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The strength enhancement usually increases its susceptibility to hydrogen (H) embrittlement in steel materials. However, the atomic-level mechanisms of solutes influence hydrogen behavior at grain boundaries (GBs) remain incompletely understood. To address this gap, first-principles calculation was utilized to analyze the interactions between 25 different solutes and H at the Σ5 (310) GB of body-centered cubic (BCC) iron. This study focused on how these solutes affect H segregation and their role in mitigating H-induced GB embrittlement, thereby elucidating the mechanisms of solute-H interactions at GBs. The results show that elements such as Cr, Mn, Ni, Zr, Nb, Mo, W, and Re not only reduce H segregation at GBs, but also effectively alleviate H-induced GB embrittlement. Furthermore, first-principles calculation tensile tests (FPCTT) simulations were employed to investigate the effect of the H segregation behavior at GB on uniaxial tensile strain, shedding light on the fundamental processes of bond break and crack initiation at GBs. The present work provides deeper insights into the mechanisms of GB embrittlement and offers strategic guidance for designing steel materials with enhanced H embrittlement resistance.

Traditional cold-rolling dual-phase steel (CR sheet), limited by poor stretch-flangeability as indicated by the hole expansion rate (HER), faces challenges in manufacturing complex automobile parts. To address this, a new type of hot-rolling dual-phase steel with an 800 MPa grade (manufactured by typical thin slab continuous casting and rolling process, TSCCR) was designed to replace the traditional one. The TSCCR sheet, with a lower carbon content of 0.047 wt%, compared to 0.093 wt% in the CR sheets, features 40.6% martensite significantly higher than 28.2% in the CR sheet. This increased martensite content, despite being softer and more ductile due to its low hardness, compensates for the tensile strength in the TSCCR sheet. Furthermore, the TSCCR sheet exhibits a unique heterostructure characterized by uneven carbon distribution from the ferrite/austenite interface to other boundaries/interfaces, estimated by the negligible partition local equilibrium (NPLE) model of ferrite transformation. This unique heterostructure diminishes the mechanical disparity between ferrite and martensite, resulting in a higher yield strength of 568 MPa, compared to 456 MPa in the CR sheet. During uniaxial tension, the ferrite and ductile martensite in the TSCCR sheet initiate cooperative plastic deformation earlier than in the CR sheet, despite initially having fewer favorable slip systems in the TSCCR martensite. The low working hardening rate of the TSCCR sheet facilitates the forming layered structure of ferrite and martensite during necking compared to the CR sheet. Consequently, the HER of the TSCCR sheet sharply increased by 144% compared to the CR sheet. This enhancement in HER can be attributed to the crack initiation area, longer crack propagation path, and higher crack propagation resistance facilitated by the ductile martensite, culminating in superior HER.

Abstract Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a major public health issue worldwide. Mtb has developed complicated strategies to inhibit the immunological clearance of host cells, which significantly promote TB epidemic and weaken the anti-TB treatments. Host-directed therapy (HDT) is a novel approach in the field of anti-infection for overcoming antimicrobial resistance by enhancing the antimicrobial activities of phagocytes through phagosomal maturation, autophagy and antimicrobial peptides. Autophagy, a highly conserved cellular event within eukaryotic cells that is effective against a variety of bacterial infections, has been shown to play a protective role in host defense against Mtb. In recent decades, the introduction of nanomaterials into medical fields open up a new scene for novel therapeutics with enhanced efficiency and safety against different diseases. The active modification of nanomaterials not only allows their attractive targeting effects against the host cells, but also introduce the potential to regulate the host anti-TB immunological mechanisms, such as apoptosis, autophagy or macrophage polarization. In this review, we introduced the mechanisms of host cell autophagy for intracellular Mtb clearance, and how functional nanomaterials regulate autophagy for disease treatment. Moreover, we summarized the recent advances of nanomaterials for autophagy regulations as novel HDT strategies for anti-TB treatment, which may benefit the development of more effective anti-TB treatments. Graphical Abstract

Tuberculosis (TB) remains the leading cause of deaths among infectious diseases worldwide. Cutaneous Tuberculosis (CTB), caused by Mycobacterium tuberculosis (Mtb) infection in the skin, is still a harmful public health issue that requires more effective treatment strategy. Herein, we introduced mannose-modified mesoporous polydopamine nanosystems (Man-mPDA NPs) as the macrophage-targeted vectors to deliver anti-TB drug rifampicin and as photothermal agent to facilitate photothermal therapy (PTT) against Mtb infected macrophages for synergistic treatment of CTB. Based on the selective macrophage targeting effects, the proposed Rif@Man-mPDA NPs also showed excellent photothermal properties to develop Rif@Man-mPDA NPs-mediated PTT for intracellular Mtb killings in macrophages. Importantly, Rif@Man-mPDA NPs could inhibit the immune escape of Mtb by effectively chelating intracellular Fe2+ and inhibiting lipid peroxidation, and up-regulating GPX4 expression to inhibit ferroptosis of Mtb infected macrophages through activating Nrf2/HO-1 signaling. Moreover, Rif@Man-mPDA NPs-mediated PTT could effectively activate host cell immune responses by promoting autophagy of Mtb infected macrophages, which thus synergizes targeted drug delivery and ferroptosis inhibition for more effective intracellular Mtb clearance. This Rif@Man-mPDA NPs-mediated PTT strategy could also effectively inhibit the Mtb burdens and alleviate the pathological lesions induced by Mtb infection without significant systemic side effects in mouse CTB model. These results indicate that Rif@Man-mPDA NPs-mediated PTT can be served as a novel anti-TB strategy against CTB by synergizing macrophage targeted photothermal therapy and host immune defenses, thus holding promise for more effective treatment strategy development against CTB.

Abstract The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal physiological conditions, the Wnt/β-catenin signaling pathway is meticulously regulated. However, aberrant activation of this pathway and downstream target genes can occur due to mutations in key components of the Wnt/β-catenin pathway, epigenetic modifications, and crosstalk with other signaling pathways. Consequently, these dysregulations contribute significantly to tumor initiation and progression. Therapies targeting the Wnt/β-catenin signaling transduction have exhibited promising prospects and potential for tumor treatment. An increasing number of medications targeting this pathway are continuously being developed and validated. This comprehensive review aims to summarize the latest advances in our understanding of the role played by the Wnt/β-catenin signaling pathway in carcinogenesis and targeted therapy, providing valuable insights into acknowledging current opportunities and challenges associated with targeting this signaling pathway in cancer research and treatment.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has decreased the efficacy of SARS-CoV-2 vaccines in containing coronavirus disease 2019 (COVID-19) over time, and booster vaccination strategies are urgently necessitated to achieve sufficient protection. Intranasal immunization can improve mucosal immunity, offering protection against the infection and sustaining the spread of SARS-CoV-2. In this study, an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum, nasal lavage fluid, and bronchoalveolar lavage fluid compared with only two doses of mRNA vaccine. After intranasal boosting with the RBD-HR vaccine, the levels of serum neutralizing antibodies against prototype and variant strains of SARS-CoV-2 pseudoviruses were markedly higher than those in mice receiving mRNA vaccine alone, and intranasal boosting with the RBD-HR vaccine also inhibited the binding of RBD to hACE2 receptors. Furthermore, the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+ dendritic cells in the respiratory mucosa, and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs, including mediastinal lymph nodes, inguinal lymph nodes, and spleen. Collectively, these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locally and systemically.

Acicular ferrite (AF) has been regarded as the optimal microstructure in steel welds and heat affect zones (HAZs), because of its superior combination of strength and toughness. Although various aspects of AF have been investigated, the crystallographic characteristics of AF, including orientation relationship, variant selection and variant pairing, are still not fully studied. In this research, a Ti-deoxidized high strength low alloy steel was prepared and subjected to HAZ thermal cycle simulation tests to attain AF microstructure. Optical micrographs were obtained and EBSD mappings of AF microstructures were conducted. Through crystallographic analysis, the orientation relationship between AF and austenite was found close to that of bainite transformed at a high temperature (580 °C). In the AF microstructure, all 24 variants are formed and variant selection is nearly random. Compared with bainite, the variant pairing of AF is more random despite the slight favour of certain variant pairs. Most of the adjacent AF laths are from different close-packed plane (CP) groups, leading to the classic interlocking morphology. Meanwhile, a large number of neighbouring AF laths belong to different Bain groups, resulting in a high density of high angle grain boundaries (HAGBs). Intragranular nucleation of primary AF laths on inclusions contributes both to the high HAGB density and to the interlocking morphology of AF, while the sympathetic nucleation of secondary AF laths only contributes to the latter. These results suggest that to increase the HAGB density in AF, promoting the intragranular nucleation on inclusions is more important than enhancing the sympathetic nucleation.

Abstract Urgent research into innovative severe acute respiratory coronavirus‐2 (SARS‐CoV‐2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus‐vectored vaccine named Ad5‐Beta/Delta. This vaccine was created by incorporating the receptor‐binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5‐Beta/Deta vaccine induced robust broad‐spectrum neutralization against Omicron BA.5‐included variants. IN immunization with Ad5‐Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue‐resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5‐Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5‐Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5‐Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS‐CoV‐2 pre‐Omicron variants of concern and BA.5‐included Omicron subvariants.

Facing extreme plasma loads, the structural integrity of the tungsten divertor is crucial for ITER, an engineering marvel in nuclear fusion reactors, to achieve its fusion performance targets. Induced by repeated transient heating from plasmas, the thermal fatigue damage of tungsten–typically accompanied by the formation of surface relief–has been identified as a critical issue but an in-depth understanding is still lacking. Here, we report the formation of amorphous and anisotropic surface relief on ITER-grade tungsten surfaces under ITER-relevant hydrogen plasma loads. Measured by both electron backscatter diffraction over large fields of view and transmission Kikuchi diffraction of site-specific lamellae, such surface relief preferentially forms on grains with {110} planes parallel to the surface. This cannot be explained by the orientation-dependent resolved shear stress according to the Schmid law, threshold displacement energy anisotropy, or oxidation anisotropy. Furthermore, surface relief amorphization is revealed by high-resolution transmission electron microscopy imaging and selected area electron diffraction analysis, and is explained by a novel vacancy-induced amorphization mechanism. The results provide new insights into the thermal fatigue behavior of tungsten for fusion applications.

Steel surface decarburization is an important defect, deteriorating the component fatigue life significantly. Although there have been great efforts over decades to investigate the steel decarburization behaviour and related factors, one important aspect is the influence of pre-decarburization microstructures. During steel production, after continuous casting, if hot charging is not applicable, steel billets/blooms are normally stacked and cooled down before reheating and hot-rolling. During the continuous casting and subsequent stacking processes, steel billet/bloom surfaces are exposed to the air at relatively high temperatures, resulting in various decarburization microstructures. These decarburization microstructures could have different impacts on the subsequent reheating decarburization behaviour. However, research on this aspect is quite limited in the literature. In this research, the total decarburization depth (TDD) evolution of a Fe-0.6C-1.8Si-0.8Mn spring steel after isothermal holding and air-cooling was investigated, and various pre-decarburization microstructures were generated and subjected to a continuous heating decarburization test to study the influences of the pre-decarburization microstructures on the subsequent continuous heating decarburization behaviour. In the meanwhile, the experimental results were compared with the predictions of a decarburization model, and the model calculation results were used to explain the possible reasons for the influences of different pre-decarburization microstructures. The results of this research indicate that the higher the pre-decarburization TDD, the severer the final TDD after continuous heating, and the larger the contribution of the pre-decarburization TDD to the final TDD.

Abstract Epithelial–mesenchymal transition (EMT) is an essential process in normal embryonic development and tissue regeneration. However, aberrant reactivation of EMT is associated with malignant properties of tumor cells during cancer progression and metastasis, including promoted migration and invasiveness, increased tumor stemness, and enhanced resistance to chemotherapy and immunotherapy. EMT is tightly regulated by a complex network which is orchestrated with several intrinsic and extrinsic factors, including multiple transcription factors, post-translational control, epigenetic modifications, and noncoding RNA-mediated regulation. In this review, we described the molecular mechanisms, signaling pathways, and the stages of tumorigenesis involved in the EMT process and discussed the dynamic non-binary process of EMT and its role in tumor metastasis. Finally, we summarized the challenges of chemotherapy and immunotherapy in EMT and proposed strategies for tumor therapy targeting EMT.

As an essential micronutrient, manganese plays an important role in the physiological process and immune process. In recent decades, cGAS-STING pathway, which can congenitally recognize exogenous and endogenous DNA for activation, has been widely reported to play critical roles in the innate immunity against some important diseases, such as infections and tumor. Manganese ion (Mn2+) has been recently proved to specifically bind with cGAS and activate cGAS-STING pathway as a potential cGAS agonist, however, is significantly restricted by the low stability of Mn2+ for further medical application. As one of the most stable forms of manganese, manganese dioxide (MnO2) nanomaterials have been reported to show multiple promising functions, such as drug delivery, anti-tumor and anti-infection activities. More importantly, MnO2 nanomaterials are also found to be a potential candidate as cGAS agonist by transforming into Mn2+, which indicates their potential for cGAS-STING regulations in different diseased conditions. In this review, we introduced the methods for the preparation of MnO2 nanomaterials as well as their biological activities. Moreover, we emphatically introduced the cGAS-STING pathway and discussed the detailed mechanisms of MnO2 nanomaterials for cGAS activation by converting into Mn2+. And we also discussed the application of MnO2 nanomaterials for disease treatment by regulating cGAS-STING pathway, which might benefit the future development of novel cGAS-STING targeted treatments based on MnO2 nanoplatforms.

For most traditional fault location methods, the fault type needs to be known in advance or there may be dead zones using the decoupled modulus. To solve the problems, an improved algorithm based on electromagnetic time reversal is proposed. The improved algorithm can realize fault location by using the coupling signal in the non-fault phase of the transmission line, so fault location can be realized effectively even when the fault phase is unknown. The feasibility of using non-fault phase coupled signals to locate faults is theoretically verified. A 750kV overhead transmission line model is established by ATP-EMTP to obtain the fault signal at the observation point. The fault signal is time reversed and then connected to the observation point as an injection source. Each hypothetical fault location is traversed and its current is calculated by the BLT super-matrix equation. The 2-norm based on current energy is proposed as the criterion, and the position with the largest norm is the fault location. The simulation results show that the algorithm is not affected by the fault types, transition resistance and the initial phase angles of the power sources on both sides, and has high accuracy.

Manganese (Mn), a nutrient inorganic trace element, is necessary for a variety of physiological processes of animal body due to their important roles in oxidative regulation effects and other aspects of activities. Moreover, manganese ion (Mn2+) has widely reported to be crucial for the regulations of different immunological responses, thus showing promising application as potential adjuvants and immunotherapeutics. Taking the advantages of Mn-based biological and immunological activities, Manganese dioxide nanoparticles (MnO2 NPs) are a new type of inorganic nanomaterials with numerous advantages, including simple preparation, low cost, environmental friendliness, low toxicity, biodegradable metabolism and high bioavailability. MnO2 NPs, as a kind of drug carrier, have also shown the ability to catalyze hydrogen peroxide (H2O2) to produce oxygen (O2) under acidic conditions, which can enhance the efficacy of radiotherapy, chemotherapy and other therapeutics for tumor treatment by remodeling the tumor microenvironment. More importantly, MnO2 NPs also play important roles in immune regulations both in innate and adaptive immunity. In this review, we summarize the biological activities of Manganese, followed by the introduction for the biological and medical functions and mechanisms of MnO2 NPs. What’s more, we emphatically discussed the immunological regulation effects and mechanisms of MnO2 NPs, as well as their potentials to serve as adjuvants and immunomodulators, which might benefit the development of novel vaccines and immunotherapies for more effective disease control.

Autophagy, one of the major intracellular degradation systems, plays an important role in maintaining normal cellular physiological functions and protecting organisms from different diseases. Selenium (Se), an essential trace element, is involved in many metabolic regulatory signaling events and plays a key role in human health. In recent years, selenium nanoparticles (Se NPs) have attracted increasing attentions in biomedical field due to their low toxicity, high bioavailability and high bioactivity. Taking the advantage of their advanced biological activities, Se NPs can be used alone as potential therapeutic agents, or combine with other agents and served as carriers for the development of novel therapeutics. More interestingly, Se NPs have been widely reported to affect autophagy signaling, which therefor allow Se NPs to be used as potential therapeutic agents against different diseases. Here, this review suggested the relationships between Se and autophagy, followed by the trends and recent progresses of Se NPs for autophagy regulation in different diseased conditions. More importantly, this work discussed the roles and potential mechanisms of Se NPs in autophagy regulating, which might enhance our understanding about how Se NPs regulate autophagy for potential disease treatment. This work is expected to promote the potential application of Se NPs as novel autophagy regulators, which might benefit the development of novel autophagy associated therapeutics.

In-situ alloying is a facile method for exploring high-performance metallic materials for additive manufacturing. However, composition inhomogeneity is inevitable, and it is a double-edged sword for the properties of in-situ alloyed parts. Appropriately controlling the composition inhomogeneity benefits the applications of in-situ alloying in specific microstructural and properties design. In this work, the Al20Cu alloy was selected as the benchmark alloy to investigate the tailoring of composition inhomogeneity. The morphology and area percentage of composition inhomogeneity in the as-built samples were firstly analyzed. These results provided evidence for the formation of composition inhomogeneity and indicate that its content is tightly dependent on processing parameters. The characteristics of the molten pool under various processing parameters were investigated by modeling the laser remelting process. Based on these, a processing map was established to guide the tailoring of composition inhomogeneity. This study expands the understanding of the formation mechanism of composition inhomogeneity in in-situ alloyed parts and sheds light on employing laser powder bed fusion in-situ alloying for new materials development.

Infectious diseases remain the most serious public health issue, which requires the development of more effective strategies for infectious control. As a kind of ultra-trace element, cobalt is essential to the metabolism of different organisms. In recent decades, nanotechnology has attracted increasing attention worldwide due to its wide application in different areas, including medicine. Based on the important biological roles of cobalt, cobalt nanomaterials have recently been widely developed for their attractive biomedical applications. With advantages such as low costs in preparation, hypotoxicity, photothermal conversion abilities, and high drug loading ability, cobalt nanomaterials have been proven to show promising potential in anticancer and anti-infection treatment. In this review, we summarize the characters of cobalt nanomaterials, followed by the advances in their biological functions and mechanisms. More importantly, we emphatically discuss the potential of cobalt nanomaterials as anti-infectious agents, drug carriers, and immunomodulators for anti-infection treatments, which might be helpful to facilitate progress in future research of anti-infection therapy.

In China, the excessive application and improper disposal of chemical inputs have posed a great threat to the agricultural ecological environment and human health. The key to solve this problem is to promote the sustainable behaviors of farmers’ agricultural green production (AGP). Based on the micro-survey data of 652 farmers, this study adopts the binary probit model to investigate the impacts of risk perception and environmental regulation on the sustainable behaviors of farmers’ AGP. Results show that both risk perception and environmental regulation have significant effects on farmers’ willingness to engage in sustainable behaviors. Moreover, environmental regulation can positively adjust risk perception to improve farmers’ willingness to engage in sustainable behaviors. In terms of the two-dimensional variables, economic risks create the greatest negative impacts, and their marginal effect is 7.3%, while voluntary regulation creates the strongest positive impacts, and its marginal effect is 14.1%. However, both constrained and voluntary regulation have an enhanced moderating effect, where the effects of voluntary regulation are more remarkable. This is mainly because the environmental regulation policy signed by the government and farmers through the letter of commitment can inspire farmers to continue to implement green agricultural production from the deep heart. Therefore, government policies should constantly reduce farmers’ risk perception in terms of economic input, and adopt restrictive behaviors measures, such as regulatory punishment and voluntary contract, to promote their sustainable behaviors of AGP to the maximum extent.

Abstract In β titanium alloys, the β stabilizers segregate easily and considerable effort has been devoted to alleviate/eliminate the segregation. In this work, instead of addressing the segregation problems, the segregation was utilized to develop a novel microstructure consisting of a nanometre-grained duplex (α+β) structure and micrometre scale β phase with superior mechanical properties. An as-cast Ti-9Mo-6W alloy exhibited segregation of Mo and W at the tens of micrometre scale. This was subjected to cold rolling and flash annealing at 820 oC for 2 and 5 mins. The solidification segregation of Mo and W leads to a locally different microstructure after cold rolling (i.e., nanostructured β phase in the regions rich in Mo and W and plate-like martensite and β phase in regions relatively poor in Mo and W), which play a decisive role in the formation of the heterogeneous microstructure. Tensile tests showed that this alloy exhibited a superior combination of high yield strength (692 MPa), high tensile strength (1115 MPa), high work hardening rate and large uniform elongation (33.5%). More importantly, the new technique proposed in this work could be potentially applicable to other alloy systems with segregation problems.

High-entropy alloys (HEAs), i.e., multicomponent alloys where (typically five or more) elements are combined in equal, or roughly equal, quantities, are of great current interest, due to their formation of single, simple structured phases, and the unusual properties they can potentially exhibit. Phase presence may be predicted using semi-empirical methods, but deviations from predictions may be seen during the course of alloy synthesis, with the formation of unexpected phases. The generation of such phases may be controlled with knowledge of the effective solidification temperature; in this full article, Chvorinov’s rule for solidification time is used to estimate this temperature as part of the design of a new multiphase alloy system, TiVCrZr-Six. Further heat treatment of the TiVCrZr-Si system confirms the applicability of this approach. The new compositions demonstrate mechanical properties that suggest potential for optimization for high-temperature applications.

As an essential micronutrient, manganese plays an important role in the physiological process and immune process. In recent decades, cGAS-STING pathway, which can congenitally recognize exogenous and endogenous DNA for activation, has been widely reported to play critical roles in the innate immunity against some important diseases, such as infections and tumor. Manganese ion (Mn2+) has been recently proved to specifically bind with cGAS and activate cGAS-STING pathway as a potential cGAS agonist, however, is significantly restricted by the low stability of Mn2+ for further medical application. As one of the most stable forms of manganese, manganese dioxide (MnO2) nanomaterials have been reported to show multiple promising functions, such as drug delivery, anti-tumor and anti-infection activities. More importantly, MnO2 nanomaterials are also found to be a potential candidate as cGAS agonist by transforming into Mn2+, which indicates their potential for cGAS-STING regulations in different diseased conditions. In this review, we introduced the methods for the preparation of MnO2 nanomaterials as well as their biological activities. Moreover, we emphatically introduced the cGAS-STING pathway and discussed the detailed mechanisms of MnO2 nanomaterials for cGAS activation by converting into Mn2+. And we also discussed the application of MnO2 nanomaterials for disease treatment by regulating cGAS-STING pathway, which might benefit the future development of novel cGAS-STING targeted treatments based on MnO2 nanoplatforms. [ABSTRACT FROM AUTHOR]