Geometric Amplitude Accompanying Local Responses: Spinor Phase Information from the Amplitudes of Spin-Polarized STM Measurements.

Solving the Hamiltonian of a system yields the energy dispersion and eigenstates. The geometric phase of the eigenstates generates many novel effects and potential applications. However, the geometric properties of the energy dispersion go unheeded. Here, we provide geometric insight into energy dispersion and introduce a geometric amplitude, namely, the geometric density of states (GDOS) determined by the Riemann curvature of the constant-energy contour. The geometric amplitude should accompany various local responses, which are generally formulated by the real-space Green's function. Under the stationary phase approximation, the GDOS simplifies the Green's function into its ultimate form. In particular, the amplitude factor embodies the spinor phase information of the eigenstates, favoring the extraction of the spin texture for topological surface states under an in-plane magnetic field through spin-polarized STM measurements. This work opens a new avenue for exploring the geometric properties of electronic structures and excavates the unexplored potential of spin-polarized STM measurements to probe the spinor phase information of eigenstates from their amplitudes.

(+)-Catechin attenuates CCI-induced neuropathic pain in male rats by promoting the Nrf2 antioxidant pathway to inhibit ROS/TLR4/NF-κB-mediated activation of the NLRP3 inflammasome.

The objective of this study was to investigate the potential mechanisms by which (+)-catechin alleviates neuropathic pain. Thirty-two male Sprague-Dawley rats were divided into four groups: the sham group, the chronic constriction injury (CCI)group, the CCI+ ibuprofen group, and the CCI+ (+)-catechin group. CCI surgery induces thermal hyperalgesia in rats and (+)-catechin ameliorated CCI-induced thermal hyperalgesia and repaired damaged sciatic nerve in rats. CCI decreased SOD levels in male rat spinal cord dorsal horn and promoted MDA production, induced oxidative stress by increasing NOX4 levels and decreasing antioxidant enzyme HO-1 levels, and also increased protein levels of TLR4, p-NF-κB, NLRP3 inflammasome components, and IL-1ß. In contrast, (+)-catechin reversed the above results. In i vitro experiments, (+)-catechin reduced the generation of reactive oxygen species (ROS) in GMI-R1 cells after LPS stimulation and attenuated the co-expression of IBA-1 and NLRP3. It also showed significant inhibition of the NF-κB and NLRP3 inflammatory pathways and activation of the Nrf2-mediated antioxidant system. Overall, these findings suggest that (+)-catechin inhibits the activation of the NLRP3 inflammasome through the triggering of the Nrf2-induced antioxidant system, the inhibition of the TLR4/NF-κB pathway, and the production of ROS to alleviate CCI-induced neuropathic pain in male rats.

Strengthening gold with dispersed nanovoids.

Materials often fail prematurely or catastrophically under load while containing voids, posing a challenge to materials manufacturing. We found that a metal (gold) containing spherical voids with a fraction of up to 10% does not fracture prematurely in tension when the voids are shrunk to the submicron or nanometer scale. Instead, the dispersed nanovoids increase the strength and ductility of the material while simultaneously reducing its weight. Apart from the suppressed stress or strain concentration, such structure provides enormous surface area and promotes surface-dislocation interactions, which enable strengthening and additional strain hardening and thus toughening. Transforming voids from crack-like detrimental defects into a beneficial "ingredient" provides an inexpensive and environmentally friendly approach for the development of a new class of lightweight, high-performance materials.

Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

Preparation of photothermal alginate/chitosan derivative/CuS@polydopamine composite fibers and application in desalination.

A polyelectrolyte system consisting of sodium alginate (SA) and quaternary ammonium chitosan (QAC) blended with polydopamine-coated copper sulfide particles (CuS@PDA) was chosen to investigate the function of CuS@PDA in the uniform binary blending of anionic and cationic polyelectrolytes in detail. A smart composite fiber SA/QAC/CuS@PDA was prepared via a dry-wet spinning technique. With the addition of CuS@PDA (about 4.3 % in fiber), the as-prepared SA/QAC/CuS@PDA-0.50 fibers (SQCuS@P-0.50 SCFs) showed notably enhanced intensity 359.2 MPa, excellent moisture response, and photothermal conversion performance, with the temperature increasing from 25.9 to 80.7 °C as irradiated under a 980 nm infrared lamp at distance 20 cm away for 120 s. The photothermal performance was maintained after 6 lighting on-and-off cycles. The tensile strength decreased ~23.8 % after 4 cycles, then remained fixed. The diameter increases to ~480 % in wet state but decreases to the original size in dry state for 10 cycles. When the fabric with 90 wt% SQCuS@P-0.50 SCFs was used as a water evaporator, the water evaporation rate and efficiency were 1.68 kg·m-2·h-1 and 102 % under 1 sun irradiation. This work provides a simple and ecofriendly strategy for fabricating photothermal fabrics by designing and preparing composite fibers.

Role of TRPC6 in apoptosis of skeletal muscle ischemia/reperfusion injury.

BACKGROUND: Skeletal muscle ischaemia-reperfusion injury (IRI) is a prevalent condition encountered in clinical practice, characterised by muscular dystrophy. Owing to limited treatment options and poor prognosis, it can lead to movement impairments, tissue damage, and disability. This study aimed to determine and verify the influence of transient receptor potential canonical 6 (TRPC6) on skeletal muscle IRI, and to explore the role of TRPC6 in the occurrence of skeletal muscle IRI and the signal transduction pathways activated by TRPC6 to provide novel insights for the treatment and intervention of skeletal muscle IRI. METHODS: In vivo ischaemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models were established, and data were comprehensively analysed at histopathological, cellular, and molecular levels, along with the evaluation of the exercise capacity in mice. RESULTS: By comparing TRPC6 knockout mice with wild-type mice, we found that TRPC6 knockout of TRPC6 could reduced skeletal muscle injury after I/R or H/R, of skeletal muscle, so as therebyto restoringe some exercise capacity inof mice. TRPC6 knockdown can reduced Ca2+ overload in cells, therebyo reducinge apoptosis. In additionAdditionally, we also found that TRPC6 functionsis not only a key ion channel involved in skeletal muscle I/R injury, but also can affects Ca2+ levels and then phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway. by knocking downTherefore, knockdown of TRPC6, so as to alleviated the injury inducedcaused by skeletal muscle I/R or and H/R. CONCLUSIONS: These findingsdata indicate that the presence of TRPC6 exacerbatescan aggravate the injury of skeletal muscle injury after I/Rischemia/reperfusion, leading towhich not only causes Ca2+ overload and apoptosis., Additionally, it impairsbut also reduces the self- repair ability of cells by inhibiting the expression of the PI3K/Akt/mTOR signalling pathway. ETo exploringe the function and role of TRPC6 in skeletal muscle maycan presentprovide a novelew approachidea for the treatment of skeletal muscle ischemia/reperfusion injury.

Comprehensive Analysis of Immune Cell Infiltration and M2-Like Macrophage Biomarker Expression Patterns in Atrial Fibrillation.

Background: Macrophages play a crucial role in the progression of AF, closely linked to atrial inflammation and myocardial fibrosis. However, the functions and molecular mechanisms of different phenotypic macrophages in AF are not well understood. This study aims to analyze the infiltration characteristics of atrial immune cells in AF patients and further explore the role and molecular expression patterns of M2 macrophage-related genes in AF. Methods: This study integrates single-cell and large-scale sequencing data to analyze immune cell infiltration and molecular characterization of the LAA in patients with AF, using SR as a control group. CIBERSORT assesses immune cell types in LAA tissues; WGCNA identifies signature genes; cell clustering analyzes cell types and subpopulations; cell communication explores macrophage interactions; hdWGCNA identifies M2 macrophage gene modules in AF. AF biomarkers are identified using LASSO and Random Forest, validated with ROC curves and RT-qPCR. Potential molecular mechanisms are inferred through TF-miRNA-mRNA networks and single-gene enrichment analyses. Results: Myeloid cell subsets varied considerably between the AF and SR groups, with a significant increase in M2 macrophages in the AF group. Signals of inflammation and matrix remodeling were observed in AF. M2 macrophage-related genes IGF1, PDK4, RAB13, and TMEM176B were identified as AF biomarkers, with RAB13 and TMEM176B being novel markers. A TF-miRNA-mRNA network was constructed using target genes, which are enriched in the PPAR signaling pathway and fatty acid metabolism. Conclusion: Over infiltration of M2 macrophages may be an important factor in the progression of AF. The M2 macrophage-related genes IGF1, RAB13, TMEM176B and PDK4 may regulate the progression of AF through the PPAR signaling pathway and fatty acid metabolism.

Synergistic N/Mn Codoping Deagglomerate Carbon Coating of LiFePO4/C To Boost Electrochemical Performance.

LiFePO4 is widely used because of its high safety and cycle stability, but its inefficient electronic conductivity combined with sluggish Li+ diffusivity restricts its performance. To overcome this obstacle, applying a layer of conductive carbon onto the surface of LiFePO4 has the greatest improvement in electronic conductivity and Li+ diffusivity. However, the rate performance of carbon-coated LiFePO4 makes it difficult to meet the application requirements. Although nitrogen doping improves electrochemical performance by providing active sites and electronic conductivity, the N-doped carbon coating is prone to agglomeration, which causes a sharp decrease in capacity when the current rate increases. In this work, a synergistic N, Mn codoping strategy is implemented to overcome the aforementioned drawbacks by disrupting the large agglomeration of C-N bonds, improving the uniformity of the surface coating layer to enhance the completeness of the conductive network and increasing the number of Li+ diffusion channels, and thus accelerating the mass transfer rate under high-rate current. Consequently, this strategy effectively improves the rate capability (119 mA h g-1 at 10 C) while maintaining excellent cycling performance (88% capacity retention over 600 cycles at 5 C). This work improves the rate of ion diffusion and the rate capability of micrometer-sized LiFePO4, thus, enabling its wider application.

Real-world pharmacological treatment of pregnant patients with rheumatic diseases from China: a retrospective analysis from 2016 to 2021.

Introduction: We investigated trends in the use of therapeutic drugs for pregnant patients with rheumatic diseases in nine Chinese cities (Beijing, Chengdu, Guangzhou, Harbin, Hangzhou, Shanghai, Shenyang, Tianjin, and Zhengzhou) to provide a reference for drug use in clinic. Methods: Outpatient prescription data for pregnant patients diagnosed with rheumatic diseases in nine cities across China in 2016-2021 were extracted from the Hospital Prescription Cooperation Project of the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association. A retrospective analysis was then performed, incorporating data on patient age, defined daily doses (DDDs), defined daily cost (DDC), and other metrics. Results: In 2016-2020, more than 70% of the pregnant patients diagnosed with rheumatic diseases in these nine cities were 25 to < 35 years of age. The most common rheumatic diseases during pregnancy were antiphospholipid antibody syndrome (APS) and systemic lupus erythematosus (SLE). In terms of the routine use of daily therapeutic drugs, the DDDs of low molecular weight heparins (LMWHs), glucocorticoids, and immunosuppressive agents dominated the top three. Intravenous immunoglobulin (IVIG) and tumor necrosis factor inhibitors (TNFi) have been used since 2019 and had been in the forefront of the DDC. Conclusion: The number and total cost of prescriptions for therapeutic drugs of pregnancy complicated by rheumatic diseases, have increased significantly over the study interval. Conventional therapeutic drugs, especially glucocorticoids, LMWHs, and hydroxychloroquine were the most widely used drugs in pregnant patients with rheumatic diseases. However, IVIG and TNFi, relatively high cost, have shown gradual increases in clinical use since 2019.

Metabolic Score for Insulin Resistance and New-Onset Type 2 Diabetes in a Middle-Aged and Older Adult Population: Nationwide Prospective Cohort Study and Implications for Primary Care.

BACKGROUND: The metabolic score for insulin resistance (METS-IR) has emerged as a noninsulin-based index for the approximation of insulin resistance (IR), yet longitudinal evidence supporting the utility of METS-IR in the primary prevention of type 2 diabetes mellitus (T2DM) remains limited. OBJECTIVE: We aimed to investigate the longitudinal association between METS-IR, which combines fasting plasma glucose (FPG), lipid profiles, and anthropometrics that can be routinely obtained in resource-limited primary care settings, and the incidence of new-onset T2DM. METHODS: We conducted a closed-cohort analysis of a nationwide, prospective cohort of 7583 Chinese middle-aged and older adults who were free of T2DM at baseline, sampled from 28 out of 31 provinces in China. We examined the characteristics of participants stratified by elevated blood pressure (BP) at baseline and new-onset T2DM at follow-up. We performed Cox proportional hazard regression analysis to explore associations of baseline METS-IR with incident T2DM in participants overall and in participants stratified by baseline BP. We also applied net reclassification improvement and integrated discrimination improvement to examine the incremental value of METS-IR. RESULTS: During a mean follow-up period of 6.3 years, T2DM occurred in 527 participants, among which two-thirds (332/527, 62.9%; 95% CI 58.7%-67.1%) had baseline FPG<110 mg/dL. A SD unit increase in baseline METS-IR was associated with the first incidence of T2DM (adjusted hazard ratio [aHR] 1.33, 95% CI 1.22-1.45; P<.001) in all participants. We obtained similar results in participants with normal baseline BP (aHR 1.41, 95% CI 1.22-1.62; P<.001) and elevated baseline BP (aHR 1.29, 95% CI 1.16-1.44; P<.001). The predictive capability for incident T2DM was improved by adding METS-IR to FPG. In study participants with new-onset T2DM whose baseline FPG was <126 mg/dL and <110 mg/dL, 62.9% (332/527; 95% CI 60%-65.9%) and 58.1% (193/332; 95% CI 54.3%-61.9%) of participants had baseline METS-IR above the cutoff values, respectively. CONCLUSIONS: METS-IR was significantly associated with new-onset T2DM, regardless of baseline BP level. Regular monitoring of METS-IR on top of routine blood glucose in clinical practice may add to the ability to enhance the early identification of primary care populations at risk for T2DM.

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.

Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial.

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Research on the Low-Temperature Impact Toughness of a New 100-mm Ultra-Thick Offshore Steel Fabricated Using the Narrow-Gap Laser Wire Filling Welding Process.

Ultra-thick offshore steel, known for its high strength, high toughness, and corrosion resistance, is commonly used in marine platforms and ship components. However, when offshore steel is in service for an extended period under conditions of high pressure, extreme cold, and high-frequency impact loads, the weld joints are prone to fatigue failure or even fractures. Addressing these issues, this study designed a narrow-gap laser wire filling welding process and successfully welded a 100-mm new type of ultra-thick offshore steel. Using finite element simulation, EBSD testing, SEM analysis, and impact experiments, this study investigates the weld's microstructure, impact toughness, and fracture mechanisms. The research found that at -80 °C, the welded joint exhibited good impact toughness (>80 J), with the impact absorption energy on the surface of the weld being 217.7 J, similar to that of the base material (225.3 J), and the fracture mechanism was primarily a ductile fracture. The impact absorption energy in the core of the weld was 103.7 J, with the fracture mechanism mainly being a brittle fracture. The EBSD results indicated that due to the influence of the welding thermal cycle and the cooling effect of the narrow-gap process, the grains gradually coarsened from the surface of the welded plate to the core of the weld, which was the main reason for the decreased impact toughness at the joint core. This study demonstrates the feasibility of using narrow-gap laser wire filling welding for 100-mm new type ultra-thick offshore steel and provides a new approach for the joining of ultra-thick steel plates.

A bowl-shaped phosphangulene-protected cubic Cu58 nanocluster.

A bowl-shaped phosphangulene-protected cubic Cu58 nanocluster has been synthesized. The structure was determined by X-ray crystallography and further analyzed by multiple techniques. The phosphangulenes not only enable ligand substitutions with triphenylphosphines in a cluster-to-cluster transformation way, but also facilitate inter-cluster interactions with fullerenes. These interactions further influence the entirety's photocurrent response and ability to liberate hydrogen when stimulated by light.

Effect of stearyl alcohol on imiquimod-induced psoriasis-like skin inflammation in mice.

Psoriasis is a chronic inflammatory skin disease. Topical medicines are the preferred treatment for mild to moderate psoriasis, but the effect of excipients used in semi-solid preparations on psoriasis-like skin inflammation is not fully understood. In the present study, we investigated the effect of stearyl alcohol, a commonly used excipient, on imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. Psoriasis-like skin inflammation was induced by topical IMQ treatment on the back of mice. Skin lesion severity was evaluated by using psoriasis area and severity index (PASI) scores. The skin sections were stained by haematoxylin-eosin and immunohistochemistry. Stearyl alcohol (20% in vaseline) treatment significantly reduced the IMQ-induced increase of PASI scores and epidermal thickness in mice. IMQ treatment increased the number of Ki67- and proliferating cell nuclear antigen (PCNA)-positive cells in the skin, and the increases were inhibited by stearyl alcohol (20% in vaseline) treatment. Stearyl alcohol treatment (1%, 5%, 10% in vaseline) dose-dependently ameliorated IMQ-induced increase of PASI scores and epidermal thickness in mice. Hexadecanol (20% in vaseline), stearic acid (20% in vaseline) and vaseline treatment had no significant effect on IMQ-induced psoriasis-like skin inflammation in mice. In conclusion, stearyl alcohol has the effect of improving IMQ-induced psoriasis-like skin inflammation in mice.

Influence of metabolic dysfunction-associated fatty liver disease on the prognosis of patients with HBV-related acute-on-chronic liver failure.

OBJECTIVES: Metabolic-associated fatty liver disease (MAFLD) has clinical relevance in patients with acute-on-chronic liver failure (ACLF). We investigated the association between MAFLD and prognosis in patients with ACLF. METHODS: We included patients with ACLF with available clinical data who visited our hospital for nearly 9 years. We compared the prognosis of patients in the different subgroups of ACLF and predicted the incidence of adverse outcomes. Moreover, a new model based on MAFLD was established. RESULTS: Among 339 participants, 75 had MAFLD. The prognosis of patients with ACLF was significantly correlated with MAFLD. Patients with ACLF with concomitant MAFLD tended to have a lower cumulative survival rate (p = 0.026) and a higher incidence of hepatorenal syndrome (9.33% versus 3.40%, p = 0.033) than those without MAFLD. We developed an TIM2 model and the area under the ROC curve of the new model for 30-day and 60-day mortality (0.759 and 0.748) was higher than other predictive methods. CONCLUSION: The presence of MAFLD in patients with HBV-related ACLF was associated with an increased risk of in-hospital mortality. Moreover, The TIM2 model is a high-performance prognostic score for HBV-related ACLF.

Low-intensity focused ultrasound stimulation promotes stroke recovery via astrocytic HMGB1 and CAMK2N1 in mice.

BACKGROUND: Low-intensity focused ultrasound stimulation (LIFUS) has been developed to enhance neurological repair and remodelling during the late acute stage of ischaemic stroke in rodents. However, the cellular and molecular mechanisms of neurological repair and remodelling after LIFUS in ischaemic stroke are unclear. METHODS: Ultrasound stimulation was treated in adult male mice 7 days after transient middle cerebral artery occlusion. Angiogenesis was measured by laser speckle imaging and histological analyses. Electromyography and fibre photometry records were used for synaptogenesis. Brain atrophy volume and neurobehaviour were assessed 0-14 days after ischaemia. iTRAQ proteomic analysis was performed to explore the differentially expressed protein. scRNA-seq was used for subcluster analysis of astrocytes. Fluorescence in situ hybridisation and Western blot detected the expression of HMGB1 and CAMK2N1. RESULTS: Optimal ultrasound stimulation increased cerebral blood flow, and improved neurobehavioural outcomes in ischaemic mice (p<0.05). iTRAQ proteomic analysis revealed that the expression of HMGB1 increased and CAMK2N1 decreased in the ipsilateral hemisphere of the brain at 14 days after focal cerebral ischaemia with ultrasound treatment (p<0.05). scRNA-seq revealed that this expression pattern belonged to a subcluster of astrocytes after LIFUS in the ischaemic brain. LIFUS upregulated HMGB1 expression, accompanied by VEGFA elevation compared with the control group (p<0.05). Inhibition of HMGB1 expression in astrocytes decreased microvessels counts and cerebral blood flow (p<0.05). LIFUS reduced CAMK2N1 expression level, accompanied by increased extracellular calcium ions and glutamatergic synapses (p<0.05). CAMK2N1 overexpression in astrocytes decreased dendritic spines, and aggravated neurobehavioural outcomes (p<0.05). CONCLUSION: Our results demonstrated that LIFUS promoted angiogenesis and synaptogenesis after focal cerebral ischaemia by upregulating HMGB1 and downregulating CAMK2N1 in a subcluster of astrocytes, suggesting that LIFUS activated specific astrocyte subcluster could be a key target for ischaemic brain therapy.

Determining optimal ALT cut-off values for predicting significant hepatic histological changes in patients with normal ALT in the grey zone of chronic hepatitis B virus infection.

BACKGROUND AND AIMS: We aimed to define gender-specific, optimal alanine aminotransferase (ALT) cut-off values for the prediction of significant liver histological changes (SLHC) in Chinese patients with grey zone (GZ) chronic hepatitis B (CHB) and normal ALT. METHODS: In a retrospective study, we included 1101 consecutive patients with GZ CHB and normal ALT assigned to training or internal validation cohorts. We included an independent cohort of 842 patients for external validation. We performed receiver operating characteristic (ROC) curve, smoothed curve fitting, and threshold effect analyses to determine optimal ALT cut-off values. Area under the curve (AUC) values were calculated to assess their predictive performance. RESULTS: A proportion of 79.3% of patients with GZ CHB and normal ALT (≤40 U/L) had SLHC. ROC curve analysis initially identified optimal ALT cut-off values of 29 U/L (male) and 22 U/L (female). After smoothed curve fitting and threshold effect analyses, new optimal cut-off values were 27 U/L for males and 24 U/L for females. AUCs for these values were 0.836 (male) and 0.833 (female) in the internal validation cohort, and 0.849 (male) and 0.844 (female) in the external validation cohort. The accuracy and discriminative ability of the newly defined ALT cut-off values were greater than those of the current recommendations. CONCLUSION: This study established novel optimal ALT cut-off values for more precise prediction of SLHC among Chinese patients with GZ CHB and normal ALT levels. This may help identify individuals who will benefit from timely antiviral therapy.