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Nanping Ai,* Hongjuan Liu,* Huanfen Zhou, Dahe Lin, Junqing Wang, Mo Yang, Honglu Song, Mingming Sun, Quangang Xu, Shihui Wei Department of Ophthalmology, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China *These authors contributed equally to this work Objective: To study the differences in immunopathogenesis based on chemokine profile in neuromyelitis optica patients positive for AQP4 antibodies or MOG antibodies.Patients and methods: We measured 52 cytokines/chemokines using ELISA in 59 serum samples, which were divided into three groups according to CBA results: HCs (n=16), AQP4+(n=20) and MOG+ (n=23). The regression equation (R2>0.98) of the standard curve was calculated according to the standard concentration and the corresponding A value. And then the corresponding sample concentration was calculated according to the A value of the sample.Results: Eleven of 52 measured serum cytokine/chemokines (CCL22/MDC, CCL13/MCP-4, CCL21/6Ckine, CCL27/CTACK, CCL8/MCP-2, CXCL14/BRAK, Contactin-1, Kallilrein 6/Neurosin, Midkine, VCAM-1 and Fas) were significantly different between MOG+ group and controls. Ten of 52 measured serum cytokine/chemokines (CCL1/I-309, CCL22/MDC, CCL28, CCL17/TARC, CCL27/CTACK, CXCL2/GRO beta, Contactin-1, Midkine, Chemerin and Synuclein-alpha) were significantly different between AQP4+ group and controls. There was no difference between serum AQP4+ and MOG+ groups for CC chemokines. All measured chemokines CXC except CXCL6/GCP-2 showed no significant differences in serum AQP4+ group compared to MOG+ group. However, there was significant difference between serum AQP4+ and MOG+ groups for C5/C5a and Midkine. C5/C5a and Midkine were significantly higher in AQP4+ group compared to MOG+ group (P

Preventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment, and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking, and physical activity. In studying this link between lifestyle and cognitive decline, brain imaging markers may be instrumental as quantitative measures or even indicators of early disease. The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition aging. In this hot topics review, we will specifically focus on obesity and physical activity.

Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of immune parameters including T helper cell type 1 (Th1) cytokine production, antigen presentation, and antigen-specific T cell proliferation. To understand the consequences of altered expression of IL-10 in immune models of autoimmune disease, the response to infectious agents, and the response to tumors, we developed transgenic mice expressing IL-10 under the control of the IL-2 promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-gamma than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels. Transfer of normally pathogenic CD4(+) CD45RBhigh splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4(+) CD45RBhigh T cells from control mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immune responses were not globally suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs restored in vivo antitumor responses in the transgenic mice. These results demonstrate that a single alteration in the T cell cytokine profile can lead to dramatic changes in immune responses in a manner that is stimulus dependent. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.

Abstract Background Radiographically, ground-glass nodules (GGN) and part-solid nodules (PSN) in lung adenocarcinoma (LUAD) have significant heterogeneity in their clinical manifestations, biological characteristics, and prognosis. This study aimed to explore the heterogeneity of LUAD in different radiological phenotypes and associated factors influencing tumor evolution. Methods We performed single-cell RNA sequencing (scRNA-seq) on tumor tissues from eight and seven cases of GGN– and PSN–LUAD, respectively, at different disease stages, including minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IAC), and metastatic lung cancer (MLC). Additionally, we analyzed adjacent normal tissues from four cases. Immunohistochemistry, multiplex immunofluorescence, and external scRNA-seq data were employed to confirm the expression of signature genes as well as the distribution patterns of CXCL9 + TAMs and TREM2 + TAMs. A LUAD mouse model was generated using gene editing, organoid culture, and orthotopic transplantation techniques, and comprehensive analyses such as histopathology, RNA sequencing, and Western blotting were performed to validate key pathways. Results Diverse cellular compositions were observed in the tumor microenvironment (TME) during GGN– and PSN–LUAD invasion and metastasis. Notably, CXCL9 + and TREM2 + tumor-associated macrophages (TAMs) exhibited the most significant enrichment changes. It was found that GGN–LUAD exhibited a stronger immune response than PSN–LUAD, with increased interaction between CXCL9 + TAMs and CD8 + tissue-resident memory T cells during invasion stage (MIA–IAC). Conversely, greater interactions between TREM2 + TAMs and tumor cells were observed in PSN–LUAD during the MLC stage. Additionally, TREM2 + TAMs were found to differentiate into TREM2 + /SPP1 + and TREM2 + /SPP1– TAMs at different stages, which promotes tumor progression. This study also emphasizes that during the transdifferentiation process of GGN– and PSN–LUAD, IFN-γ activates the STAT1 signaling pathway to regulate the activation of CXCL9 + TAMs, and further recruiting CD8 + Trm cells and activating T cells through MHC class I antigen presentation. The role of the IFN-γ/STAT1 pathway in the occurrence and development of LUAD was further validated by animal experiments. Conclusions Our findings offer a potential therapeutic strategy to maintain a dynamic balance within the TME and improve the immunotherapy efficacy by modulating the relative proportions and functional states of CXCL9 + TAMs and TREM2 + TAMs.

Abstract In current studies for testing Bell inequalities at colliders, the reconstruction of spin correlations from scattering cross-sections relies on the bilinear form of the spin correlations, but not all local hidden variable models (LHVMs) have such a property. To demonstrate that a general LHVM cannot be rule out via scattering cross-section data, we propose a specific LHVM, which can exactly duplicate the same scattering cross-section for particle production and decay as the standard quantum theory, making it indistinguishable at colliders in principle. Despite of this, we find that reconstructing spin correlations through scattering cross-sections can still exclude a broad class of LHVMs, e.g., those models employing classical spin correlations as a surrogate for quantum spin correlations.

In response to the current challenges of low cutting efficiency and poor surface quality in processing single-crystal silicon, this article proposes the utilization of the micro-discharge abrasive cutting (MDAC) method for processing single-crystal silicon. A comprehensive comparison is conducted among the processing characteristics of the new cutting method and fixed abrasive wire sawing (FAWS) and wire electrical discharge machining (WEDM), including cutting efficiency, surface morphology, subsurface damage, surface roughness, wire saw wear, elemental spectrum analysis, and kerf width. Besides, two material removal modes at different feed rates are discussed. The results indicate that compared with WEDM, MDAC has the advantages of minimal subsurface damage, low surface roughness, low residual elements, and small kerf width. MDAC has higher cutting efficiency and shallower scratch depth than FAWS. However, compared with WEDM and FAWS, MDAC results in more significant wire saw wear and leaves a small amount of residual nickel on the silicon surface. In MDAC, the discharge occurs first. When the discharge energy within the pulse width is sufficient to remove the material within the current pulse cycle, the material is completely removed by the discharge action, the discharge products remain on the surface of the silicon wafer. When the discharge energy is insufficient to remove the material within the current pulse cycle, the silicon ingot is removed under the combined action of discharge and grinding, the diamond on wire saw surface will remove most of the discharge products.

The load-bearing capacity of reinforced concrete (RC) beams primarily relies on internal reinforced bars. However, limited research has been conducted on the dynamic response of these bars. To address this gap, this study has established an analytical model using dimensional analysis for calculating the deformation of reinforced bars within RC beams subjected to contact explosion. Comparison with experimental data reveals that the model has a relative error of 5.22%, effectively reflecting the deformation of reinforced bars. Additionally, based on this model, the study found that while concrete does influence the deformation of reinforced bars, this influence can be disregarded in comparison to the material properties of the bars themselves. The findings of this study have implications for calculating the residual load-bearing capacity of damaged RC beams, evaluating the extent of damage to RC beams after blast loading, and providing guidance for the blast-resistant design of RC structures.

Abstract Objectives Delirium is a prominent symptom of sepsis-associated encephalopathy (SAE) and is highly prevalent in septic patients hospitalized in the intensive care unit, being closely connected with raised mortality rates. Acute hyperglycemia (AH) has been recognized as a separate risk factor for delirium and a worse prognosis in critically sick patients. Nevertheless, the exact contribution of AH to the advancement of SAE is still unknown. Methods This research retrospectively evaluated the connection between blood glucose levels (BGLs) and the incidence of delirium and death rates in septic patients in the ICU of a tertiary comprehensive hospital. In addition, a septic rat model was induced through cecal ligation and puncture (CLP), after which continuous glucose infusion was promptly initiated via a central venous catheter post-surgery to evaluate the potential implications of AH on SAE. Next, septic rats were assigned to four groups based on target BGLs: high glucose group (HG, ≥ 300 mg/dL), moderate glucose group (MG, 200–300 mg/dL), normal glucose group (NG,

Abstract Background Biorefinery using microorganisms to produce biofuels and value-added biochemicals derived from renewable biomass offers a promising alternative to meet our sustainable energy and environmental goals. The ethanologenic strain Zymomonas mobilis is considered as an excellent chassis for constructing microbial cell factories for diverse biochemicals due to its outstanding industrial characteristics in ethanol production, high specific productivity, and Generally Recognized as Safe (GRAS) status. Nonetheless, the restricted substrate range constrains its application. Results The truncated ice nucleation protein InaK from Pseudomonas syringae was used as an autotransporter passenger, and α-amylase was fused to the C- terminal of InaK to equip the ethanol-producing bacterium with the capability to ferment renewable biomass. Western blot and flow cytometry analysis confirmed that the amylase was situated on the outer membrane. Whole-cell activity assays demonstrated that the amylase maintained its activity on the cell surface. The recombinant Z. mobilis facilitated the hydrolysis of starch into oligosaccharides and enabled the streamlining of simultaneous saccharification and fermentation (SSF) processes. In a 5% starch medium under SSF, recombinant strains containing P eno reached a maximum titer of 13.61 ± 0.12 g/L within 48 h. This represents an increase of 111.0% compared to the control strain's titer of titer of 6.45 ± 0.25 g/L. Conclusions By fusing the truncated ice nucleation protein InaK with α-amylase, we achieved efficient expression and surface display of the enzyme on Z. mobilis. This fusion protein exhibited remarkable enzymatic activity. Its presence enabled a cost-effective bioproduction process using starch as the sole carbon source, and it significantly reduced the required cycle time for SSF. This study not only provides an excellent Z. mobilis chassis for sustainable bioproduction from starch but also highlights the potential of Z. mobilis to function as an effective cellular factory for producing high-value products from renewable biomass.

Abstract Though several anti-PD-1/PD-L1 antibodies approved for monotherapy in microsatellite instability-high or mismatch repair-deficient unresectable/metastatic solid tumors, novel immunotherapy with better anti-tumor activity is needed in clinic. In this single-arm, multicenter, pivotal, phase II study, patients received iparomlimab (a novel humanized anti-PD-1 mAb, 200 mg or 3 mg/kg for patients with body weight

Erodium stephanianum (Erodium stephanianum Willd. Sp. Pl. 1800) has not had its complete chloroplast genome reported, which limits our understanding of its genetics and evolution. In this study, we assembled and annotated its chloroplast genome, revealing a quadripartite structure with 76 protein-coding genes. Repeat analysis indicated the presence of simple sequence repeats. Phylogenetic analysis confirmed E. stephanianum's placement within the genus Erodium of the Geraniaceae family. These findings offer valuable genomic resources for comparative studies in Erodium and Geraniaceae, aiding genetic diversity and phylogenetic analyses.

Abstract Exploring the spatial pattern and its influencing mechanism of cultural heritage is of great significance for the systematic protection, inheritance and utilization of cultural heritage. In this study, the national-level cultural heritage of China as the research object, and the spatial patterns of the cultural heritage (CH), tangible cultural heritage (TCH) and intangible cultural heritage (ICH) are analyzed are summarized using the multiple geospatial analysis method, and their spatial distribution differences. Then, the optimal parameter geodetector model was further used to analyze the influencing and interaction effect of natural environment (NE) factors, socioeconomic and cultural environment (SCE) factors on the spatial distribution of CH, TCH and ICH, and the interaction mechanism was deeply discussed. The results show that high-density region of CH are mainly located in the southeastern Heihe-Tengchong Line of China, while low-density region are mostly located in the northwestern Heihe-Tengchong Line. In terms of local spatial differences, the spatial distribution of material cultural heritage is different in different river basins, different terrains and different climates. The spatial distribution of ICH mainly shows significant differences in terrain and climate, and does not show significant differences in river basins. In terms of influencing factors, sociocultural environment, education level, historical settlement environment, road traffic, climate, economy, population and terrain factors all have a significant impact on the spatial distribution of CH and TCH. Sociocultural environment, education level, historical settlement environment, road traffic, climate, economy and population have a significant impact on the spatial distribution of ICH, while topographic factors and water system factors have no significant impact on the spatial distribution of ICH. Compared with ICH, TCH is more likely to be directly affected by topographic conditions (altitude, relief of terrain) and hydrological conditions (production and living water sources and flood risk) during its formation stage. At the same time, topographic and hydrological conditions can also indirectly affect the spatial distribution of TCH by directly affecting human agricultural activities, economic activities and cultural activities.

AIM: To investigate the causal effect of inflammatory bowel disease (IBD) on ocular inflammation using Mendelian randomization (MR) analysis. METHODS: Genetic instruments associated with inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD) were derived from the largest genome-wide association studies (GWAS) published to date. The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis, keratitis, iridocyclitis, chorioretinitis, episcleritis, and optic neuritis. All participants were of European ancestry. Three methods which included inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression were performed to estimate the causal association in this study. IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes, to summarize the effect sizes of multiple independent studies, which could provide the most precise estimated results. IVW was used as the primary outcome, while WM and MR-Egger were used to improve the estimation of IVW. RESULTS: A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis, keratitis, iridocyclitis, and optic neuritis, but not on chorioretinitis or episcleritis. After Bonferroni correction, the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis (IVW: OR, 1.17; 95%CI, 1.10-1.24, P=2.54×10-7). CD was significantly associated with conjunctivitis (IVW: OR, 1.05; 95%CI, 1.03-1.08, P=3.20×10-5), keratitis (IVW: OR, 1.06; 95%CI, 1.02-1.09; P=1.13×10-3), and iridocyclitis (IVW: OR, 1.09; 95%CI, 1.04-1.14; P=1.43×10-4). CONCLUSION: IBD causally poses a risk of inflammation of conjunctiva, cornea, Iris-ciliary body complex, and optic neuritis. CD is more closely associated with the eye inflammation than UC. These impliy that the relationship of IBD and different parts of the eye structure are different, and provide novel evidence linking based on the association of the gut-eye axis.

The semirigid pavement base is known for its high strength and good stability. However, it faces challenges owing to the generation of shrinkage stress during the development of its strength subsequent service. This stress arises from internal changes in relative humidity and temperature. When this shrinkage stress exceeds the bonding force of the cementitious material, the base may develop dry shrinkage cracks and temperature shrinkage cracks. Addressing this issue, cementitious material based on red mud emerges as a novel solution for roadbed construction, potentially replacing traditional cement entirely. Despite its promise, the crack resistance evolution of this material is still unclear. This study focuses on the dry shrinkage and temperature shrinkage properties of the stabilized gravel layer made from red mud-based cementitious material. It investigates how various factors, including the content of red mud-based cementitious material and duration of maintenance, affect these shrinkage properties. Additionally, it establishes a correlation between dry shrinkage, temperature shrinkage, and their maximum strain values through grey correlation degree analysis. Experimental results reveal a positive correlation between the cumulative dry shrinkage strain of stabilized crushed stone based on red mud cementitious material and the curing age, with the growth rate diminishing over time. The cumulative dry shrinkage strain first decreases and then increases as the content of red mud cementitious material rises, hitting its lowest point at 7% content. The cumulative dry shrinkage coefficient of stabilized crushed stone of red mud–based cementation material reaches the peak value at the age of 1 d and before gradually decreasing and stabilizing. Notably, at an 8% dosage, this coefficient is significantly higher than in other groups. Regarding temperature shrinkage, the coefficient first increases and then decreases with rising temperature. The average temperature shrinkage coefficient follows a similar pattern based on the content of red mud-based cementitious material, with the 7-day coefficient substantially exceeding the 28-day figure. Microcracks fill the stable gravel matrix at 7 days of age, whereas at 28 days, the matrix becomes denser owing to the increase in hydration products. Scanning electron microscope morphology analysis further elucidates the mechanisms of dry and temperature shrinkage. Employing grey relational analysis, the study identifies the dry shrinkage resistance index and temperature shrinkage coefficient as optimal indicators for assessing the cracking resistance of stabilized crushed stone using red mud-based cementitious material. Optimal cracking resistance is achieved when the content of red-mud cementitious material is 7%.

ObjectivesIn the application of sandwich composite materials in ship structures, to ensure the structural strength characteristics, bolt connections are usually used between the sandwich composite structure and steel main hull. However, due to local stress concentration around the holes and the boundary effects at the connection locations, the bolt connection position is often becomes the most critical area of the structure, necessitating strength and fatigue assessments. MethodsFor a full-scale steel-sandwich composite panel structure, the strength characteristics of the plate frame under a 0.1 MPa uniform load are studied using experimental and finite element methods. The accuracy of the finite element method is then verified by comparing its results with those from the experimental method. Subsequently, based on the finite element method, fatigue tests for two equivalent bolted joints are designed through structural stress equivalence, and the fatigue life of the steel-sandwich composite structure is evaluated and verified. ResultsIt is determined that the fatigue life of the panel structure under the design load meets the design requirement of 5 million cycles.ConclusionsRegarding the fatigue problem of large bolted connections, equivalent joints can be designed for fatigue testing, and load equivalence can be achieved through structural stress equivalence.

Abstract Objective Oblique lateral interbody fusion (OLIF) is becoming widely used in patients with single-segment spinal tuberculosis (STB). The learning curve and complications associated with OLIF for the treatment of STB are still unknown. This study aims to figure out the learning curve and associated complications experience of OLIF for the treatment of STB. Methods Between September 2018 and August 2023, 61 STB patients underwent OLIF plus percutaneous pedicle screw fixation (PPSF) were consecutively included in this research. Cumulative sum analysis (CUSUM) was applied to establish the learning curve of OLIF and determine the cut-off case number. All cases were divided into learning and experienced groups based on the cut-off case number. Clinical characteristics and relating surgical complications were compared and analyzed between the two groups. Results The best-fitting curve was quadratic. The fitting equation was CUSUM (min) = 95.83 + 34.16x − 0.611 x 2 (x means operation case). The cut-off operation case number was 27 cases. The presence of significant differences particularly in the duration of operation, operative blood loss, overall incidence, and severity of postoperative complications was noteworthy between the two groups. Conclusion A total of 27 cases is the minimum number to master OLIF combined with PPSF for the treatment of patients with single-segment STB. When surgeons master this operation, the operative time, operative blood loss, overall incidence, and severity of postoperative complications will improve.

Abstract Neurogenic lower urinary tract dysfunction (NLUTD) is a frequent consequence of spinal cord injury (SCI), leading to symptoms that significantly impact quality of life. Although many life-saving techniques are available, current treatment strategies for managing NLUTD still exhibit limitations and drawbacks. Here, we introduce a new electrical neuromodulation strategy involving electrical stimulation of the major pelvic ganglion (MPG) to initiate bladder contraction, in conjunction with innovative programmable (IPG) electrical stimulation on the pudendal nerve (PN) to induce external urethral sphincter (EUS) relaxation in freely moving or anesthetized SCI mice. Furthermore, we conducted the void spot assay, and cystometry coupled with EUS electromyography (EMG) recordings to evaluate voiding function, and monitor bladder pressure and EUS activity. Our findings demonstrate that our novel electrical neuromodulation approach effectively triggers coordinated bladder muscle contraction and EUS relaxation, effectively counteracting SCI-induced NLUTD. Additionally, this electrical neuromodulation method enhances voiding efficiency, closely resembling natural reflexive urination in SCI mice. Thus, our study offers a promising electrical neurostimulation approach aimed at restoring physiological coordination and potentially offering personalized treatment for improving voiding efficiency in individuals with SCI-associated NLUTD.

Abstract Photonics offers a transformative approach to artificial intelligence (AI) and neuromorphic computing by enabling low-latency, high-speed, and energy-efficient computations. However, conventional photonic tensor cores face significant challenges in constructing large-scale photonic neuromorphic networks. Here, we propose a fully integrated photonic tensor core, consisting of only two thin-film lithium niobate (TFLN) modulators, a III-V laser, and a charge-integration photoreceiver. Despite its simple architecture, it is capable of implementing an entire layer of a neural network with a computational speed of 120 GOPS, while also allowing flexible adjustment of the number of inputs (fan-in) and outputs (fan-out). Our tensor core supports rapid in-situ training with a weight update speed of 60 GHz. Furthermore, it successfully classifies (supervised learning) and clusters (unsupervised learning) 112 × 112-pixel images through in-situ training. To enable in-situ training for clustering AI tasks, we offer a solution for performing multiplications between two negative numbers.

Abstract Psoriasis is a chronic inflammatory skin disorder with multiple causes, including genetic and environmental factors. Despite advances in treatment, there remains a need to identify novel therapeutic targets. A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets for psoriasis. Data on cis-expression quantitative trait loci were obtained from the eQTLGen Consortium (n = 31,684). Summary statistics for psoriasis (outcome) were sourced from the GWAS Catalog with a sample size of 484,598, including 5,427 cases and 479,171 controls. Colocalization analysis was used to assess whether psoriasis risk and gene expression were driven by shared single nucleotide polymorphisms. Drug prediction and molecular docking were utilized to validate the pharmacological value of the drug targets. The MR analysis found that 81 drug targets were significantly associated, and two (TYK2 and PRSS36) were supported by colocalization analysis (PP.H4 > 0.80). Phenome-wide association studies did not show any associations with other traits at the gene level. Biologically, these genes were closely related to immune function. Molecular docking revealed strong binding with drugs and proteins, as supported by available structural data. This study validated TYK2 as a drug target for psoriasis, in line with its existing clinical use, including the development of decucravacitinib. PRSS36 is a potential novel target requiring further investigation.

Abstract Background Vitamin D deficiency has been linked to poor muscle function, cartilage degeneration, and the development of knee osteoarthritis. However, the impact of serum 25-hydroxyvitamin D [25(OH)D] level on quadriceps muscle strength remains inconclusive, largely due to variations in study designs, differences in study populations, and the influence of confounding factors such as co-supplementation with other vitamins. The existing literature presents mixed findings, highlighting the need for a comprehensive evaluation of the available evidence. Purpose This systematic review and meta-analysis aim to summarise. Study design Systematic review; Level of evidence, 4. Methods Searches were conducted using Medline (Ovid), Embase (Ovid), CINAHL (EBSCOhost), and SPORTDiscus (EBSCOhost), which aimed to summarise recent (published after 2000 and before March 1st, 2024) studies reporting the effects of serum 25(OH)D levels on quadriceps strength. Appraisal tool for Cross-Sectional Studies (AXIS) for cross-sectional studies and Quality in Prognosis Studies (QUIPS) for longitudinal studies. Results from the AXIS and QUIPS tools were used for GRADE quality assessment. The review was carried out using PRIMSA guidelines and registered in PROSPERO (ID: CRD42022313240). Results Four hundred studies were screened and 28 studies with 5752 participants were included. 28 published studies (24 cross-sectional and 4 longitudinal) were identified. Key results supported the significant positive correlation between serum 25(OH)D levels and isokinetic quadriceps strength at 180°/s in elderly and athletic populations with a correlation coefficient of 0.245 (95%CI: 0.078–0.398, p = 0.004). However, no significant correlation was found with isometric quadriceps strength or isokinetic strength at 60°/s (r = 0.190, p = 0.085). There was only a weak negative correlation with MVC. Conclusion This review found a statistically significant positive correlation between serum 25(OH)D levels and isokinetic quadriceps strength. This has important clinical implications, especially in the elderly cohort, with higher 25(OH)D levels being associated with a reduced incidence of falls and fragility fractures.

Abstract Latexin (LXN) is abundant in macrophages and plays critical roles in inflammation. Much is known about macrophages in atherosclerosis, the role of macrophage LXN in atherosclerosis has remained elusive. Here, the expression of LXN in human and mouse atherosclerotic lesions was examined by immunofluorescence and immunohistochemistry. LXN knockout and LXN/ApoE double-knockout mice were generated to evaluate the functions of LXN in atherosclerosis. Bone marrow transplantation (BMT) experimentation was carried out to determine whether macrophage LXN regulates atherosclerosis. We found that LXN is enriched in human and murine atherosclerotic lesions, mainly localized to macrophages. LXN deletion ameliorated atherosclerosis in ApoE -/- mice. BMT demonstrate that deletion of LXN in bone marrow protects ApoE -/- mice against atherosclerosis. Mechanistically, we found that LXN targets and inhibits JAK1 in macrophages. LXN deficiency stimulates the JAK1/STAT3/ABC transporter pathway, thereby enhancing the anti-inflammatory and anti-oxidant phenotype, cholesterol efflux, subsequently minimizing foam cell formation and atherosclerosis. Gene therapy by treatment of atherosclerotic mice with adeno-associated virus harbouring LXN-depleting shRNA attenuated the disease phenotype. In summary, our study provides new clues for the role of LXN in the pathological regulation of atherosclerosis, and determines that LXN is a target for preventing atherosclerosis, which may be a potential new anti-atherosclerosis therapeutic target.

Abstract The rise of object detection models has brought new breakthroughs to the development of clinical decision support systems. However, in the field of gastrointestinal polyp detection, there are still challenges such as uncertainty in polyp identification and inadequate coping with polyp scale variations. To address these challenges, this paper proposes a novel gastrointestinal polyp object detection model. The model can automatically identify polyp regions in gastrointestinal images and accurately label them. In terms of design, the model integrates multi-channel information to enhance the ability and robustness of channel feature expression, thus better coping with the complexity of polyp structures. At the same time, a hierarchical structure is constructed in the model to enhance the model’s adaptability to multi-scale targets, effectively addressing the problem of large-scale variations in polyps. Furthermore, a channel attention mechanism is designed in the model to improve the accuracy of target positioning and reduce uncertainty in diagnosis. By integrating these strategies, the proposed gastrointestinal polyp object detection model can achieve accurate polyp detection, providing clinicians with reliable and valuable references. Experimental results show that the model exhibits superior performance in gastrointestinal polyp detection, which helps improve the diagnostic level of digestive system diseases and provides useful references for related research fields.

Abstract This paper adopts the Mariotte siphon to simplify the nutrient solution preparation structure while improving the liquid mixing accuracy for nutrient solution. A liquid mixing model suitable for EC and pH regulation was constructed by combining fuzzy control algorithms, and a set of fertigation nutrient solution control equipment was designed and developed. During the experiment, comparison was made between the Fuzzy-PID algorithm and the traditional PID algorithm in terms of nutrient solution configuration. The results show that the Fuzzy-PID algorithm is smoother and more stable compared to the PID algorithm. Through analysis of the liquid mixing accuracy with the venturi type fertigation machine, it was found that the fertigation machine designed with the Mariotte structure is more accurate for liquid mixing, and can better meet the needs of crop growth.

Abstract Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.

Abstract Microbial fuel cells (MFCs) use the metabolic actions of microorganisms in an anode chamber to convert the chemical energy from wastewater into electrical energy. To improve the MFC power generation performance and chemical oxygen demand (COD) removal efficiency, Stenotrophomonas acidaminiphila was added to the anode chamber of a dual-compartment MFC. In this process, Stenotrophomonas acidaminiphila promotes the degradation of macromolecules such as bis(2-ethylhexyl) phthalate in food waste oil. Additionally, the generated electrical energy reduced Cu2+ in the copper-containing wastewater in the cathode chamber to Cu monomers. The maximum power density of the MFC was 49.5 ± 3.5 mW/m2, the maximum removal efficiencies of COD and Cu2+ were 63.5 ± 5.8% and 96.5 ± 1.0%, respectively, and Cu2+ was reduced to brick-red Cu monomers. This study provides insights into the simultaneous implementation of food waste oil treatment and metal resource recovery.

Abstract Fibroblast growth factor 21 (FGF21) is essential for modulating hepatic homeostasis, but the impact of FGF21 on liver graft injury remains uncertain. Here, we show that high FGF21 levels in liver graft and serum are associated with improved graft function and survival in liver transplantation (LT) recipients. FGF21 deficiency aggravates early graft injury and activates arachidonic acid metabolism and regional inflammation in male mouse models of hepatic ischemia/reperfusion (I/R) injury and orthotopic LT. Mechanistically, FGF21 deficiency results in abnormal activation of the arachidonate 15-lipoxygenase (ALOX15)/15-hydroxy eicosatetraenoic acid (15-HETE) pathway, which triggers a cascade of innate immunity-dominated pro-inflammatory responses in grafts. Notably, the modulating role of FGF21/ALOX15/15-HETE pathway is more significant in steatotic livers. In contrast, pharmacological administration of recombinant FGF21 effectively protects against hepatic I/R injury. Overall, our study reveals the regulatory mechanism of FGF21 and offers insights into its potential clinical application in early liver graft injury after LT.

The Vehicle On-Board Controller (VOBC) is a core component of urban rail transit trains, with high maintenance costs and serious consequences in case of failure. Ensuring long-term VOBC operation while minimizing maintenance costs is of paramount importance. This paper proposes a multi-objective preventive maintenance (PM) strategy and optimization considering system unavailability and maintenance costs. Firstly, we provide a statement of the problem and analyze the impact of different maintenance actions on VOBC. Next, the decreasing process parameter is introduced to adjust the PM interval dynamically. The mathematical models of system unavailability and maintenance costs are derived to construct a multi-objective PM strategy. Then, we develop a hybrid heuristic algorithm including multi-objective particle swarm optimization and genetic algorithm (MOPSO-GA), which is used to obtain the optimal Pareto frontier for maintenance strategies. In the study, we select maintenance strategies by introducing an aversion factor to fulfill the preferences of different decision-makers. A comprehensive sensitivity analysis is performed to illustrate the impact of several critical parameters on the multi-objective PM strategy. The case study on Beijing subway’s VOBC is also executed. The outcomes indicate that the proposed method can dynamically adjust to match the preferences of diverse decision-makers and the MOPSO-GA algorithm has excellent robustness on most parameters. This approach allows for creating field maintenance strategies catering to the varied maintenance requirements of urban rail transit VOBC.

Pyomyoma, a rare complication of leiomyoma, presents a unique clinical challenge due to its infrequency with potentially fatal complications. Herein, we report the case of a 44-year-old Para 3+1 woman with red degeneration of uterine fibroids during pregnancy, who experienced worsening abdominal pain and foul smelling vaginal discharge 1 week post Caesarean section. Despite hemodynamic stability, her septic markers were markedly raised. A bedside ultrasound noted a pelvic complex cystic collection, further confirmed on CT scan as spontaneous ruptured of pyomyoma complicated by complex fistulas with surrounding organs. She underwent total abdominal hysterectomy and abdominal washout the next day, with intravenous antibiotic on-board. Histology examination confirmed acute suppurative inflammation of the uterine fibroid with endometritis. This case report contributes to the existing medical literature by shedding light on a rare and potentially life-threatening leiomyoma complication. Its potential to mimic acute puerperal endometritis, makes its diagnosis especially challenging, necessitating a high index of suspicion.

The novel active flow control technology based on plasma synthetic jet (PSJ) has great application potential in the field of shock wave control due to its advantages such as no gas source, strong control ability, and wide excitation frequency band. The control effect of single-pulsed PSJ on head bow shock and wing shock of a hypersonic vehicle model and the drag reduction effect were experimentally studied in a hypersonic wind tunnel. The results show that the opposing PSJ can significantly increase the standoff distance of the head bow shock, and the transverse PSJ can basically eliminate the wing shock completely. The maximum instantaneous drag reduction rate of the vehicle measured by the dynamic force sensor is about 15.5%, but the drag change measured by the sensor has a delay of about 250 μs. The influence of discharge energy, incoming flow total pressure, exit diameter, and cavity volume on the control effect of the head bow shock was also studied.

Abstract Background We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. Methods This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. Results Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI − 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). Conclusions The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Abstract Background This study investigated the clinical value of breast magnetic resonance imaging (MRI) radiomics for predicting axillary lymph node metastasis (ALNM) and to compare the discriminative abilities of different combinations of MRI sequences. Methods This study included 141 patients diagnosed with invasive breast cancer from two centers (center 1: n = 101, center 2: n = 40). Patients from center 1 were randomly divided into training set and test set 1. Patients from center 2 were assigned to the test set 2. All participants underwent preoperative MRI, and four distinct MRI sequences were obtained. The volume of interest (VOI) of the breast tumor was delineated on the dynamic contrast-enhanced (DCE) postcontrast phase 2 sequence, and the VOIs of other sequences were adjusted when required. Subsequently, radiomics features were extracted from the VOIs using an open-source package. Both single- and multisequence radiomics models were constructed using the logistic regression method in the training set. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and precision of the radiomics model for the test set 1 and test set 2 were calculated. Finally, the diagnostic performance of each model was compared with the diagnostic level of junior and senior radiologists. Results The single-sequence ALNM classifier derived from DCE postcontrast phase 1 had the best performance for both test set 1 (AUC = 0.891) and test set 2 (AUC = 0.619). The best-performing multisequence ALNM classifiers for both test set 1 (AUC = 0.910) and test set 2 (AUC = 0.717) were generated from DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging single-sequence ALNM classifiers. Both had a higher diagnostic level than the junior and senior radiologists. Conclusions The combination of DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging radiomics features had the best performance in predicting ALNM from breast cancer. Our study presents a well-performing and noninvasive tool for ALNM prediction in patients with breast cancer.

Abstract Background T cell-based immunotherapies are facing great challenges in the recruitment and activation of tumor-specific T cells against solid tumors. Among which, utilizing nanobody (Nb) or nanobodies (Nbs) to construct T cell engager has emerged as a more practical potential for enhancing the anti-tumor effectiveness of T cells. Here, we designed a new Nb-guided multifunctional T cell engager (Nb-MuTE) that not only recruited effector T cells into the tumor tissues, but also efficiently activated T cells anti-tumor immunity when synergies with photothermal effect. Results The Nb-MuTE, which was constructed based on an indocyanine green (ICG)-containing liposome with surface conjugation of CD105 and CD3 Nbs, and showed excellent targetability to both tumor and T cells, following enhancement of activation, proliferation and cytokine secretion of tumor-specific T cells. Notably, the immunological anti-tumor functions of Nb-MuTE-mediated T cells were further enhanced by the ICG-induced photothermal effect in vitro and in vivo. Conclusions Such a new platform Nb-MuTE provides a practical and “all-in-one” strategy to potentiate T cell responses for the treatment of solid tumor in clinic.

The completely autotrophic nitrogen removal over nitrite (CANON) is a new type of nitrogen removal process developed in recent years. The control of dissolved oxygen (DO) in this process is relatively stringent, especially in low-substrate wastewater treatment. However, the results of studies on the operation of the process in different aeration modes are still controversial, and investigations on biofilm type CANON reactors are limited. In this study, a pilot-scale CANON bioreactor filled with suspended carriers was investigated on the treatment of wastewater at low ammonium concentrations, and the effect of the aeration mode on autotrophic nitrogen removal was evaluated. Seven conditions with various aeration on/off times and DO levels were tested. The results showed that an intermittent aeration with a 20-min/20-min aeration on/off time and DO concentrations of 1.0–1.3 mg/L at the end of the aeration period was appropriate, potentially inhibiting nitrite oxidizing bacteria (NOB) and keeping the total nitrogen (TN) removal rate at a relatively high level of 76.7% ± 2.5%. In the optimal aeration mode, the reactor achieved effluent TN and NH4+-N concentrations of (11.1 ± 3.3) mg/L and (3.6 ± 2.3) mg/L, respectively, with a hydraulic retention time of 12 h and an influent NH4+-N concentration of (48.6 ± 9.4) mg/L at 30.1°C ± 2.2°C. The results of metagenomic sequencing for microorganisms on carriers indicated that the main nitrogen removal bacteria in the reactor were Proteobacteria, Planctomycetes, and Nitrospirae. The NOB genus Nitrospira was completely inhibited by intermittent aeration. Candidatus Kuenenia had strong adaptability to low-concentration wastewater.

Background: Preterm premature rupture of membranes (PPROM) contributes to over one-third of preterm births, and PPROM infants are more susceptible to infections. However, the risk factors remain poorly understood. We here aim to investigate the association of duration of premature rupture of membranes (PROM) and environmental microbiota with the gut microbiota and infection in PPROM infants. Methods: Forty-six premature infants were recruited from two hospitals, and infant fecal and environmental samples were collected. 16 s rRNA sequencing was performed to analyze the fecal and environmental microbiome. Human inflammatory cytokines in cord vein plasma were measured. Results: The gut microbiota composition of PPROM infants was different from that of non-PPROM infants, and the microbiome phenotypes were predicted to be associated with a higher risk of infection, further evidenced by the significantly increased levels of IL-6 and IL-8 in cord vein plasma of PPROM infants. The diversity of the gut microbiota in PPROM infants increased significantly as the duration of PROM excessed 12 h, and Pseudomonas contributed significantly to the dynamic changes. The Pseudomonas species in the gut of PPROM infants were highly homologous to those detected in the ward environment, suggesting that prolonged PROM is associated with horizontal transmission of environmental pathogens, leading to a higher risk of infection. Conclusions: This study highlights that the duration of PROM is associated with the accumulation of environmental pathogens in the gut of PPROM infants, which is a risk factor for nosocomial infections. Improving environmental hygiene could be effective in optimizing the clinical care of PPROM infants.

The path planning of Unmanned Aerial Vehicle (UAV) is a critical issue in emergency communication and rescue operations, especially in adversarial urban environments. Due to the continuity of the flying space, complex building obstacles, and the aircraft's high dynamics, traditional algorithms cannot find the optimal collision-free flying path between the UAV station and the destination. Accordingly, in this paper, we study the fast UAV path planning problem in a 3D urban environment from a source point to a target point and propose a Three-Step Experience Buffer Deep Deterministic Policy Gradient (TSEB-DDPG) algorithm. We first build the 3D model of a complex urban environment with buildings and project the 3D building surface into many 2D geometric shapes. After transformation, we propose the Hierarchical Learning Particle Swarm Optimization (HL-PSO) to obtain the empirical path. Then, to ensure the accuracy of the obtained paths, the empirical path, the collision information and fast transition information are stored in the three experience buffers of the TSEB-DDPG algorithm as dynamic guidance information. The sampling ratio of each buffer is dynamically adapted to the training stages. Moreover, we designed a reward mechanism to improve the convergence speed of the DDPG algorithm for UAV path planning. The proposed TSEB-DDPG algorithm has also been compared to three widely used competitors experimentally, and the results show that the TSEB-DDPG algorithm can archive the fastest convergence speed and the highest accuracy. We also conduct experiments in real scenarios and compare the real path planning obtained by the HL-PSO algorithm, DDPG algorithm, and TSEB-DDPG algorithm. The results show that the TSEB-DDPG algorithm can archive almost the best in terms of accuracy, the average time of actual path planning, and the success rate.

Abstract Abnormal cardiac development has been observed in individuals with Cornelia de Lange syndrome (CdLS) due to mutations in genes encoding members of the cohesin complex. However, the precise role of cohesin in heart development remains elusive. In this study, we aimed to elucidate the indispensable role of SMC3, a component of the cohesin complex, in cardiac development and its underlying mechanism. Our investigation revealed that CdLS patients with SMC3 mutations have high rates of congenital heart disease (CHD). We utilized heart-specific Smc3-knockout (SMC3-cKO) mice, which exhibit varying degrees of outflow tract (OFT) abnormalities, to further explore this relationship. Additionally, we identified 16 rare SMC3 variants with potential pathogenicity in individuals with isolated CHD. By employing single-nucleus RNA sequencing and chromosome conformation capture high-throughput genome-wide translocation sequencing, we revealed that Smc3 deletion downregulates the expression of key genes, including Ets2, in OFT cardiac muscle cells by specifically decreasing interactions between super-enhancers (SEs) and promoters. Notably, Ets2-SE-null mice also exhibit delayed OFT development in the heart. Our research revealed a novel role for SMC3 in heart development via the regulation of SE-associated genes, suggesting its potential relevance as a CHD-related gene and providing crucial insights into the molecular basis of cardiac development.

Abstract Tuberculosis is a serious global health burden, resulting in millions of deaths each year. Several circulating cell subsets in the peripheral blood are known to modulate the host immune response to Mycobacterium tuberculosis (Mtb) infection in different ways. However, the characteristics and functions of these subsets to varying stages of tuberculosis infection have not been well elucidated. Peripheral blood immune cells (PBICs) were isolated from healthy donors (HD group), individuals with mild tuberculosis (MI group), and individuals with severe tuberculosis (SE group). CD4+ naive T cells and CD8+ T cells were decreased in the SE and MI groups, while CD14+ monocytes were increased in the SE group. Further analysis revealed increased activated CD4+ T cells, transitional CD8+ T cells, memory-like NK cells, and IGHG3highTTNhighFCRL5high B cells were increased in all patients with tuberculosis (SE and MI group). In contrast, Th17 cells, cytotoxic NK cells, and cytotoxic CD4+ T cells were decreased. Moreover, the increase of CD14+CD16+ monocytes correlated with severe tuberculosis, and the GBP5highRSAD2high neutrophils were unique to patients with severe tuberculosis. Cellular communication analysis revealed that CD8+ T cells exhibited the highest incoming interaction strength in the SE group. The increased CD8+ T cell incoming interactions are associated with the MHC-I and LCK pathways, with HLA-(A-E)-CD8A, HLA-(A-E)-CD8B, and LCK-(CD8A+CD8B) being ligand–receptor pairs. Patients with tuberculosis, especially severe tuberculosis, have profound changes in peripheral blood immune cell profiles. CD8+ T cells showed the highest incoming interaction strength in patients with severe tuberculosis, with the main signals being MHC-I and LCK pathways.

Abstract Fast-charging, non-aqueous lithium-based batteries are desired for practical applications. In this regard, LiMn2O4 is considered an appealing positive electrode active material because of its favourable ionic diffusivity due to the presence of three-dimensional Li-ion diffusion channels. However, LiMn2O4 exhibits inadequate rate capabilities and rapid structural degradation at high currents. To circumvent these issues, here we introduce quintuple low-valence cations to increase the entropy of LiMn2O4. As a result, the entropy-increased LiMn2O4-based material, i.e., LiMn1.9Cu0.02Mg0.02Fe0.02Zn0.02Ni0.02O4, when tested in non-aqueous lithium metal coin cell configuration, enable 1000 cell cycles at 1.48 A g−1 (corresponding to a cell charging time of 4 minutes) and 25°C with a discharge capacity retention of about 80%. We demonstrate that the increased entropy in LiMn2O4 leads to an increase in the disordering of dopant cations and a contracted local structure, where the enlarged LiO4 space and enhanced Mn-O covalency improve the Li-ion transport and stabilize the diffusion channels. We also prove that stress caused by cycling at a high cell state of charge is relieved through elastic deformation via a solid-solution transition, thus avoiding structural degradation upon prolonged cycling.

Abstract Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIVAD8-EO infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs. Emergence of virus in plasma and lymph nodes (LNs) was delayed by bNAb treatment and occurred earlier in monkeys given DEL bNAbs than in those given WT bNAbs, consistent with faster clearance of DEL bNAbs from plasma. DEL bNAb-treated monkeys had higher levels of circulating virus-specific IFNγ single-producing CD8+ CD69+ T cells than the other groups. In LNs, WT bNAbs were evenly distributed between follicular and extrafollicular areas, but DEL bNAbs predominated in the latter. At week 8 post-challenge, LN monocytes and NK cells from DEL bNAb-treated monkeys upregulated proinflammatory signaling pathways and LN T cells downregulated TNF signaling via NF-κB. Overall, bNAbs with increased affinity to FcγRs shape innate and adaptive cellular immunity, which may be important to consider in future strategies of passive bNAb therapy.

Abstract Dietary micronutrients are integral to the development and progression of constipation; however, the specific relationship between dietary copper intake and constipation has not been thoroughly investigated. This study aims to examine the correlation between dietary copper intake and constipation among U.S. adults, thereby offering novel insights and recommendations for the clinical management and prevention of constipation. Bowel health data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were analyzed. Subjects’ dietary information was collected through questionnaire records. Multivariate logistic regression analysis, subgroup analysis, and curve fitting analysis were used to assess the correlation between dietary copper intake and chronic constipation. After adjusting for all possible confounders, each unit increase in dietary copper intake (converted to natural logarithms) was associated with a 20% reduction in the prevalence of constipation (OR = 0.80; 95% CI 0.65–0.98; P = 0.037). The interaction P-values for all subgroups were greater than 0.05, indicating that the findings were stable and consistent across subgroups. The present study showed a significant negative association between dietary copper intake and chronic constipation in adults. This finding raises clinical and healthcare professionals’ awareness of the impact of dietary trace elements on intestinal health and has important implications for the development of personalized meal plans and rational supplementation of trace copper in patients with constipation.

Abstract Background Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). Methods This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman’s rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. Results Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p

Abstract Background Squama Manis is a valuable traditional Chinese medicine with a long history of medicinal use in the treatment of breast-related diseases. However, owing to the excessive exploitation and utilization of the resources, Squama Manis has been included in the list of rare and endangered wild animals. The conservation of the resources of Squama Manis and continuing its clinical application has become an urgent problem, and the search for small-molecule substitutes for Squama Manis is an effective way to achieve this goal. Previous studies have identified PA3264 as a possible active ingredient in Squama Manis. In this study, we systematically investigated the pharmacological effects and mechanisms of PA3264 in the treatment of triple-negative breast cancer (TNBC), a representative breast-related disease. Methods Cell viability and colony formation assays were performed after treatment with the target dipeptide PA3264 in vitro. Next, 4T1 orthotopic tumors and humanized PBMC-CDX mouse models were generated to examine the antitumor effect of PA3264 in vivo. Transcriptome sequencing and molecular docking experiments were performed to predict pathways to function. Western blotting and quantitative real-time PCR were used to validate the molecular mechanisms underlying the anticancer effects of PA3264. Results PA3264 significantly inhibited cell viability and migration of breast cancer cells in vitro. Furthermore, PA3264 suppressed the tumor size and reduced the tumor weight in vivo. Finally, it was verified that PA3264 prevented the progression of breast cancer by inhibiting the PI3K/AKT/NF-κB pathway, causing cell cycle arrest, and promoting apoptosis. Conclusions This study elucidated that PA3264 derived from rare and endangered Squama Manis was a novel bioactive peptide for treating triple-negative breast cancer from a scientific research perspective.

Color features carries rich information and directly influencing people’s regional perception. This exploration originates from the serial research conducted in the Huizhou area. By analyzing the color features of Hongcun, Nanping, and Xidi, this study probes into the descriptive cognition of independent dimensions, advancing to visual cognition of combined dimensions and psychological cognition of system dimensions. The study established a systematic technical route. Firstly, it sets up spatial sequence paths in typical regional built spaces, uses 3D laser scanning technology for high-quality modeling. Secondly, this study utilizes color as an independent dimension, conducting descriptive statistics on the color attributes – namely, Lightness, Chroma, and Hue – of architectural components to determine their distinct color features in absolute terms. Thirdly, exploring the combined dimension of color, the research delves into visual similarity, examining commonalities within architectural elements. Lastly, from a systemic color perspective, it focuses on the stability of psychological cognition, identifying Huizhou’s color identity through a “black-grey-white” tri-color sequence as a stable composition. Additionally, this technical system features advantages of being systematic and precise. It promotes the scientific and rationality in the color research field, guiding the integrated application of urban design.

Abstract Background An important signaling pathway connecting illness and natural immunity is the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, but aberrant activation of this pathway is associated with the development of autoimmune and inflammatory diseases. Hence, targeted inhibition of the activation of the cGAS-STING pathway is potentially valuable in the treatment of disease. The primary active component of Salvia miltiorrhiza is total tanshinone (TTN). Research has indicated that TTN possesses noteworthy anti-inflammatory properties. However, the protective mechanism of TTN against acute liver injury (ALI) and autoimmune diseases is unknown. Methods A model of aberrant activation of the cGAS-STING pathway was established in various cells and treated with TTN, and the expression of cGAS-STING pathway-related proteins, type I interferon, interferon stimulated genes and inflammatory factors was assessed by western blotting, real-time qPCR. Immunofluorescence analysis of the effect of TTN on the entry of associated proteins into the nucleus following aberrant activation of the cGAS-STING pathway. The effect of TTN on STING oligomerisation was investigated using 2'-3'-cyclic GMP-AMP (2',3'-cGAMP) to induce STING oligomerisation. Western blotting was used to examine the impact of TTN on the interactions of STING, tank-binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3) after HA or Flag-labelled plasmids were transfected into HEK-293 T cells. A dimethylxanthenone-4-acetic acid (DMXAA) -induced activation model of the cGAS-STING pathway in mice was established to study the effect of TTN on aberrant activation of the cGAS-STING pathway in vivo. On the other hand, an animal model of lipopolysaccharide/D-galactosamine (LPS/D-GaIN)-induced ALI and an autoimmune disease model induced by trex1 knockout were established to study the effects of TTN on inflammatory and autoimmune diseases mediated by the cGAS-STING pathway in vivo. Results In several models of aberrant activation of the cGAS-STING pathway, TTN significantly inhibited the phosphorylation of STING and IRF3, thereby suppressing the expression of type I interferon, interferon-stimulated genes and inflammatory factors. Additionally, TTN prevented P65 and IRF3 from entering the nucleus after the cGAS-STING signalling pathway was abnormally activated. Subsequent research indicated that TTN was not involved in the oligomerization of STING or the integration of STING-TBK1 and TBK1-IRF3. However, TTN was found to have a substantial effect on the binding process between STING and IRF3. On the other hand, DMXAA-induced STING activation and activation of downstream signalling in vivo are inhibited by TTN. Furthermore, TTN exhibits positive treatment effects on autoimmune diseases caused by deficiency of trex1 and LPS/D-GaIN-induced ALI. Conclusion Our research indicates that TTN effectively treats ALI and autoimmune illnesses mediated by the cGAS-STING pathway by inhibiting the abnormal activation of this pathway. Graphical Abstract

【Objective】The symbol decomposition technique aims to decompose Optical Orthogonal Frequency Division Multiplexing (O-OFDM) symbols into multiple symbols with a small Peak to Average Power Ratio (PAPR) to mitigate the non-linear effects of Light Emitting Diodes (LEDs). However, O-OFDM generates more decomposed symbols with a higher PAPR, thereby reducing the information rate and degrading the Bit Error Rate (BER) performance.【Methods】The proposed design of Precoding O-OFDM Adaptive Symbol Decomposition with Serial Transmission (PCO-OFDM-ASDST) system uses precoding scheme to reduce the PAPR of O-OFDM symbols. The proposed method can reduce the average number of symbol decompositions for adaptive symbol decomposition. The theoretical Signal-to-Noise Ratio (SNR) expressions are derived for multipath channels, and the performance of PAPR, BER, and information rate is analyzed using Monte Carlo BER simulations.【Results】The results demonstrate that under 4 Quadrature Amplitude Modulation (QAM) modulation in Asymmetrically Clipped Optical Orthogonal Frequency Division Multiplexing (ACO-OFDM) systems, the symbol power required for PCO-OFDM-ASDST is 7 dB less than that of Adaptive Symbol Decomposition with Serial Transmission (ASDST) when the BER is 10-4. Moreover, under 64QAM, the information rate can be increased by 10 Mbit/s when the symbol power is 20 dBm.【Conclusion】The results indicate that the PCO-OFDM-ASDST outperforms ASDST systems in terms of BER and information transmission rate.

Abstract Transcriptional heterogeneity of tumor-associated macrophages (TAMs) has been investigated in individual cancers, but the extent to which these states transcend tumor types and represent a general feature of cancer remains unclear. We performed pan-cancer single-cell RNA sequencing analysis across nine cancer types and identified distinct monocyte/TAM composition patterns. Using spatial analysis from clinical study tissues, we assessed TAM functions in shaping the tumor microenvironment (TME) and influencing immunotherapy. Two specific TAM clusters (pro-inflammatory and pro-tumor) and four TME subtypes showed distinct immunological features, genomic profiles, immunotherapy responses, and cancer prognosis. Pro-inflammatory TAMs resided in immune-enriched niches with exhausted CD8+ T cells, while pro-tumor TAMs were restricted to niches associated with a T-cell-excluded phenotype and hypoxia. We developed a machine learning model to predict immune checkpoint blockade response by integrating TAMs and clinical data. Our study comprehensively characterizes the common features of TAMs and highlights their interaction with the TME.