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Machine learning (ML) approaches, widely used in civil engineering, have the potential to reduce computing costs and enhance predictive capabilities. However, many ML methods have yet to be applied to develop models that accurately analyze the nonlinear dynamic response of cross-fault hydraulic tunnels (CFHTs). To predict CFHT models and fragility curves effectively, we identify the most effective ML techniques and improve prediction capacity and accuracy by initially creating an integrated multivariate earthquake intensity measure (IM) from nine univariate earthquake IMs using principal component analysis. Structural reactions are then performed using incremental dynamic analysis by a multimedium-coupled interaction system. Four techniques are used to test ML–principal component analysis (PCA) feasibility. Meanwhile, mathematical statistical parameters are compared to standard probabilistic seismic demand models of expected and computed values using ML-PCA. Eventually, multiple stripe analysis–maximum likelihood estimation (MSA-MLE) is applied to assess the seismic performance of CFHTs. This study highlights that the Gaussian process regression and integrated IM can improve reliable probability and reduce uncertainties in evaluating the structural response. Thorough numerical analysis, using the suggested methodology, one can efficiently assess the seismic fragilities of the tunnel by the predicted model. ML-PCA techniques can be viewed as an alternate strategy for seismic design and CFHT performance enhancement in real-world engineering.

Iron is an important trace element that affects the growth and development of animals and regulates oxygen transport, hematopoiesis, and hypoxia adaptations. Wujin pig has unique hypoxic adaptability and iron homeostasis; however, the specific regulatory mechanisms have rarely been reported. This study randomly divided 18 healthy Wujin piglets into three groups: the control group, supplemented with 100 mg/kg iron (as iron glycinate); the low-iron group, no iron supplementation; and the high-iron group, supplemented with 200 mg/kg iron (as iron glycinate). The pre-feeding period was 5 days, and the formal period was 30 days. Serum was collected from empty stomachs before slaughter and at slaughter to detect changes in the serum iron metabolism parameters. Gene expression in the liver was analyzed via transcriptome analysis to determine the effects of low- and high-iron diets on transcriptome levels. Correlation analysis was performed for apparent serum parameters, and transcriptome sequencing was performed using weighted gene co-expression network analysis to reveal the key pathways underlying hypoxia regulation and iron metabolism. The main results are as follows. (1) Except for the hypoxia-inducible factor 1 (HIF-1) content (between the low- and high-iron groups), significant differences were not observed among the serum iron metabolic parameters. The serum HIF-1 content of the low-iron group was significantly higher than that of the high-iron group (p < 0.05). (2) Sequencing analysis of the liver transcriptome revealed 155 differentially expressed genes (DEGs) between the low-iron and control groups, 229 DEGs between the high-iron and control groups, and 279 DEGs between the low- and high-iron groups. Bioinformatics analysis showed that the HIF-1 and transforming growth factor-beta (TGF-β) signaling pathways were the key pathways for hypoxia regulation and iron metabolism. Four genes were selected for qPCR validation, and the results were consistent with the transcriptome sequencing data. In summary, the serum iron metabolism parameter results showed that under the influence of low- and high-iron diets, Wujin piglets maintain a steady state of physiological and biochemical indices via complex metabolic regulation of the body, which reflects their stress resistance and adaptability. The transcriptome results revealed the effects of low-iron and high-iron diets on the gene expression level in the liver and showed that the HIF-1 and TGF-β signaling pathways were key for regulating hypoxia adaptability and iron metabolism homeostasis under low-iron and high-iron diets. Moreover, HIF-1α and HEPC were the key genes. The findings provide a theoretical foundation for exploring the regulatory pathways and characteristics of iron metabolism in Wujin pigs.

Taking the nonlocal effect into account, the vibration governing differential equation and boundary conditions of a magnetostrictive composite cantilever resonator were established based on the Euler magnetoelastic beam theory. The frequency equation and vibration mode function of the composite cantilever were obtained by means of the separation of variables method and the analytic solution of ordinary differential equations. The lateral deflection, vibration governing equations, and boundary conditions were nondimensionalized. Furthermore, the natural frequency and modal function of the composite beam were quantitatively analyzed with different nonlocal parameters and transverse geometry dimensions using numerical examples. Compared with the results without considering the nonlocal effect, the influence of the nonlocal effect on the vibration characteristics was analyzed. The numerical results show that the frequency shift and frequency band narrowing of the magnetostrictive cantilever resonator are induced by nonlocal effects. In particular, the high-frequency vibration characteristics, such as vibration amplitude and modal node of the composite beam, are significantly affected. These analysis results can provide a reference for the functional design and optimization of magnetostrictive resonators.

The cross-line operation (CO) of trains in urban rail transit is an effective method to efficiently satisfy transfer passenger travel demand as well as relieve the pressure of transfer stations. The primary problem of CO is designing train services to satisfy travel demand with an uneven spatial distribution of passengers. This study constructs a nonlinear integer programming model with a novel train operation scheme, i.e., virtual coupling (VC) technology, which allows the coupling/decoupling of trains on different lines at both ends of each operation zone. This scheme makes the train capacity equitably distributed in each operation zone, thereby balancing train capacity utilization over the whole CO system. Regarding the nonlinear characteristics of the proposed model, an adaptive simulated annealing genetic algorithm (ASA-GA) was designed to quickly generate high-quality solutions. Based on real-world data from the Beijing Changping Line and Line 13, the effectiveness of the proposed model and algorithm were verified. The computation results show that in comparison to a single grouping train composition scheme without CO, a VC scheme with CO would reduce operation costs by 46.8%, with 80.6% savings of train capacity equity. Furthermore, the average passenger residence time would be reduced by 25.9%.

The effective vibration area includes most of the catenary vibration caused by pantograph–catenary interactions and is the basis of the real-time catenary model for hardware-in-the-loop simulation. However, while the length of the effective vibration area is one of the most important parameters of the real-time catenary model, it has not been fully studied at present. In this paper, the length of the effective vibration area is first investigated. A pantograph–catenary interaction model is developed based on the modal superposition method. After the validation of the model, the vibration energy distribution of the catenary is used to determine the length of the effective vibration area based on the converged total energy. The influence of vehicle velocity and contact wire tension on the vibration energy distribution and length of the effective vibration area is investigated. The obtained appropriate length of effective vibration area is validated by a real-time catenary model and online measurement data of the contact force. The investigation results show that the energy distribution of the catenary can accurately determine the length of effective vibration area, and it increases with increasing vehicle velocity but decreases with increasing contact wire tension. The appropriate length of effective vibration area should be at least 160 m (approximately three spans) in the pantograph–catenary system.

This study aimed to explore the effects of Bacillus amyloliquefaciens GSBa-1 treatment on anthracnose disease resistance and the metabolism of reactive oxygen species (ROS) and phenylpropanoids in mangoes during storage. Mangoes were soaked in a solution containing 1 × 108 CFU/mL of B. amyloliquefaciens GSBa-1. The anthracnose disease incidence, disease index, respiration intensity, ethylene release, reactive oxygen species content, and the activities of related metabolic enzymes, phenylpropanoid-related metabolic enzymes, and phenolic acids in the skin and pulp of mangoes were investigated under normal temperature storage conditions. The results showed that the antagonistic bacterial treatment (ABT) did not significantly inhibit the growth of Colletotrichum gloeosporioides in vitro. However, it significantly reduced the incidence of mango anthracnose disease when applied to the mango peel. ABT enhanced the latent resistance of mango to anthracnose disease by activating its reactive oxygen and phenylpropanoid metabolism. It maintained higher levels of ROS production and elimination in the peel. Moreover, it rapidly activated manganese superoxide dismutase, induced the accumulation of H2O2, and enhanced the activity of manganese superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase in the mango peel. Furthermore, ABT activated phenylalanine ammonia-lyase, cinnamic acid-4-hydroxylase, 4-coumaroyl-CoA ligase, and cinnamyl alcohol dehydrogenase in the mango peel and pulp, promoting the accumulation of antifungal phenolic acids such as gallic acid, catechins, and ellagic acid. Bacillus amyloliquefaciens GSBa-1 may be a potent inhibitor of mango anthracnose, primarily enhancing the resistance of mangoes to anthracnose by synergistically activating ROS in the peel and phenylpropanoid metabolism in the pulp, thereby reducing the incidence of anthracnose effectively.

This study aimed to develop Janus-, cross-network-, and coaxial-structured piezoelectric–conductive polymer nanofibers through electrospinning to mimic the piezoelectricity of bone and facilitate the conduction of electrical signals in bone tissue repair. These nanofibers were constructed using the piezoelectric polymer polyvinylidene fluoride, and the conductive fillers reduced graphene oxide and polypyrrole. The influence of structural features on the electroactivity of the fibers was also explored. The morphology and components of the various structural samples were characterized using SEM, TEM, and FTIR. The electroactivity of the materials was assessed with a quasi-static d33 meter and the four-probe method. The results revealed that the piezoelectric–conductive phases were successfully integrated. The Janus-structured nanofibers demonstrated the best electroactivity, with a piezoelectric constant d33 of 24.5 pC/N and conductivity of 6.78 × 10−2 S/m. The tensile tests and MIP measurements showed that all samples had porosity levels exceeding 70%. The tensile strength of the Janus and cross-network structures exceeded that of the periosteum (3–4 MPa), with average pore sizes of 1194.36 and 2264.46 nm, respectively. These properties indicated good mechanical performance, allowing material support while preventing fibroblast invasion. The CCK-8 and ALP tests indicated that the Janus-structured samples were biocompatible and significantly promoted the proliferation of MC3T3-E1 cells.

Potassium-ion batteries (PIBs) have been widely studied owing to the abundant reserves, widespread distribution, and easy extraction of potassium (K) resources. Molybdenum disulfide (MoS2) has received a great deal of attention as a key anode material for PIBs owing to its two-dimensional diffusion channels for K+ ions. However, due to its poor electronic conductivity and the huge influence of embedded K+ ions (with a large ionic radius of 3.6 Å) on MoS2 layer, MoS2 anodes exhibit a poor rate performance and easily collapsed structure. To address these issues, the common strategies are enlarging the interlayer spacing to reduce the mechanical strain and increasing the electronic conductivity by adding conductive agents. However, simultaneous implementation of the above strategies by simple methods is currently still a challenge. Herein, MoS2 anodes on reduced graphene oxide (MoS2/rGO) composite were prepared using one-step hydrothermal methods. Owing to the presence of rGO in the synthesis process, MoS2 possesses a unique scaled structure with large layer spacing, and the intrinsic conductivity of MoS2 is proved. As a result, MoS2/rGO composite anodes exhibit a larger rate performance and better cycle stability than that of anodes based on pure MoS2, and the direct mixtures of MoS2 and graphene oxide (MoS2-GO). This work suggests that the composite material of MoS2/rGO has infinite possibilities as a high-quality anode material for PIBs.

A Zn2TiO4 crystalline photovoltaic glass ink was prepared by fast firing at 700 °C for 5 min by the glass crystallisation method, which effectively improved the reflectivity and acid resistance of the photovoltaic glass ink coating. The phase, morphology and properties of the samples were tested by XRD, SEM and UV-vis diffuse reflection, etc. The enhanced reflectivity mechanism was proposed. The results showed that the increase in ZnO/SiO2 ratio reduced the transition temperature (Tg) and crystallisation temperature (Tp) of the glass melt, which could promote the crystallinity of Zn2TiO4 in photovoltaic glass ink coatings and thus improve the acid resistance of photovoltaic glass inks. Significant improvement in reflectance and whiteness is due to the Zn2TiO4 crystallinity growth, which fills in the pores of the ink surface, and TiO2 fillers keep almost the same surface roughness (0.2 µm) and wetting angle (5.2°). Typical samples achieved 89.2% of the whiteness and 88.0% of the reflectance, and the weight loss in acid was 3.9 mg/cm2, which could improve the efficiency of solar power generation.

The objective of this investigation was to fabricate a photothermally responsive composite bone scaffold aimed at facilitating bone tissue regeneration and remedying bone defects via mild thermal stimulation. The photothermal-sensitive nanomaterial SiO2 coated Fe3O4 (SiO2@Fe3O4), synthesized through the hydrolysis–condensation process of tetraethyl orthosilicate (TEOS), displayed a uniform distribution of SiO2 coating, effectively preventing the aggregation of Fe3O4 particles within the scaffold matrix. The composite scaffold containing 5% mass fraction of photothermal-sensitive nanoparticles exhibited evenly dispersed microstructural porosity, a compressive strength of 5.722 MPa, and a water contact angle of 58.3°, satisfying the mechanical property requisites of cancellous bone while demonstrating notable hydrophilic characteristics. Upon exposure to near-infrared light at ambient temperature, the 5% composite scaffold underwent a temperature elevation of 3–6 °C within 40–45 s, attaining a temperature range (40–43 °C) conducive to fostering osteogenic differentiation. Experimental findings validated that the SiO2@Fe3O4/polyvinyl alcohol (PVA)/hydroxyapatite (HA)/polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) bone scaffold showcased outstanding mechanical and photothermal attributes, thereby presenting a pioneering avenue for advancing bone tissue cell proliferation and addressing bone defect rehabilitation.

The Yellow River Delta is considered one of the most water-stressed regions in China as the competition for water between various industrial sectors and agriculture is increasing. Since 2007, the regional governments have taken a leading role in agricultural water-saving planning by upgrading irrigation systems and constructing water-saving facilities. In this study, the effects of water-saving irrigation strategies on the groundwater table and quality were investigated in the Yellow River basin during the last two decades. The average phreatic water level of bore-wells was monitored as 13.47 m during 2011–2020 compared to the level of 12.09 m during 2011–2020. Besides, the depth of the deep confined aquifer dropped dramatically during 2001–2013 with a declining rate of 2.55 meters per annum (m/a) compared to the value of 0.385 m/a after 2014, suggesting the reduced exploitation of deep groundwater and increased availability of groundwater after the water-saving campaign. In addition, the physicochemical parameters of both phreatic water and deep confined aquifer indicated improved water quality. Consequently, understanding how the water-saving planning influences the groundwater availability is important, which would provide an insightful guidance for the water managers to protect the groundwater environment in the Yellow River Delta. HIGHLIGHTS Irrigation strategies affected the groundwater table in the Yellow River Delta.; The phreatic water could be more significantly affected by the water-saving irrigation planning than the deep confined aquifers.; Water-saving irrigation strategy improved the groundwater quality.;

Abstract Background To three-dimensionally evaluate changes of the alveolar bone around the mandibular anterior teeth and pharyngeal airway dimensions in adults with Class III malocclusion before and after orthodontic treatment of mandibular dentition distalization. Methods In this retrospective study, cone-beam computed tomography (CBCT) scans of 20 patients with Class III malocclusion who underwent mandibular dentition distalization were obtained both before and after treatment. Three-dimensional changes of the thickness and vertical marginal bone levels around mandibular incisors and canines were assessed and compared. And airway volumes of the palato-, glosso-, laryngopharynx and the minimum axial area were measured and compared before and after treatment. Results A significant decrease of lingual bone thickness of mandibular incisors, partial labial and lingual bone thickness of canines were observed (P

Abstract Solar flares are explosions on the Sun. They happen when energy stored in magnetic fields around solar active regions (ARs) is suddenly released. Solar flares and accompanied coronal mass ejections are sources of space weather, which negatively affects a variety of technologies at or near Earth, ranging from blocking high-frequency radio waves used for radio communication to degrading power grid operations. Monitoring and providing early and accurate prediction of solar flares is therefore crucial for preparedness and disaster risk management. In this article, we present a transformer-based framework, named SolarFlareNet, for predicting whether an AR would produce a $$\gamma$$ γ -class flare within the next 24 to 72 h. We consider three $$\gamma$$ γ classes, namely the $$\ge$$ ≥ M5.0 class, the $$\ge$$ ≥ M class and the $$\ge$$ ≥ C class, and build three transformers separately, each corresponding to a $$\gamma$$ γ class. Each transformer is used to make predictions of its corresponding $$\gamma$$ γ -class flares. The crux of our approach is to model data samples in an AR as time series and to use transformers to capture the temporal dynamics of the data samples. Each data sample consists of magnetic parameters taken from Space-weather HMI Active Region Patches (SHARP) and related data products. We survey flare events that occurred from May 2010 to December 2022 using the Geostationary Operational Environmental Satellite X-ray flare catalogs provided by the National Centers for Environmental Information (NCEI), and build a database of flares with identified ARs in the NCEI flare catalogs. This flare database is used to construct labels of the data samples suitable for machine learning. We further extend the deterministic approach to a calibration-based probabilistic forecasting method. The SolarFlareNet system is fully operational and is capable of making near real-time predictions of solar flares on the Web.

Abstract Background Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms. Methods Male adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting. Results NAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA. Conclusion NAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA.

Abstract This paper presents a deep reinforcement learning based data‐driven solution to the microgrid bidding in the electricity market considering offers for the reserve market. The framework, based on the Markov decision process, models the microgrid's participation in the electricity market at different stages, including bidding, market‐clearing, and reserve activation. The problem is split into two stages: day‐ahead submission and real‐time market period, and the proposed method mainly focus on the first stage. The state information from state‐space models of distributed energy resources serves as input for the policy network. A deep deterministic policy gradient is employed to train the network and produce a deterministic bidding strategy. The second stage can then adjust this strategy based on the results from the first stage. The method is validated with real‐world microgrid systems and data from the Singapore spot market.

Abstract At present, enzyme debridement preparation has shown a good curative effect on eschar removal of burn wounds. Keratinase has shown great potential in enzymatic debridement because of its good fibrin-degrading ability. In this study, the debridement of keratinase was examined by using a third degree burn wound model in rats. We observed the wound, and keratinase shortened the time of eschar dissolution after debridement. Histopathology and immunofluorescence staining showed that the eschar in the keratinase group became thinner, inflammatory cell infiltration in the wound increased, the fluorescence intensity of the macrophage surface marker CD68 increased, and the CD163/CD86 ratio increased. In bone marrow-derived macrophages (BMDMs), there was no significant difference in the activity of CCK-8 in cells in the keratinase group compared with the control group. The fluorescence intensity of the keratinase group was higher than that of the control group. At 12 h, the cell scratches were obviously closed. The number of migrated Transwell cells increased. Flow cytometry and immunofluorescence analysis showed increased expression of CD206 and Arg-1 and decreased expression of CD86 and iNOS. The gene expression of the Arg-1, iNOS and IL-10 was increased, as shown by qPCR. The secretion of IL-10 was increased and TNF-α was decreased, as shown by ELISA. We concluded that keratinase dissolution of eschar not only has a hydrolytic effect on eschar but may also affect immune regulation to enhance the migration and phagocytosis of macrophages, promote the polarization of macrophages, and further enhance the effect of eschar dissolution. Therefore, keratinase may have good prospects for the debridement of burn wounds.

MicroRNAs (MiRNAs) carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment. Our study aimed at identifying the expression profile of exosomal miRNAs (exo-miRNAs) in the serum of multiple myeloma (MM) patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis. Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing. Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted. CytoHubba was applied to identify the hub miRNAs and core target genes. The LASSO Cox regression model was used to develop the prognostic model, and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients. The top six hub differentially expressed serum exo-miRNAs were identified. 513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset. Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing, cellular response to stress, and deubiquitination. 13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients, which is associated with the immune microenvironment of MM patients. Our study comprehensively investigated the exo-miRNA profiles in MM patients. A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.

Abstract Background Induction of cellulase in cellulolytic fungi Trichoderma reesei is strongly activated by cellulosic carbon sources. The transport of cellulosic inducer and the perception of inducing signal is generally considered as the critical process for cellulase induction, that the inducing signal would be perceived by a sugar transporter/transceptor in T. reesei. Several sugar transporters are coexpressed during the induction stage, but which function they serve and how they work collaboratively are still difficult to elucidate. Results In this study, we found that the constitutive expression of the cellulose response transporter-like protein CRT2 (previously identified as putative lactose permease TRE77517) improves cellulase induction on a cellulose, cellobiose or lactose medium. Functional studies indicate that the membrane-bound CRT2 is not a transporter of cellobiose, lactose or glucose in a yeast system, and it also does not affect cellobiose and lactose utilization in T. reesei. Further study reveals that CRT2 has a slightly similar function to the cellobiose transporter CRT1 in cellulase induction. Overexpression of CRT2 led to upregulation of CRT1 and the key transcription factor XYR1. Moreover, overexpression of CRT2 could partially compensate for the function loss of CRT1 on cellulase induction. Conclusions Our study uncovers the novel function of CRT2 in cellulase induction collaborated with CRT1 and XYR1, possibly as a signal transductor. These results deepen the understanding of the influence of sugar transporters in cellulase production.

Abstract Accurate cell type identification is a key and rate-limiting step in single-cell data analysis. Single-cell references with comprehensive cell types, reproducible and functionally validated cell identities, and common nomenclatures are much needed by the research community for automated cell type annotation, data integration, and data sharing. Here, we develop a computational pipeline utilizing the LungMAP CellCards as a dictionary to consolidate single-cell transcriptomic datasets of 104 human lungs and 17 mouse lung samples to construct LungMAP single-cell reference (CellRef) for both normal human and mouse lungs. CellRefs define 48 human and 40 mouse lung cell types catalogued from diverse anatomic locations and developmental time points. We demonstrate the accuracy and stability of LungMAP CellRefs and their utility for automated cell type annotation of both normal and diseased lungs using multiple independent methods and testing data. We develop user-friendly web interfaces for easy access and maximal utilization of the LungMAP CellRefs.

Abstract Background The discovery of immune checkpoint inhibitors (ICIs) is a breakthrough in the field of cancer therapy. However, ICIs may cause immune‐related adverse reactions, including checkpoint inhibitor‐related pneumonitis (CIP). The aim of this study was to investigate cytokines in bronchoalveolar lavage fluid (BALF) of patients with CIP compared with patients with pulmonary infection and patients with cancer. Methods We retrospectively analyzed 34 cytokine levels and T cell subsets in BALF supernatant samples from ICI‐treated patients with CIP (n = 13), pulmonary infection (n = 10), and progressive cancer (n = 12). Cytokine levels and T cell subsets were compared among the three groups of patients. Results We observed significantly higher levels of IFN‐γ‐induced protein 10(IP‐10) (p = 0.002), and percentage of CD3 + CD8 + T cells (p = 0.020) in BALF of patients with CIP compared with the other two groups. However, we found significantly lower levels of interleukin‐21 (p = 0.008) in BALF of patients with progressive disease compared with the other two groups. Conclusions Cytokine profile and character of cell subsets in BALF was helpful for the differential diagnosis of CIP. IP‐10 may play an important role in pathophysiology for CIP and also be a potential therapeutic target.

Abstract Three basic deformation modes of an object (bending, twisting, and contraction/extension) along with their various combinations and delicate controls lead to diverse locomotion. As a result, seeking mechanisms to achieve simple to complex deformation modes in a controllable manner is a focal point in related engineering fields. Here, a pneumatic-driven, origami-based deformation unit that offers all-purpose deformation modes, namely, three decoupled basic motion types and four combinations of these three basic types, with seven distinct motion modes in total through one origami module, was created and precisely controlled through various pressurization schemes. These all-purpose origami-based modules can be readily assembled as needed, even during operation, which enables plug-and-play characteristics. These origami modules with all-purpose deformation modes offer unprecedented opportunities for soft robots in performing complex tasks, which were successfully demonstrated in this work.

Abstract Immobilized microbial technology has been widely used in wastewater treatment, but it has been used less frequently for soil remediation, particularly in sites that are co-contaminated with organic compounds and heavy metals. In addition, there is limited knowledge on the efficiency of remediation and microbial preferences to colonize the immobilized carriers. In this study, biochar immobilized with Sphingobium abikonense was introduced to remediate soils that were co-contaminated with phenanthrene (PHE) and copper (Cu), and the mechanisms of microbial assemblage were investigated. The immobilized microbial biochar maintained a degradation rate of more than 96% in both the first (0–6 d) and second (6–12 d) contamination periods. The addition of biochar increased the proportion of Cu bound to organic matter, and Fe–Mn oxide bound Cu in the soil. In addition, both Cu and PHE could be adsorbed into biochar pellets in the presence or absence of immobilized S. abikonense. The presence of biochar significantly increased the abundance of bacteria, such as Luteibacter, Bordetella and Dyella, that could degrade organic matter and tolerate heavy metals. Notably, the biochar could specifically select host microbes from the soil for colonization, while the presence of S. abikonense affected this preference. The autonomous selection facilitates the degradation of PHE and/or the immobilization of Cu in the soil. These results provide a green approach to efficiently and sustainably remediate soil co-contaminated with PHE and Cu and highlight the importance of microbial preference colonized in immobilized carriers. Graphical Abstract

Additive manufactured bimetallic structures provide site-specific functions by joining two metallic materials in the designed area, offering customized solutions for biomedical and engineering applications. However, cracking, delamination, or cross-contamination frequently occurs at the joint between two dissimilar metallic materials due to their different thermal properties. In the paper, porous bimetallic structures made of biomedical materials (Fe, Ti6Al4V, and Inconel 718) for bone implants are fabricated via direct ink writing (DIW) with a dual syringe system. After subsequent heat treatment, the original shapes of the bimetallic structures are well-preserved, and the shrinkages of the two materials are equalized by adjusting the sintering temperature. All joints are free of cracks and delamination, and the material deposition sequence has no impact on them, according to microstructural analyses of the interface. The pores created by binder pyrolysis and metallic powder sintering are necessary for bone growth, cell migration, body fluid flow, etc. The Fe–Ti6Al4V and Fe-Inconel 718 bimetallic structures have better mechanical properties than the Fe structures and can perform multiple functions that are challenging for monometallic implants.

Abstract Background Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This meta-analysis aimed to investigate the correlation between aspirin consumption and HCC. Methods A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science databases. The search period was from the establishment of the database to July 1, 2022 with no language restrictions. Results A total of 19 studies including three prospective studies and 16 retrospective ones with 2,217,712 patients were included. Compared with those who did not take aspirin, those who took aspirin had a 30% lower risk of HCC (hazard ratio [HR] = 0.70, 95% confidence interval [CI] 0.63–0.76, I 2 = 84.7%, P

Abstract Objective The aim of this study was to investigate the incidence of chromosome anomalies in different types of congenital gastrointestinal obstruction and assess pregnancy outcomes of fetuses with congenital gastrointestinal obstruction. Methods A total of 64 cases with gastrointestinal obstruction between January 2014 and December 2020 were enrolled in this study. They were divided into three groups according to sonographic images. Group A: isolated upper gastrointestinal obstruction; Group B: isolated lower gastrointestinal obstruction; Group C: non-isolated gastrointestinal obstruction. The rate of chromosome anomalies in different groups was calculated. Pregnant women with amniocentesis were followed up by medical records and telephone. The follow-up included pregnancy outcomes and development of the live born infants. Result From January 2014 to December 2020, there were 64 fetus with congenital gastrointestinal obstruction underwent chromosome microarray analysis(CMA), the overall detection rate of CMA testing was 14.1%(9/64). The detection rate of Group A, B and C were 16.2%, 0 and 25.0% respectively. 9 fetuses with abnormal CMA results were all terminated. Among 55 fetuses with normal chromosomes, 10(18.2%) fetuses were not found to have any gastrointestinal obstruction after birth. 17(30.9%) fetuses were diagnosed with gastrointestinal obstruction and underwent surgical treatment after birth, one of which had lower gastrointestinal obstruction combined with biliary obstruction and died due to liver cirrhosis. 11(20.0%) pregnancy were terminated due to multiple abnormalities. 5(9.1%) fetuses were intrauterine death. 3(5.5%) fetuses were neonatal deaths. 9(16.4%) fetuses were lost to follow-up. Conclusion It is crucial to understand whether the gastrointestinal tract abnormality is isolated or associated to other findings. The risk of chromosomal abnormalities in fetuses with isolated lower gastrointestinal obstruction is lower than upper gastrointestinal obstruction. While genetic abnormalities excluded, a promising prognosis is expected for fetuses with congenital gastrointestinal obstruction.

Abstract. Background:. Lung cancer has been the leading cause of cancer-related deaths worldwide for many years. This study aimed to investigate the global patterns and trends of lung cancer. Methods:. Lung cancer incidence and mortality were derived from the GLOBOCAN 2020 database. Continuous data from Cancer Incidence in Five Continents Time Trends were used to analyze the temporal trends from 2000 to 2012 using Joinpoint regression, and average annual percent changes were calculated. The association between the Human Development Index and lung cancer incidence and mortality was assessed by linear regression. Results:. An estimated 2.2 million new lung cancer cases and 1.8 million lung cancer-related deaths occurred in 2020. The age-standardized incidence rate (ASIR) ranged from 36.8 per 100,000 in Demark to 5.9 per 100,000 in Mexico. The age-standardized mortality rate (ASMR) varied from 32.8 per 100,000 in Poland to 4.9 per 100,000 in Mexico. Both ASIR and ASMR were approximately twice higher in men than in women. The ASIR of lung cancer showed a downward trend in the United States of America (USA) between 2000 and 2012, and was more prominent in men. The age-specific incidence rates of lung cancer for ages of 50 to 59 years showed an upward trend in China for both men and women. Conclusions:. The burden of lung cancer is still unsatisfactory, especially in developing countries like China. Considering the effectiveness of tobacco control and screening in developed countries, such as the USA, there is a need to strengthen health education, accelerate the establishment of tobacco control policies and regulations, and improve early cancer screening awareness to reduce the future burden of lung cancer.

Abstract. Lung cancer has the highest risk of brain metastasis (BM) among all solid carcinomas. The emergence of BM has a significant impact on the selection of oncologic treatment for patients. Immune checkpoint inhibitors (ICIs) are the most promising treatment option for patients without druggable mutations and have been shown to improve survival in patients with non-small cell lung cancer (NSCLC) BM in clinical trials with good safety. Moreover, ICI has shown certain effects in NSCLC BM, and the overall intracranial efficacy is comparable to extracranial efficacy. However, a proportion of patients showed discordant responses in primary and metastatic lesions, suggesting that multiple mechanisms may exist underlying ICI activity in BM. According to studies pertaining to tumor immune microenvironments, ICIs may be capable of provoking immunity in situ. Meanwhile, systematic immune cells activated by ICIs can migrate into the central nervous system and exert antitumor effects. This review summarizes the present evidence for ICI treatment efficacy in NSCLC BM and proposes the possible mechanisms of ICI treatment for NSCLC BMs based on existing evidence.

Since the high penetration of renewable energy complicates the dynamic characteristics of the AC power electronic system (ACPES), it is essential to establish an accurate dynamic model to obtain its dynamic behavior for ensure the safe and stable operation of the system. However, due to the no or limited internal control details, the state-space modeling method cannot be realized. It leads to the ACPES system becoming a black-box dynamic system. The dynamic modeling method based on deep neural network can simulate the dynamic behavior using port data without obtaining internal control details. However, deep neural network modeling methods are rarely systematically evaluated. In practice, the construction of neural network faces the selection of massive data and various network structure parameters. However, different sample distributions make the trained network performance quite different. Different network structure hyperparameters also mean different convergence time. Due to the lack of systematic evaluation and targeted suggestions, neural network modeling with high precision and high training speed cannot be realized quickly and conveniently in practical engineering applications. To fill this gap, this paper systematically evaluates the deep neural network from sample distribution and structural hyperparameter selection. The influence on modeling accuracy is analyzed in detail, then some modeling suggestions are presented. Simulation results under multiple operating points verify the effectiveness of the proposed method.

China is the largest steel producer in the world. Effective methods to alleviate the contradiction between water supply and water demand of the iron and steel industry in China are to implement the recycling of wastewater from the iron and steel industry and develop unconventional water resources. This paper reviews the development of wastewater recycling in the iron and steel industry in China in the past 40 years (1980–2020). During this period, steel output has increased from 36 to 1,053 million tons, freshwater consumption per ton of steel has decreased from 35.9 to 2.45 tons, and water resources reuse has soared from 61.2 to 98.02%. Four typical cases, including the Anyang Steel Group, the Tangshan Steel Group, the Tianjin Steel Group, and the Taihang Steel Group, were analyzed. In addition, a water efficiency research project of iron and steel enterprises in China was carried out in 2019. Statistical analyses on wastewater recycling rate, reuse rate, direct cooling water circulation rate, and other indicators were performed. The recycling of wastewater in the iron and steel industry would be continuously improved by policy drivers, economic drivers, and technical drivers. HIGHLIGHTS History of steel wastewater reuse and typical projects in China were presented.; Effective methods to alleviate the contradiction between water supply and demand were introduced.; Comparisons of the water use efficiency of steel industries in China were conducted.; Perspectives and challenges of future development of the steel industry were proposed.;

Abstract Background Neoadjuvant immunotherapy combined with chemotherapy has been used to treat locally advanced non–small cell lung cancer (NSCLC). Several systems have been developed for response evaluation. The aim of this study was to evaluate the predictive value of response evaluation criteria in solid tumors (RECIST) and propose modified RECIST (mRECIST). Methods Eligible patients received chemotherapy combined with personalized neoadjuvant immunotherapy. Radical resection was subsequently performed for potentially resectable tumors evaluated by RECIST. The resected specimens were evaluated to determine the response to neoadjuvant therapy. Results A total of 59 patients received radical resection following neoadjuvant immunotherapy combined with chemotherapy. According to RECIST, four patients had complete remission, 41 had partial remission, and 14 had progressive disease. Postoperative pathological examination showed 31 patients achieved complete pathological remission, and 13 achieved major pathological remission. The final pathological results were uncorrelated with RECIST assessment (p = 0.086). The ycN stage and pN stage were irrelevant (p

Abstract Background Preimplantation genetic testing (PGT) for monogenic disorders (PGT-M) for germline mosaicism was previously highly dependent on polymerase chain reaction (PCR)-based directed mutation detection combined with linkage analysis of short tandem repeats (STRs). However, the number of STRs is usually limited. In addition, designing suitable probes and optimizing the reaction conditions for multiplex PCR are time-consuming and laborious. Here, we evaluated the effectiveness of next generation sequencing (NGS)-based haplotype linkage analysis in PGT of germline mosaicism. Methods PGT-M with NGS-based haplotype linkage analysis was performed for two families with maternal germline mosaicism for an X-linked Duchenne muscular dystrophy (DMD) mutation (del exon 45–50) or an autosomal TSC1 mutation (c.2074C > T). Trophectoderm biopsy and multiple displacement amplification (MDA) were performed for a total of nine blastocysts. NGS and Sanger sequencing were performed in genomic DNA of family members and embryonic MDA products to detect DMD deletion and TSC1 mutation, respectively. Single nucleotide polymorphism (SNP) sites closely linked to pathogenic mutations were detected with NGS and served in haplotype linkage analysis. NGS-based aneuploidy screening was performed for all embryos to reduce the risk of pregnancy loss. Results All nine blastocytes showed conclusive PGT results. Each family underwent one or two frozen-thawed embryo transfer cycles to obtain a clinical pregnancy, and the prenatal diagnosis showed that the fetus was genotypically normal and euploid for both families. Conclusions NGS-SNP could effectively realize PGT for germline mosaicism. Compared with PCR-based methods, the NGS-SNP method with increased polymorphic informative markers can achieve a greater diagnostic accuracy. Further studies are warranted to verify the effectiveness of NGS-based PGT of germline mosaicism cases in the absence of surviving offsprings.

Objective There has been no definite consensus on the ideal depth of acetabuloplasty, especially in cases of global pincer femoroacetabular impingement (FAI). This study aims to determine whether the depth of acetabuloplasty influences postoperative outcomes in cases of global pincer FAI. Methods Data were retrospectively collected from patients with global pincer FAI who underwent hip arthroscopy with a minimum follow‐up period of 2 years from May 2014 to December 2018. Patients with global pincer FAI were subdivided into low or high resection depth groups based on whether the intraoperative acetabular rim was resected by more than 3 mm. Radiographic measurements; arthroscopic procedures; preoperative and postoperative PROs were recorded. Achievement of MCID and PASS was compared for the VAS, mHHS, HOS‐ADL, and iHOT‐12. A paired Student t‐test was used to evaluate the significance of preoperative and postoperative PROs and two‐tailed unpaired Student t‐test was used to compare demographic data and PROs between different groups. MCID and PASS were evaluated using the chi‐square test or the Fisher's exact test. Results A total of 41 hips with global pincer FAI (15 and 26 patients in low or high resection depth groups, respectively) were included in this study. Both groups showed significant postoperative improvements in the scores of all PROs (p < 0.001). Compared to the low resection depth group, the high resection depth group had a lower degree of improvement through hip arthroscopy, which manifested as lower postoperative mHHS scores (94.29 vs. 85.08, p = 0.006), higher VAS scores (0.93 vs. 2.54, p = 0.002), and lower improvements in VAS (−5.00 vs. −3.35, p = 0.028), HOS‐ADL (34.99 vs. 23.90, p = 0.017) and iHOT‐12 (39.89 vs. 29.27, p = 0.036). Patients in high resection depth group were less likely to achieve the MCID for the VAS score compared to low resection depth group in significant (73.3 vs. 26.9%, p = 0.004). Conclusions For patients with global pincer, the outcomes in high resection depth group were slightly worse than the the low resection depth group. It is indicated that excessive resection of the acetabular rim during the procedure should be avoided.

Abstract Virus‐induced gene silencing (VIGS) is a powerful tool for transient gene functional analysis in plants, especially for monocot species (e.g., grasses) that are recalcitrant to transformation. Despite various VIGS systems that have been developed in different plant species, none was previously available for the bioenergy crop Miscanthus. Here, we report the establishment of an efficient and robust VIGS system mediated by Tobacco Rattle Virus (TRV) in Miscanthus. We first investigated the impact of various factors that may affect gene silencing efficiency using the Miscanthus sinensis Phytoene Desaturase (MsPDS) gene as a visual indicator of photobleaching. Then, we optimized the TRV‐elicited VIGS procedure using an orthogonal experimental design with four factors (sprout size, Agrobacterium concentration, vacuum infiltration time, and co‐incubation time) each at three levels. The following led to the highest silencing efficiency (~76%): inoculation of germinating seedlings (1.0–2.0 mm), Agrobacterium tumefaciens culture grown to optical density at 600 nm (OD600) of 0.4, vacuum infiltration for 90 min, and co‐incubation for 5 h. The VIGS system established was applicable for both M. sinensis and M. lutarioriparius, with comparable gene silencing efficiency. We verified the efficacy of the VIGS system via the functional characterization of the role of a MYB transcription factor, MsMYB112, in salt stress tolerance. Expression of MsMYB112 was successfully knocked down using the VIGS system, and this led to compromised salt tolerance in the silenced Miscanthus plants. The TRV‐based VIGS system established may, therefore, substantially facilitate functional genomic studies in Miscanthus.

Abstract Introduction Adalimumab (ADA) and etanercept (ETN) are the most commonly applied biologics for rheumatoid arthritis (RA) management in China; however, the evidence regarding their superiority is controversial. In addition, in real‐world clinical settings, many factors may affect the application of these agents, such as dosage and administration period. Therefore, the present real‐world study aimed to compare the efficacy and safety of ADA and ETN treatment in RA patients via the propensity score matching method. Methods In total, 105 RA patients receiving ADA (n = 66) or ETN (n = 39) were reviewed in this retrospective study. The propensity score matching method was used to eliminate discrepancies in baseline features. Clinical response, low disease activity (LDA), and remission were evaluated based on the DAS28. Results Before propensity score matching, compared with ETN, ADA yielded higher rates of clinical response at W24 (97.0% vs. 84.6%, p = .021), LDA at W12 (78.8% vs. 51.3%, p = .003), and remission at W24 (75.8% vs. 46.2%, p = .002). After propensity score matching, compared with ETN, ADA only achieved a higher rate of clinical response at W24 (96.3% vs. 77.8%, p = .043), whereas the rates of LDA and remission were not different between ADA and ETN treatments at any time point (all p > .05). In addition, the incidence of adverse events was not significantly different between the ADA and ETN treatments (all p > .05). Conclusion ADA shows superiority over ETN in terms of a numerically greater response rate and equivalent adverse events.

ABSTRACTMicrobial inoculation is an effective way to improve the quality of fermented foods via affecting the microbiota structure. However, it is unclear how the inoculation regulates the microbiota structure, and it is still difficult to directionally control the microbiota function via the inoculation. In this work, using the spontaneous fermentation of the starter (Daqu) for Chinese liquor fermentation as a case, we inoculated different microbiota groups at different time points in Daqu fermentation, and analyzed the effect of the inoculation on the final metabolic profile of Daqu. The inoculated microbiota and inoculated time points both significantly affected the final metabolites via regulating the microbial succession (P < 0.001), and multiple inoculations can promote deterministic assembly. Twenty-seven genera were identified to be related to microbial succession, and drove the variation of 121 metabolites. We then constructed an elastic network model to predict the profile of these 121 metabolites based on the abundances of 27 succession-related genera in Daqu fermentation. Procrustes analysis showed that the model could accurately predict the metabolic abundances (average Spearman correlation coefficients >0.3). This work revealed the effect of inoculation on the microbiota succession and the metabolic profile. The established predicted model of metabolic profile would be beneficial for directionally improving the food quality.IMPORTANCEThis work revealed the importance of microbial succession to microbiota structure and metabolites. Multi-inoculations would promote deterministic assembly. It would facilitate the regulation of microbiota structure and metabolic profile. In addition, we established a model to predict final metabolites based on microbial genera related to microbial succession. This model was beneficial for optimizing the inoculation of the microbiota. This work would be helpful for controlling the spontaneous food fermentation and directionally improving the food quality.

Abstract In order to repair critical‐sized bone defects, various polylactic acid‐glycolic acid (PLGA)‐based hybrid scaffolds are successfully developed as bone substitutes. However, the byproducts of these PLGA‐based scaffolds are known to acidify the implanted site, inducing tiresome acidic inflammation. Moreover, these degradation productions cannot offer an osteo‐friendly microenvironment at the implanted site, matching natural bone healing. Herein, inspired by bone microenvironment atlas of natural bone‐healing process, an osteo‐microenvironment stage‐regulative scaffold (P80/D10/M10) is fabricated by incorporating self‐developed decellularized bone matrix microparticles (DBM‐MPs) and multifunctional magnesium hydroxide nanoparticles (MH‐NPs) into PLGA with an optimized proportion using low‐temperature rapid prototyping (LT‐RP) 3D‐printing technology. The cell experiments show that this P80/D10/M10 exhibits excellent properties in mechanics, biocompatibility, and biodegradability, meanwhile superior stimulations in osteo‐immunomodulation, angiogenesis, and osteogenesis. Additionally, the animal experiments determined that this P80/D10/M10 can offer an osteo‐friendly microenvironment in a stage‐matched pattern for enhanced bone regeneration, namely, optimization of early inflammation, middle neovascularization, and later bone formation. Furthermore, transcriptomic analysis suggested that the in vivo performance of P80/D10/M10 on bone defect repair is mostly attributed to regulating artery development, bone development, and bone remodeling. Overall, this study reveals that the osteo‐microenvironment stage‐regulative scaffold provides a promising treatment for bone defect repair.

Background: SQSTM1/p62 is an autophagy-related receptor protein that participates in regulating tumorigenesis and multiple signaling pathways. Gastric cancer (GC) is a common tumor in the digestive tract and continues to pose a significant threat to human health. Therefore, this study aims to investigate the impact of p62 on gastric cancer. Methods: Immunohistochemistry and Western blotting were employed to assess the expression level of the p62 protein in gastric cancer tissues and its correlation with prognosis. Subsequently, in vitro cell experiments were conducted to determine the role of p62 in gastric cancer cell proliferation, migration, and metastasis. Result: The expression of p62 in gastric cancer tissues was significantly higher than in normal tissues. The expression of p62 was positively correlated with poor prognosis in gastric cancer patients. In vitro cell experiments indicated that p62 promotes gastric cancer cell proliferation and migration. Mechanistically, elevated p62 expression induced epithelial-mesenchymal transition (EMT), leading to upregulation of E-cadherin and downregulation of N-cadherin and vimentin. Conclusion: This study provides novel and robust evidence for the mechanism by which elevated p62 expression promotes the progression of gastric cancer. It offers promising therapeutic targets for anti-tumor treatment strategies in gastric cancer patients.

Background: Chronic ketamine use has been associated with cognitive impairments, while depressive symptoms are commonly observed in individuals using ketamine. However, the influence of depressive symptoms on cognitive impairments in chronic ketamine users remains unclear. This study aimed to examine the impact of depressive symptoms on cognitive function in this population. Methods: A cross-sectional study was conducted with a sample of chronic ketamine users. Participants underwent comprehensive cognitive assessments, including measures of attention, executive function, working memory, verbal and visual memory. Depressive symptoms were assessed using Beck Depression Inventory (BDI) scores. Multivariate analyses were utilized to compare the cognitive performance of individuals who use ketamine, both with and without depressive symptoms, as well as a control group, while controlling for relevant covariates. Results: The results revealed a significant negative impact of depressive symptoms on cognitive impairments, particularly in the domains of memory and executive function, among chronic ketamine users. The analysis of partial correlations revealed that among individuals who use ketamine and have depressive symptoms, those with higher levels of depressive symptoms demonstrated poorer cognitive performance compared to individuals with lower levels of depressive symptoms, controlling for potential confounding factors. Conclusions: The findings suggest that depressive symptoms contribute to cognitive impairments, specifically in memory and executive function, in chronic ketamine users. Therefore, it is crucial to evaluate depressive symptoms when considering cognitive enhancement treatment for this population.

Thus far, human development has been achieved at the cost of the destruction of cultural landscapes. With advent of industrial civilization, people have gained happiness and conveniences, but also confronted various cultural landscape predicaments. Environmental philosophy, a contemporary philosophy that regards the relationship between humans and nature as a fundamental issue, has focused on the protection of cultural landscapes. An analysis of ancient Chinese environmental philosophy demonstrates that ancient thinkers cared about everything in heaven and earth, and explored issues, such as a harmonious development between humans and nature, offering a novel approach to the preservation of Chinese cultural landscapes. Using Taoist environmental philosophy as an exemplar, this article provides a preliminary analysis of the definition of cultural landscapes, development of environmental philosophy and Taoist environmental philosophy. Building upon this foundation, it explores the role of environmental philosophies, such as “unity of heaven and man” in construction of ecological civilization, providing fresh perspectives for cultural landscape conservation.

Tumor microenvironment (TME) is essential for the development and progression of hepatocellular carcinoma (HCC). Exosomes participate in constructing TME by passing biological information, but the regulatory effect of PDL1 in exosomes on anticancer activity of CD8+ T cells in HCC still needs to be further explored. In this study, high level of PDL1 was found in plasma exosomes of HCC patients, which turned out to be significantly associated with the increased number of tumor nodules, the upregulated level of serum AFP, the raised tendency of TNM stage, and the poor prognosis of HCC. The expression of CD8 may be inhibited in HCC that is characterized with high level of PDL1, and the protein level of exosomal PDL1 was determined by intracellular PDL1 abundance. High level of exosomal PDL1 inhibited the proliferation and activation of CD8+ T cells, but exhibited limited effect on the proliferation of hepatic cancer cells. Moreover, the growth of tumors formed by hepatic cancer cells Hepa1–6 in C57L mice was significantly promoted by the exosomal PDL1, which might be caused by the inhibitory effect of exosomal PDL1 on CD8+ T cells. Thus, exosomal PDL1 promotes the development and progression of HCC through inhibiting the anticancer activity of CD8+ T cells. This study provides sights for understanding the oncogenic role of PDL1 and a reasonable explanation for the low efficacy of anti-PD1/PDL1 immunotherapies in HCC.

Acute lymphoblastic leukemia (ALL) is a prevalent hematologic malignancy in children, and methotrexate (MTX) is a widely employed curative treatment. Despite its common use, clinical resistance to MTX is frequently encountered. In this study, an MTX-resistant cell line (Reh-MTXR) was established through a stepwise selection process from the ALL cell line Reh. Comparative analysis revealed that Reh-MTXR cells exhibited resistance to MTX in contrast to the parental Reh cells. RNA-seq analysis identified an upregulation of ATP-binding cassette transporter G1 (ABCG1) in Reh-MTXR cells. Knockdown of ABCG1 in Reh-MTXR cells reversed the MTX-resistant phenotype, while overexpression of ABCG1 in Reh cells conferred resistance to MTX. Mechanistically, the heightened expression of ABCG1 accelerated MTX efflux, leading to a reduced accumulation of MTX polyglutamated metabolites. Notably, the ABCG1 inhibitor benzamil effectively sensitized Reh-MTXR cells to MTX treatment. Moreover, the observed upregulation of ABCG1 in Reh-MTXR cells was not induced by alterations in DNA methylation or histone acetylation. This study provides insight into the mechanistic basis of MTX resistance in ALL and also suggests a potential therapeutic approach for MTX-resistant ALL in the future.

The remarkable optoelectronic properties of organometal halide perovskite solar cells have captivated significant attention in the energy sector. Nevertheless, the instability of 3D perovskites, despite their extensive study and attainment of high-power conversion efficiency, remains a substantial obstacle in advancing PSCs for practical applications and eventual commercialization. To tackle this issue, researchers have devised mixed-dimensional perovskite structures combining 1D and 3D components. This innovative approach entails incorporating stable 1D perovskites into 3D perovskite matrices, yielding a significant improvement in long-term stability against various challenges, including moisture, continuous illumination, and thermal stress. Notably, the incorporation of 1D perovskite yields a multitude of advantages. Firstly, it efficiently passivates defects, thereby improving the overall device quality. Secondly, it retards ion migration, a pivotal factor in degradation, thus further bolstering stability. Lastly, the inclusion of 1D perovskite facilitates charge transport, ultimately resulting in an elevated device efficiency. In this succinct review, we thoroughly encapsulate the recent progress in PSCs utilizing 1D/3D mixed-dimensional architectures. These advancements encompass both stacked bilayer configurations of 1D/3D structures and mixed monolayer structures of 1D/3D. Additionally, we tackle critical challenges that must be surmounted and offer insights into the prospects for further advancements in this domain.

A novel wrist-inspired soft actuator, which is driven by a magneto-pneumatic hybrid system and based on a Kresling origami unit, is proposed. The geometric model, kinematic analysis model, and quasistatic analysis model of the Kresling origami unit are presented. A key focus is on the formulation and investigation of the variation in rotation angle using the kinematic analysis model. A wrist-inspired soft actuator is designed, and its quasistatic characteristics are validated through various experiments. The paper proposes an innovative magneto-pneumatic hybrid actuation method, capable of achieving bidirectional torsion. This actuation method is experimentally validated, demonstrating the actuator's ability to maintain 3 steady states and its capability for bidirectional torsion deformation. Furthermore, the paper highlights the potential of the Kresling origami unit in designing soft actuators capable of achieving large rotation angles. For instance, an actuator with 6 sides (n = 6) is shown to achieve a rotation angle of 239.5°, and its rotation ratio exceeds 277°, about twice the largest one reported in other literature. The actuator offers a practical and effective solution for bidirectional torsion deformation in soft robotic applications.

Abstract Background The optimal systemic treatment for pulmonary large‐cell neuroendocrine carcinoma (LCNEC) remains controversial, and recent advances in LCNEC molecular subtype classification have provided potential strategies for assisting in treatment decisions. Our study aimed to investigate the impact of treatment regimens, molecular subtypes and their concordance on clinical outcomes of patients diagnosed with LCNEC. Patients and Methods All patients diagnosed with advanced pulmonary LCNEC in Peking Union Medical College Hospital (PUMCH) between January 2000 and October 2021 were enrolled in this retrospective study. The tumor samples were collected and sequenced using a tumor‐specific gene panel, while clinical information was retrieved from the medical records system. The survival and therapeutic response were analyzed and compared between different subgroups classified by treatment regimen (SCLC or NSCLC‐based), molecular subtype (type I or II) or the combination. Results In univariate subgroup analysis categorized only by treatment regimen or molecular subtype, there were no differences identified in DCR, ORR, PFS, or OS. Nevertheless, the group with consistent treatment regimen and molecular subtype exhibited significantly longer OS than that of the inconsistent group (median OS 37.7 vs. 8.3 months; p = 0.046). Particularly, the OS of patients with type II LCNEC treated with SCLC‐based regimen was significantly prolonged than that of others (median 37.7 vs. 10.5 months; p = 0.039). Conclusions Collectively, our study revealed the clinical outcomes of different treatment regimens for LCNEC patients highly depend on their molecular subtypes, highlighting the need for sequencing‐guided therapy.

Waldenstrom macroglobulinemia (WM) is a type of incurable, indolent B-cell lymphoma that is prone to relapse. Over time, treatment strategies have progressed from cytotoxic drugs to rituximab (R)- or bortezomib (V)-based regimens, and have now entered into an era of Bruton tyrosine kinase inhibitor (BTKi)-based regimens. However, the optimal treatment for the relapsed patients is still unclear. Herein, we analyzed the outcomes of the first- and second-line therapies in 377 patients with WM to illustrate the optimal choices for second-line therapy. After a median follow-up of 45.4 months, 89 patients received second-line therapy, and 53 patients were evaluated for response. The major response rates (MRR) of first- and second-line treatment were 65.1% and 67.9% (P = 0.678). The median progression-free survival (PFS) for the second-line therapy (PFS2) was shorter than that for the first-line therapy (PFS1) (56.3 vs 40.7 months, P = 0.03). However, PFS2 in targeted drugs group (R-/V-/BTKi-based regimens) was comparable to PFS1 (60.7 months vs 44.7 months, respectively, P = 0.21). Regarding second-line therapy, patients who underwent sequential treatment escalation—such as transitioning from cytotoxic drugs to R-/V-/BTKi-based regimens or from R-/V-based to BTKi-based regimens (escalation group) —had higher MRR (80.6% vs 47.1%, respectively, P = 0.023) and longer PFS2 (50.4 vs 23.5 months, respectively, P < 0.001) compared to the non-escalation group. Patients in the escalation group also had longer post-relapse overall survival compared with the non-escalation group (median, not reached vs 50.7 months, respectively, P = 0.039). Our findings indicate that sequential treatment escalation may improve the survival of patients with WM.