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Highlights Efficient activation of Ni electrode employs chronopotentiostatic superoxidation. Novel superoxide activation mechanism realizes the redox reaction with three-electron transfer (Ni ↔ Ni3+). As-prepared CPS-Ni||Zn batteries exhibit simultaneously ultrahigh energy and power densities.

The microstructure details of the interface, mechanical properties and failure mechanism of laser welding-brazing (LWB) steel-Al joints with various welding parameters were comparatively investigated. The emergence of ternary Fe–Al–Si intermetallic compounds (IMCs) was observed in the interfacial area of the joints prepared utilizing ER4047 filler. In contrast, only the binary Fe–Al IMCs were formed in the interfacial area of the joints prepared employing ER5356 filler. With the same laser tilt angle, the IMCs layer of the joints prepared with ER4047 was thinner than that of the joints prepared with ER5356, implying the rapid growth of the IMCs welded via the ER5356 filler. The tensile strength exhibited by the former surpassed that of the latter. Employing the same filler metal, the average thickness of the IMCs layer of the joints with laser tilt angle of 10° was smaller than that of the joints with laser tilt angle of 20°. The strength of the joints with smaller tilt angle was better than that of the ones with bigger tilt angle. The tensile test outcomes revealed that there existed failure competition among the Al alloy base metal (Al-BM), weld metal (WM) and interface structure. If the interface structure was Fe–Al IMC with high brittleness, the cracks propagated along the interface, and finally fractured at the interface. If the interface structure was Fe–Al–Si IMC with good toughness, the crack propagation in the interface region could be hampered. In this case, the joint was prone to occur via WM failure or even Al-BM failure modes.

As a challenge to avoid the strength-ductility trade-off for Ti alloys, strength and ductility are contradictory, especially at a high content of primary α phase. This study proposed a new strategy to evade this trade-off dilemma by designing an 81% primary α phase/ultrafine-grained (UFG) secondary α phase lamellar heterogeneous structure(LPSlow-HS) in near-α Ti alloys. Compared to the bimodal structure, the LPSlow-HS offers a remarkable increase in the ultimate tensile strength(1119 MPa) and yield strength(1069 MPa), respectively, while the elongation (15%) is not sacrificed. Owing to the strong heterogeneous deformation-induced(HDI) strengthening, more number of delamination of interfaces, UFG microstructures and strong strain hardening render the Ti alloys high strength. This strategy may provide a new approach for achieving higher HDI strengthening effects in heterogeneous structures (HS) under high soft phases, and offer a feasible method for producing high strength-ductility Ti alloys under high primary α phase.

Considering energy conservation and emission reductions, lightweight automobiles have become a research focus in the automotive industry. Steel/aluminum joining is regarded as an ideal lightweight structure, which can not only reduce the energy consumption but also ensure safety and is already attracting extensive attention. In this study, aluminum alloy 6061 and B410LA steel sheets were successfully joined by refill friction stir spot welding. The tensile properties, microhardness distribution and interfacial microstructure characteristics of the steel/Al welded joints were investigated. The maximum tensile load of the steel/Al joint was 4.3 kN. The mechanical properties of the steel/Al refill friction stir spot welded joint were largely determined by the bonding quality of the sleeve-plunging zone. With the stirring of the sleeve and the pin during the refill friction stir spot welding, work hardening occurred in the stir zone (SZ). The microhardness of the SZ was significantly higher than that of the steel base metal (BM) and could be detected on the steel side. The Fe-Al intermetallic compound (IMC) layer was continuously distributed at the interface of the sleeve-plunging zone, revealing good uniformity in the thickness. In particular, a hook-and-vortex-like structure formed during the refill friction stir spot welding process in the sleeve-plunging zone, producing a mechanical interlock effect at the interface. The ideal mechanical properties of the welded joint could be attributed to the good quality of the metallurgical and mechanical bonding at the interface, especially the mechanical interlock effect, thereby depending on the hook-and-vortex-like structure.

ABSTRACT: Hepatitis-hydropericardium syndrome (HHS) is a highly fatal disease in chickens caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4), which has severe economic consequences. The fiber2 protein exhibits excellent potential as a candidate for a subunit vaccination against FAdV-4. Despite having a high safety profile, subunit vaccines have low immunogenicity due to their lack of infectivity, which leads to low levels of immune response. As a vaccine adjuvant, Salmonella flagellin possesses the potential to augment the immunological response to vaccinations. Additionally, a crucial strategy for enhancing vaccine efficacy is efficient presentation of immune antigens to dendritic cells (DC) for targeted vaccination. In this study, we designed FAdV-4-fiber2 protein, and a recombinant protein called FliBc-fiber2-SP which based on FAdV-4-fiber2 protein, was generated using the gene sequence FliBc, which retains only the conserved sequence at the amino and carboxyl termini of the flagellin B subunit, and a short peptide SPHLHTSSPWER (SP), which targets chicken bone marrow-derived DC. They were separately administered via intramuscular injection to 14-day-old specific pathogen-free (SPF) chickens, and their immunogenicity was compared. At 21 d postvaccination (dpv), it was found that the FliBc-fiber2-SP recombinant protein elicited significantly higher levels of IgG antibodies and conferred a vaccine protection rate of up to 100% compared to its counterpart fiber2 protein. These results suggest that the DC-targeted peptide fusion strategy for flagellin chimeric antigen construction can effectively enhance the immune protective efficacy of antigen proteins.

This work aims to study the influence of laser power on the microstructural evolution of novel Ti–6Zr–5Fe alloy fabricated by selective laser melting (SLM). The microstructural evolutions of all top surfaces in SLM Ti–6Zr–5Fe alloy samples fabricated from 80 W to 140 W were investigated in depth. The microstructure in SLM Ti–6Zr–5Fe alloy includes α phase and β phase, the size of the β phase and α phase increases with the increase of laser power due to the decrease of cooling rate. Meanwhile, the melt pool overlapping width increases with the increase of melt pool width due to the increase of laser power. The increase of melt pool overlapping causes the re-heating or re-melting of SLM Ti–6Zr–5Fe alloy. Moreover, as the laser power increases from 80 W to 140 W, the change of the melt pool greatly influenced the size, morphology, crystallographic orientation of the β phase, and their distributions. The increase of laser power causes adequate precipitation of the α phase, which improves the microhardness from 466 HV to 533 HV. The laser power can effectively regulate and control the microstructure and microhardness of SLM Ti alloys.

Microstructural evolution and its effect on microhardness and Young's modulus of Ti–6Zr–4Fe alloy solution and aging treated at different temperatures were studied. The α phase transformed into β phase completely at 860 °C, meanwhile, the athermal ω phase was found at 860 °C and it resulted in a higher Young's modulus. The ω phase content increased from 250 °C to 400 °C, and the content decreased with further increase of aging temperature, there were only α phase and β phase at 600 °C. The phase transformation sequence was β → ω + β → ω + α + β → α + β during aging treatment. The microhardness increased from 315 HV to 492 HV due to the element solution strengthening and phase transformation strengthening. The peak microhardness of Ti–6Zr–4Fe alloy aged at 400 °C reached 652 HV. The formation of ω phase resulted in the increase of microhardness and Young's modulus in Ti–6Zr–4Fe alloy.

When tunnel boring machines (TBMs) excavate through jointed rock masses, the cutting efficiency is strongly affected by the shear strength of joints, the mechanism of which, however, remains poorly understood. In this study, a series of disc-cutter indentation tests were conducted on granite rock mass specimens with different joint shear strengths. During the indentation, the cracking process was recorded by a digital image correlation (DIC) system. The deformation and strength of specimens, cracking behavior, rock breakage mode and cutting efficiency were quantitatively investigated. In addition, to investigate the combined effects of joint shear strength, orientation and spacing on the rock breakage mechanism, numerical rock mass models were established based on a particle flow code PFC2D. Experimental results reveal that the cracking of primary and secondary cracks changes from the mixed shear-tensile to tensile mode in the initial stage, while the joint shear strength does not affect the cracking mode in the subsequent propagation process. The rock breakage mode is classified to an internal block breakage mode, a cross-joint breakage mode and a cutters-dependent breakage mode. The cross-joint breakage mode is optimal for improving the cutting efficiency. Numerical simulation results reveal that the increase in the joint shear strength changes the internal block breakage mode to cross-joint breakage mode for rock masses of particular ranges of joint orientation and spacing. These findings provide basis for improving the TBM cutting efficiency through jointed rock masses.

Abstract Resistance to immunotherapy in bladder cancer has greatly limited its clinical application. Through single-cell sequencing, we determined that ACSM6, an oncogene that is highly expressed in bladder cancer, promotes the abilities of proliferation, cloning, migration, and invasion. The key point is that ACSM6 can also lead to a non-inflammatory immune microenvironment by inhibiting the chemotaxis and tumor killing ability of CD8+ T cells. Survival analysis revealed that high ACSM6 expression was associated with shorter overall survival in the immunotherapy cohort. In summary, ACSM6 is expected to become a novel biomarker for predict bladder cancer progression.

The effect of the dry–wet cycle, characterized by periodic water level changes in the Three Gorges Reservoir, will severely degrade the bearing performance of rock formations. In order to explore the effect of the dry–wet cycle on the mesoscopic damage mechanism of jointed sandstone, a list of meso-experiments was carried out on sandstone subjected to dry–wet cycles. The pore structure, throat features and mesoscopic damage evolution of jointed sandstone with the action of the dry–wet cycle were analyzed using a-low-field nuclear magnetic resonance (NMR) technique. Subsequently, the impact on the mineral content of dry–wet cycles was studied by small angle X-ray scattering (SAXS). Based on this, the mesoscopic damage mechanism of sandstone subjected to dry–wet cycles was revealed. The results show that the effects of the drying–wetting cycle can promote the development of porous channels within sandstone, resulting in cumulative damage. Besides, with an increase in dry–wet cycles, the proportion of small pores and pore throats decreased, while the proportion of medium and large pores and pore throats increased. The combined effects of extrusion crush, tensile fracture, chemical reaction and dissolution of minerals inside the jointed sandstone contributed to the development of mesoscopic pores, resulting in the increase of porosity and permeability of rock samples under the dry–wet cycles. The results provide an important reference value for the stability evaluation of rock mass engineering under long-term dry–wet alternation.

There are currently no studies exploring omicron infection and male sexual function and semen quality. Our aim was to estimate changes in sexual function and semen quality in men recovering from infection since the COVID-19 Omicron pandemic started in China in late 2022. We collected 1540 questionnaires and assessed male function before infection and acute phase after infection by using International Index of Erectile Function-5, Premature Ejaculation Diagnostic Tool, and Arizona Sexual Experience Scale. We also collected the before and after semen analysis results of 247 male patients. During the acute phase after infection, the proportion of erectile dysfunction was significantly higher than before infection, but ejaculatory function was not significantly altered; In addition, semen analysis showed significant difference in semen concentration, semen activity and PR a+b sperm forward movement after infection compared to pre-infection.: COVID-19 Omicron can affect erectile function as well as sexual experience in male patients in the acute phase. Decreased sexual function due to COVID-19 Omicron may be related to body temperature and anxiety during infection.

Macrophage is located in different tissue to serve diverse functions. Here the authors use mass spectrometry and bulk RNA-sequencing to profile 11 mouse macrophage populations from 8 tissues, and combine their de novo data with public datasets to report an integrated proteomic and transcriptomic landscape of mouse macrophage as a valuable resource.

The microscale mechanisms underlying the suction anchor–sandy soil interaction under slidable pulling actions of mooring lines remain poorly understood. This technical note addresses this knowledge gap by investigating the suction anchor–sandy soil interaction from micro to macro, with a particular emphasis on the effect of interface friction. The discrete element method (DEM) was utilized to simulate the sandy soil, while the finite element method (FEM) was employed to model the suction anchors. The peak pulling forces in numerical simulations were verified by centrifuge test results. The research findings highlight the significant influence of interface friction on the pulling force–displacement curves, as it affects the patterns of suction anchor–sandy soil interactions. Furthermore, clear relationships were established between the magnitude of interface friction, rotation angle, and pullout displacement of suction anchors. By examining the macro-to-micro behaviors of suction anchor–sandy soil interactions, this study concludes with a comprehensive understanding of failure patterns and their key characteristics under different interface friction conditions. The findings proved that the interface friction not only influences the anti-pullout capacity but also changes the failure patterns of suction anchor–soil interactions in marine engineering.

Background: ACSMs play critical roles in lipid metabolism; however, their immunological function within the tumor microenvironment (TME) remains unclear, especially that of ACSM6. In this study, we investigate the latent effect of ACSM6 on bladder cancer (BLCA).Methods: Several real-world cohorts, including the Xiangya (in-house), The Cancer Genome Atlas (TCGA-BLCA), and IMvigor210 cohorts, with TCGA-BLCA cohort serving as the discovery cohort were compared. We investigated the potential immunological effects of ACSM6 in regulating the BLCA tumor microenvironment by analyzing its correlation with immunomodulators, anti-cancer immune cycles, immune checkpoints, tumor-infiltrating immune cells, and the T-cell inflamed score (TIS). Additionally, we assessed the precision of ACSM6 in predicting BLCA molecular subtypes and responses to several treatments using ROC analysis. To ensure the robustness of our findings, all results were confirmed in two independent external cohorts: the IMvigor210 and Xiangya cohorts.Results: ACSM6 expression was markedly upregulated in BLCA. Our analysis suggests that ACSM6 might have significant impact to promote the formation of a non-inflamed tumor microenvironment because of its negative correlation with immunomodulators, anticancer immune cycles, immune checkpoints, tumor-infiltrating immune cells, and the T-cell inflamed score (TIS). Additionally, high ACSM6 expression levels in BLCA may predict the luminal subtype, which is typically associated with resistance to chemotherapy, neoadjuvant chemotherapy, and radiotherapy. These findings were consistent across both the IMvigor210 and Xiangya cohorts.Conclusion: ACSM6 has the potential to serve as a valuable predictor of the tumor microenvironment phenotypes and treatment outcomes in BLCA, thereby contributing to more precise treatment.

Abstract Background Neuroinflammation in spinal dorsal horn (SDH) plays an important role in the pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) exert potent anti-inflammatory activities in the treatment of various diseases. This study aimed to determine the therapeutic effects of MSC-EVs on IC and furtherly investigate the potential mechanism to attenuate neuroinflammation. Methods Female IC rat model was established by intraperitoneal injection of cyclophosphamide (50 mg/kg, every 3 days for 3 doses). Inhibition of NLRP3 inflammasome was performed by intraperitoneal injection of MCC950 (10 mg/kg). MSC-EVs were isolated from the culture supernatants of human umbilical cord derived MSCs using ultracentrifugation, and then injected intrathecally into IC rats (20 μg in 10 μl PBS, every other day for 3 doses). Suprapubic mechanical allodynia was assessed using up-down method with von Frey filaments, and micturition frequency was examined by urodynamics. The expression of NLRP3 inflammasome components (NLRP3 and Caspase-1), glial cell markers (IBA-1 and GFAP), proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-18) and TLR4/NF-κB signal pathway (TLR4, p65 NK-κB and phospho-p65 NK-κB) in L6–S1 SDH was measured by Western blot analysis. The cellular localization of NLRP3 in SDH was detected using immunofluorescence co-staining. Results NLRP3 inflammasome was activated in neurons in SDH of IC rats. NLRP3 inflammasome activation contributed to activation of glial cells and process of spinal neuroinflammation in IC rats, and was related to suprapubic mechanical allodynia and frequent micturition. Intrathecal injection of MSC-EVs alleviated suprapubic mechanical allodynia and frequent micturition in IC rats, restrained activation of glial cells and attenuated neuroinflammation in SDH. In addition, MSC-EV treatment significantly inhibited activation of both NLRP3 inflammasomes and TLR4/NF-κB signal pathway. Conclusions NLRP3 inflammasome activation is involved in the neuroinflammation of IC. Intrathecal injection of MSC-EVs alleviates neuroinflammation and mechanical allodynia in IC by inhibiting the activation of NLRP3 inflammasome, and TLR4/NF-κB signal pathway may be the potential regulatory target.

Interstitial cystitis/bladder pain syndrome (IC/BPS) seriously reduces the patient’s quality of life, yet current therapies only provide partial relief. In the spinal dorsal horn (SDH), neuroinflammation plays a pivotal role in the development of IC. Injection of human umbilical cord mesenchymal stem cells (hUMSCs) to reduce inflammation is an effective strategy, and heme oxygenase-1 (HO-1) exhibits anti-nociceptive effect in neuroinflammatory pain. This study aimed to test the therapeutic effects of hUMSCs overexpressing HO-1 on cyclophosphamide-induced cystitis rat model. Cystitis rats were transplanted with altered cells and then assessed for 3 weeks. A series of behavioral measurements would be trial including suprapubic mechanical allodynia, depressive-like behaviors, micturition frequency, and short-term memory function. Additionally, western blot, immunofluorescence staining, and ELISA kit test for anti-inflammation effect. HUMSCs were capable of being transduced to overexpress HO-1. Injection of hUMSCs overexpressing HO-1 was more effective than hUMSCs alone in alleviating behavioral symptoms in rats. Furthermore, hUMSCs overexpressing HO-1 inhibited the activation of glial and TLR4/p65/NLRP3 pathway, decreased the levels of pro-inflammatory cytokines in the SDH region. Surprisingly, it markedly increased anti-inflammatory cytokine IL-10, reduced MDA content, and protected GSH concentrations in local environment. Our results suggest that injecting hUMSCs overexpressing HO-1 intrathecally can significantly promote functional outcomes in cystitis rats by reducing neuroinflammation, at least, partly through downregulating TLR4/p65/NLRP3 signaling pathway in the SDH region. This cell therapy affords a new strategy for IC/BPS treatment.

NLRP3 inflammasome is involved in the pathology of multiple human inflammatory diseases but there are still no clinically available medications targeting the NLRP3 inflammasome. We have previously identified RRx-001 as a highly selective and potent NLRP3 inhibitor, however, it contains high-energy nitro functional groups and may cause potential processing problems and generates highly toxic oxidants. Here, we show that compound 149-01, an RRx-001 analogue without high-energy nitro functional groups, is a potent, specific and covalent NLRP3 inhibitor. Mechanistically, 149-01 binds directly to cysteine 409 of NLRP3 to block the NEK7-NLRP3 interaction, thereby preventing NLRP3 inflammasome complex assembly and activation. Furthermore, treatment with 149-01 effectively alleviate the severity of several inflammatory diseases in mice, including lipopolysaccharide (LPS)-induced systemic inflammation, monosodium urate crystals (MSU)-induced peritonitis and experimental autoimmune encephalomyelitis (EAE). Thus, our results indicate that 149-01 is a potential lead for developing therapeutic agent for NLRP3-related inflammatory diseases.