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Material and structure made by additive manufacturing (AM) have received much attention lately due to their flexibility and ability to customize complex structures. This study first implements multiple objective topology optimization simulations based on a projectile perforation model, and a new topologic projectile is obtained. Then two types of 316L stainless steel projectiles (the solid and the topology) are printed in a selective laser melt (SLM) machine to evaluate the penetration performance of the projectiles by the ballistic test. The experiment results show that the dimensionless specific kinetic energy value of topologic projectiles is higher than that of solid projectiles, indicating the better penetration ability of the topologic projectiles. Finally, microscopic studies (scanning electron microscope and X-ray micro-CT) are performed on the remaining projectiles to investigate the failure mechanism of the internal structure of the topologic projectiles. An explicit dynamics simulation was also performed, and the failure locations of the residual topologic projectiles were in good agreement with the experimental results, which can better guide the design of new projectiles combining AM and topology optimization in the future.

The millimeter-sized glass (SiO2) shells play key roles in inertial confinement fusion (ICF) experiments, especially for the so-called ''direct-drive'' configuration. The preparation of large diameter/thickness ratio glass shells and the exploration of transformation mechanisms for silicon-doped glow discharge polymer (Si-GDP) to SiO2 still face challenges. Here, we prepared large diameter/thickness ratio glass shells with the diameter of ∼1200 μm and shell thickness of ∼5 μm by increasing the Si contents in Si-GDP precursors. The influence of Si contents in Si-GDP shells on the compositions, morphologies and geometrical properties of glass shells were carefully investigated. The formability and uniformity of micro morphologies of the glass shells will improve with the increase of Si contents in precursors. The chemical composition of the prepared glass shells is SiO2 with some carbides adsorbed on their surfaces and the compositions present negligible relationship with the Si contents. The sphericity, thickness uniformity and surface quality will increase with the increase of Si contents in precursors. Besides, the oxidation mechanisms for Si-GDP to SiO2 were explored by the combination of an in situ high temperature infrared spectroscopy and a simultaneous thermal analyzer.

Abstract Purpose The main objective is to quantify the lens nuclear opacity using spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with Lens Opacities Classification System III (LOCS-III) system, lens thickness (LT), and surgical parameters. The secondary objective is to assess the diagnostic model performance for hard nuclear cataract. Methods This study included 70 eyes of 57 adults with cataract, with 49 (70%) and 21 (30%) in training and validation cohort, respectively. Correlations of the average nuclear density (AND) /maximum nuclear density (MND) with LOCS-III scores, LT, and surgical parameters were analyzed. Univariate and multivariate logistic regression analysis, receiver operating characteristic curves and calibration curves were performed for the diagnostic of hard nuclear cataract. Results The pre-operative uncorrected distance visual acuity (UDVA), intraocular pressure (IOP), mean axial length (AL), and LT were 1.20 ± 0.47 log MAR, 15.50 ± 2.87 mmHg, 27.34 ± 3.77 mm and 4.32 ± 0.45 mm, respectively. The average nuclear opalescence (NO) and nuclear colour (NC) scores were 3.61 ± 0.94 and 3.50 ± 0.91 (ranging from 1.00 to 6.90), respectively. The average AND and MND were 137.94 ± 17.01 and 230.01 ± 8.91, respectively. NC and NO scores both significantly correlated with the AND (rNC = 0.733, p = 0.000; rNO = 0.755, p = 0.000) and MND (rNC = 0.643, p = 0.000; rNO = 0.634, p = 0.000). In the training cohort, the area under the curve (AUC) of the model was 0.769 (P

Abstract Background Growth hormone (GH) has been proposed as an adjunct in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, especially in women with poor ovarian response. However, it is unclear whether GH supplementation is effective in women with poor embryonic development in the previous IVF cycle. The aim of this study was to evaluate the effectiveness of GH supplementation in IVF/ICSI cycles in women with poor embryonic development in the previous cycle. Methods This is a retrospective cohort study from a public fertility center in China, in which we performed propensity score-matching (PSM) for female age and AFC in a ratio of 1:1. We compared the cumulative live birth rate per started cycle, as well as a series of secondary outcomes. We included 3,043 women with poor embryonic development in the previous IVF/ICSI cycle, of which 1,326 had GH as adjuvant therapy and 1,717 had not. After PSM, there were 694 women in each group. Results After PSM, multivariate analyses showed the cumulative live birth rate to be significantly higher in the GH group than the control group [N = 694, 34.7% vs. N = 694, 27.5%, risk ratio (RR): 1.4 (95%CI: 1.1–1.8)]. Endometrial thickness, number of oocytes retrieved, number of embryos available, and number of good-quality embryos were significantly higher in the GH group compared to controls. Pregnancy outcomes in terms of birth weight, gestational age, fetal sex, preterm birth rate, and type of delivery were comparable. When we evaluated the impact of GH on different categories of female age, the observed benefit in the GH group did not appear to be significant. When we assessed the effect of GH in different AFC categories, the effect of GH was strongest in women with an AFC5-6 (32.2% versus 19.5%; RR 2.0; 95% CI 1.2–3.3). Conclusions Women with poor embryonic quality in the previous IVF/ICSI cycles have higher rates of cumulative live birth with GH supplementation.

High silicon steel has excellent soft magnetic properties, but a poor plasticity limits its practical application seriously. In this research, a novel FeSiCrNi alloy short for Fe-6.5Si–2Cr–12Ni (wt%) was designed and deformed via the local canning compression process at room temperature. It was shown that the FeSiCrNi alloy presents a relatively high plasticity in a triaxial compressive stress state. Geometrically necessary dislocations ensure the compatibility of plastic deformation for FeSiCrNi alloy. There are a small number of η and γ textures inside the FeSiCrNi sample. The intensity of η texture nearly keeps steady, while the intensity of γ texture increases slightly with the level of plastic deformation increasing. Additionally, the intensity of {112} copper texture increases with the increase of plastic deformation. Lath structures dominate the inhomogeneous plastic deformation of FeSiCrNi alloy and then integrate with the phase α-Fe. The main deformation mechanism of FeSiCrNi alloy is dislocation slip rather than twinning which has not been observed yet. The order degree of FeSiCrNi alloy continuously decreases, and deformation bands, dislocation walls and dislocation cells are successively formed, as the compression proceeds. It is feasible to produce FeSiCrNi components in cold forming process.

Methane explosion is one of the major disasters that seriously threaten the safety of coal mine production, the development of efficient methane explosion suppression technology can effectively improve the prevention and control level of methane explosion accidents, and its focus is on the function of explosion suppression materials. In order to systematically study the effect of typical haloalkanes extinguishing agents on methane explosion, the effects of typical haloalkanes such as heptafluoropropane (C3HF7), hexafluoropropane (C3H2F6) and trifluoromethane (CHF3) on the ignition and explosion characteristics of methane were systematically studied by combining experimental tests and theoretical analysis. The effects of haloalkanes on methane explosion pressure parameters and laminar burning velocity were tested by a 20 L spherical explosive vessel and a self-developed Bunsen burner laminar flame propagation velocity system. The variation laws of peak explosion pressure, maximum pressure rise rate, laminar burning velocity, and laminar flame morphology evolution were obtained. The results show that with the increase of the added volume fraction, the haloalkanes had a double effect of promoting and inhibiting the methane explosion process. Under the chemical equivalent condition, only C3HF7 can first promote and then inhibit the peak explosion pressure and maximum pressure rise rate of methane, while CHF3 and C3H2F6 can inhibit the effect. The three haloalkanes all showed inhibition on the combustion rate of methane laminar flow. In the oxygen-poor condition, the three haloalkanes inhibited the peak explosion pressure, the maximum pressure boost rate, and the laminar burning velocity of methane. In general, C3H2F6 and C3HF7 have better inhibition effects on methane explosion pressure characteristic parameters and laminar burning velocity than CHF3. The theoretical analysis results show that the double effect of promoting and inhibiting the haloalkanes with the increase of the mixture volume fraction can be attributed to the competition between the improvement of the heat release characteristics of the system reaction and the inhibition of the key free radicals such as H, O, and OH by the main intermediates containing F. The results of this paper provide a theoretical basis for the theoretical research and technical development of methane explosion prevention and control.

We confirm the previously revised stereochemistry of spiroviolene by X-ray crystallographically characterizing a hydrazone derivative of 9-oxospiroviolane, which is synthesized by hydroboration/oxidation of spiroviolene followed by oxidation of the resultant hydroxy group. An unexpected thermal boron migration occurred during the hydroboration process of spiroviolene that resulted in the production of a mixture of 1α-hydroxyspiroviolane, 9α- and 9β-hydroxyspiroviolane after oxidation. The assertion of the cis-orientation of the 19- and 20-methyl groups provided further support for the revised cyclization mechanism of spiroviolene.

This is an article in the field of mining engineering. Graphite is an inorganic nonmetallic material widely used in China, and it also plays an important role in chemical industry, electrical industry, national defense and high-tech fields. Graphite mining will produce a large number of tailings, it not only occupies a lot of land but also causes serious pollution to the ecological environment. By consulting a large number of documents, the current research status of graphite tailings resource utilization is summarized in this paper, and the problem of massive accumulation of graphite tailings is discussed, and some suggestions are put forward to help its resource utilization.

Abstract Background Two-tiered plant immune responses involve cross-talk among defense-responsive (DR) genes involved in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), effector-triggered immunity (ETI) and effector-triggered susceptibility (ETS). Bacterial leaf streak (BLS), caused by Xanthomonas oryzae pv. oryzicola (Xoc) is an important bacterial disease that causes serious threats to rice yield and quality. Transcriptomic profiling provides an effective approach for the comprehensive and large-scale detection of DR genes that participate in the interactions between rice and Xoc. Results In this study, we used RNA-seq to analyze the differentially expressed genes (DEGs) in susceptible rice after inoculation with two naturally pathogenic Xoc strains, a hypervirulent strain, HGA4, and a relatively hypovirulent strain, RS105. First, bacterial growth curve and biomass quantification revealed that differential growth occurred beginning at 1 day post inoculation (dpi) and became more significant at 3 dpi. Additionally, we analyzed the DEGs at 12 h and 3 days post inoculation with two strains, representing the DR genes involved in the PTI and ETI/ETS responses, respectively. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the common DEGs, which included 4380 upregulated and 4019 downregulated genes and 930 upregulated and 1383 downregulated genes identified for the two strains at 12 h post inoculation (hpi) and 3 dpi, respectively. Compared to those at 12 hpi, at 3 dpi the number of common DEGs decreased, while the degree of differential expression was intensified. In addition, more disease-related GO pathways were enriched, and more transcription activator-like effector (TALE) putative target genes were upregulated in plants inoculated with HGA4 than in those inoculated with RS105 at 3 dpi. Then, four DRs were randomly selected for the BLS resistance assay. We found that CDP3.10, LOC_Os11g03820, and OsDSR2 positively regulated rice resistance to Xoc, while OsSPX3 negatively regulated rice resistance. Conclusions By using an enrichment method for RNA-seq, we identified a group of DEGs related to the two stages of response to the Xoc strain, which included four functionally identified DR genes.

ABSTRACTAccurate evaluation of terrestrial carbon balance is essential for designing climate change mitigation policies, and capabilities of remote sensing techniques in monitoring carbon fluxes are widely recognized for their great contributions to regional and global carbon budget accounting. In this review, we synthesized satellite-based data and methodologies to estimate the main flux components of terrestrial carbon balance and their uncertainties over the past two decades. The global gross primary production (GPP) during the period 2001–2022 is 134 ± 14 PgC yr−1, and nearly half of them occurs in tropical forest regions such as South America and Africa. Less than 2% of global GPP is converted into a net carbon sink of 2.28 ± 1.12 PgC yr−1 using satellite-based atmospheric inversion during 2015–2020, and this sink is comparable to the stock change-based estimate (2.49 PgC yr−1) but twice as large as model-based estimate (1.08 ± 0.78 PgC yr−1). By decomposing satellite-derived net carbon balance into different terms including satellite-derived carbon emissions from land-use change and wildfires (3.55 PgC yr−1), we inferred that ~ 43% of global GPP would be respired through soil microbes (57.1 PgC yr−1), but which is higher than the previous bottom-up estimate (39–46 PgC yr−1). We then propose that an accurate remote sensing of terrestrial carbon balance requires to enhance representations of photosynthetic responses to rising CO2 and disturbances, develop satellite-constrained belowground carbon dynamics and separate natural fluxes from anthropogenic CO2 emissions, by integrating multi-source satellite sensors in orbit, revolutionized remote sensing capabilities with focused field campaigns in data-scarce regions.

Abstract Background Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. Methods We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women’s Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria–diabetes associations are explained by altered metabolites and proteins. Results Seven gut bacterial genera were identified to be associated with diabetes (FDR-q

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract To study the aerodynamic performance and wind-induced response of carbon fiber-reinforced polymer (CFRP) cables, CFRP cable was designed by replacing a steel cable in a tied arch bridge based on stiffness, strength and area equivalent criteria, respectively. The aerodynamic performance and wind-induced response of CFRP cable and steel cable were studied and compared by computational fluid dynamics (CFD) model. Based on the computational results, optimal cable replacement criterion was proposed for CFRP cable to replace steel cable. In addition, surface modification was conducted by engrooving vertical symmetric (VS), vertical asymmetric (VA) and helical symmetric (HS) V-shaped grooves to improve the aerodynamic performance and wind-induced response of CFRP cable. Results showed that CFRP cables exhibited inferior aerodynamic performance and wind-induced response in most cases. However, CFRP cable based on stiffness equivalent criterion exhibited better aerodynamic performance and wind-induced vibration properties compared to the other two cable replacement criteria, thus is regarded as the optimal substitute for steel cable. In addition, HS grooves generated symmetric disturbances and caused approximately equivalent boundary layer separation delays uniformly and continuously along the cable length, thus exhibiting better effect in decreasing the reverse flow region, the maximum negative flow velocity, the vortex shedding frequency and the wind-induced vibration amplitude of CFRP cable. Hence, the stiffness equivalent criterion combined with surface modification with HS V-shaped grooves was proposed to replace steel cable with CFRP cable. This study can provide insights into the aerodynamic performance and wind-induced response of CFRP cable and instructions for cable replacement practice.

Abstract Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis.

Abstract We explore the controls of stress magnitude and orientation relative to bedding on the resulting morphology/topology of hydraulic fractures using a combined finite-discrete element method (FDEM). Behavior is shown conditioned by the ratio of principal stresses $$\lambda ={\sigma }_{3}/{\sigma }_{1}$$ λ = σ 3 / σ 1 and relative inclination of the bedding. When the lateral pressure coefficient ( $$\lambda$$ λ ) is less than 0.67, hydraulic fractures predominantly initiate as tensile fractures along the wellbore, aligning with the maximum principal stress direction. Conversely, for $$\lambda \ge 0.67$$ λ ≥ 0.67 , shear cracks are favored to initiate for the minor stress difference, leading to a less predictable initiation and extension direction. Simultaneously, diminished stress differences correspond to elevated reservoir breakdown pressures, displaying a linear correlation with lateral pressure coefficients and little influenced by equivalent bedding orientation. Bedding plane orientation significantly impacts the mode and morphology of hydraulic fracture propagation. Bedding parallel to the direction of the minimum principal stress ( $${\sigma }_{3}$$ σ 3 ) favors layer-penetrating and bifurcated fractures, whereas inclined bedding facilitates the emergence of numerous steering-type and capture-type fractures. Especially at steeper inclinations ( $$\beta =60^\circ$$ β = 60 ∘ ), hydraulic fractures readily extend along the bedding surface, inducing macroscopic shear slip failure. Under high-stress disparities, the breakdown pressure exhibits greater sensitivity to bedding inclination, and its influence pattern aligns with the variations in tensile strength, typically reaching maximum and minimum values at bedding inclination angles of 0° and 60°, respectively.

ABSTRACT Purpose: This study aims to evaluate the safety and efficacy of ultrasound-guided balloon dilation compared to non-balloon dilation for percutaneous nephrolithotomy (PCNL). Materials and methods: A systematic review and meta-analysis were conducted by searching PubMed, EMBASE, and the Cochrane Library. Results were filtered using predefined inclusion and exclusion criteria as described and meta-analysis was performed using Review Manager 5.4 software. Results: A total of six studies involving 1189 patients who underwent PCNL were included. The meta-analysis results demonstrated that compared to non-balloon dilation, balloon dilation was associated with reduced haemoglobin drop [mean difference (MD) = -0.26, 95% CI = -0.40 ~ -0.12, P = 0.0002], decreased transfusion rate [odds ratio (OR) = 0.47, 95% CI = 0.24 ~ 0.92, P = 0.03], shorter tract establishment time (MD = -1.30, 95% CI = -1.87 ~ -0.72, P < 0.0001) and shorter operation time (MD = -5.23, 95% CI = -10.19 ~ -0.27, P = 0.04). Conclusions: Overall, ultrasound-guided balloon dilatation offered several advantages in PCNL procedures. It facilitated faster access establishment, as evidenced by shorter access creation time. Additionally, it reduced the risk of kidney injury by minimizing postoperative haemoglobin drop and decreasing the need for transfusions. Moreover, it enhanced the efficiency of surgery by reducing the operation time. However, it is important to note that the quality of some included studies was subpar, as they did not adequately control for confounding factors that may affect the outcomes. Therefore, further research is necessary to validate and strengthen these findings.

Abstract Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated with cystoscopy, and low sensitivity to urine cytology. Therefore, there is an urgent need to identify highly sensitive, specific, and noninvasive biomarkers for the early detection of this neoplasm. Hypermethylated TWIST1/Vimentin promoter may be a noninvasive biomarker using urine sample. We assessed the TWIST1/Vimentin promoter methylation status in urine samples using the Methylated Human TWIST1 and Vimentin Gene Detection Kit (Jiangsu MicroDiag Biomedicine Co., Ltd., China). The samples were collected from five groups: group 1 consisted of patients with BUC, group 2 contained other patients with urologic tumors, group 3 consisted of patients with benign diseases (e.g., urinary tract infections, lithiasis, and benign prostatic hyperplasia), Group 4 included UTUC (upper tract urothelial carcinoma) patients and group5 comprised healthy individuals. The study encompassed 77 BUC patients, and we evaluated the degree of methylation of the TWIST1/Vimentin gene in their urine samples. Notably, TWIST1/Vimentin positivity was significantly elevated in comparison to groups 2, 3 and 5 (all p

Abstract Zinc-ion hybrid supercapacitors (ZHSCs) are attracting significant attention due to their high energies/power densities, safety, and low cost. In this review, recent advances in the development of ZHSCs are summarized. Particular emphasis is placed on state-of-the-art cathodes (including carbon, metal oxides, MXenes, and redox-active polymers), anodes (including Zn-based composites and Zn-free materials) and electrolytes for ZHSCs. Furthermore, the latest research on functional ZHSC devices with miniaturized ZHSCs, fiber-shaped ZHSCs, self-chargeable ZHSCs and self-healing devices is reported. Finally, further developments with ZHSCs are envisaged for future research in this thriving field.

Abstract Background The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within the tumor microenvironment (TME). Unveiling the immune landscape of ESCC in the context of NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. Methods We analyzed single cells from 22 baseline and 24 post-NAT treatment samples of stage II/III ESCC patients to explore the association between the immune landscape and pathological response to neoadjuvant anti-PD-1 combination therapy, including pathological complete response (pCR), major pathological response (MPR), and incomplete pathological response (IPR). Results Single-cell profiling identified 14 major cell subsets of cancer, immune, and stromal cells. Trajectory analysis unveiled an interesting link between cancer cell differentiation and pathological response to NAT. ESCC tumors enriched with less differentiated cancer cells exhibited a potentially favorable pathological response to NAT, while tumors enriched with clusters of more differentiated cancer cells may resist treatment. Deconvolution of transcriptomes in pre-treatment tumors identified gene signatures in response to NAT contributed by specific immune cell populations. Upregulated genes associated with better pathological responses in CD8 + effector T cells primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, and negative regulation of the T cell apoptotic process, whereas downregulated genes were dominated by those in the immune response-activating cell surface receptor signaling pathway. Natural killer cells in pre-treatment tumors from pCR patients showed a similar upregulation of gene expression in response to IFNγ but a downregulation of genes in the neutrophil-mediated immunity pathways. A decreased cellular contexture of regulatory T cells in ESCC TME indicated a potentially favorable pathological response to NAT. Cell–cell communication analysis revealed extensive interactions between CCL5 and its receptor CCR5 in various immune cells of baseline pCR tumors. Immune checkpoint interaction pairs, including CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, and TNFSF4-TNFRSF4, might serve as additional therapeutic targets for ICI therapy in ESCC. Conclusions This pioneering study unveiled an intriguing association between cancer cell differentiation and pathological response in esophageal cancer patients, revealing distinct subgroups of tumors for which neoadjuvant chemo-immunotherapy might be effective. We also delineated the immune landscape of ESCC tumors in the context of clinical response to NAT, which provides clinical insights for better understanding how patients respond to the treatment and further identifying novel therapeutic targets for ESCC patients in the future.

Abstract The coupling capacitance between the line and the transducer cannot be ignored when making non‐contact voltage measurements on low‐voltage three‐phase power lines. This leads to an increase in the number of unknown capacitances, and the number of correlatable response voltage equations is less than the number of unknown coupling capacitances. In this paper, a simplified decoupling method is proposed based on the characteristics of triangular three‐phase lines erected in distribution areas. Firstly, the equivalent circuit measured by the voltage sensing mechanism during three‐phase operation is established, and the three‐phase line response voltage equation is derived. Secondly, this paper proposes a three‐phase line response voltage decoupling algorithm after designing the decoupling matrix. Then, this paper uses the least squares method to solve the coefficients in the equations. Finally, the three‐phase voltage fluctuations of the actual low‐voltage stations are simulated by simulation. The measured sensor voltage values are substituted into the algorithm to invert and calculate the three‐phase line voltage. The three‐phase phase error is less than 2°. The amplitude error is less than 1.77%. The experiment verifies the stability and accuracy of the proposed decoupling method.

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins. In recent years, toxins have been widely used as warheads for antibody‒drug conjugates (ADCs) due to their efficient killing activity against various cancer cells. Although ADCs confer certain targeting properties to the toxins, low drug loading capacity, possible immunogenicity, and other drawbacks also limit the potential application of ADCs. Recently, non-ADC delivery strategies for toxins have been extensively investigated. To further understand the application of toxins in anti-tumor, this paper provided an overview of prodrugs, nanodrug delivery systems, and biomimetic drug delivery systems. In addition, toxins and their combination strategies with other therapies were discussed. Finally, the prospect and challenge of toxins in cancer treatment were also summarized.

The distribution and evolution of nutrients in the Yellow River estuary and its adjacent waters have always been a hot research topic on the geochemical cycle of biogenic elements in the northwest continental margin of the west Pacific Ocean as well as the focus of research on the eutrophication, environmental quality supervision, and comprehensive pollution control in the Bohai Sea. We conducted a survey on the current status of nutrients and related environmental factors in the Yellow River estuary and its adjacent waters in May and August 2023, during which period the primary production was high. Historical data from the past 20 years were collected and summarized to analyze and reveal the potential trends of nutrient composition and structure in the Yellow River estuary and to elaborate the current status and main influencing factors of nutrients in the Yellow River estuary. The main results are presented as follows.The concentrations of dissolved inorganic nitrogen (DIN) varied wider and higher in August than that in May, 2023. The higher concentration was located outside the Yellow River mouth and west Laizhou Bay, and the DIN concentration gradually decreased toward the northwest and southeast from the Yellow River mouth. The lower value appeared in the northern waters of the Yellow River estuary. Although the average DIN concentrations in August were about half that in May, the variation of DIN concentrations in August was larger than that in May, with the highest value in August being about twice that of May and the lowest value being only about 1/10 that of May. Vertically, the surface layer showed the highest DIN concentrations, followed by the bottom layer, and the middle layer showed the lowest concentration. The concentration of DIP located at wider and higher ranges in August than that in May, which was similar to DIN. The DIP distribution was generally similar to that of DIN in tendency, whereas the average DIP concentration in May was comparable to that in August. Meanwhile, the difference in the surface, middle, and bottom concentrations in August was smaller than that in May. The concentration of DIN and DIP in the lower reaches of the Yellow River in May was about 4 and 2 times higher than that outside the mouth of Yellow River, whereas that in August was about 10 and 4 times higher, respectively.Nitrate was the main component of DIN, accounting for 50.7%–96.5% (average 85.2%) in May and 3.9%–99.1% (average 57.1%) in August, respectively. Although the DIN composition was consistent between May and August, the percentage variation in the DIN composition was significant, and the percentage variation between DIN compositions in August was much larger than that in May. The DIN to phosphate ratio (N/P) waved at a wide range in both May and August, with a high average N/P of far from Redfield Ratio, among which the lowest N/P of 43.7 was observed in May. The average N/P of the lower reaches of the Yellow River was 910.7 in May and 410.9 in August. In comparison, the surface N/P was relatively high, approximately 1.5 and 3 times that of the bottom and middle layers.The DIN concentration in the Yellow River estuary increased to 60 μmol/L before 2006, decreased to 30 μmol/L in 2009, and then remained under 30 μmol/L until 2023. The DIP concentration showed peak vales in 2005 and 2013 after increasing from those in 2006 to 2008 and were maintained at lower levels in the other years. The DIN was dominated mainly by nitrate in the past 20 years, followed by ammonia, and then nitrite. In episodic cases, ammonia and nitrite contributed to more than 80% of the total DIN, which may be related to strong terrestrial inputs and weak oxidizing conditions in the bottom water. The nitrogen/phosphorus ratio in the Yellow River estuary continued to increase in the past 20 years. Based on the developing trend of nutrient composition and structure in the Yellow River estuary and its adjacent waters, the imbalance of "more nitrogen and less phosphorus" may be further intensified. DIN and silicate both showed a significant linear correlation with salinity, indicating that surface runoff was the major input pathway for nutrients in the Yellow River estuary. The discrete point plots of DIN components and DO indicated a clustered distribution, indicating that DIN components and DO were influenced by some common factors, and the direct interaction between the two was weak or rapidly reached an equilibrium state. There was no obvious evidence of groundwater transport in study area, and the contribution and mechanism of dissolved organic matter conversion and primary production to nutrients must be understood through further investigation.The results of principal component analysis indicated that the composition and structure of nutrients may significantly characterize the water properties of the Yellow River estuary. The extreme variations in the composition and distribution of nutrients, as well as the high nitrogen/phosphorus ratio, could push the water environment quality situation into a more severe status in the Yellow River estuary.

Novel (Cr,V)-ZrSiO4 jewel green pigments with near-infrared reflection performance were prepared at a low temperature of 900 °C. Effects of Cr/Si mole ratio on phase composition, microstructure, Vis–NIR reflection performance, optical properties and thermal stability were studied. The results show that with the increase of Cr/Si mole ratio from 0 to 0.4, the color of the pigment changes from blue to jewel green and then to dark green. When the Cr/Si mole ratio is 0.2, the (Cr,V)-ZrSiO4 jewel green pigment shows the best comprehensive properties, which has rendering performance (L* = 56.69, a* = −18.52, b* = −9.28), thermal stability, and near-infrared reflection performance. The properties especially excellent near-infrared reflection performance make it promising functional pigment in heat insulation. Resumen: Se prepararon nuevos pigmentos verde joya (Cr,V)-ZrSiO4 con rendimiento por reflejo en el infrarrojo cercano a una temperatura baja de 900 ̊C. Se estudiaron los efectos de la relación molar Cr/Si sobre la composición de fase, la microestructura, el rendimiento de reflexión Vis-NIR, las propiedades ópticas y la estabilidad térmica. Los resultados muestran que con el aumento de la relación molar Cr/Si de 0 a 0,4, el color del pigmento cambia de azul a verde joya y luego a verde oscuro. Cuando la relación molar Cr/Si es 0.2, el pigmento verde joya (Cr,V)-ZrSiO4 muestra las mejores propiedades integrales, que tiene rendimiento de renderizado (L* = 56.69, a* = -18.52, b* = -9.28), estabilidad térmica y rendimiento de reflexión en el infrarrojo cercano. Las propiedades especialmente excelente rendimiento de reflexión en el infrarrojo cercano lo convierten en un pigmento funcional prometedor en el aislamiento térmico.

To address the issue of low accuracy and inefficiency in the traditional parameter calibration methods for the SWMM model, this paper constructs an automatic parameter calibration model based on multi-objective optimisation algorithms. Firstly, the Sobol method and GLUE method are utilised to determine sensitive parameters and their ranges, aiming to narrow down the solution space and expedite the model-solving speed. Secondly, the NSGA-3 multi-objective optimisation algorithm based on the Pareto theory is applied for the optimisation and calibration of sensitive parameter sets. The model is validated in the rainwater drainage system with independent runoff in a residential area in a northwestern city in China. The results show that parameters such as N-Imperv and KSlope are highly sensitive to the model output under the land-use conditions of the study area. The simulation accuracy of the multi-objective continuous optimisation algorithm is significantly better than that of the single-objective genetic algorithm. The simulation results of the SWMM model under multi-objective optimisation demonstrate a certain level of reliability and stability. The research findings can provide technical support for the automatic calibration of SWMM model parameters, accurate model simulation, and application. HIGHLIGHTS The study provides a quantitative interpretation of the results of sensitivity parameter screening and ranking for the SWMM model.; During the construction of the objective function, the SWMM model system's multi-objective continuous optimisation criteria were adopted.; Combining the concepts of uncertainty and optimisation.;

Abstract Acute pancreatitis (AP) continues to pose a major challenge as targeted therapeutic interventions are absent. Mitochondrial dysfunction and inflammasome-dependent pyroptosis are involved in the pathogenic mechanisms of AP. CIRP is a stress-response protein and a damage-associated molecular pattern (DAMP) molecule. In our previous studies, we discovered that excessive CIRP can directly damage pancreatic acinar cells. Nonetheless, the precise involvement of CIRP in AP is still unexplored. The primary aim of this study was to examine the potential involvement of CIRP in the development of pyroptosis and mitochondrial dysfunction in AP. To study this, an L-arginine-induced AP mouse model was used. Our results showed that Caspase-1-mediated pyroptosis and mitochondria-derived reactive oxygen species (ROS) were crucial factors in the occurrence of tissue damage and inflammation in AP. A substantial increase in the CIRP serum levels was observed in AP mice. Blocking CIRP by either CIRP gene knockout or systemic administration of C23, a competing inhibitor of CIRP, reduced ROS accumulation and pyroptosis in AP mice. These effects were associated with attenuated pancreatic injury and inflammation. In addition, CIRP-triggered mitochondrial dysfunction, autophagy impairment, and pyroptosis in pancreatic acinar cells were prevented by TAK242, an inhibitor of CIRP receptor TLR4. In conclusion, CIRP can induce mitochondrial dysfunction and pyroptosis in pancreatic acinar cells, and blocking CIRP may be a valuable approach to treating patients with AP.

Abstract The Tibetan grassland ecosystems possess significant carbon sink potential and have room for improved carbon sequestration processes. There is a need to uncover more ambitious and coherent solutions (e.g., Nature-based Solutions) to increase carbon sequestration. Here, we investigated the rationale and urgency behind the implementation of Nature-based Solutions on sequestering carbon using literature review and meta-analysis. We also project the changes in terrestrial carbon sink of Tibetan Plateau grassland ecosystems using model simulations with different future emissions scenario. The results show that the Nature-based Solution projects are expected to increase the carbon sink of Tibetan Plateau grassland ecosystems by 15 to 21 tetragrams of carbon by 2060. We defined a conceptual framework of Nature-based Solutions that integrates initiatives for the restoration of degraded grasslands and carbon sequestration. Our framework consists of four stages: theory, identification, practice, and goal. Traditional Tibetan knowledge plays an important role in reframing the proposed Nature-based Solutions framework. We also apply this framework to optimize ecological restoration techniques and projects and to evaluate the annual changes in the carbon sink under different socioeconomic pathway scenarios.

Abstract The rapid proliferation of tumors is highly dependent on the nutrition supply of blood vessels. Cutting off the nutrient supply to tumors is an effective strategy for cancer treatment, known as starvation therapy. Although various hydrogel-based biomaterials have been developed for starvation therapy through glucose consumption or intravascular embolization, the limitations of single-mode starvation therapy hinder their therapeutic effects. Herein, we propose a dual-function nutrition deprivation strategy that can block the nutrients delivery through extravascular gelation shrinkage and inhibit neovascularization through angiogenesis inhibitors based on a novel NIR-responsive nanocomposite hydrogel. CuS nanodots-modified MgAl-LDH nanosheets loaded with angiogenesis inhibitor (sorafenib, SOR) are incorporated into the poly(n-isopropylacrylamide) (PNIPAAm) hydrogel by radical polymerization to obtain the composite hydrogel (SOR@LDH-CuS/P). The SOR@LDH-CuS/P hydrogel can deliver hydrophobic SOR with a NIR-responsive release behavior, which could decrease the tumor vascular density and accelerate cancer cells apoptosis. Moreover, the SOR@LDH-CuS/P hydrogel exhibits higher (3.5 times) compressive strength than that of the PNIPAAm, which could squeeze blood vessels through extravascular gelation shrinkage. In vitro and in vivo assays demonstrate that the interruption of nutrient supply by gelation shrinkage and the prevention of angiogenesis by SOR is a promising strategy to inhibit tumor growth for multimode starvation therapy.

Abstract Deep learning achieves an outstanding success in the edge scene due to the appearance of lightweight neural network. However, a number of works show that these networks are vulnerable for adversarial examples, bringing security risks. The classical adversarial detection methods are used in white-box setting and show weak performances in black-box setting, like the edge scene. Inspired by the experimental results that different models give various predictions for the same adversarial example with a high probability, we propose a novel adversarial detection method called Ensemble-model Adversarial Detection Method (EADM). EADM defenses the prospective adversarial attack on edge devices by cloud monitoring, which deploys ensemble-model in the cloud and give the most possible label for each input copy received in the edge. The comparison experiment in the assumed edge scene with baseline methods demonstrates the effect of EADM, with a higher defense success rate and a lower false positive rate by an ensemble-model consisted of five pretrained models. The additional ablation experiment explores the influence of different model combinations and adversarial trained models. Besides, the possibility about transfering our method to other fields is discussed, showing the transferability of our method across domains.

Abstract The study aimed to investigate the effect of fermentation brines and containers on the composition and functional dissimilarity of microbiota in fermented chili peppers: pool with fresh brine (PFB), pool with aged brine (PAB), jar with FB, and jar with AB. The results showed that brines had a greater impact on microbial diversity and fungal community structure than containers, whereas containers had a greater impact on bacterial community structure than brines. At the end of chili pepper fermentation, the dominant bacteria were unclassified_g__Pseudomonas, Lactobacillus_alimentarius, and Halococcus_thailandensis, whereas the dominant fungi were Pichia_membranifaciens and Wallemia_ichthyophaga. Based on the metagenomics functional analysis, the dominant bacteria and fungi were highly related to amino acid metabolism, glycerophospholipid metabolism, and most enzymes that promote carbohydrate substrate modulation. The fermented brines had a larger impact than containers on microbial function. Specifically, the use of FB was found to be beneficial for the biosynthesis of tetracycline, carotenoid, and isoflavonoid. On the other hand, AB was found to be beneficial for the biosynthesis of unsaturated fatty acids, amino acids, and various types of N‐glycan.

Abstract The mining of the protective coal seam usually produces different pressure relief effects on the different areas of protected coal seam, the reason is that the stress paths of protected seam coal body in different areas caused by mining effect are different. In order to explore the differential pressure relief damage effect of coal body under different pressure relief conditions, the stress evolution path of coal body in different areas of the protected coal seam is obtianed by using theoretical analysis and the macro–micro damage characteristics of coal body under different stress paths by using numerical simulation in this paper. The results show that: The damage characteristics of the sample models are basically the same in the in-situ stress recovery stage and the mining disturbance stage of the two stress paths. With ith the sequence of stress stages experienced by the sample model, the distribution of acoustic emission events concentrates in the high-intensity area and the porosity continues to decrease. The number of cracks increases slowly in the stage of in-situ stress recovery stage, most of which are tensile cracks, while the number of cracks increases sharply in the mining disturbance stage, most of which are shear cracks. The difference of the deformation and macro meso damage characteristics of the sample models under the two stress paths is mainly reflected in the post mining pressure relief stage. At the post mining pressure relief stage of path 1, the number of cracks in the sample has little growth, and most of them are small energy tensile cracks, and the porosity increases, which verifies its obvious pressure relief activation antireflection effect; At this stage of path 2, the crack growth of the sample is obvious, and most of them are high-energy shear cracks, and the porosity continues to decrease. Compared with path 1, the pressure relief expansion effect of the sample model is suppressed and the compression damage continues to develop in this stage of path 2.

Abstract Staphylococcus aureus (S. aureus) is a common pathogenic bacterium in animal husbandry that can cause diseases such as mastitis, skin infections, arthritis, and other ailments. The formation of biofilms threatens and exacerbates S. aureus infection by allowing the bacteria to adhere to pathological areas and livestock product surfaces, thus triggering animal health crises and safety issues with livestock products. To solve this problem, in this review, we provide a brief overview of the harm caused by S. aureus and its biofilms on livestock and animal byproducts (meat and dairy products). We also describe the ways in which S. aureus spreads in animals and the threats it poses to the livestock industry. The processes and molecular mechanisms involved in biofilm formation are then explained. Finally, we discuss strategies for the removal and eradication of S. aureus and biofilms in animal husbandry, including the use of antimicrobial peptides, plant extracts, nanoparticles, phages, and antibodies. These strategies to reduce the spread of S. aureus in animal husbandry help maintain livestock health and improve productivity to ensure the ecologically sustainable development of animal husbandry and the safety of livestock products.

Abstract Background Tuberculosis (TB) continues to be a major global health burden, and co-infection with other pathogens further complicates the diagnosis and treatment of this infectious disease. The present retrospective study aimed to evaluate the clinical utility of nanopore sequencing in identifying co-infection caused by Mycobacterium tuberculosis (M.tb) and other pathogens. Methods Patients with M.tb co-infection from December 2021 to March 2023 at the Jiangxi Provincial Chest Hospital were retrospectively studied. Data were collected including demographics, symptoms, imaging findings, pathogen diagnosis tests, and treatment history. Pathogen tests involved culture, AFB smear, Xpert MTB/RIF, and nanopore sequencing. Results The enrolled patients included 20 M.tb cases and three nontuberculous mycobacteria (NTM) cases co-infected with other pathogens. Common clinical symptoms included cough (47.83%), expectoration (34.78%), and asthma (17.39%). Radiological examinations showed typical features of pulmonary tuberculosis, including nodules (73.91%), cord-like shadows (34.78%), cavities (34.78%), and destroyed lung manifestations (17.39%). Nanopore sequencing identified M.tb in a significant majority of the cases (86.96%), outperforming traditional culture tests (39.13%), acid-fast bacilli (AFB) tests (27.27%), and Xpert MTB/RIF (53.84%) tests. Notably, nanopore sequencing revealed that M.tb was frequently co-infected with Candida albicans, Klebsiella pneumoniae, and Mycobacterium abscessus. Three specific cases of co-infection with distinct diagnosis and treatment characteristics were presented in detail. They illustrated the complexity of TB co-infection management and the potential of nanopore sequencing for accurate diagnosis and informing the tailored therapeutic approaches. Conclusion Nanopore sequencing-based metagenomics method can help clinicians to identify TB co-infection patterns and formulate a rational drug regimen in time.

Water is the key factor limiting dryland wheat grain yield. Mulching affects crop yield and yield components by affecting soil moisture. Further research is needed to determine the relationships between yield components and soil moisture with yield, and to identify the most important factor affecting grain yield under various mulching measures. A long-term 9-year field experiment in the Loess Plateau of Northwest China was carried out with three treatments: no mulch (CK), plastic mulch (MP) and straw mulch (MS). Yield factors and soil moisture were measured, and the relationships between them were explored by correlation analysis, structural equation modeling and significance analysis. The results showed that compared with CK, the average grain yields of MP and MS increased by 13.0 and 10.6%, respectively. The average annual grain yield of the MP treatment was 134 kg ha−1 higher than the MS treatment. There were no significant differences in yield components among the three treatments (P

Abstract Background In China, respiratory syncytial virus (RSV) infections traditionally occur during the spring and winter seasons. However, a shift in the seasonal trend was noted in 2020–2022, during the coronavirus disease 2019 (COVID-19) pandemic. Methods This study investigated the seasonal characteristics of RSV infection in children hospitalized with acute lower respiratory tract infections (ALRTIs). The RSV epidemic season was defined as RSV positivity in > 10% of the hospitalized ALRTI cases each week. Nine RSV seasons were identified between 2013 and 2022, and nonlinear ordinary least squares regression models were used to assess the differences in year-to-year epidemic seasonality trends. Results We enrolled 49,658 hospitalized children diagnosed with ALRTIs over a 9-year period, and the RSV antigen-positive rate was 15.2% (n = 7,566/49,658). Between 2013 and 2022, the average onset and end of the RSV season occurred in week 44 (late October) and week 17 of the following year, respectively, with a typical duration of 27 weeks. However, at the onset of the COVID-19 pandemic, the usual spring RSV peak did not occur. Instead, the 2020 epidemic started in week 32, and RSV seasonality persisted into 2021, lasting for an unprecedented 87 weeks before concluding in March 2022. Conclusions RSV seasonality was disrupted during the COVID-19 pandemic, and the season exhibited an unusually prolonged duration. These findings may provide valuable insights for clinical practice and public health considerations.

Abstract Background This study aimed to develop and validate an interpretable machine-learning model that utilizes clinical features and inflammatory biomarkers to predict the risk of in-hospital mortality in critically ill patients suffering from sepsis. Methods We enrolled all patients diagnosed with sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV, v.2.0), eICU Collaborative Research Care (eICU-CRD 2.0), and the Amsterdam University Medical Centers databases (AmsterdamUMCdb 1.0.2). LASSO regression was employed for feature selection. Seven machine-learning methods were applied to develop prognostic models. The optimal model was chosen based on its accuracy, F1 score and area under curve (AUC) in the validation cohort. Moreover, we utilized the SHapley Additive exPlanations (SHAP) method to elucidate the effects of the features attributed to the model and analyze how individual features affect the model’s output. Finally, Spearman correlation analysis examined the associations among continuous predictor variables. Restricted cubic splines (RCS) explored potential non-linear relationships between continuous risk factors and in-hospital mortality. Results 3535 patients with sepsis were eligible for participation in this study. The median age of the participants was 66 years (IQR, 55–77 years), and 56% were male. After selection, 12 of the 45 clinical parameters collected on the first day after ICU admission remained associated with prognosis and were used to develop machine-learning models. Among seven constructed models, the eXtreme Gradient Boosting (XGBoost) model achieved the best performance, with an AUC of 0.94 and an F1 score of 0.937 in the validation cohort. Feature importance analysis revealed that Age, AST, invasive ventilation treatment, and serum urea nitrogen (BUN) were the top four features of the XGBoost model with the most significant impact. Inflammatory biomarkers may have prognostic value. Furthermore, SHAP force analysis illustrated how the constructed model visualized the prediction of the model. Conclusions This study demonstrated the potential of machine-learning approaches for early prediction of outcomes in patients with sepsis. The SHAP method could improve the interoperability of machine-learning models and help clinicians better understand the reasoning behind the outcome.

Abstract The boom-type roadheader plays a crucial role in coal mining. However, conducting the real-time monitoring of the mechanical performance and comprehensive adaptive cutting in the dynamic cutting process are challenging. To address these issues, a digital twin system that integrates the elements of “shape, performance, and control” for roadheaders is presented in this paper. The system comprises three components: physical space, service space, and twin space. The service space forms the core of the entire system. Within this space, twin models and control models are created using numerical simulation, artificial intelligence and multi-source data fusion technology. These models serve the purpose of predicting the roadheader’s mechanical performance and controlling the swing speed of the cutting arm. The physical space is built using technologies such as robot kinematics, electrical systems, hydraulic transmission, and other relevant techniques. This approach facilitates the transmission of multi-sensor data to twin models. The control model then manages the roadheader’s function based on the output signals from the control model. The twin space is constructed utilizing physical rendering engines, databases, and 3D modelling tools. This space visualizes and stores the movement, performance, and control parameters of the roadheader. The results demonstrate that the average absolute error between the measured data from the test’s three position strain gauges and the predicted data from the twin system is 10.38 MPa. Furthermore, the twin system achieves an average update interval of 0.34 s, allowing real-time stress monitoring of the structural components of the roadheader and preventing damage caused by overload. The proposed control model enables adaptive adjustment of the swing speed of the cutting arm in approximately 0.3 s. This improvement significantly enhances the adaptive cutting capabilities of roadheaders when dealing with complex coal and rock formations.

Abstract Background Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. Results Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T 2 -weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. Conclusions Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma. Graphic Abstract

Abstract Increased plasma homocysteine (Hcy) has been identified as one of the important risk factors for cardiovascular disease. However, the association between plasma Hcy and peripheral artery disease (PAD) is still controversial. This study aimed to investigate the association between plasma Hcy and PAD and the potential modifier factors in Chinese hypertensive adults. A total of 25 300 hypertensive patients aged 18 years or older were included in the analysis in this cross‐sectional study. The outcome was PAD, which defined as an ankle‐brachial index ≤0.90 in either limb. Multiple logistic regression was used to analyze the relationship between plasma Hcy and PAD. The median plasma Hcy was 14.00 (interquartile range: 11.60–17.80) μmol/L. There was a significant positive association between plasma Hcy and PAD (per SD increment; OR: 1.13; 95% CI: 1.06–1.19). Patients in the upper plasma Hcy tertile (≥16.16 μmol/L) were associated with a 53% increased risk of PAD compared with patients in the lower tertile (

Abstract Background The caffeoyl-CoA-O methyltransferase (CCoAOMT) family plays a crucial role in the oxidative methylation of phenolic substances and is involved in various plant processes, including growth, development, and stress response. However, there is a limited understanding of the interactions among CCoAOMT protein members in tea plants. Results In this study, we identified 10 members of the CsCCoAOMT family in the genome of Camellia sinensis (cultivar ‘HuangDan’), characterized by conserved gene structures and motifs. These CsCCoAOMT members were located on six different chromosomes (1, 2, 3, 4, 6, and 14). Based on phylogenetic analysis, CsCCoAOMT can be divided into two groups: I and II. Notably, the CsCCoAOMT members of group Ia are likely to be candidate genes involved in lignin biosynthesis. Moreover, through the yeast two-hybrid (Y2H) assay, we established protein interaction networks for the CsCCoAOMT family, revealing 9 pairs of members with interaction relationships. Conclusions We identified the CCoAOMT gene family in Camellia sinensis and conducted a comprehensive analysis of their classifications, phylogenetic and synteny relationships, gene structures, protein interactions, tissue-specific expression patterns, and responses to various stresses. Our findings shed light on the evolution and composition of CsCCoAOMT. Notably, the observed interaction among CCoAOMT proteins suggests the potential formation of the O-methyltransferase (OMT) complex during the methylation modification process, expanding our understanding of the functional roles of this gene family in diverse biological processes.

Abstract Deep neural networks combined with superpixel segmentation have proven to be superior to high-resolution remote sensing image (HRI) classification. Currently, most HRI classification methods that combine deep learning and superpixel segmentation use stacking on multiple scales to extract contextual information from segmented objects. However, this approach does not take into account the contextual dependencies between each segmented object. To solve this problem, a joint superpixel and Transformer (JST) framework is proposed for HRI classification. In JST, HRI is first segmented into superpixel objects as input, and Transformer is used to model the long-range dependencies. The contextual relationship between each input superpixel object is obtained and the class of analyzed objects is output by designing an encoding and decoding Transformer. Additionally, we explore the effect of semantic range on classification accuracy. JST is also tested by using two HRI datasets with overall classification accuracy, average accuracy and Kappa coefficients of 0.79, 0.70, 0.78 and 0.91, 0.85, 0.89, respectively. The effectiveness of the proposed method is compared qualitatively and quantitatively, and the results achieve competitive and consistently better than the benchmark comparison method.

Abstract Background The shoulder joint is the most commonly dislocated joint in the human body, and the recurrence rate exceeds 50% after nonsurgical treatment. Although surgical treatment reduces the recurrence rate, there is controversy regarding the optimal surgical approach. Previous studies suggest that the Latarjet procedure yields favourable outcomes for specific populations at risk of recurrence, such as competitive athletes with significant glenoid defects. However, most of the existing related research consists of nonrandomized controlled trials with small sample sizes, and there is a lack of strong evidence regarding the efficacy and safety of the Latarjet procedure. Methods The PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched. Athletes with ≥ 20% glenoid defects were selected for inclusion. The following data were extracted: general patient information, instability rates, return to sports (RTS) rates, imaging features (graft positioning rate and graft healing rate), functional assessments [Rowe score, Athletic Shoulder Outcome Scoring System(ASOSS), visual analogue scale (VAS), forward flexion function, and external rotation function], and complications. Results After excluding suspected duplicate cases, a total of 5 studies were included in this meta-analysis. The studies involved a total of 255 patients, including 237 males (93%) and 18 females (7%). The average age at the time of surgery was 25.4 ± 8.5 years. All the studies had a minimum follow-up period of 2 years, with an average follow-up time of 48.7 ± 18.9 months. The pooled rate of return to sport (RTS) was 94.3% (95% CI: 87.3%, 98.8%), and 86.1% (95% CI: 78.2%, 92.5%) of patients returned to their preoperative level of activity. The pooled redislocation rate was 1.1% (95% CI: 0%, 3.8%). Regarding the imaging results, the combined graft retention rate was 92.1% (95% CI: 88.1%, 95.5%), and the graft healing rate was 92.1% (95% CI: 88%, 95.4%). Postoperative functional evaluation revealed that the combined Rowe score, ASOSS score, and VAS score were 93.7 ± 6.5 points, 88.5 ± 4.4 points, and 1.1 ± 10 points, respectively. The forward flexion and external rotation angles were 170.9 ± 6.9 degrees and 65.6 ± 4.5 degrees, respectively. After excluding one study with unclear complications, the combined complication rate was 9.4% (95% CI: 1.0%, 23.6%). Conclusion For athletes with shoulder instability and a total of ≥ 20% glenoid bone defects, the Latarjet procedure can achieve excellent functional outcomes, with the majority of patients returning to preoperative levels of sports activity. This procedure also leads to a low recurrence rate. Therefore, the Latarjet procedure has been proven to be a safe and effective treatment.

Abstract Background Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells. Methods In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059. Results GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile. Conclusion GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer.

Abstract Background The labial salivary glands (LSGs) are important for the diagnosis, evaluation of therapeutic efficacy, and genetic analyses of primary Sjögren’s syndrome (pSS). In autoimmune diseases, the recognition of self nucleic acids and viral RNA and DNA through endogenous Toll-like receptor(TLR) triggers the production of type I IFN and pro-inflammatory cytokines, leading to the occurrence and progression of the disease. Here, we detected the expression of TLR7 in LSGs and analyse its correlation with clinical features and serum cytokines in pSS patients. Methods LSGs and serum samples were obtained from 56 pSS patients and 19 non-SS patients (non-pSS patients). The expression of TLR7 in the LSGs was evaluated with immunohistochemistry. The serum levels of interferon-α (IFN-α) and interleukin-6 (IL-6) were quantified by ELISA. Laboratory parameters were measured by clinical standard laboratory techniques. Results TLR7-positive cells in pSS were localized in the ductal epithelial cells and lymphocytes of LSGs. The expression of TLR7 was upregulated in pSS patients compared with controls. Patients with anti-Ro52 antibody positivity showed higher TLR7 levels than those who were negative but not those with anti-Ro60 and anti-SSB. TLR7 levels were positively associated with the levels of IgG, IgA, ANA, IL-6, IFN-α and serum globulin but were not associated with IgM, C3, C4, or rheumatoid factor (RF) in serum. Conclusion TLR7 may be involved in the inflammatory response and the production of antibodies in pSS and plays an important role in local and systemic pSS manifestations. This research showed that TLR7 is involved in pSS pathogenesis.

Abstract Cone‐beam computed tomography (CBCT) system can provide real‐time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Dual-phase amorphous-nanocrystalline Al-x at.% Mo (x = 20, 26, 30) alloy films prepared in the way of dual-phase co-growth directly through magnetron sputtering were studied in terms of thermally induced microstructural evolution and mechanical properties via annealing at 550 °C. It was observed that, the annealed Al-26 and 30 at.% Mo alloy films maintained stable dual-phase amorphous-nanocrysatlline structure and precipitated Al8Mo3 nano-grains dispersed in amorphous matrix uniformly. After annealing, the surface roughness of Al-26 and 30 at.% Mo alloy films remained unchanged of 7.5 nm and the hardness and elastic modulus of them were as high as 13 and 210 GPa which enhanced about 50 % and 24 % than before, respectively. In contrast, the Al-20 at.% Mo alloy film crystallized completely and mainly contained intermetallic Al12Mo phase along with apparent grain coarsening after annealing, which resulted in significant increase of surface roughness and deterioration of hardness. The excellent thermal stability of dual-phase amorphous-nanocrystalline Al-26 and 30 at.% Mo alloy films stem from the small driving force for precipitated Al8Mo3 nano-grain growth, as well as benefit from effect of diffusion field impingement.

In the mammalian heart, cardiomyocytes are forced to withdraw from the cell cycle shortly after birth, limiting the ability of the heart to regenerate and repair. The development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal. With the continuous development of genetic lineage tracking technology, it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic, juvenile, and adult stages of cardiogenesis, but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction. It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury, which offers hope for the clinical treatment of myocardial infarction. However, the regeneration frequency and source of cardiomyocytes are still low, and the mechanism of regulating cardiomyocyte proliferation remains further explained. It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration. Here, we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration. In addition, myocardial transcription factors, non-coding RNAs, cyclins, and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation. Ultimately, awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.