenging to precisely co-deliver two or more drugs into tumors. Methods A carrier-free co-delivery nanoassembly of gambogic acid (GA, a HSP90 inhibitor) and DiR is ingeniously fabricated based on a facile and precise molecular co-assembly technique. The assembly mechanisms, photothermal conversion efficiency, laser-triggered drug release, cellular uptake, synergistic cytotoxicity of the nanoassembly are investigated in vitro. Furthermore, the pharmacokinetics, biodistribution and self-enhanced PTT efficacy were explored in vivo. Results The nanoassembly presents multiple advantages throughout the whole drug delivery process, including carrier-free fabrication with good reproducibility, high drug co-loading efficiency with convenient dose adjustment, synchronous co-delivery of DiR and GA with long systemic circulation, as well as self-tracing tumor accumulation with efficient photothermal conversion. As expected, HSP90 inhibition-augmented PTT is observed in a 4T1 tumor BALB/c mice xenograft model. Conclusion Our study provides a novel and facile dual-drug co-assembly strategy for self-sensitized cancer therapy. Graphic abstract

Phototherapy has been intensively investigated as a non-invasive cancer treatment option. However, its clinical translation is still impeded by unsatisfactory therapeutic efficacy and severe phototoxicity. To achieve high therapeutic efficiency and high security, a nanoassembly of Forster Resonance Energy Transfer (FRET) photosensitizer pairs is developed on basis of dual-mode photosensitizer co-loading and photocaging strategy. For proof-of-concept, an erythrocyte-camouflaged FRET pair co-assembly of chlorine e6 (Ce6, FRET donor) and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR, FRET acceptor) is investigated for breast cancer treatment. Notably, Ce6 in the nanoassemby is quenched by DiR and could be unlocked for photodynamic therapy (PDT) only when DiR is photobleached by 808-nm laser. As a result, Ce6-caused phototoxicity could be well controlled. Under cascaded laser irradiation (808–660 nm), tumor-localizing temperature rise following laser irradiation on DiR not only induces tumor cell apoptosis but also facilitates the tumor penetration of NPs, relieves tumor hypoxia, and promotes the PDT efficacy of Ce6. Such FRET pair-based nanoassembly provides a new strategy for developing multimodal phototherapy nanomedicines with high efficiency and good security.

CONSTANS/CONSTANS-like (CO/COL) transcription factors play a vital role in the photoperiodic flowering pathway. However, the biological functions of COL genes in mango are unclear. In this study, we identified 31 COL genes from the ‘Jin Huang’ mango genome and divided them into three groups according to the specific gene structure and protein domain characteristics. These 31 MiCOL genes were heterogeneously distributed on 14 chromosomes. Expression pattern analysis showed that most MiCOL genes were mainly expressed in leaves and stems and during the floral induction period, followed by the floral differentiation period. The expression of COL genes was induced by drought and salt stress, but the expression patterns of different genes were different, which may suggest that MiCOL genes are involved in the abiotic stress response of mango. Under salt and drought conditions, two MiCOL9 genes can improve the resistance of Arabidopsis by improving the scavenging ability of ROS and proline accumulation and reducing the MDA content. Additionally, overexpression of MiCOL9 genes significantly inhibited flowering in transgenic Arabidopsis. This work provides an important foundation for understanding the biological roles of mango COL genes in plant growth, development and stress responses.

Many researchers have studied low-grade glioma and the immune microenvironment have been studied by many researchers. Recent studies suggest that macrophages and dendritic cells trigger part of the local immune dysregulation in the tumor microenvironment, and they have been polarized into a mixed pro-inflammatory and immunosuppressive phenotype. It is suggested that the degree of immune infiltration is related to the survival, therapeutic effect, and prognosis of patients. This opens up new avenues for cancer treatment. On the basis of immune infiltration degree, a protein interaction network (PIN) and a prognosis model were established, and we chose the top 20 pathways from enrichment analysis to provide potential targets for glioma clinical treatment.

BackgroundPostoperative atrial fibrillation (POAF) is often associated with serious complications. In this study, we collected long-term single-lead electrocardiograms (ECGs) of patients with preoperative sinus rhythm to build statistical models and machine learning models to predict POAF.MethodsAll patients with preoperative sinus rhythm who underwent cardiac surgery were enrolled and we collected long-term ECG data 24 h before surgery and 7 days after surgery by single-lead ECG. The patients were divided into a POAF group a no-POAF group. A clinical model and a clinical + ECG model were constructed. The ECG parameters were designed and support vector machine (SVM) was selected to build a machine learning model and evaluate its prediction efficiency.ResultsA total of 100 patients were included. The detection rate of POAF in long-term ECG monitoring was 31% and that in conventional monitoring was 19%. We calculated 7 P-wave parameters, Pmax (167 ± 31 ms vs. 184 ± 37 ms, P = 0.018), Pstd (15 ± 7 vs. 19 ± 11, P = 0.031), and PWd (62 ± 28 ms vs. 80 ± 35 ms, P = 0.008) were significantly different. The AUC of the clinical model (sex, age, LA diameter, GFR, mechanical ventilation time) was 0.86. Clinical + ECG model (sex, age, LA diameter, GFR, mechanical ventilation time, Pmax, Pstd, PWd), AUC was 0.89. In the machine learning model, the accuracy (Ac) of the train set and test set was above 80 and 60%, respectively.ConclusionLong-term ECG monitoring could significantly improve the detection rate of POAF. The clinical + ECG model and the machine learning model based on P-wave parameters can predict POAF.

Objectives The overexpansion of CD3+B220+ cells is the hallmark and main pathological mechanism of clinical manifestations of spontaneously developed MRL/lpr mice, which are primarily used as a mouse model of SLE. Our recent report demonstrated that blocking brain-derived neurotrophic factor precursor (proBDNF) suppressed the antibody-secreting cell differentiation and proliferation and inhibited the progression of SLE; however, the effect of proBDNF blockade on these CD3+B220+ cells in MRL/lpr mice is unclear.Methods To explore the effect of proBDNF on CD3+B220+ cells, MRL/lpr mice at 12 weeks old were intraperitoneally injected with monoclonal anti-proBDNF antibody (McAb-proB) or control IgG continuously for 8 weeks. The manifestations in mice were observed, and peripheral blood and splenocytes were collected and analysed via flow cytometry at 20 weeks old. In addition, splenic CD3+B220+ cells were subjected to RNA sequencing (RNA-seq) analysis to identify transcriptomic alterations.Results CD3+B220+ cells in peripheral blood (p=0.0101) and spleen (p

BackgroundMetastasis is the leading cause of lung adenocarcinoma (LUAD) patient death. However, the mechanism of metastasis is unclear. We performed bioinformatic analyses for HMOX1 (Heme oxygenase-1), aiming to explore its role in LUAD metastasis.MethodsPan-cancer analysis was first used to identify the metastasis-associated role of HMOX1 in LUAD. HMOX1-related genomic alterations were then investigated. Based on functional enrichment, we systematically correlated HMOX1 with immunological characteristics and mitochondrial activities. Furthermore, weighted gene co-expression network analysis (WGCNA) was applied to construct the HMOX1-mediated metastasis regulatory network, which was then validated at the proteomic level. Finally, we conducted the survival analysis and predicted the potential drugs to target the HMOX1 network.ResultsHMOX1 expression was significantly associated with epithelial-mesenchymal transition (EMT) and lymph and distant metastasis in LUAD. High HMOX1 levels exhibited higher macrophage infiltration and lower mitochondrial complex expression. WGCNA showed a group of module genes co-regulating the traits mentioned above. Subsequently, we constructed an HMOX1-mediated macrophage-mitochondrion-EMT metastasis regulatory network in LUAD. The network had a high inner correlation at the proteomic level and efficiently predicted prognosis. Finally, we predicted 9 potential drugs targeting HMOX1-mediated metastasis in LUAD, like chloroxine and isoliquiritigenin.ConclusionsOur analysis elaborates on the role of HMOX1 in LUAD metastasis and identified a highly prognostic HMOX1-mediated metastasis regulatory network. Novel potential drugs targeting the HMOX1 network were also proposed, which should be tested for their activity against LUAD metastasis in future studies.

One of the major applications (40% in Europe) of plastic is packaging, which is often printed to display required information and to deliver an attractive aesthetic for marketing purposes. However, printing ink can cause contamination in the mechanical recycling process. To mitigate this issue, the use of surfactants in an alkaline washing process, known as de-inking, has been employed to remove printing ink and improve the quality of recyclates. Despite the existence of this technology, there are currently no data linking the de-inking efficiency with typical printing ink compositions. Additionally, it is necessary to investigate the de-inking process under the process parameters of existing recycling plants, including temperature, NaOH concentration, and retention time. This study aims to evaluate the performance of commonly used printing inks with different compositions under various washing scenarios for plastic recycling in conjunction with different de-inking detergents containing surfactants or mixtures of surfactants. The results indicate that the pigments applied to the ink have no significant effect on the de-inking process, except for carbon black (PBk 7). Nitrocellulose (NC) binder systems exhibit high de-inkability (over 95%) under the condition of 55 °C and 1 wt.% NaOH. However, crosslinked binder systems can impede the de-inking effect, whether used as a binder system or as an overprint varnish (OPV). The de-inking process requires heating to 55 °C with 1 wt.% NaOH to achieve a substantial effect. Based on the findings in this work, breaking the Van der Waals forces, hydrogen bonds, and covalent bonds between the printing ink and plastic film is an essential step to achieve the de-inking effect. Further research is needed to understand the interaction between surfactants and printing inks, enabling the development of de-inkable printing inks and high-performance surfactants that allow for de-inking with less energy consumption. The surfactant and NaOH have a synergistic effect in cleaning the printing ink. NaOH provides a negative surface charge for the adsorption of the cationic head of the surfactant and can hydrolyze the covalent bonds at higher concentrations (>2 wt.%).

Abstract Purpose To evaluate the efficacy and safety of everolimus and sirolimus in patients with tuberous sclerosis complex-associated angiomyolipomas (TSC-AML). Materials and methods We performed a multi-institutional retrospective study of TSC-AML patients treated with oral everolimus 10 mg or sirolimus 2 mg per day for at least 3 months. Angiomyolipoma volume was estimated using orthogonal measurements by MRI or CT. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events. All analyses were performed using SPSS 19.0 software. Results Response rates were high in both groups. With the prolonged medication durations, the therapeutic efficacy of both agents became more significant. The TSC-AML volume reduction after 6 and 12 months was more pronounced in patients with everolimus than those with sirolimus. More than half of the patients treated with everolimus had ≥ 50% reduction, and approximately 80% of them had ≥ 30% reduction, which was higher than that in patients treated with sirolimus. Regarding safety, there was no significant difference in the incidence of AEs between the two groups. Conclusions Both everolimus and sirolimus are excellent therapeutic options for TSC-AML. However, everolimus has a better therapeutic efficacy than sirolimus, particularly in reducing TSC-AML volume. Everolimus is therefore recommended as the first choice of therapy for TSC-AML.

Alternating current poling (ACP) in air by changing poling temperature (70–130 °C) and voltages (2–6 kVrms/cm) on pseudo-ternary 0.24 Pb(In1/2Nb1/2)O3-0.46 Pb(Mg1/3Nb2/3)O3-0.30PbTiO3 (PIMN-0.30PT) single crystals (SCs) manufactured by continuous-feeding Bridgman (CF BM) method was investigated. Free dielectric permittivity (εT33/ε0) and piezoelectric constant (d33) were improved to be 7000 and 2340 pC/N, which were 29% higher than those of direct current poling (DCP) at 90 °C with 4 kV/cm (εT33/ε0 = 5440, d33 = 1810 pC/N). However, phase change temperature (Tpc) decreased from 94 °C to 78 °C as opposite results reported by other groups. We demonstrated that the high temperature (HT) ACP improved piezoelectric performance of CF BM SCs, however, the Tpc were different from other crystal growth method. The well-designed ACP process was a promising method for mass production not only to enhance the electrical properties for the pseudo-ternary SCs but also reduce the risk of breakdown and realizes organic solvent-free poling process.

As an important geophysical data processing technique, seismic inversion estimates subsurface rock properties with seismic observations. However, anisotropic inversion, intended for a vertical transverse isotropy (VTI) media that primarily describes shale gas/oil resources, suffers from high nonlinearity. Simulated annealing is a widely used global optimization algorithm for solving nonlinear seismic inverse problems, but it involves multiple optimization parameters (e.g., initial temperature, search limit, and perturbation range). The importance of such parameters has been proven whilst the relevant analysis is limited in seismic inversion studies. This work hereby proposes a sequential anisotropic inversion method for VTI media, wherein we combine Bayesian linear and simulated annealing nonlinear inversion schemes. The simulated annealing is featured by adaptive optimization parameters aided by the linear result. Rather than the conventional method, the adaptive setting can be implemented trace by trace for complex reservoirs, which endows the method with enhanced stability and extended applicability. Synthetic tests and practical application demonstrate the validity of the method, wherein the obtained stiffness parameters facilitate the characterization of potential shale reservoirs with an improved accuracy.