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Abstract Background Qin-Yu-Qing-Chang decoction (QYQC), an herbal formula from China, is extensively employed to manage ulcerative colitis (UC) and exhibits potential benefits for colonic function. Nevertheless, the fundamental molecular mechanisms of QYQC remain largely uncharted. Methods The primary constituents of QYQC were determined utilizing UHPLC-MS/MS analysis and the effectiveness of QYQC was assessed in a mouse model of colitis induced by dextran sulfate sodium. Evaluations of colon inflammatory responses and mucosal barrier function were thoroughly assessed. RNA sequencing, molecular docking, colonic energy metabolism, and 16S rRNA sequencing analysis were applied to uncover the complex mechanisms of QYQC in treating UC. Detect the signal transduction of the peroxisome proliferator-activated receptor-γ (PPAR-γ) both in the nucleus and cytoplasm. Furthermore, a PPAR-γ antagonist was strategically utilized to confirm the functional targets that QYQC exerts. Results Utilizing UHPLC-MS/MS, the principal constituents of the nine traditional Chinese medicinal herbs comprising QYQC were systematically identified. QYQC treatment substantially ameliorated colitis in mice, as evidenced by the improvement in symptoms and the reduction in colonic pathological injuries. Besides, QYQC treatment mitigated the inflammatory response and improved mucosal barrier function. Furthermore, QYQC enhanced the mitochondria citrate cycle (TCA cycle) by triggering PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus. This prevented the unconstrained expansion of facultative anaerobes, particularly pathogenic Escherichia coli (E. coli, family Enterobacteriaceae) and thus improved colitis. Results of molecular docking indicated that the representative chemical components of QYQC including Baicalin, Paeoniflorin, Mollugin, and Imperatorin bound well with PPAR-γ. The impact of QYQC on colitis was diminished in the presence of a PPAR-γ antagonist. Conclusions In summary, QYQC ameliorates UC by activating PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus, which enhances the energy metabolism of intestinal epithelial cells and thereby preventing the uncontrolled proliferation of facultative anaerobes.

To reduce CO2 emissions from coal-fired power plants, the development of low-carbon or carbon-free fuel combustion technologies has become urgent. As a new zero-carbon fuel, ammonia (NH3) can be used to address the storage and transportation issues of hydrogen energy. Since it is not feasible to completely replace coal with ammonia in the short term, the development of ammonia–coal co-combustion technology at the current stage is a fast and feasible approach to reduce CO2 emissions from coal-fired power plants. This study focuses on modifying the boiler and installing two layers of eight pure-ammonia burners in a 300-MW coal-fired power plant to achieve ammonia–coal co-combustion at proportions ranging from 20% to 10% (by heat ratio) at loads of 180- to 300-MW, respectively. The results show that, during ammonia–coal co-combustion in a 300-MW coal-fired power plant, there was a more significant change in NOx emissions at the furnace outlet compared with that under pure-coal combustion as the boiler oxygen levels varied. Moreover, ammonia burners located in the middle part of the main combustion zone exhibited a better high-temperature reduction performance than those located in the upper part of the main combustion zone. Under all ammonia co-combustion conditions, the NH3 concentration at the furnace outlet remained below 1 parts per million (ppm). Compared with that under pure-coal conditions, the thermal efficiency of the boiler slightly decreased (by 0.12%–0.38%) under different loads when ammonia co-combustion reached 15 t·h−1. Ammonia co-combustion in coal-fired power plants is a potentially feasible technology route for carbon reduction.

Background Simplified left atrial appendage occlusion (LAAO) is one of the important treatment methods for preventing thromboembolism in patients with nonvalvular atrial fibrillation. Currently, there are few studies on the value of cardiac 3-dimensional computed tomography (3D-CT) in the simplified LAAO. Objective To investigate the feasibility, safety, surgical efficacy and postoperative follow-up value of 3D-CT in simplified LAAO. Methods We prospectively recruited 52 patients who underwent simplified LAAO in the Second Affiliated Hospital of Anhui Medical University from May 2021 to January 2024. They were randomly assigned into the control group and study group by lottery. Preoperative transesophageal echocardiography (TEE) and preoperative cardiac 3D-CT were performed in the control group and study group, respectively. The baseline data, maximum ostium diameter and maximum depth of the left atrial appendage (LAA), match rate between the delivered sheath and the axis of LAA, operation time, time for x-ray exposure and dose, consumption of contrast agent, the rate of non-recapture and non-change of occlusion device, peri-device leakage (PDL), and perioperative complications were collected. A 3D-CT follow-up was performed for 90 days after LAAO. Results Both the control group and the study group comprised 26 cases each, using the WATCHMAN device for LAAO, with no serious perioperative complications. Preoperative examinations showed no intracardiac thrombus in all patients. In the control group, the maximum ostium diameter of the LAA measured by preoperative TEE and intraoperative DSA was (22.9±4.1) mm and (25.4±2.9) mm, respectively, not showing a positive correlation (r=0.374, P=0.060). The usable depth of the LAA in the control group measured by preoperative TEE and intraoperative DSA was (25.7±8.1) mm and (23.7±3.4) mm, respectively, showing a positive correlation (r=0.392, P=0.048). In the study group, the maximum ostium diameter of the LAA measured by preoperative 3D-CT and intraoperative DSA was (25.0±3.3) mm and (24.9±5.8) mm, respectively, showing a positive correlation (r=0.566, P=0.003). The usable depth of the LAA in the study group measured by preoperative 3D-CT and intraoperative DSA was (23.5±4.2) mm and (23.1±4.0) mm, respectively, showing a positive correlation (r=0.774, P

Abstract Our previous clinical metabolomics study illustrated that energy metabolism disorder is an underlying pathogenesis mechanism for the development of alcoholic liver disease (ALD). Supplementation of nicotinamide (NAM), the precursor of nicotinamide adenine dinucleotide (NAD+), may restore the energy metabolism homeostasis of ALD and thus serves as potential therapeutics to treat ALD. In this bedside‐to‐bench study, the protective effect of NAM against ALD was investigated by using the NIAAA mice model (chronic‐plus‐binge ethanol), and the liver regeneration boosting capability of NAM was evaluated by the partial hepatectomy mice model. Our results showed that NAM supplements not only protected the liver from alcohol‐induced injury and improved alcohol‐induced mitochondrial structure and function change, but also boosted liver regeneration in postpartial hepatectomy mice by increasing liver NAD+ content. These findings suggested that NAM, a water‐soluble form of vitamin B3, can promote liver regeneration and improves liver function by alleviating alcohol‐induced energy metabolism disorder.

Abstract Background Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. Methods The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. Results We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient’s imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. Conclusions Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

In order to achieve the intelligent height adjustment control of the shearer, the key techniques are the coal-rock interface recognition, cutting path optimization, and shearer height adjustment control. Although the coal-rock interface is accurately identified, the shearer drum cannot completely follow the estimated coal-rock interface due to the flatness requirement for the roof and floor of the coal seam which guarantees the working of hydraulic supports. Therefore, the cutting trajectory should be optimized based on the coal-rock interface recognition results, which is regarded as the target trajectory of shearer height-adjusting control. To solve this issue, the cutting path optimization is required. Based on the estimated coal-rock interface and considering the limitations in practical application, the cutting path is optimized to maximize the recovery ratio. To improve the optimization results, satisfy the restricting condition, and reduce the computational complexities, this paper proposed a novel constraint optimization method of shearer cutting path based on the mayfly algorithm and B-spline curve fitting. A novel objective function is built, in which the curve node coefficients are chosen as the design variants, and the optimization target is minimizing the difference between the fitness curve and the coal-rock interface, leading to the much less designed variants and the lower computational load. The piecewise penalty function is used to deal with the constraints, which assists the exploration process in escaping from local maxima and make sure the constraints work. And then the modified mayfly algorithm is used to find the optimized cutting path to further improve the optimization effect and the convergence rate. Finally, the simulations of cutting path optimization are conducted under the condition of folds, subsidence and faults, which indicate that the proposed method can obtain the optimized smooth cutting path with the limitation of the constraints quickly, and have high real-time behavior, and good applicability.

Abstract Background Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow for reduction in intensity of conditioning regimen. Methods In this phase II clinical trial (NCT01807611), 72 patients with hematological malignancies (complete remission (CR)1: 25, ≥ CR2: 28, refractory disease: 19) received haploidentical CD34 + enriched and CD45RA-depleted hematopoietic progenitor cell grafts followed by NK-cell infusion. Conditioning included fludarabine, thiotepa, melphalan, cyclophosphamide, total lymphoid irradiation, and graft-versus-host disease (GVHD) prophylaxis consisted of a short-course sirolimus or mycophenolate mofetil without serotherapy. Results The 3-year overall survival (OS) and event-free-survival (EFS) for patients in CR1 were 92% (95% CI:72–98) and 88% (95% CI: 67–96); ≥ CR2 were 81% (95% CI: 61–92) and 68% (95% CI: 47–82) and refractory disease were 32% (95% CI: 11–54) and 20% (95% CI: 6–40). The 3-year EFS for all patients in morphological CR was 77% (95% CI: 64–87) with no difference amongst recipients with or without minimal residual disease (P = 0.2992). Immune reconstitution was rapid, with mean CD3 and CD4 T-cell counts of 410/μL and 140/μL at day + 30. Cumulative incidence of acute GVHD and chronic GVHD was 36% and 26% but most patients with acute GVHD recovered rapidly with therapy. Lower rates of grade III-IV acute GVHD were observed with NK-cell alloreactive donors (P = 0.004), and higher rates of moderate/severe chronic GVHD occurred with maternal donors (P = 0.035). Conclusion The combination of a CD45RA-depleted graft and NK-cell addback led to robust immune reconstitution maximizing the GVL effect and allowed for use of a submyeloablative, TBI-free conditioning regimen that was associated with excellent EFS resulting in promising long-term outcomes in this high-risk population. The trial is registered at ClinicalTrials.gov (NCT01807611).

Abstract Background Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500–1/250 individuals, predominantly affecting those aged 30–40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation. Case presentation Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient’s chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient’s heart failure was successfully treated with heart transplantation. Conclusions Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation.

Abstract Despite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly understood. In this study, we uncover a critical role for SmD2, a core component of the spliceosome machinery, in modulating DNA damage in HCC through its impact on BRCA1/FANC cassette exons and expression. Our findings reveal that SmD2 depletion sensitizes HCC cells to PARP inhibitors, expanding the potential therapeutic targets. We also demonstrate that SmD2 acetylation by p300 leads to its degradation, while HDAC2-mediated deacetylation stabilizes SmD2. Importantly, we show that the combination of Romidepsin and Olaparib exhibits significant therapeutic potential in multiple HCC models, highlighting the promise of targeting SmD2 acetylation and HDAC2 inhibition alongside PARP inhibitors for HCC treatment.

Abstract Global maritime emissions, a 3% contributor to greenhouse gases, anticipate a surge of 90–130% by 2050. Regulatory challenges persist due to international governance gaps. Legislative strides, including the EU Emission Trading System, highlight global efforts. In the U.S., despite legislative commitment, consensus hurdles impede cross-regional carbon management. Prevailing top-down emissions estimation methods warrant scrutiny. This paper unveils U.S. maritime emissions intricacies, focusing on carbon accounting, transfer, and compensation for cargo and tanker vessels. Leveraging AIS data (2018–2022), an activity-based/bottom-up approach navigates emissions calculations, aiming to reshape understanding and foster strategic reductions. The study bridges gaps in U.S. maritime emission research, promising insights into transfer and compensation dynamics. By concentrating on high-impact vessel types, it contributes to emissions mitigation strategies, steering towards a sustainable U.S. maritime future.

Abstract Conventional wind speed distribution methods (e.g., Rayleigh distribution and Weibull distribution) may not adequately capture complex characteristics of wind fields in mountainous areas. To address this problem, this study proposes a semi-parametric mix method for modeling the distribution of average wind speeds based on the combination of nonparametric Kernel Density Estimation (KDE) and Generalized Pareto Distribution (GPD). In the proposed method, KDE focuses on capturing the distribution in the main part of average wind speeds, while GPD aims at performing the distribution in terms of those in the extreme part. The segment point (i.e., the threshold) between KDE and GPD distributions is determined based on the combination of conditional mean excesses criterion and empirical rule. Meanwhile, the selection of modeling parameters should ensure that the mix distribution model is continuous and differentiable at the identified threshold point. Then, the commonly-used conditional probability model is further introduced to describe the wind direction distribution. Finally, a case study based on the measured 10-min average wind speeds at a mountainous bridge site is employed to demonstrate the effectiveness of the proposed method. The results indicate that: (1) the distribution of omnidirectional average wind speeds in the mountainous bridge site exhibits an obviously single-peak characteristic, while those considering wind directionality present a certain bimodal characteristic; (2) the proposed method can effectively describe wind speed distributions with different statistical characteristics, and the fitting accuracy outperforms the frequently-employed Weibull distribution model.

Abstract Defining genetic factors impacting chemotherapy failure can help to better predict response and identify drug resistance mechanisms. However, there is limited understanding of the contribution of inherited noncoding genetic variation on inter-individual differences in chemotherapy response in childhood acute lymphoblastic leukemia (ALL). Here we map inherited noncoding variants associated with treatment outcome and/or chemotherapeutic drug resistance to ALL cis-regulatory elements and investigate their gene regulatory potential and target gene connectivity using massively parallel reporter assays and three-dimensional chromatin looping assays, respectively. We identify 54 variants with transcriptional effects and high-confidence gene connectivity. Additionally, functional interrogation of the top variant, rs1247117, reveals changes in chromatin accessibility, PU.1 binding affinity and gene expression, and deletion of the genomic interval containing rs1247117 sensitizes cells to vincristine. Together, these data demonstrate that noncoding regulatory variants associated with diverse pharmacological traits harbor significant effects on allele-specific transcriptional activity and impact sensitivity to antileukemic agents.

Environmental pollutants are considered as a cause of tumorigenesis, but approaches to assess their risk of causing tumors remain insufficient. As an alternative approach, the adverse outcome pathway (AOP) framework is used to assess the risk of tumors caused by environmental pollutants. Arsenic is a pollutant associated with lung cancer, but early assessment of lung cancer risk is lacking. Therefore, we applied the AOP framework to arsenic-induced lung cancer. A systematic review revealed increased risks of lung cancer following exposure to a range of arsenic concentrations in drinking water (OR = 1.83, 95 % CI = 1.46–2.30). We obtained, from public databases, genes related to risk of arsenic-induced lung cancer. Then, Cox and LASSO regressions were used to screen target genes from the risk genes. Subsequently, target genes, phenotypes, and pathways were used to construct the computational AOP network, which was determined by Cytoscape to have 156 edges and 45 nodes. Further, target genes, phenotypes, and pathways were used as molecular initiating events and key events to construct the AOP framework depending on upstream and downstream relationships. In the AOP framework, by Weight of Evidence, arsenic exposure increased levels of EGFR, activated the PI3K/AKT pathway, regulated cell proliferation by promoting the G1/S phase transition, and caused generation of lung cancers. External validation was achieved through arsenite-induced, malignant transformed human bronchial epithelial (HBE) cells. Overall, these results, by integration into existing data to construct an AOP framework, provide insights into the assessment of lung cancer risk for arsenic exposure. Special attention needs to be focused on populations with low-dose arsenic exposure.

BackgroundIn individuals receiving treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), those exhibiting positive PD-L1 expression might experience reduced progression-free survival (PFS). However, the effects on overall survival (OS) and the determination of efficacious treatment approaches are still not well-defined.MethodsIn our retrospective study, we examined data from 193 NSCLC patients with advanced EGFR mutations who received first-line TKI treatments, treated at two centers of Shaw Hospital in Zhejiang, China. This analysis covered a period from 1 January 2016 to 30 April 2023.ResultsPatients with PD-L1 positivity exhibited a markedly shorter average PFS (9.5 months versus 17.8 months, P < 0.001) and OS (44.4 months versus 65.7 months, P = 0.016) relative to those without PD-L1 expression. This difference in both PFS and OS remained statistically significant even after adjusting for multiple factors (P < 0.001 for PFS and P = 0.028 for OS). In the PD-L1-positive cohort, introducing combination antiangiogenic significantly extended both PFS (from 9.1 to 25.7 months, P = 0.026) and OS (from 42 to 53.5 months, P = 0.03). Post-first-line TKI therapy, 39.3% of PD-L1-positive patients and 54.5% of PD-L1-negative patients developed the T790M mutation (P = 0.212), with no notable difference in PFS from second-line TKI treatments between the groups. Additionally, subsequent combination therapy with immunotherapy markedly prolonged OS in the PD-L1-positive group. However, for PD-L1-negative patients, neither combination antiangiogenic therapy nor later-line immunotherapy demonstrated significant benefits in PFS or OS.ConclusionFor PD-L1-positive patients, combined antiangiogenic treatments and immunotherapy can significantly improve survival outcomes. In contrast, PD-L1-negative patients show less benefit from these therapies, highlighting the greater efficacy of these treatments in PD-L1-positive individuals.

Cigarette smoke (CS), an indoor environmental pollutant, is a prominent risk factor for emphysema, which is a pathological feature of chronic obstructive pulmonary disease (COPD). Emerging function of circRNAs in immune responses and disease progression shed new light to explore the pathogenesis of emphysema. In this research, we demonstrated, by single-cell RNA sequencing (scRNAseq), that the ratio of M2 macrophages were increased in lung tissues of humans and mice with smoking-related emphysema. Further, our data showed that circADAMTS6 was associated with cigarette smoke extract (CSE)-induced M2 macrophage polarization. Mechanistically, in macrophages, circADAMTS6 stabilized CAMK2A mRNA via forming a circADAMTS6/IGF2BP2/CAMK2A RNA-protein ternary complex to activate CREB, which drives M2 macrophage polarization and leads to emphysema. In addition, in macrophages of mouse lung tissues, downregulation of circADAMTS6 reversed M2 macrophage polarization, the proteinase/anti-proteinase imbalance, and the elastin degradation, which protecting against CS-induced emphysema. Moreover, for macrophages and in a model with co-cultured lung organoids, the target of circADAMTS6 restored the growth of lung organoids compared to CSE-treated macrophages. Our results also demonstrated that, for smokers and COPD smokers, elevation of circADAMTS6 negatively correlated with lung function. Overall, this study reveals a novel mechanism for circADAMTS6-driven M2 macrophage polarization in smoking-related emphysema and postulates that circADAMTS6 could serve as a diagnostic and therapeutic marker for smoking-related emphysema.

Monkeypox (Mpox) is an acute febrile rash illness caused by the Mpox virus. The ongoing international outbreak since mid-2022 has spread worldwide, including Taiwan. Ocular involvement in Mpox infection is uncommon, including external and ocular surface lesions. Here, we describe a man who developed unilateral blepharoconjunctivitis and preseptal cellulitis, followed by the appearance of skin symptoms 6 days after the ocular manifestations. Samples taken from his oropharynx and skin lesions tested positive for the Mpox virus through a polymerase chain reaction test. He was hospitalized for isolation with topical lubricant, antibiotic, and acyclovir eye ointment until the skin lesions healed. However, on the day of discharge, punctate epithelial keratitis was observed in the same eye. The corneal lesion also tested positive for the Mpox virus. His keratitis progressed to dendritic ulceration, and treatment with tecovirimat was initiated. Initially, his corneal ulcer responded well to tecovirimat, but 12 days later, it deteriorated along with cells in the anterior chamber. To treat his condition, low-dose steroid and ganciclovir eye drops were administered. Eventually, the patient experienced resolution of the corneal lesion, leaving a scar.

Abstract We measured the levels of High‐Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child‐care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme‐linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)‐17, IL‐6, transforming growth factor β (TGF‐β), IL‐10, and NT‐proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P

Tumor microenvironment (TME), as the “soil” of tumor growth and metastasis, exhibits significant differences from normal physiological conditions. However, how to manipulate the distinctions to achieve the accurate therapy of primary and metastatic tumors is still a challenge. Herein, an innovative nanoreactor (AH@MBTF) is developed to utilize the apparent differences (copper concentration and H2O2 level) between tumor cells and normal cells to eliminate primary tumor based on H2O2-dependent photothermal-chemodynamic therapy and suppress metastatic tumor through copper complexation. This nanoreactor is constructed using functionalized MSN incorporating benzoyl thiourea (BTU), triphenylphosphine (TPP), and folic acid (FA), while being co-loaded with horseradish peroxidase (HRP) and its substrate ABTS. During therapy, the BTU moieties on AH@MBTF could capture excessive copper (highly correlated with tumor metastasis), presenting exceptional anti-metastasis activity. Simultaneously, the complexation between BTU and copper triggers the formation of cuprous ions, which further react with H2O2 to generate cytotoxic hydroxyl radical (•OH), inhibiting tumor growth via chemodynamic therapy. Additionally, the stepwise targeting of FA and TPP guides AH@MBTF to accurately accumulate in tumor mitochondria, containing abnormally high levels of H2O2. As a catalyst, HRP mediates the oxidation reaction between ABTS and H2O2 to yield activated ABTS•+. Upon 808 nm laser irradiation, the activated ABTS•+ performs tumor-specific photothermal therapy, achieving the ablation of primary tumor by raising the tissue temperature. Collectively, this intelligent nanoreactor possesses profound potential in inhibiting tumor progression and metastasis.

Acute aortic dissection is one of the most life-threatening cardiovascular diseases, with a high mortality rate. Its prevalence ranges from 0.2% to 0.8% in humans, resulting in a significant number of deaths due to being missed in manual examinations. More importantly, the aortic diameter—a critical indicator for surgical selection—significantly influences the outcomes of surgeries post-diagnosis. Therefore, it is an urgent yet challenging mission to develop an automatic aortic dissection diagnostic system that can recognize and classify the aortic dissection type and measure the aortic diameter. This paper offers a dual-functional deep learning system called aortic dissections diagnosis-aiding system (DDAsys) that enables both accurate classification of aortic dissection and precise diameter measurement of the aorta. To this end, we created a dataset containing 61 190 computed tomography angiography (CTA) images from 279 patients from the Division of Cardiovascular Surgery at Tongji Hospital, Wuhan, China. The dataset provides a slice-level summary of difficult-to-identify features, which helps to improve the accuracy of both recognition and classification. Our system achieves a recognition F1 score of 0.984, an average classification F1 score of 0.935, and the respective measurement precisions for ascending and descending aortic diameters are 0.994 mm and 0.767 mm root mean square error (RMSE). The high consistency (88.6%) between the recommended surgical treatments and the actual corresponding surgeries verifies the capability of our system to aid clinicians in developing a more prompt, precise, and consistent treatment strategy.

Free bending forming (FBF) technology is widely used for manufacturing complex-shaped Ti pipes without changing the forming die. Nevertheless, the characteristics of Ti alloys, such as low ductility and high yield stress, pose challenges in achieving high-quality components at room temperature. Therefore, the hot FBF technology is used to manufacture and optimize the process parameters to produce complex-shaped TA18 pipes. Combining theoretical analysis, FE modeling, and experimentation, the forming characteristics of TA18 alloy pipes at elevated temperatures were revealed, and the process parameters were optimized. The Johnson-Cook constitutive model was established in this study and coupled with FE modeling providing accurate simulations of the hot FBF process under various conditions. The FE model of the TA18 alloy pipe was verified by comparing its results with the actual TA18 pipe trials. The hot FBF process can improve the wall thickening and cross-sectional distortion of TA18 bending components and reduce the bending radius of the pipe by weakening the dynamic rebound at the end of the bending and forming of titanium pipes. The increase in heating length is also generally conducive for forming TA18 pipe, and the component's external wall thickness reduction and cross-sectional distortion can be inhibited when the heating length is 250 mm. Moreover, the increase in axial propulsion speed improves the thickening of the inner wall thickness of the TA18 bending components but also increases the thinning of the wall thickness and the distortion of the cross-section. Finally, the process parameters were optimized, and the forming quality of the complex-shape TA18 pipe can be improved. The microstructure of the TA18 pipe hardly changes during the hot FBF process.

Abstract Background Though (1S, 3R)-RSL3 has been used widely in basic research as a small molecular inducer of ferroptosis, the toxicity on normal cells and poor pharmacokinetic properties of RSL3 limited its clinical application. Here, we investigated the synergism of non-thermal plasma (NTP) and low-concentration RSL3 and attempted to rise the sensitivity of NSCLC cells on RSL3. Methods CCK-8 assay was employed to detect the change of cell viability. Microscopy and flowcytometry were applied to identify lipid peroxidation, cell death and reactive oxygen species (ROS) level respectively. The molecular mechanism was inspected with western blot and RT-qPCR. A xenograft mice model was adopted to investigate the effect of NTP and RSL3. Results We found the synergism of NTP and low-concentration RSL3 triggered severe mitochondria damage, more cell death and rapid ferroptosis occurrence in vitro and in vivo. NTP and RSL3 synergistically induced xCT lysosomal degradation through ROS/AMPK/mTOR signaling. Furthermore, we revealed mitochondrial ROS was the main executor for ferroptosis induced by the combined treatment. Conclusion Our research shows NTP treatment promoted the toxic effect of RSL3 by inducing more ferroptosis rapidly and provided possibility of RSL3 clinical application. Graphical Abstract Video Abstract

Rationale and objectives: This study aimed to assess the feasibility and image quality of free-breathing 3D isotropic zero echo time (ZTE) whole-lung imaging and explore a clinically appropriate protocol for MR lung imaging. Materials and methods: The study was approved by the local ethics committee. A total of thirty healthy volunteers were enrolled in this study from October 2022 to May 2023. Free-breathing pulmonary 3D isotropic ZTE scans were implemented with various acquisition planes and the number of excitations (NEX). ZTE images were evaluated by two radiologists for the overall Image quality and visibility of intrapulmonary structures as well as the signal-to-noise ratio (SNR) of the lung parenchyma. ZTE images with different acquisition parameters were compared. For preliminary clinical visual assessment, three patients with interstitial lung disease underwent both ZTE imaging and computed tomography (CT). Results: The overall image quality of the lung in healthy subjects was good to excellent. The visibilities of pulmonary arteries and bronchus were up to the 7th and 5th generation, respectively. The display of lung fissures was poor. The overall image quality, the visibility of the pulmonary artery, and lung fissures in the axial acquisition were better than in the coronal acquisition (P = 0.011, 0.008, 0.010, respectively) but not statistically different from those in the sagittal acquisition (all P > 0.05). Conclusion: The free-breathing pulmonary ZTE is feasible and may serve as an alternative method in chest imaging. Either axial or sagittal ZTE image acquisition would be preferred in clinical practice.

Background: Lupus, known as a chronic multisystem autoimmune disease, has become more common in China currently. Above all, most Chinese Lupus patients haven't ample knowledge and adequate understanding of this complicated chronic disease. In recent years, social networking sites have created an interactive environment in which patients can obtain health information and also can exchange personal experiences with others having similar health concerns. Objective: The overall aim of this study is to develop a better understanding of the social support requested and received during the routine social media use of lupus activists and their referents. In other words. This paper seeks to explore whether the lupus-related posts disseminated on the Sina microblog platform can serve and satisfy the needs of this group. Methods: Content analysis and descriptive analysis were conducted to ascertain the core topics of lupus-related posts on the Sina microblog. Chi-square tests were performed to determine the differences in types of social support between provision and request groups, as well as engaged and non-engaged groups. Finally, negative binomial regression was undertaken to investigate which types of social support generated more audience engagement. Results: By analyzing 9822 lupus-related posts derived from the Sina microblog, disease description was the most prominent theme. Evidence is presented which shows that information support was requested and supplied more frequently than emotional and instrumental support. Specifically, information support was provided more than requested, while the instrumental and emotional support provisions were less numerous than the requests. Analysis revealed that posts containing information support provisions attracted more engagement than those with the other five types of social support. Conclusions: Social networking sites play a critical role on disseminating lupus-related information and provide an interactive space in which users can freely communicate their health conditions and seek peer support. However, health practitioners not only have to present more communication strategies to provide emotional and instrumental support through social media, but also have to boost audience engagement.

Summary: The swift advancement of the solid oxide fuel cell (SOFC) sector necessitates a harmony between electrode performance and commercialization cost. The economic value of elements is frequently linked to their abundance in the Earth’s crust. Here, we develop abundant rare-earth iron perovskite electrodes of Ln0.6Sr0.4FeO3-δ (Ln = La, Pr, and Nd) with high abundant rare-earth metals and preferred iron metal for SOFCs. All three symmetric electrode materials display a cubic perovskite phase and excellent chemical compatibility with Gd0.2Ce0.8O2-δ electrolyte. All three electrodes possess exceptional surface oxygen exchange ability. At 800°C, single cells with La0.6Sr0.4FeO3-δ, Pr0.6Sr0.4FeO3-δ, and Nd0.6Sr0.4FeO3-δ symmetric electrodes attained excellent open circuit voltages of 1.108, 1.101, and 1.097 V, respectively, as well as peak powers of 213.52, 281.12, and 254.58 mW cm−2. The results suggest that overall performance of abundant rare-earth iron perovskite electrodes has a favorable impact on the extensive expansion of SOFCs, presenting significant potential for practical applications.

The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a primary driver of these conditions, commencing silently at an early age and culminating in adverse cardiovascular events that severely impact patients’ quality of life or lead to fatality. Dyslipidemia, particularly elevated levels of low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in AS pathogenesis as an independent risk factor. Research indicates that abnormal LDL-C accumulation within arterial walls acts as a crucial trigger for atherosclerotic plaque formation. As the disease progresses, plaque accumulation may rupture or dislodge, resulting in thrombus formation and complete blood supply obstruction, ultimately causing myocardial infarction, cerebral infarction, and other common adverse cardiovascular events. Despite adequate pharmacologic therapy targeting LDL-C reduction, patients with cardiometabolic abnormalities remain at high risk for disease recurrence, highlighting the importance of addressing lipid risk factors beyond LDL-C. Recent attention has focused on the causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), and their remnants in AS risk. Genetic, epidemiologic, and clinical studies suggest a causal relationship between TRLs and their remnants and the increased risk of AS, and this dyslipidemia may be an independent risk factor for adverse cardiovascular events. Particularly in patients with obesity, metabolic syndrome, diabetes, and chronic kidney disease, disordered TRLs and its remnants levels significantly increase the risk of atherosclerosis and cardiovascular disease development. Accumulation of over-synthesized TRLs in plasma, impaired function of enzymes involved in TRLs lipolysis, and impaired hepatic clearance of cholesterol-rich TRLs remnants can lead to arterial deposition of TRLs and its remnants, promoting foam cell formation and arterial wall inflammation. Therefore, understanding the pathogenesis of TRLs-induced AS and targeting it therapeutically could slow or impede AS progression, thereby reducing cardiovascular disease morbidity and mortality, particularly coronary atherosclerotic heart disease.

The early Cambrian period is a critical time in Earth’s history, marked by the second oxygenation of the atmosphere (known as the Neoproterozoic Oxidation Event) and the rapid evolution of animals, as well as the worldwide large-scale deposits. Polymetallic Ni-Mo deposits have been previously reported in the black rocks at the base of the Cambrian strata on the Yangtze Block, South China, while their genesis is still controversial, and their global occurrences are uncertain. Therefore, we conduct a comprehensive analysis of trace elements and rare earth elements in the black rocks at the base of the Yurtus Formation in the Sugaitblak section (SGT) in Aksu, Tarim Block, and then make a comprehensive study by combining our and other data from the Tarim and Yangtze Block. The distribution patterns of the trace and rare earth element data from our study and another two sections in the Aksu area have shown that the black rocks in the Tarim were strongly enriched in V, Sr, Mo, Ba, and U, moderately enriched in Zn, Cu, Cr, and Pb, and slightly depleted in Ni, and Co during the early Cambrian. These enriched elements could mainly originate from the waning hydrothermal fluids, and then precipitate and preserve in sediments under anoxic environment. The comparison of trace elements in the black rocks between the Tarim and the Yangtze Block suggests that the types of enriched metal elements in these two regions were different, and metal concentrations in the Yangtze Block were much higher than those in the Tarim by 1–3 orders of magnitude. This result indicates that there are no polymetallic Ni-Mo enrichment layers in the black rocks in the Tarim during the early Cambrian, and the widespread polymetallic Ni-Mo enrichments in South China have been more likely influenced by the local hydrothermal activity. It could be further speculated that the early Cambrian period may have been an active period for seafloor hydrothermal activity, with locally different chemical components in hydrothermal fluids. Abundant metal nutrients brought by these hydrothermal activities may have been a potential factor for the rapid evolution of life during this period.

Based on the porous structure of classic simple-cubic hollow sphere (SHS) materials, two novel configurations—simple-cubic perforated hollow sphere (SPHS) and hollow ellipsoidal sphere (SHES) structures were designed by introducing perforations in sphere walls and altering the ellipsoid ratio, defined as the ratio of the major and minor axes of an ellipsoid. Using 316L stainless steel as the raw material, a series of specimens were fabricated employing additive manufacturing technology. Corresponding finite element models were established using Abaqus. Then the experimental and numerical investigations were conducted to analyze the deformation behavior of these structures subjected to quasi-static compression. Further numerical research was conducted to analyze the mechanical properties of multi-cell hollow sphere structures with varied parameters, including wall thickness, perforation diameter, and ellipsoid ratio. The results confirmed that a perforation diameter of 4 mm resulted in optimal performance for the SPHS. In comparison to the basic structure SHS with identical relative density, this configuration exhibited a 60 % higher specific yield strength. Additionally, for SHES, when the ellipsoid ratio exceeded 1 while less than 1.8, the specific yield strength demonstrated a maximum increase of 69 % ∼ 105 % and the maximum enhancement in specific energy absorption was 60 % ∼ 85 %.

Abstract Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV. Cryo-EM analyses reveal D5 to recognize a cleavage-dependent site-of-vulnerability at the trimer apex. The recognized site appears specific to GPC intermediates, with protomers lacking full cleavage between GP1 and GP2 subunits. Guinea pig immunizations with the prefusion-stabilized cleavage-intermediate LASV GPC, first as trimer and then as a nanoparticle, induce neutralizing responses, targeting multiple epitopes including that of D5; we identify a neutralizing antibody (GP23) from the immunized guinea pigs. Collectively, our findings define a prefusion-stabilized GPC trimer, reveal an apex-situated site-of-vulnerability, and demonstrate elicitation of LASV-neutralizing responses by a cleavage-intermediate LASV trimer.

In this paper, a modified bidirectional CLLC DC/DC converter is proposed to improve the efficiency in wide voltage range applications. The proposed converter adopts a LC series resonant branch parallel with the transformer, so that the equivalent inductance of the parallel branch and the equivalent transformer magnetizing inductor varies with the switching frequency. When the required gain is small and the operating frequency is high, the switch’s turn-off current and the circulating power can be reduced through the large impedance of the LC resonant circuit; When the required gain is large, the switching frequency decreases and the auxiliary branch impedance decreases to obtain a higher voltage conversion ratio. The steady state operation and characteristics of the presented converter are analyzed, a design flowchart and a design example of the modified CLLC are also presented. Furthermore, the model of modified CLLC is established and is reduced for simple analysis. A 48V/400V/800W prototype was built and the experimental results verified the correctness of the proposed converter and the feasibility of the modeling results. Compared with the traditional CLLC resonant converter, the efficiency under wide voltage range application is significantly improved.

Abstract Background The lung has a sophisticated microbiome, and respiratory illnesses are greatly influenced by the lung microbiota. Despite the fact that numerous studies have shown that lung cancer patients have a dysbiosis as compared to healthy people, more research is needed to explore the association between the microbiota dysbiosis and immune profile within the tumor microenvironment (TME). Methods In this study, we performed metagenomic sequencing of tumor and normal tissues from 61 non‐small cell lung cancer (NSCLC) patients and six patients with other lung diseases. In order to characterize the impact of the microbes in TME, the cytokine concentrations of 24 lung tumor and normal tissues were detected using a multiple cytokine panel. Results Our results showed that tumors had lower microbiota diversity than the paired normal tissues, and the microbiota of NSCLC was enriched in Proteobacteria, Firmicutes, and Actinobacteria. In addition, proinflammatory cytokines such as IL‐8, MIF, TNF‐ α, and so on, were significantly upregulated in tumor tissues. Conclusion We discovered a subset of bacteria linked to host inflammatory signaling pathways and, more precisely, to particular immune cells. We determined that lower airway microbiome dysbiosis may be linked to the disruption of the equilibrium of the immune system causing lung inflammation. The spread of lung cancer may be linked to specific bacteria.

Abstract Proton-conducting materials are essential to the emerging hydrogen economy. Covalent triazine frameworks (CTFs) are promising proton-conducting materials at high temperatures but need more effective sites to strengthen interaction for proton carriers. However, their construction and design in a concise condition are still challenges. Herein, we show a low temperature approach to synthesize CTFs via a direct cyclotrimerization of aromatic aldehyde using ammonium iodide as facile nitrogen source. Among the CTFs, the perfluorinated CTF (CTF-TF) was successfully synthesized with much lower temperature ( ≤ 160 °C) and open-air atmosphere. Due to the additional hydrogen-bonding interaction between fluorine atoms and proton carriers (H3PO4), the CTF-TF achieves a proton conductivity of 1.82 × 10−1 S cm−1 at 150 °C after H3PO4 loading. Moreover, the CTF-TF can be readily integrated into mixed matrix membranes, displaying high proton conduction abilities and good mechanical strength. This work provides an alternative strategy for rational design of proton conducting media.

Ultra-high strength steel (UHSS) pipes find widespread application in the automotive industry. To address the challenges associated with forming complex structural parts from UHSS pipes, the three-dimensional free thermal bending (3D-FTB) technology for UHSS pipes based on a robotic arm and a bending roller mold was firstly developed. A finite element simulation prediction model for accurately describing the forming process is established and discussed. In this paper, the thermal-mechanical coupling model of the material is established by Gleeble thermal tensile test and modified Arrhenius model. The effects of parameters such as current frequency, current density, axial feed rate, and quenching conditions on forming temperature and microstructure transformation are thoroughly investigated via finite element simulation analysis. The mechanical properties and potential defects of the pipe fittings after forming are analyzed and validated experimentally. The results demonstrate that the finite element simulation and analysis method based on the thermal-force coupling model of the BR1500HS UHSS pipe can accurately predict the forming process parameters. The optimal process conditions are identified as follows: current frequency of 55 kHz, current density of 650 A/mm2, and feed rate of 8 mm/s. Under these parameters, the austenite transformation rate of the pipe fittings reaches an impressive 98 % and the maximum tensile strength reaches 1540 MPa. Lastly, the overall wall thickness distortion rate of the formed pipe remains below 0.2 % and the bending rebound angle exhibits an average reduction of over 80 % compared to that under room temperature conditions.

Abstract Nuclear receptor related-1 (Nurr1), a ligand-activated transcription factor, is considered a potential susceptibility gene for Parkinson’s disease (PD), and has been demonstrated to possess protective effects against inflammation-induced neuronal damage. Despite the evidence showing decreased NURR1 level and increased pro-inflammatory cytokines in cell and animal models as well as in PD patients’ peripheral blood mononuclear cells (PBMCs), the underlying mechanism remains elusive. In this study, we investigated the molecular mechanism of Nurr1 in PD-related inflammation. Through the miRNA-sequencing and verification in PBMCs from a cohort of 450 individuals, we identified a significant change of a Nurr1-dependent miRNA miR-30e-5p in PD patients compared to healthy controls (HC). Additionally, PD patients exhibited an elevated plasma interleukin-1β (IL-1β) level and increased nucleotide-binding domain-like receptor protein 3 (NLRP3) expression in PBMCs compared to HC. Statistical analyses revealed significant correlations among NURR1, miR-30e-5p, and NLRP3 levels in the PBMCs of PD patients. To further explore the involvement of Nurr1-miR-30e-5p-NLRP3 axis in the inflammation-mediated PD pathology, we developed a mouse model (Nurr1flox+/Cd11b−cre+, Nurr1cKO) conditionally knocking out Nurr1 in Cd11b-expressing cells. Our investigations in Nurr1cKO mice unveiled significant dopaminergic neurodegeneration following lipopolysaccharide-induced inflammation. Remarkably, Nurr1 deficiency triggered microglial activation and activated NLRP3 inflammasome, resulting in increased IL-1β secretion. Coincidently, we found that miR-30e-5p level was significantly decreased in the PBMCs and primary microglia of Nurr1cKO mice compared to the controls. Furthermore, our in vitro experiments demonstrated that miR-30e-5p specifically targeted NLRP3. In Nurr1-knockdown microglia, NLRP3 expression was upregulated via miR-30e-5p. In summary, our findings highlight the involvement of Nurr1-miR-30e-5p-NLRP3 axis in the inflammation-mediated neurodegeneration in PD, the results of which may offer promising prospects for developing PD biomarkers and targeted therapeutic interventions.

This study employs the finite element method to investigate the microstructural evolution and deformation behavior of a 40Cr steel automobile front axle during the quenching process. By establishing a multi-physics field coupling model, the study elucidates the variation patterns of the microstructure field in the quenching process of the front axle under different immersion orientations. It is found that along the length direction, the bainite and martensite structures decrease from the center to the edge region, while the ferrite structure shows an increasing trend. Additionally, the influence of immersion orientation on the hardness of the front axle’s microstructure and deformation behavior is thoroughly discussed. The results indicate that, firstly, when quenched horizontally, the hardness difference among different regions of the front axle is approximately 8.2 HRC, whereas it reaches 10.3 HRC when quenched vertically. Considering the uniformity of the microstructure, the horizontal immersion method is preferable. Secondly, due to the different immersion sequences in different regions of the front axle leading to varying heat transfer rates, as well as the different amounts of martensite structures obtained in different regions, the deformation decreases along the length direction from the center to the edge region. Horizontal immersion quenching, compared to vertical immersion, results in a reduction of approximately 56.2% and 48.9% in deformation on the representative central cross-section (A-A) and the total length of the front axle, respectively. Therefore, considering aspects such as microstructure uniformity and deformation, the horizontal immersion quenching orientation is more favorable.

With the growing maturity of electric vehicles technology and the increase in environmental awareness, electric vehicles have emerged as a feasible way to reduce carbon emissions due to transportation. In response, numerous cities have adopted electric vehicles into taxi and bus fleets to increase their use. As the use of electric taxis increases, the strategic deployment of charging stations becomes crucial to ensuring taxi operations. This study aims to optimize the deployment of electric taxi charging stations, with a focus on improving service quality. A heuristic algorithm, Improved K-means iterated with Queuing Theory (IKQT), is proposed. To validate the algorithm, over 11,000 GPS tracking trajectory data from Shanghai Qiangsheng taxis in April 2018 were analyzed. The results of the study demonstrate that the IKQT algorithm can significantly increase the utilization rate of charging stations, enabling them to serve more electric taxis during peak hours and thereby improving overall service quality. Specifically, the total waiting time for all charging services was reduced by approximately 6%, while the total number of unserved taxis across all charging stations decreased by roughly 19%. These improvements underscore the novelty and practical value of the IKQT in the deployment of electric taxi charging stations.

Nypa fruticans, commonly known as the Nipa palm, belongs to the true mangrove plants of the Arecaceae family. In China, it is naturally distributed only on Hainan Island and designated as a second-class National Key Protected Wild Plants List. Field research and indoor simulation experiments were systematically employed to study the resource status of N. fruticans and the adaptation of seed germination to environmental factors. The results showed that: (1) Four natural populations of N. fruticans, approximately 9319 trees within a total area of 3.96 hm2, were distributed in Haikou, Wenchang, Qionghai, and Wanning on Hainan Island. Only the Wanning population was developed in small patches, while other populations were scattered sporadically. (2) A total of 23 mangrove species belonged to 19 genera in 13 families, which were recorded in all study sites, of which 18 were true mangroves and 5 were semi-mangrove species. The vertical structures of 4 N. fruticans communities exhibited the consistent pattern, characterized by distinct layers including the tree, shrub, and herb layers. However, notable differences in species composition and dominant species were observed among the layers of each community. (3) The population dynamics of N. fruticans in Haikou, Qionghai, and Wanning were declining, while the population in Wenchang was growing. (4) Seed germination of N. fruticans was not resistant to strong light and required some shade treatment with an optimal light intensity of 60%. The suitable salinity range for seed germination was 0‰ to 10‰. With the increase of salinity, the germination rate and seedling rate showed an increasing and then decreasing trend with maximum values of 63.3% and 50.0% at 5‰, which showed the sensitivity of seed germination to salinity, with low salinity promoting germination whereas high salinity inhibiting germination. Around 8 h/d of flooding time was most suitable for the seed germination, and 10 h/d was a critical flooding time. This study provides a theoretical basis for population recovery, resource utilization, and other further research of N. fruticans.

ObjectiveDiabetic peripheral neuropathy frequently occurs and presents severely in individuals suffering from type 2 diabetes mellitus, representing a significant complication. The objective of this research was to develop a risk nomogram for DPN, ensuring its internal validity and evaluating its capacity to predict the condition.MethodsIn this retrospective analysis, Suqian First Hospital’s cohort from January 2021 to June 2022 encompassed 397 individuals diagnosed with T2DM. A random number table method was utilized to allocate these patients into two groups for training and validation, following a 7:3 ratio. By applying univariate and multivariable logistic regression, predictive factors were refined to construct the nomogram. The model’s prediction accuracy was assessed through metrics like the ROC area, HL test, and an analysis of the calibration curve. DCA further appraised the clinical applicability of the model. Emphasis was also placed on internal validation to confirm the model’s dependability and consistency.ResultsOut of 36 evaluated clinicopathological characteristics, a set of four, duration, TBIL, TG, and DPVD, were identified as key variables for constructing the predictive nomogram. The model exhibited robust discriminatory power, evidenced by an AUC of 0.771 (95% CI: 0.714-0.828) in the training cohort and an AUC of 0.754 (95% CI: 0.663-0.845) in the validation group. The congruence of the model’s predictions with actual findings was corroborated by the calibration curve. Furthermore, DCA affirmed the clinical value of the model in predicting DPN.ConclusionThis research introduces an innovative risk nomogram designed for the prediction of diabetic peripheral neuropathy in individuals suffering from type 2 diabetes mellitus. It offers a valuable resource for healthcare professionals to pinpoint those at elevated risk of developing this complication. As a functional instrument, it stands as a viable option for the prognostication of DPN in clinical settings.

Introduction Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found.Methods/design The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35–45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases.Ethics and dissemination The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal.Trial registration number Chinese Clinical Trial Registry (ChiCTR2300072472).

Summary: Soluble ‘SOSIP’-stabilized HIV-1 envelope glycoprotein (Env) trimers elicit dominant antibody responses targeting their glycan-free base regions, potentially diminishing neutralizing responses. Previously, using a nonhuman primate model, we demonstrated that priming with fusion peptide (FP)-carrier conjugate immunogens followed by boosting with Env trimers reduced the anti-base response. Further, we demonstrated that longer immunization intervals further reduced anti-base responses and increased neutralization breadth. Here, we demonstrate that long trimer-boosting intervals, but not long FP immunization intervals, reduce the anti-base response. Additionally, we identify that FP priming before trimer immunization enhances antibody avidity to the Env trimer. We also establish that adjuvants Matrix M and Adjuplex further reduce anti-base responses and increase neutralizing titers. FP priming, long trimer-immunization interval, and an appropriate adjuvant can thus reduce anti-base antibody responses and improve Env-directed vaccine outcomes.

Abstract Fringe projection profilometry is widely used in 3D structured light due to its fast speed and accuracy. However, in the process of phase unwrapping, it is easy to cause invalid points in the edges and shadows of objects, which leads to error points in 3D reconstruction. To solve this problem, we propose an invalid points removal method based on Markov random fields. Specifically, the proposed method formulates unwrapped phase and mask maps as energy functions and uses iterative methods to minimize them. Furthermore, we validate the proposed method in a monocular structured light system and compare it with existing algorithms. Results show that the proposed method effectively identifies edges and shadows while preserving valid points, and has strong robustness and correctness.

Abstract Calorie restriction (CR) or a fasting regimen is considered one of the most potent non-pharmacological interventions to prevent chronic metabolic disorders, ameliorate autoimmune diseases, and attenuate aging. Despite efforts, the mechanisms by which CR improves health, particularly brain health, are still not fully understood. Metabolic homeostasis is vital for brain function, and a detailed metabolome atlas of the brain is essential for understanding the networks connecting different brain regions. Herein, we applied gas chromatography-mass spectrometry-based metabolomics and lipidomics, covering 797 structurally annotated metabolites, to investigate the metabolome of seven brain regions in fasted (3, 6, 12, and 24 h) and ad libitum fed mice. Using multivariate and univariate statistical techniques, we generated a metabolome atlas of mouse brain on the global metabolic signature dynamics across multiple brain regions following short-term fasting (STF). Significant metabolic differences across brain regions along with STF-triggered region-dependent metabolic remodeling were identified. We found that STF elicited triacylglycerol degradation and lipolysis to compensate for energy demand under fasting conditions. Besides, changes in amino acid profiles were observed, which may play crucial roles in the regulation of energy metabolism, neurotransmitter signaling, and anti-inflammatory and antioxidant in response to STF. Additionally, this study reported, for the first time, that STF triggers a significant elevation of N-acylethanolamines, a class of neuroprotective lipids, in the brain and liver. These findings provide novel insights into the molecular basis and mechanisms of CR and offer a comprehensive resource for further investigation.

Abstract Background Triple negative breast cancer (TNBC) is a major subtype of breast cancer, with limited therapeutic drugs in clinical. Epidermal growth factor receptor (EGFR) is reported to be overexpressed in various TNBC cells. Cantharidin is an effective ingredient in many clinical traditional Chinese medicine preparations, such as Delisheng injection, Aidi injection, Disodium cantharidinate and vitamin B6 injection. Previous studies showed that cantharidin had satisfactory pharmacological activity on a variety of tumors. In this study, we aimed to study the therapeutic potential of cantharidin for TNBC treatment by targeting EGFR, and expound its novel regulator miR-607. Methods The effect of cantharidin on breast cancer in vivo was evaluated by 4T1 mice model. Then the effects of cantharidin on TNBC cells was assessed by the MTT, colony formation, and AnnexinV-PE/7AAD staining. Cantharidin acts on EGFR were verified using the cell membrane chromatography, RT-PCR, Western blotting, MTT, and so on. Mechanistic studies were explored by dual-luciferase report assay, RT-PCR, western blotting, and immunofluorescence staining assay. Results Cantharidin inhibited TNBC cell growth and induce apoptosis by targeting EGFR. miR-607 was a novel EGFR regulator and exhibited suppressive functions on TNBC cell behaviors. Mechanistic study showed that cantharidin blocked the downstream PI3K/AKT/mTOR and ERK/MAPK signaling pathway. Conclusion Our results revealed that cantharidin may be served as a potential candidate for TNBC treatment by miR-607-mediated downregulation of EGFR. Graphical Abstract

This study presents a one-surface plasticity constitutive model combined with phenomenological and micromechanical damage models to be applied to the large plastic deformation during tube hydroforming. These factors lead to simulating the Bauschinger effect and transient behavior in large plastic strain ranges and predicting fracture onset. By using the integration approach, a numerical integration algorithm of implementation by explicit schemes was carried out. A comparison of several cyclic loading tests between experiments and numerical simulation was accomplished. The accuracy of these models is verified, which could be expanded to a large strain range forming process. Adopting the proposed models, finite element modeling is performed in the tube hydroforming process. The simulation and experimental results comparison showed that the proposed framework accurately predicted the tube formability in the hydroforming process.

Currently, research on the dynamic features of gas desorption mainly focuses on single particle size coal samples. There is less research on the dynamic features of gas desorption of mixed coal samples with different particle sizes. To solve this problem, a multi field coupled seepage desorption experimental system is used to mix coal samples with three different particle sizes (0,0.25) mm, [0.25, 0.5) mm, and [0.5, 1] mm in different proportions. Gas desorption experiments are conducted on mixed coal samples with different particle sizes. The changes in gas desorption kinetic parameters such as gas desorption amount, diffusion coefficient, and desorption attenuation coefficient are analyzed under different particle size coal sample proportions. The results indicate the following points. ① During the gas desorption process of mixed coal samples with different particle sizes, the main factor affecting the gas desorption amount in the early stage is particle size. In the later stage, the main factor affecting the gas desorption amount is the proportion of coal samples with different particle sizes. The larger the proportion of small coal particles, the greater the amount of gas desorption in the coal sample. ② The gas diffusion coefficient of mixed coal samples with different particle sizes exhibits temporal variability. As the gas desorption time increases, the gas diffusion coefficient decreases and eventually approaches 0. The initial gas diffusion coefficient decreases with the increase of the proportion of small particle coal. ③ The larger the proportion of small particle coal, the greater the attenuation coefficient of gas desorption. Therefore, in the process of underground gas content measurement, the proportion of large particle coal in the coal samples obtained should be increased as much as possible to reduce gas loss during the sampling process and improve the accuracy of gas content measurement.

Abstract While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a six-proline-stabilized WA1 (wild type, WT) spike S6P on a HBsAg core. These S6P-HBsAgs bound diverse domain-specific SARS-CoV-2 monoclonal antibodies. In mice with and without a HBV pre-vaccination, DNA immunization with S6P-HBsAgs elicited significantly more potent and durable neutralizing antibody (nAb) responses against diverse SARS-CoV-2 strains than that of soluble S2P or S6P, or full-length S2P with its coding sequence matching mRNA-1273. The nAb responses elicited by S6P-HBsAgs persisted substantially longer than by soluble S2P or S6P and appeared to be enhanced by HBsAg pre-exposure. These data show that genetic delivery of SARS-CoV-2 S6P-HBsAg nanoparticles can elicit greater and more durable nAb responses than non-nanoparticle forms of stabilized spike. Our findings highlight the potential of S6P-HBsAgs as next generation genetic vaccine candidates against SARS-CoV-2.

Abstract Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease, but the role of natriuretic peptide receptor C (NPRC) in the pathogenesis of atherosclerosis (AS) remains unknown. This study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress, inflammation, and apoptosis via protein kinase A (PKA) signaling. ApoE−/− mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice. Systemic NPRC knockout mice were crossed with ApoE−/− mice to generate ApoE−/−NPRC−/− mice, and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE−/−NPRC−/− versus ApoE−/− mice. In addition, endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in mice. In contrast, endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in mice. Experiments in vitro showed that NPRC knockdown in human aortic endothelial cells (HAECs) inhibited ROS production, pro-inflammatory cytokine expression and endothelial cell apoptosis, and increased eNOS expression. Furthermore, NPRC knockdown in HAECs suppressed macrophage migration, cytokine expression, and phagocytosis via its effects on endothelial cells. On the contrary, NPRC overexpression in endothelial cells resulted in opposite effects. Mechanistically, the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway, leading to downstream upregulated AKT1 pathway and downregulated NF-κB pathway. In conclusion, NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE−/− mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB pathways. Thus, targeting NPRC may provide a promising approach to the prevention and treatment of atherosclerosis.

The warning of the potential faults occurring in the future in a sucker rod well can help technicians adjust production strategies in time. It is of great significance for safety during well production. In this paper, the key characteristic parameters of dynamometer cards were predicted by a temporal neural network to implement the warning of different working conditions which might result in failures. First, a one-dimensional damped-wave equation was used to eliminate the dynamic loads’ effect of surface dynamometer cards by converting them into down-hole dynamometer cards. Based on the down-hole dynamometer cards, the characteristic parameters were extracted, including the load change, the position of the valve opening and closing point, the dynamometer card area, and so on. The mapping relationship between the characteristic parameters and working conditions (classification model) was obtained by the Xgboost algorithm. Meanwhile, the noise in these parameters was reduced by wavelet transformation, and the rationality of the results was verified. Second, the Encoder–Decoder and multi-head attention structures were used to set up the time series prediction model. Then, the characteristic parameters were predicted in a sequence-to-sequence way by using historical characteristic parameters, date, and pumping parameters as input. At last, by inputting the predicted results into the classification model, a working conditions warning method was created. The results showed that noise reduction improved the prediction accuracy significantly. The prediction relative error of most characteristic parameters was less than 15% after noise reduction. In most working conditions, their F1 values were more than 85%. Most Recall values could be restored to over 90% of those calculated by real parameters, indicating few false negative cases. In general, the warning method proposed in this paper can predict faulty working conditions that may occur in the future in a timely manner.

In order to investigate the infection status and genotypes of Enterocytozoon bieneusi (E. bieneusi) in sheep and goats in Jiangsu Province, a total of 786 fresh fecal samples from 18 farms across five regions in Jiangsu were collected and examined for the presence of E. bieneusi, and the genotype of E. bieneusi was examined using nested-PCR and sequencing of the ribosomal internal transcribed spacer. The results showed that E. bieneusi was detected in the fecal samples of sheep and goats in all regions, with infection rates ranging from 23.65% to 42.81%. The overall infection rate was 36.51% (287/786). The infection rate of E. bieneusi showed no significant difference between sheep and goats, as well as among different ages of animals (p > 0.05), but showed a significant difference in sheep and goats with different health conditions (p < 0.05). The positive products were amplified and cloned and subjected to sequenced analysis. Six genotypes, BEB6, CHG2, CHG3, CHC8, CHG14, and COS-I, were found. Phylogenetic analysis indicated that the six genotypes belonged to Group 2, which had previously been described as a non-zoonotic group.

Focusing on the requirements for efficient and accurate control in large-scale process industries with integrated “distributed-decentralized” characteristics, a novel hierarchical coordinated predictive control strategy for process industries is proposed with a multiagent system as the computational paradigm. This approach comprehensively considers the overall state of the system, the interactions of control actions among agents, the constraints of processes and energy consumption to solve the problems of poor flexibility of agent decision-making in the narrow consensus strategy and strong interaction of parts of the system. The proposed hierarchical control strategy requires each agent to perform three tasks at each time step. First, each agent iteratively obtains a consistent basis for closed-loop prediction in a distributed way. Then, each agent independently proposes a control scheme and determines its own priority by playing games based on the economic performance of the scheme. Next, each agent calculates its own optimal dynamic predictive control sequence in order of priority based on the system’s dynamic process model. Finally, by considering the temperature-control process of heating an alumina ceramic block in a high-power microwave reactor with six microwave sources, the effectiveness of the proposed hierarchical coordinated predictive control strategy is verified under different communication topologies by comparing it with the centralized model predictive control strategy.