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Preventive cancer vaccines are highly effective in preventing viral infection-induced cancer, but advances in therapeutic cancer vaccines with a focus on eliminating cancer cells through immunotherapy are limited. To develop therapeutic cancer vaccines, the integration of optimal adjuvants is a potential strategy to enhance or complement existing therapeutic approaches. However, conventional adjuvants do not satisfy the criteria of clinical trials for therapeutic cancer vaccines. To improve the effects of adjuvants in therapeutic cancer vaccines, effective vaccination strategies must be formulated and novel adjuvants must be identified. This review offers an overview of the current advancements in therapeutic cancer vaccines and highlights in situ vaccination approaches that can be synergistically combined with other immunotherapies by harnessing the adjuvant effects. Additionally, the refinement of adjuvant systems using cutting-edge technologies and the elucidation of molecular mechanisms underlying immunogenic cell death to facilitate the development of innovative adjuvants have been discussed.

Introduction: Several approaches to expand human hematopoietic stem cells (HSCs) have been reported, but the ability of these methods to expand long-term hematopoietic stem cells (LT-HSCs) remains to be improved, which limits the application of HSCs-based therapies. Methods: CD34+ cells were purified from umbilical cord blood using MacsCD34 beads, and then cultured for 12 d in a serum-free medium. Flow cytometry was used to detect phenotype, cell cycle distribution, and apoptosis of the cultured cells. Colony-forming cell (CFC) assays can evaluate multi-lineage differentiation potential of HSCs. Real-time polymerase chain reaction was employed to detect the expression of genes related to self-renewal programs and antioxidant activity. DCFH-DA probes were used to evaluate intracellular production of reactive oxygen species (ROS). Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead array. Results: Here, we show a combination, Nicotinamide (NAM) combined with pyrimidoindole derivative UM171, can massively expand LT-HSCs ex vivo, and the expanded cells maintained the capability of self-renewal and multilineage differentiation. Additionally, our data indicated that UM171 promoted self-renewal of HSCs by inducing HSCs entry into the cell cycle and activating Notch and Wnt pathways, but the infinite occurrence of this process may lead to mitochondrial metabolism disorder and differentiation of HSCs. NAM kept HSCs in their primitive and dormant states by reducing intracellular ROS levels and upregulating the expression of stemness related genes, so we believed that NAM can act as a brake to control the above process. Conclusions: The discovery of the synergistic effect of NAM and UM171 for expanding LT-HSCs provides a new strategy in solving the clinical issue of limited numbers of HSCs.

The global food crisis has intensified with climate change, and hybrid rice (Oryza sativa L.) is expected to play a crucial role in ensuring world food security. This study analyzed the parental origins and variety characteristics of 930 hybrid rice varieties bred in Sichuan Province, a typical low-light region and one of the main production areas for hybrid rice, from 2002 to 2022. The results indicate that these varieties were hybridized using 329 direct female and 539 direct male parents. Notably, the female parent Peiai 64 and the male parents Yuehesimiao and Fenghuazhan demonstrated a higher probability of breeding rice varieties with high yield and good quality. An ideal panicle type should possess more grains, a lower 1000-grain weight, a higher seed setting percentage, and greater grain density. It is recommended to increase the utilization of excellent parents in Sichuan Province, such as parents with ideal panicle type to improve resistance to climate change, particularly global dimming.

The utilization of plant extracts as environmentally friendly corrosion inhibitors has garnered considerable interest in the field of metallic corrosion protection. The primary objective of this study was to explore a new approach for utilizing Dillenia suffruticosa leaves extract (DSLE) to provide corrosion protection for mild steel (MS) in a molar hydrochloric acid solution. The phytocompounds responsible for corrosion prevention were extracted using ethanol with Soxhlet apparatus. The effectiveness of the extract as a corrosion inhibitor was evaluated through gravimetric and electrochemical methods, along with surface analysis of the corroded steel samples. This analysis involved the use of scanning electron microscopy (SEM) and Fourier-transformed infrared spectroscopy (FTIR) to examine the specimens with and without addition of the extract as inhibitor. The findings demonstrate that DSLE exhibits notable efficacy as a corrosion inhibitor for MS in an acidic environment. The inhibition efficiency (IE) demonstrates a positive correlation with the concentration of the extract, ultimately reaching a maximum value of 81.4 % at the optimum concentration of 1000 mg/L of the extract investigated. Potentiodynamic polarization data revealed that the DSLE functions as a mixed-type inhibitor.

The negative impacts of greenhouse gas emissions, particularly CO2 emissions, have garnered widespread attention. Various old residential areas in China, built more than 20 years ago, have been undergoing urgent transformation to improve citizens’ quality of life, which may significantly reduce carbon emissions. This study developed a carbon emissions accounting framework for residential areas to account the emissions impact of residential transformation. The framework addressed the inventory classifications of landscape greening, residential buildings, water resources, solid waste, infrastructure and transportation. The consumption-based calculation model and bottom-up data collection methods were used. The results show that the transformation of two old residential areas achieved considerable carbon reductions of 17.16% and 33.37% in South and North China, respectively. The macro guidance of local policies, specifically those regarding local urban infrastructure construction, significantly aided the carbon emissions reductions. Based on the calculation results, a list of recommended technologies was proposed to reduce carbon emissions, and four measures (adding greening, improving the garbage recovery rate, separating rain and sewage and transforming envelope structures for energy savings in northern China) were recommended to promote low carbon development in residential areas.

The microstructure, texture, and mechanical properties of as-extruded and cold-rolled Mg–8Li–3Al–2Zn-1Gd-0.2Zr (LAZ832-1Gd-0.2Zr) alloys were investigated with the aim of strengthening the alloy by combining hot extrusion and cold rolling. Cold rolling does not change the phase composition of as-extruded LAZ832-1Gd-0.2Zr alloy, but introduces a larger number of dislocations and twins into alloy matrix. Cold rolling leads to the weakening of the original {0001} basal and {112‾0}-{011‾0} prismatic textures in α-Mg matrix, as well as the α and γ fiber textures in β-Li matrix. But new slip systems that are favorable for cold rolling are activated, resulting in the formation of {033‾8} pyramidal and new prismatic ({112‾0}⟨101‾4⟩ and {101‾0}⟨21‾1‾10⟩) texture components. Cold rolling further strengthens LAZ832-1Gd-0.2Zr alloy on the basis of hot extrusion, mainly through work hardening effect caused by introducing a large number of dislocations into α-Mg matrix. When the rolling reduction is 45%, the yield strength and tensile strength of LAZ832-1Gd-0.2Zr alloy are increased to 269.8 ± 4.0 and 308.6 ± 4.1 MPa, respectively, and the elongation is higher than 15%.

This study investigates the creep behavior of bentonite-sand mixtures as potential buffer materials for low-level radioactive waste (LLW) repositories, with a specific case study in Taiwan. To assess the long-term hydro-mechanical properties, constant-volume swelling pressure, hydraulic conductivity, strain-controlled shear, and stress-controlled shear tests were conducted on MX80 and KV1 bentonite-sand mixtures. The experimental results indicate that MX80-sand 70/30 mixtures are prioritized as the buffer materials with 2.10 MPa swelling pressure and 1 × 10−13 m/s hydraulic conductivity. However, the shear strength of mixtures was reduced by almost 50 % when fully saturated. Furthermore, this study proposed a novel stress-controlled direct shear apparatus to retrieve the creep model parameters. The numerical method based on the creep model efficiently supports and simulates the saturation process and creep displacement. The finite element method (FEM) result predicts that the buffer of both bentonite-sand mixtures will achieve an average degree of saturation of 95 % at the end of three decades and full saturation in 100 years. The simulated creep displacement results at key nodes suggest that both top and bottom parts in the buffer, assembled from MX80-sand 70/30 mixtures or KV1-sand 70/30 mixtures, will have almost equivalent values of 4 mm in the horizontal and 2 mm in the vertical directions eventually.

Introduction: Cytochrome P450 enzymes (P450s) are recognized as the most versatile catalysts worldwide, playing vital roles in numerous biological metabolism and biosynthesis processes across all kingdoms of life. Despite the vast number of P450 genes available in databases (over 300,000), only a small fraction of them (less than 0.2 %) have undergone functional characterization. Objectives: To provide a convenient platform with abundant information on P450s and their corresponding reactions, we introduce the P450Rdb database, a manually curated resource compiles literature-supported reactions catalyzed by P450s. Methods: All the P450s and Reactions were manually curated from the literature and known databases. Subsequently, the P450 reactions organized and categorized according to their chemical reaction type and site. The website was developed using HTML and PHP languages, with the MySQL server utilized for data storage. Results: The current version of P450Rdb catalogs over 1,600 reactions, involving more than 590 P450s across a diverse range of over 200 species. Additionally, it offers a user-friendly interface with comprehensive information, enabling easy querying, browsing, and analysis of P450s and their corresponding reactions. P450Rdb is free available at http://www.cellknowledge.com.cn/p450rdb/. Conclusions: We believe that this database will significantly promote structural and functional research on P450s, thereby fostering advancements in the fields of natural product synthesis, pharmaceutical engineering, biotechnological applications, agricultural and crop improvement, and the chemical industry.

Introduction: Sepsis-induced cardiac injury is the leading cause of death in patients. Recent studies have reported that reactive oxygen species (ROS)-mediated ferroptosis and macrophage-induced inflammation are the two main key roles in the process of cardiac injury. The combination of ferroptosis and inflammation inhibition is a feasible strategy in the treatment of sepsis-induced cardiac injury. Objectives: In the present study, ceria nanozyme coordination with curcumin (CeCH) was designed by a self-assembled method with human serum albumin (HSA) to inhibit ferroptosis and inflammation of sepsis-induced cardiac injury. Methods and results: The formed CeCH obtained the superoxide dismutase (SOD)-like and catalase (CAT)-like activities from ceria nanozyme to scavenge ROS, which showed a protective effect on cardiomyocytes in vitro. Furthermore, it also showed ferroptosis inhibition to reverse cell death from RSL3-induced cardiomyocytes, denoted from curcumin. Due to the combination therapy of ceria nanozyme and curcumin, the formed CeCH NPs could also promote M2 macrophage polarization to reduce inflammation in vitro. In the lipopolysaccharide (LPS)-induced sepsis model, the CeCH NPs could effectively inhibit ferroptosis, reverse inflammation, and reduce the release of pro-inflammatory factors, which markedly alleviated the myocardial injury and recover the cardiac function. Conclusion: Overall, the simple self-assembled strategy with ceria nanozyme and curcumin showed a promising clinical application for sepsis-induced cardiac injury by inhibiting ferroptosis and inflammation.

Background: Flavonoids are one of the most important metabolites with vast structural diversity and a plethora of potential pharmacological applications, which have drawn considerable attention in the laboratory. Nevertheless, it remains uncertain how many candidates were progressed to clinical application. Aim of Review: We carried out a critical review of natural and semi-synthetic flavonoid drugs and candidates undergoing different clinical phases worldwide by applying an adequate search method and conducted a brief cheminformatic and bioinformatic analysis. It was expected that the obtained results might narrow the screening scope and reduce the cost of drug research and development. Key scientific Concepts of Review: To our knowledge, this is the most systematic summarization of flavonoid-based drugs and clinical candidates to date. It was found that a total of 19 flavonoid-based drugs have been approved for the market, and of these, natural flavonoids accounted for 52.6%. Besides, a total of 36 flavonoid-based clinical candidates are undergoing or suspended in different phases, and of these, natural flavonoids account for 44.4%. Thus, natural flavonoids remain the best option for finding novel agents/active templates, and when investigated in conjunction with synthetic chemicals and biologicals, they offer the potential to discover novel structures that can lead to effective agents against a variety of human diseases. Additionally, flavonoid-based marketed drugs have been successful in cardiovascular treatment, and the related drugs account for more than 30% of marketed drugs. However, the use of flavonoids as antineoplastic and immunomodulating agents is not likely for approximately 50% of the candidates suspended in the clinical stage. Interestingly, the marketed drugs covered a broader range of chemical spaces based on size, polarity, and three-dimensional structure compared to the clinical candidates. In addition, flavonoid glycosides with poor oral bioavailability account for 36.8% of the marketed drugs, and thus, they could be thoroughly investigated.

The keyhole phenomenon, frequently found in LPBF, is critically responsible for the formation of internal porosities which degrades the part quality. Owing to the ultra-high transience and complexity of the LPBF process, the underlying mechanisms during the keyholing process have not been well understood. In this work, a Multiphysics-based CFD model is developed to simulate the keyhole-penetration process in LPBF of CuCrZr alloy, and the ray-tracing laser heat source is implemented to visualize the multiple laser reflections. The simulation results are well validated in terms of the track size, porosity distribution and laser absorption by conducting the single-track experiment, X-CT scanning and calorimetric measurement, respectively. The flow patterns, driving forces and laser irradiation behaviors in the keyhole mode are collectively elucidated to understand the formation mechanisms of the keyhole-induced pores. The reduction of laser ray entries into the emerging cavity with a shrinking opening is noticed and contributes to the pore formation.

A novel zirconium (Zr)-core-aluminum (Al)-shell wire (ZCASW) combined with oscillating laser-arc hybrid welding (O-LAHW) process was employed for the welding of aluminum alloy 2024 (AA2024). The arc stability and characteristics, droplet transfer behavior and weld formation were systematically investigated. The results show that electrical signal waveform determines wire feeding rate, which affects the welding stability and weld quality. The increment in wire feeding rate increases magnetic field intensity and narrows arc cross-sectional area, which leads to arc contraction. The oscillating laser increases arc width and arc area, thereby expanding the conductive channel and greatly improving conductive ability of hybrid plasma, which promotes interactions between plasmas and helps to droplet transfer. Meanwhile, owing to the melting points differences between Zr wire and Al wire in ZCASW filler material, the melting rate of outer Al wire is larger than that of central Zr wire during welding, thereby resulting in two kinds of droplet transfer modes, and electromagnetic force and metal vapor reaction force strongly influence droplet transfer behavior. The oscillating laser improves the weld quality, which is deteriorated due to the appearance of spatters as wire feeding rate increases. When 1 m/min wire feeding rate is selected, a perfect formation is obtained. The current study offers insight into the formation mechanism of high-quality weld and welding stability during O-LAHW of AA2024 combined with ZCASW filler material.

In this study, the processing parameters of a laser powder bed fusion (LPBF)-fabricated CoCrNi alloy were systematically investigated for their impact on mechanical properties, microstructure, and fracture characteristics when the relative density exceeds 99%. The maximum relative density of 99.89% was attained at a laser power of 225 W, and scan speed of 1000 mm/s, accompanied by a hardness value of 276.83 HV. However, it is important to note that the highest relative density did not correspond to the maximum σUTS. Tensile testing revealed that increasing the laser power at the same scan speeds led to a decrease in elongation. The LPBF-fabricated CoCrNi alloy exhibited enhanced defect tolerance due to its cellular microstructure, which confined ductile dimple sizes to the nanoscale and impeded crack propagation through pinning effects. At scan speeds of 1000 mm/s and energy densities below 83 J/mm³, an increased presence of unmelted powder and pores was observed. Besides, it was confirmed that the crystallographic texture displayed the strongest orientation within the sample. Theoretical calculations indicated that over 50% of the yield strength is attributed to the dislocation structure. These findings contribute to the process optimization of LPBF, providing a valuable reference for adjusting process parameters to enhance material mechanical properties, particularly when targeting relative densities above 99%.

The microstructure evolution, cyclic oxidation, and hot corrosion behavior of the unheated-treated (As-built) and solution + double aging (SDA)-treated Inconel 718 alloys fabricated through laser-induction hybrid cladding (LIHC) were investigated. It was found that the as-built Inconel 718 alloy exhibits a columnar dendritic with intergranular Laves phase. After SDA-treated, γ'', γ′, δ and carbide phases precipitated, the Laves phase became fine and dispersed. After cyclic oxidation, the Cr2O3 scales were formed on both as-built and SDA-treated LIHC-produced Inconel 718 alloy, which could provide good cyclic oxidation resistance for the Inconel 718 alloy. However, the as-built and SDA-treated LIHC-produced Inconel 718 alloy suffered severe hot corrosion in 95 wt% Na2SO4 + 5 wt% NaCl mixed salt solution and many corrosion products were generated, including Cr2O3, NiCr2O4, NaNbO3, Na2CrO4, NiFe2O4, Fe3O4, and NiO. Nevertheless, the SDA-treated sample showed better cyclic oxidation and hot corrosion resistance than the as-built sample, owing to the more compact Cr2O3 scale.

MgLi alloys are one of the lightest structural materials, but suffer from severe corrosion due to the hyperactivity of Mg and Li. In this work, an electrically conductive and corrosion-resistant chemical conversion coating was fabricated on a duplex MgLi alloy LA103Z by two different routes: the first route using a conventional immersion treatment (Im-PCCs); and the second route using a brushing conversion treatment (Br-PCCs). Results demonstrate that chemical composition of conversion coatings remained, but surface morphology was altered. The Im-PCC depicts many lamellar CaHPO4 when the immersion time was longer than 60 s. The Br-PCC shows no lamellas on surface till a treatment time of 120 s. These lamellar crystals are detrimental to the electrical contact resistance (ECR), and the ECR for the Br-PCC was one order of magnitude lower than that for the Im-PCCs. Corrosion resistance for Br-PCCs, however, was slightly lower than Im-PCCs.

TiO2–Y2O3–ZrO2 composite ceramics exhibit excellent abrasion resistance, corrosion resistance, and high-temperature resistance, making them vital structural-functional materials in ceramics and refractories. The key to preparing high-quality TiO2–Y2O3–ZrO2 ceramic powders lies in controlling the agglomeration rate, which can be optimized by choosing an appropriate drying method. This study utilized microwave drying techniques to dehydrate TiO2–Y2O3–ZrO2 ceramic powders. It was found that the average drying rate is proportional to initial masses, initial moisture contents and microwave heating powers. To describe the drying process, four models—the Quadratic, Wang and Singh, Modified Page, and Page—were employed. The best model for the drying process was the Modified Page model. The specimens were analyzed to assess the alterations in the samples pre and post-drying by scanning electron microscopy and Fourier transform infrared spectroscopy. The findings revealed that microwaves can hasten the drying process of TiO2–Y2O3–ZrO2 and enhance its spread. Utilizing Fick's second law, the effective diffusion coefficient was ascertained, showing an inverse proportionality to the sample mass, and a proportionality to the microwave heating power and initial moisture content. Using the Arrhenius exponential model, it was ascertained that the microwave drying process's activation energy stands at 13.81834 W/g. This paper demonstrates that microwave drying effectively achieves efficient drying and lays the theoretical and experimental groundwork for the microwave heating and drying of other powdered materials.

Background: Vascularized composite allotransplantation (VCA) has become a viable option for restoration of devastating injuries that are not amenable to conventional reconstructive techniques. However, the relative scarcity of procedures performed worldwide, as well as the potential for iatrogenic injury with biopsies, makes studying the immunopathogenesis of acute rejection challenging. Translational VCA research focuses on developing strategies to overcome these barriers with the use of animal models can be technically challenging and difficult to replicate without highly trained microsurgeons. Methods: We describe a modified model of a femur-based composite tissue allograft using an adapted vascular cuff anastomotic technique with a tunneled skin flap in a rodent model. Results: The use of a heterotopic osteomyocutaneous flap with a subcutaneously tunneled-skin paddle to the posterolateral aspect of the recipient rodent allows for ease of flap monitoring and reduces the risk of self-mutilation. A total of six transplantations were conducted with no signs of self-mutilation. Operative time decreased as our surgical technique improved, and long-term graft tolerance was possible under our immunosuppressive regimen. Additionally, we demonstrate cases of successful transplantation in both an allogeneic and syngeneic rodent model. Conclusion: Animal models, although technically challenging, are a reliable and reproducible modality that has been used to investigate various aspects of VCA immunology. We describe the success of an osteomyocutaneous flap with a modified vascular cuff anastomosis that can be used by investigators with less experience in microsurgical techniques to further our understanding of VCA physiology. Furthermore, tunneling of the skin paddle reduces the risk of self-mutilation and other external factors affecting the graft.

Moistube irrigation is a new micro-irrigation technology. Accurately estimating its wetting pattern dimensions presents a challenge. Therefore, it is necessary to develop models for efficient assessment of the wetting transport pattern in order to design a cost-effective moistube irrigation system. To achieve this goal, this study developed a multivariate nonlinear regression model and compared it with a dimensional model. HYDRUS-2D was used to perform numerical simulations of 56 irrigation scenarios with different factors. The experiments showed that the shape of the wetting soil body approximated a cylinder and was mainly affected by soil texture, pressure head, and matric potential. A multivariate nonlinear model using a power function relationship between wetting size and irrigation time was developed, with a determination coefficient greater than 0.99. The model was validated for cases with six soil texture types, with mean average absolute errors of 0.43–0.90 cm, root mean square errors of 0.51–0.95 cm, and mean deviation percentage values of 3.23%–6.27%. The multivariate nonlinear regression model outperformed the dimensional model. It can therefore provide a scientific foundation for the development of moistube irrigation systems.

Mobile learning allows for an interactive way of learning through devices like smartphones. However, current methods usually rely on pre-set situations and struggle to recognize new contexts when they come up during testing. To solve this, we suggest the Open-set Learning Context Recognition Model (OLCRM). This model uses data extracted from smartphone sensors to identify whether a learning context is known or unknown. It also uses a Dual Discriminator Generative Adversarial Network (DDGAN) to create high-quality fake examples, which helps improve the accuracy of recognizing contexts. Experimental results demonstrate the effectiveness of OLCRM in open-set learning context recognition problems.

This study investigated antimicrobial resistance in Salmonella enterica serovar Choleraesuis (S. Choleraesuis) isolates from diseased pigs in Taiwan (2015–2020). Among 272 isolates, florfenicol (96.7%), enrofloxacin (96.3%), doxycycline (91.2%), gentamicin (84.6%), and tiamulin (80.5%) exhibited high resistance. 99.3% of the isolates were resistant to at least one antibiotic, and 97.8% of the isolates were multidrug resistant. This study illustrated that S. Choleraesuis isolates exhibited high resistance to antimicrobials currently used in the Taiwanese swine industry.

The burden of respiratory syncytial virus (RSV) infection among older adults in Taiwan is not well understood due to a scarcity of published epidemiological data. Nonetheless, the increasing proportion of older adults is anticipated to translate to increased burden of RSV infection, presenting a challenge to the healthcare system. Thus, an expert meeting was convened among a panel of infectious disease specialists from Taiwan to evaluate the existing local evidence and data gaps related to RSV infection in older adults (aged ≥50 years), and propose steps to generating evidence on disease burden among this population. Overall, there are few studies on the clinical and economic burden of RSV infection in Taiwan, and existing data are limited by small sample sizes and highly selected populations. Inconsistent RSV testing practices among older adults contribute to under-diagnosis and under-reporting, driven by limitations to reimbursement policies that discourage proactive RSV testing in older adults, and the lack of appropriate, targeted RSV treatment. Crucially, the paucity of epidemiological data may perpetuate a lack of awareness of RSV among clinicians and the public, hinder investments into RSV testing at a policymaker level, and thereby impede implementation of consistent diagnostic practices, precluding a deeper understanding of RSV. To overcome these challenges, it is imperative to prioritize generation of epidemiological data to establish the burden of RSV infection among older adults in Taiwan. Such data would also support a multi-stakeholder group in assessing the impact of future RSV-related interventions, such as educational initiatives and preventative strategies including vaccines.

Background: The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored. Methods: This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists. Results: A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) is a promising therapeutic target for cancer therapy. In this work, we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors, leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent, selective, orally bioavailable allosteric SHP2 inhibitor (SHP2WT IC50 = 2.7 nmol/L) with favorable pharmacokinetic profiles (F = 42.5%; t1/2 = 2.47 h). Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the “tunnel” allosteric site of SHP2. TK-642 could effectively suppress cell proliferation (KYSE-520 cells IC50 = 5.73 μmol/L) and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling pathways. Additionally, oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model, with a T/C value of 83.69%. Collectively, TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.

Bile acids (BAs) are synthesized by the host liver from cholesterol and are delivered to the intestine, where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various transporters. They serve to emulsify dietary lipids and act as signaling molecules, regulating the host's metabolism and immune homeostasis through specific receptors. Therefore, disruptions in BA metabolism, transport, and signaling are closely associated with cholestasis, metabolic disorders, autoimmune diseases, and others. Botanical triterpenoids and steroids share structural similarities with BAs, and they have been found to modulate BA metabolism, transport, and signaling, potentially exerting pharmacological or toxicological effects. Here, we have updated the research progress on BA, with a particular emphasis on new-found microbial BAs. Additionally, the latest advancements in targeting BA metabolism and signaling for disease treatment are highlighted. Subsequently, the roles of botanical triterpenoids in BA metabolism, transport, and signaling are examined, analyzing their potential pharmacological, toxicological, or drug interaction effects through these mechanisms. Finally, a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, which is crucial for innate immunity. This pathway responds to mitochondrial DNA and is associated with cellular stress response. Our review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS–STING pathway. We critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions, primarily through the accumulation of damaged mitochondria, which activates the cGAS–STING pathway. This activation prompts the production of pro-inflammatory cytokines, exacerbating neuroinflammation. This review emphasizes the interaction between mitophagy and the cGAS–STING pathways. Effective mitophagy may suppress the cGAS–STING pathway, offering protection against neuroinflammation. Conversely, impaired mitophagy may activate the cGAS–STING pathway, leading to chronic neuroinflammation. Additionally, we explored how this interaction influences neurodegenerative disorders, suggesting a common mechanism underlying these diseases. In conclusion, there is a need for additional targeted research to unravel the complexities of mitophagy–cGAS–STING interactions and their role in neurodegeneration. This review highlights potential therapies targeting these pathways, potentially leading to new treatments for neuroinflammatory and neurodegenerative conditions. This synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

Understanding interactions between viruses and their hosts is conducive to enabling better application of viruses as biocontrol agents. Certain viruses carried by parasitic wasps enhance the parasitic efficiency of wasp-larvae by protecting them against the immune system of their Lepidopteran host. However, the relationship between prey pests and viruses found in predatory natural enemies remains unclear. Herein, we report the interaction between Arma chinensis virus-1 (AcV-1), originally isolated from a predatory natural enemy, Arma chinensis (Hemiptera: Pentatomidae), and one of its prey species, Spodoptera frugiperda (Lepidoptera: Noctuidae). The results showed that the AcV-1 virus appeared harmful to the novel host S. frugiperda by inhibiting larval diet consumption and increasing pupal mortality. Meanwhile, sequencing data indicated that the virus altered the gene expression profiles of S. frugiperda. KEGG analysis showed that the proteasome and phagosome pathways related to protein degradation and immune response were significantly enriched. Although the expression levels of digestive enzyme genes did not change significantly, the total protease activity of AcV-1 virus-positive individuals was significantly decreased, suggesting that the virus inhibited diet consumption of S. frugiperda via the down-regulation of digestive enzyme activities. These results indicate that a virus initially isolated in a predatory natural enemy can decrease the fitness of its prey species. The virus was found to impact the host proteasome and phagosome pathways related to protein degradation and immunity, providing a potential mechanism to enhance controlling efficiency.

The H9N2 subtype of avian influenza virus (AIV) is widely prevalent in poultry and wild birds globally, and has become the predominant subtype circulating in poultry in China. The H9N2 AIV can directly or indirectly (by serving as a “donor virus”) infect humans, posing a significant threat to public health. Currently, there is a lack of in-depth research on the prevalence of H9N2 viruses in Shanxi Province, central China. In this study, we isolated 14 H9N2 AIVs from October 2020 to April 2022 in Shanxi Province, and genetic analysis revealed that these viruses belonged to 7 different genotypes. Our study on animals revealed that the H9N2 strains we identified displayed high transmission efficiency among chicken populations, and exhibited diverse replication abilities within these birds. These viruses could replicate efficiently in the lungs of mice, with one strain also demonstrating the capacity to reproduce in organs like the brain and kidneys. At the cellular level, the replication ability of different H9N2 strains was evaluated using plaque formation assays and multi-step growth curve assays, revealing significant differences in the replication and proliferation efficiency of the various H9N2 viruses at the cellular level. The antigenicity analysis suggested that these isolates could be classified into 2 separate antigenic clusters. Our research provides crucial data to help understand the prevalence and biological characteristics of H9N2 AIVs in central China. It also highlights the necessity of enhancing the surveillance of H9N2 AIVs.

Background: Given the limited studies addressing the issue about the effect of different surgical modalities for metastatic spinal cord compression (MSCC) as the first malignancy manifestation, we conducted a retrospective case-control study to evaluate the surgical outcome of MSCC as the first malignancy manifestation. Methods: A total of 128 patients who were suspected of having metastatic spinal cord compression and underwent surgery from 2008 to 2021 were enrolled in the study. All patients were categorized into either ‘debulking group’ or ‘palliative group’. Results: The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), Frankel scale, and Karnofsky scores. All the outcomes were analyzed with a data cutoff of December 31, 2021. There was a significant difference between groups in progression-free survival (PFS) (p = 0.0094). However, there was no significant difference between groups in the overall survival (OS) (p = 0.0746). Age of onset, gender, duration of symptoms, and location of spinal metastasis, initial Frankel, initial Tomita scores, and initial Karnofsky performance scale showed no significant differences between groups. Conclusion: In conclusion, debulking surgery was shown to provide better neurological recoveries and could be considered first in patients with metastatic spinal cord compression as the first malignancy manifestation.

Summary: Background: High ulnar nerve injuries result in intrinsic muscle weakness and are inconvenient for patients. Moreover, conventional surgical techniques often fail to achieve satisfactory motor recovery. A potential reconstructive solution in the form of the supercharge end-to-side (SETS) anterior interosseous nerve (AIN) transfer method has emerged. Therefore, this study aims to compare surgical outcomes of patients with transected and in-continuity high ulnar nerve lesions following SETS AIN transfer. Methods: Between June 2015 and May 2023, patients with high ulnar palsy in the form of transection injuries or lesion-in-continuity were recruited. The assessment encompassed several objective results, including grip strength, key pinch strength, compound muscle action potential, sensory nerve action potential, and two-point discrimination tests. The muscle power of finger abduction and adduction was also recorded. Additionally, subjective questionnaires were utilized to collect data on patient-reported outcomes. Overall, the patients were followed up for up to 2 years. Results: Patients with transected high ulnar nerve lesions exhibited worse baseline performance than those with lesion-in-continuity, including motor and sensory functions. However, they experienced greater motor improvement but less sensory recovery, resulting in comparable final motor outcomes in both groups. In contrast, the transection group showed worse sensory outcomes. Conclusions: Our findings suggest that SETS AIN transfer benefits patients with high ulnar nerve palsy, regardless of the lesion type. Nonetheless, improvements may be more pronounced in patients with transected lesions.

Background: Diabetes Mellitus (DM), a chronic metabolic disease characterized by elevated blood glucose, is caused by various degrees of insulin resistance and dysfunctional insulin secretion, resulting in hyperglycemia. The loss and failure of functional β-cells are key mechanisms resulting in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Aim of review: Elucidating the underlying mechanisms of β-cell failure, and exploring approaches for β-cell neogenesis to reverse β-cell dysfunction may provide novel strategies for DM therapy. Key scientific concepts of review: Emerging studies reveal that genetic susceptibility, endoplasmic reticulum (ER) stress, oxidative stress, islet inflammation, and protein modification linked to multiple signaling pathways contribute to DM pathogenesis. Over the past few years, replenishing functional β-cell by β-cell neogenesis to restore the number and function of pancreatic β-cells has remarkably exhibited a promising therapeutic approach for DM therapy. In this review, we provide a comprehensive overview of the underlying mechanisms of β-cell failure in DM, highlight the effective approaches for β-cell neogenesis, as well as discuss the current clinical and preclinical agents research advances of β-cell neogenesis. Insights into the challenges of translating β-cell neogenesis into clinical application for DM treatment are also offered.

Void drift between subchannels in a rod bundle is a crucial phenomenon affecting the calculation accuracy of thermal-hydraulic parameters in SMRs. It holds significant importance in enhancing the precision of safety analysis for SMRs. Existing research on experiment and model of void drift between rod bundle subchannels is relatively rare, and the accuracy of model calculations requires improvement. In this study, experiments on gas-liquid two-phase non-equilibrium flow were conducted to measure the redistribution of two-phase flow induced by void drift in a 1 × 2 rod bundle. The experiment results indicated that in bubby flow regime with void fraction less than 0.3, the void diffusion coefficient showed little variation with changes in void fraction. However, in slug flow and annular flow regimes with void fraction exceeding 0.3, the void diffusion coefficient significantly increased with an increase in void fraction. Furthermore, a new void drift model was developed and validated based on a subchannel code. The overall predicted uncertainty for the outlet void fraction in the rod bundle benchmark was less than 13%.

We present a case of an 81-year-old woman who presented to the emergency department with bleeding from a right breast wound. The patient had prior imaging suggestive of bilateral silicone implant rupture and a history of low tolerance for MRI scans. Ultrasound imaging in the emergency setting showed findings in the right breast suggestive of a fistula with free silicone and hematoma. A subsequent photon-counting CT scan with custom silicone-specific segmentation allowed differentiation of silicone from hematoma, provided anatomic assessment and location of the fistula, and revealed bilateral silicone-induced lymphadenopathy.

Clonorchis sinensis infections persist globally among humans. These pathogens mainly inhabit the intrahepatic biliary system. Most individuals with clonorchiasis exhibit mild symptoms. The absence of distinctive symptoms often results in delayed diagnosis and treatment, potentially leading to chronic infection. We herein report a case of a 29-year-old female presented with a year-long history of abdominal distention and dyspepsia. Imaging revealed intrahepatic bile duct dilatation, intrahepatic bile duct cyst, and associated deposits. One month post-cystectomy, the patient developed massive ascites and a significant increase in eosinophil count. After treatment, multiple worms were observed in the drainage tube. Morphological and DNA metagenomic analyses confirmed the presence of C. sinensis. Clinical manifestations of C. sinensis vary widely. Imaging serves as a valuable diagnostic tool in endemic areas, especially in detecting intrahepatic duct dilation where the flukes reside. In addition to intrahepatic bile duct dilation, abnormal echoes within the bile duct and the presence of floating objects in the gallbladder significantly aid in diagnosis. Clinicians may encounter these parasitic diseases unexpectedly, underscoring the importance of understating such cases in routine practice and contributing to our broader understanding of managing similar cases in clinical settings.

The multi-material components formed by laser powder bed fusion (LPBF) have shown potential in advanced equipment due to their superior performance. The uneven distribution of immiscible in the molten pool is a challenge for the performance of multi-material components. In this study, a thermo-fluidic particle scale numerical model coupled with a ray-tracing method is established to understand the formation of the immiscible CuCrZr/316L multi-material. The impact of process parameters on the distribution of CuCrZr and 316L is investigated. Results reveal that the experimental and simulation results agree well with a maximum molten pool width and depth difference of 7%. The recoil pressure and Marangoni convection contribute to the mixing of 316L and CuCrZr. As the scanning speed decreases or the scanning power increases, a longer molten pool lifetime is obtained, which increases the immiscible CuCrZr/316L mixing. A large number of CuCrZr islands are formed inside the molten pool at high energy density with improved homogeneity. This work can provide fundamental insights into understanding the distribution of immiscible metal material in the multi-materials LPBF process.

Al2TiO5 porous ceramics with high density and excellent thermal stability were prepared by the replica template method. MgO was introduced into Al2TiO5 by adding magnesite (MgCO3) to the slurry during the preparation process. The density and compressive strength of Al2TiO5 porous ceramics with varying MgCO3 content were studied. Additionally, the atomic-scale microstructure, thermal stability, and thermal shock resistance of the Al2TiO5 porous ceramics with 2 wt% MgCO3 were investigated. The results show that the Al2TiO5 porous ceramics doped with 2 wt% MgCO3 exhibit the highest density and compressive strength. The crystallographic orientation relationships of Al2TiO5 (ATO) - Mg0.3Al1.4Ti1.3O5 (MATO) and Mg0.3Al1.4Ti1.3O5 (MATO) - MgAl2O4 (MAO) are observed as (1 1 3) ATO//(1 1 2) MATO and [1‾ 2‾ 1] ATO//[1‾ 2‾ 1] MATO, (1 1 2) ATO//(2 2 0) MAO and [1‾ 2‾ 1] MATO//[1‾ 1 0] for the first time. In addition, the Al2TiO5 porous ceramics with 2 wt% MgCO3 remain phase stable after annealing at 1200 °C for 20 h, and the residual compressive strength is still higher than 88% after 20 cycles of the heating-cooling process at 1400 °C. These results indicate that the Al2TiO5 porous ceramics containing 2 wt% MgCO3 have potential applications in the porous media combustion (PMC) field.

This paper examines the effect of the microstructure and electrical conductivity (EC) on the swelling ratio and pressure in red-bed mudstone sampled from arid areas in the Xining region in the northeastern Tibetan Plateau. A series of laboratory tests, including swelling experiments, X-ray diffraction (XRD), and scanning electron microscope (SEM), was carried out for mechanical and microstructural analysis. The coupled influence of the EC and microstructural parameters on the expansion ratio and pressure was investigated, and the weight coefficients were discussed by the entropy weight method. The results revealed an increasing exponential trend in EC, and the maximum swelling speed occurred at an EC of approximately 10 μS/cm. In addition, a method for predicting the expansion potential is proposed based on the microstructure, and its reliability is verified by comparing with swelling experimental results. In addition, according to the image analysis results, the ranges of the change in the clay minerals content (CMC), the fractal dimension (FD), the average diameter (AD) of pores, and the plane porosity (PP) are 23.75%–53%, 1.08–1.17, 7.53–22.45 μm, and 0.62%–1.25%, respectively. Moreover, mudstone swelling is negatively correlated with the plane porosity, fractal dimension and average diameter and is linearly correlated with the clay mineral content. Furthermore, the weight values prove that the microstructural characteristics, including FD, AD, and PP, are the main factors influencing the expansion properties of red-bed mudstones in the Xining region. Based on the combination of macro and micro-analyses, a quantitative analysis of the swelling process of mudstones can provide a better reference for understanding the mechanism of expansion behavior.

For projects near the tectonic belt, mylonite of varying metamorphic degrees may be present. The matrix proportion of rock reflects its internal microscopic characteristics, thus it is beneficial for engineering geology to study the effect of the matrix proportion on the mechanical properties and rupture behaviors of rock. Samples of mylonitic granite and granitic protomylonite with varying matrix proportions were obtained from a ductile shear zone for a series of uniaxial compression and acoustic emission (AE) tests. The results showed that with the increase in matrix proportion, the average strength and elastic modulus of the samples increased, and the rock sample with the largest matrix proportion exhibited the maximum peak stress of 244.42 MPa, which was 45.86% greater than the average peak stress of the rock samples with the smallest matrix proportions. For the rock samples with larger matrix proportion, their mechanical parameters exhibited greater dispersion and the large-scale appearance of AE events occurred earlier, showing a relatively gradual failure process. These samples had larger accumulated AE parameter values and greater degree of failure. In contrast, for samples with smaller matrix proportions, the large-scale appearance of AE events occurred close to the peak stress, indicating that the occurrence of damage and fractures was centralized and instantaneous. These samples had lower accumulated AE parameter values and fewer cracks after failure. Additionally, for the rock samples with more matrix proportion, the average variance of the b-value was 1.1, which was lower than that of rock samples with the smallest matrix proportion (the average variance of the b-value was 3.7). Furthermore, it can be predicted that under certain stress, the failure depth around a tunnel is generally smaller when the strength of rock samples with larger matrix proportion is greater.

Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in adverse drug reaction (ADR) enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs.

Background/purpose: The diagnosis and treatment of Sjogren's syndrome (SS) are commonly conducted by rheumatologists and stomatologists. The purpose of this study was to compare the scientometric characteristics of SS publications by rheumatologists and stomatologists. Materials and methods: All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into rheumatologists and stomatologists groups. Results: There were 3245 and 1209 papers on SS were published by rheumatologists and stomatologists, respectively. For the most-cited top-200 papers, the total citation count was 29,764 and the h index was 108 for SS publications by rheumatologists; whereas the count is 19,891 and h index is 81 for publications by stomatologists. Interestingly, we observed that accumulated citations of the publications by stomatologists cooperated with rheumatologists were larger than those by stomatologists alone during 2012–2022. The more common keywords such as saliva, salivation, minor salivary glands, parotid gland, submandibular gland, sialography, lip, dental caries, and hyposalivation were reported by stomatologists. The more frequent keywords such as rheumatoid factor, fatigue, lymphoma, interstitial lung disease, arthralgia, Raynaud phenomenon, lymphadenopathy, and vasculitis were reported by rheumatologists. Conclusion: This study firstly reports the scientometric characteristics of SS publications by rheumatologists and stomatologists. The scale and citations of rheumatologists' publications greatly outweigh those of stomatologists, suggesting stomatologists can cooperate more with rheumatologists regarding SS research.

Backgrounds: The functional recovery after peripheral nerve injury remains unsatisfactory. This study aims to perform a comprehensive evaluation of the efficacy of Fasudil Hydrochloride at treating the sciatic nerve transection injury in rats and the mechanism involved. Materials and methods: In animal experiments, 75 Sprague Dawley rats that underwent transection and repair of the right sciatic nerve were divided into a control, Fasudil, and Fas + LY group, receiving daily intraperitoneal injection of saline, Fasudil Hydrochloride (10 mg/kg), and Fasudil Hydrochloride plus LY294002 (5 mg/kg), respectively. At day 3 after surgery, the expression of ROCK2, p-PI3K, and p-AKT in L4-5 DRG and the lumbosacral enlargement was determined using Western blotting. At day 7 and 14, axon density in the distal stump was evaluated with immunostaining using the anti-Neurofilament-200 antibody. At day 30, retrograde tracing by injecting Fluoro-gold in the distal stump was performed. Three months after surgery, remyelination was analyzed with immostaining using the anti-MPZ antibody and the transmission electron microscope; Moreover, Motion-Evoked Potential, and recovery of sensorimotor functions was evaluated with a neuromonitor, Footprint, Hot Plate and Von Frey Filaments, respectively. Moveover, the Gastrocnemius muscles were weighed, and then underwent H＆E staining, and staining of the neuromuscular junction using α-Bungarotoxin to evaluate the extent of atrophy and degeneration of the endplates in the Gastrocnemius. In vitro, spinal motor neurons (SMNs) and dorsal root ganglia (DRG) were cultured to examine the impact of Fasudil Hydrochloride and LY294002 on the axon outgrowth. Results: Three days after injury, the expression of ROCK2 increased significantly (P＜0.01), and Fasudil application significantly increased the expression of p-PI3K and p-AKT in L4-6 DRG and the lumbosacral enlargement (P

The effect of the volume fraction of nanocrystals on the macroscopic mechanical properties and microscopic atomic structure of Fe-based nanocrystalline alloys, as well as the relationship between the two, is an urgent issue to be explored. Seven nanocrystalline alloys with different volume fractions of nanocrystals were formed by annealing treatment of (Fe0·9Ni0.1)86B14 amorphous precursor. Through hardness, flat plate bending, and nanoindentation experiments, it is found that when the volume fraction of nanocrystals reaches the range of 45–55 %, there is an abrupt change in the macroscopic mechanical properties. Specifically, when the volume fraction is less than this range, the properties inherit the amorphous matrix, however, larger than this range, the properties are dominated by precipitated nanocrystalline phases. Meanwhile, based on the molecular dynamics simulation method, seven Fe90Ni10 amorphous nanocrystalline models with different volume fractions of body-centered cubic nanocrystals are established, and the deformation mechanism of models and the evolution of their microstructures during the nanoindentation process are obtained intuitively. Moreover, it is further revealed that the significant changes in the Voronoi polyhedral index, which represents the microscopic atomic structure in this range of nanocrystal volume fractions, are the main reason for the abrupt changes in the mechanical properties at the macroscopic level.

Sclerostin emerges as a novel target for bone anabolic therapy in bone diseases. Osteogenesis imperfecta (OI) and X-linked hypophosphatemia (XLH) are rare bone diseases in which therapeutic potential of sclerostin inhibition cannot be ignored. In OI, genetic/pharmacologic sclerostin inhibition promoted bone formation of mice, but responses varied by genotype and age. Serum sclerostin levels were higher in young OI-I patients, while lower in adult OI-I/III/IV. It's worth investigating whether therapeutic response of OI to sclerostin inhibition could be clinically predicted by genotype and age. In XLH, preclinical/clinical data suggested factors other than identified FGF23 contributing to XLH. Higher levels of circulating sclerostin were detected in XLH. Sclerostin inhibition promoted bone formation in Hyp mice, while restored phosphate homeostasis in age-/gender-dependent manner. The role of sclerostin in regulating phosphate metabolism deserves investigation. Sclerostin/FGF23 levels of XLH patients with/without response to FGF23-antibody warrants study to develop precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy. Notably, OI patients were associated with cardiovascular abnormalities, so were XLH patients receiving conventional therapy. Targeting sclerostin loop3 promoted bone formation without cardiovascular risks. Further, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.The Translational Potential of this Article.Preclinical data on the molecular understanding of sclerostin inhibition in OI and therapeutic efficacy in mouse models of different genotypes, as well as clinical data on serum sclerostin levels in patients with different phenotypes of OI, were reviewed and discussed. Translationally, it would facilitate to develop clinical prediction strategies (e.g. based on genotype and age, not just phenotype) for OI patients responsive to sclerostin inhibition. Both preclinical and clinical data suggested sclerostin as another factor contributing to XLH, in addition to the identified FGF23. The molecular understanding and therapeutic effects of sclerostin inhibition on both promoting bone anabolism and improving phosphate homostasis in Hyp mice were reviewed and discussed. Translationaly, it would facilitate the development of precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy for the treatment of XLH. Cardiovascular risk could not be ruled out during sclerostin inhibition treatment, especially for OI and XLH patients with cardiovascular diseases history and cardiovascular abnormalities. Studies on the role of sclerostin in inhiting bone formation and protecting cardiovascular system were reviewed and discussed. Translationaly, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.

A series of engineering application studies related to hydrogen damage has been carried out for the eutectic high-entropy alloy (HEA) AlCoCrFeNi2.1 with excellent comprehensive properties. This work mainly introduces the element segregation and microstructure evolution phenomenon near the surface phase boundary and around the precipitated phase found in the hydrogen damage experiment of the material. Studies have shown that the evolution of the near-surface phase boundary microstructure of HEAs caused by hydrogen charging has a great influence on the hydrogen trap density inside the alloy. The “self-resistance hydrogen effect” is produced, that is, hydrogen-induced microstructure evolution causes the effect of delayed hydrogen diffusion. In this phenomenon, the synergy between hydrogen atoms and vacancies and dislocations on the alloy surface is crucial.

Lightweight refractory high-entropy alloy (LRHEA) is one of potential structural materials in aerospace industry for its excellent high-temperature comprehensive properties and low density. In this work, a new high-throughput method to develop LRHEAs was proposed. The equimolar HfNbTaTiZr alloy was immersed with melting pure aluminum for a given time, and a thick layer with composition gradient was obtained. Further characterizations of the layer result in relations between composition and nanohardness or Young's modulus, which facilitate the selection of the optimal composition with desired properties. Finally, three LRHEAs were designed and casted into bulk samples with arc-melting method. The alloys show superhigh Vickers hardness of 8.29–9.56 GPa and low densities of 6.27–7.08 g/cm3, showing great potentials in applications as wear-resistant materials. The high-throughput method developed here may also accelerate the development of new LRHEAs.

Additive manufacturing (AM) has obtained great attentions in the productions of customizable implants with complex shapes and good mechanical properties. AM fabricated implants of Ti alloy (Ti), stainless steel (SS), cobalt chromium (CoCr), iron (Fe) have been revolutionized in the productions of medical instruments, such as in artificial organs, including heart stents, drug delivery, scaffolds and orthopedic implants. However, high Young's modulus, superior mechanical characteristic, lack of surface integration, high corrosions, failed bone remodeling, and antibacterial performance are still incomparable to be used in anatomical structure. This review studied the issue of metallic implants designed by powder bed fusion of selective laser melting (SLM) techniques on the surface morphology, stress shielding effects, osseointegration, and antibacterial capabilities owing to implant failure. The rate of degradation and corrosion resistance of the metallic SLM implant, which would have an impact on cell proliferation and bone remodeling between the surrounding tissue, were discussed. The current review article also highlighted the various SLM parameters, like mechanical, chemical, and biological modifications, that might enhance the implant. Finally, applications, challenges, opportunities, and future developments of metallic implants using SLM techniques were addressed.

Laser powder bed fusion of 316 L (LPBF-316 L) has been known to exhibit high ductility but low strength, along with strong corrosion resistance and weak anti-friction properties. Graphene is commonly utilized as a reinforcement phase in metals fabricated through LPBF, as this process helps reduce the tendency of graphene to agglomerate. Therefore, it is crucial to investigate the impact of incorporating graphene into the LPBF-316 L alloy, aiming to enhance toughening and anti-friction properties while maintaining the original corrosion resistance. Various concentrations of graphene were incorporated into 316 L powder and processed using LPBF. The study examined the impact of graphene concentration on the electrochemical, mechanical, and friction properties of the resulting composites. The study revealed a significant reduction in corrosion current from 8.05 ± 0.6 × 10−7 A/cm2 to 6.61 ± 0.8 × 10−8 A/cm2. The 15-day immersion experiment further validated that the incorporation of graphene contributed to enhancing the stability of corrosion resistance. Additionally, the presence of graphene led to improved strength and ductility in LPBF-316 L through grain refinement and precipitation. Notably, samples containing 0.2 wt% graphene exhibited a tensile fracture strength of 927.4 MPa and ductility of 54.75%. In addition, the compressive fracture strength of 2342.8 MPa, both surpassing that of LPBF-316 L. Furthermore, the study investigated the impact of graphene content on the friction of LPBF-316 L, revealing that graphene addition increased matrix hardness, reduced COF, and enhanced wear resistance. Overall, the findings suggest that graphene serves as an effective reinforcing agent for 316 L stainless steel matrix composites, enhancing mechanical properties, friction resistance, and wear resistance while preserving original corrosion resistance.

The correlation between Vickers microhardness and microstructure of low-temperature Sn-xBi-M(Ag, Sb) solders was investigated. The β-Sn grains were refined with increasing Bi content, as well as the additions of Ag and Sb. Fine β-Sn grains in general should strengthen the mechanical properties of solders, however, the Vickers microhardness of Sn-xBi-M(Ag, Sb) solders decreased with increasing Bi content (i.e., fine β-Sn grains). It was shown that the microhardness of Sn-xBi-M(Ag, Sb) solders depended on the amount of Bi/β-Sn interfaces rather than the fine-grain strengthening effect. The smaller the amount of Bi/β-Sn interfaces was, the higher the Vickers microhardness of Sn-xBi-M(Ag, Sb) solders.

The effects of cooling rate on isothermal spheroidizing annealing (SA) of hot-rolled GCr15 bearing steel have been investigated. The results show that controlling the cooling rate between austenitizing and secondary annealing within a specific range is crucial to prevent the formation of lamellar carbide (LC). With a suitable cooling rate, more uniform carbide distribution, lower dislocation density and hardness can be achieved. An increase in the cooling rate results in a decrease in Ar1 and an increase in undercooling. However, an excessively high cooling rate suppresses the divorced eutectoid transformation (DET), leading to an increase in the amount of LC, dislocation density and hardness in rapidly cooled samples. Conversely, in the sample cooled too slowly, the appearance of LC may be attributed to the sufficient precipitation and coarsening of carbides, resulting in a high density of carbides before phase transformation. LCs can be eliminated by extending the secondary annealing time appropriately. This work demonstrates that for isothermal SA, using an appropriate cooling rate can effectively reduce the secondary annealing time, which provides a new idea for the rapid and complete spheroidization of carbides in GCr15 bearing steel.

Rapid heating is a promising technique for achieving excellent mechanical properties. This study innovatively applies rapid heating to a novel Ti–Mo martensite steel through in-situ observation experiments. By comparing the microstructure evolutions at heating rates of 1 and 30 °C/s, the relationship between microstructure and property evolution was elucidated. The results indicate that the refined austenite grains resulting from rapid heating stem from enhanced grain nucleation, accumulated dislocations, and the increased formation of new carbides under the large superheat. Furthermore, carbide maturation predominates during the slow heating process, while rapid heating accelerates new carbide precipitation with limited carbide maturation. Moreover, during rapid heating, both coherent and non-coherent relationships were observed between the (Ti, Mo, Fe)C particles and the martensite matrix, demonstrating a remarkable pinning effect on grain boundary migration. Nevertheless, during slow heating, large-sized (Ti, Mo)C carbides were formed, presenting a non-coherent relationship with the martensite matrix. Additionally, the primary differences in strength caused by rapid heating compared to slow heating include grain refinement, dislocation, and precipitation strengthenings, with dislocation strengthening playing the dominant role.

In a neutral, flexible, grounded distribution network, the phenomenon that a single-phase ground fault with high impedance connected in parallel with a low resistance can result in a relatively lower zero-sequence current flowing through the faulty feeder. This zero-sequence current can make it a challenge to use zero-sequence protection schemes to accurately identify and effectively protect the faulty feeder. In terms of the aforementioned challenge, based on the zero-sequence equivalent circuit of a single-phase-to-earth fault, this paper conducts an investigation on the phase difference between the zero-sequence current and the non-fault phase line voltage at power frequency in flexible grounding distribution network with different grounded conditions, both before and after the introduction of a parallel low-resistor connection. Subsequently, a criterion for selecting the faulty feeder is developed based on the observed phase difference characteristics following the implementation of the parallel low-resistor connection. Furthermore, a disposal strategy for single-phase-to-earth faults is formulated, which takes fault resistance estimation into account. To validate the proposed method, a simulation model of a flexible grounding distribution network is implemented with PSCAD/EMTDC. The effectiveness and reliability of this method in multiple scenes, including the initial fault conditions, sampling frequency, and distributed generation (DG), are proved through simulation results.