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In response to the inability of the flexible DC transmission system connected to the AC grid under conventional control strategies to provide inertia to the system as well as to participate in frequency regulation, a virtual synchronous generator (VSG) control strategy is proposed for a voltage source converter (VSC)-based multi-terminal high-voltage direct current (VSC-MTDC) interconnection system. First, the virtual controller module is designed by coupling AC frequency and active power through virtual inertia control, so that the VSC-MTDC system can provide inertia response for AC grid frequency. Second, by introducing the power margin of the converter station into the droop coefficient, the unbalanced power on the DC side is reasonably allocated to reduce the overshoot of the DC voltage in the regulation process. Finally, the power regulation capability of the normal AC system is used to provide power support to the fault end system, reducing frequency deviations and enabling inter-regional resource complementation. The simulation model of the three-terminal flexible DC grid is built in PSCAD/EMTDC, and the effectiveness of the proposed control strategy is verified by comparing the conventional control strategy and the additional frequency control strategy.

Resource-rich shale gas plays a pivotal role in new energy types. The key to scientifically and efficiently developing shale gas fields is to clarify the main factors that affect the production of shale gas wells. In this paper, according to the shale gas reservoir characteristic of the Fuling marine Longmaxi Formation, a single-well geological model was established using the reservoir numerical simulation software CMG. Then, 10,000 different reservoir models were randomly generated for different formation physical parameters, completion parameters, and fracturing parameters using the Monte Carlo method, and these 10,000 models were simulated numerically. The machine learning model uses a dataset of 10,000 different geological, completion, and fracturing parameters as input and 10,000 production curves as output. Multiple machine learning regression methods were used to train and test the dataset, and the optimal method (GBDT algorithm) was selected, and the accuracy R2 of the test set of the GBDT prediction model is 0.96. A fracturing parameter optimization workflow was constructed by combining a production prediction model with a particle swarm optimizer (PSO). The process can quickly optimize the fracturing parameters and predict the production for each time by targeting the cumulative gas production under different geological conditions. The optimized parameters are Fracture Spacing, Fracture Width, Intrinsic Permeability, Fracture Half-length, Langmuir Pressure, and Langmuir Volume. The initial predicted cumulative gas production was 4.59 × 108 m3, which was optimized to 4.90 × 108 m3. The proposed PSO-GBDT proxy model can instantly predict the production of shale gas wells with considerable accuracy, reliability, and efficiency, which is a vital tool for optimizing fracture design. This investigation provides a solid foundation for predicting the production of unconventional gas reservoirs and for parameter optimization.

Abstract The identification of effective drug targets and the development of bioactive molecules are areas of high need in cancer therapy. The phosphatidylinositol transfer protein alpha/beta isoform (PITPα/β) has been reported to play an essential role in integrating phosphoinositide trafficking and lipid metabolism in diverse cellular processes but remains unexplored as a potential target for cancer treatment. Herein, data analysis of clinical cancer samples revealed that PITPα/β expression is closely correlated with the poor prognosis. Target identification by chemical proteomic methods revealed that microcolin H, a naturally occurring marine lipopeptide, directly binds PITPα/β and displays antiproliferative activity on different types of tumour cell lines. Furthermore, we identified that microcolin H treatment increased the conversion of LC3I to LC3II, accompanied by a reduction of the level of p62 in cancer cells, leading to autophagic cell death. Moreover, microcolin H showed preeminent antitumour efficacy in nude mouse subcutaneous tumour models with low toxicity. Our discoveries revealed that by targeting PITPα/β, microcolin H induced autophagic cell death in tumours with efficient anti-proliferating activity, which sheds light on PITPα/β as a promising therapeutic target for cancer treatment.

Abstract Objectives Vascular stiffening is highly predictive of major adverse cardiovascular events. It is not clear whether microangiopathy, such as fundus arteriosclerosis, is related to carotid atherosclerosis. Hence, this study was designed to investigate the relationship between carotid atherosclerosis and fundus arteriosclerosis among individuals of different sexes in the Chinese health-examination population. Methods This retrospective cross-sectional study involved 20,836 participants, including 13050 males and 7786 females. All participants underwent a detailed health examination, including medical history assessment, physical examination, assessment of lifestyle factors, fundus photography, Doppler ultrasound examination of the neck, and laboratory examinations. Two trained ophthalmologists analysed fundus arteriosclerosis based on fundus photographs, while carotid atherosclerosis was diagnosed using colour Doppler sonography of the neck. Binary logistic regression was used to analyse the relationship between carotid atherosclerosis and fundus arteriosclerosis. Results In participants with fundus arteriosclerosis, the incidence of carotid atherosclerosis was higher than that of participants without fundus arteriosclerosis (52.94% vs. 47.06%). After adjustments for potential confounding factors, fundus arteriosclerosis was significantly associated with the risk of carotid atherosclerosis. The OR with 95% CI for fundus arteriosclerosis was 1.17 (1.02, 1.34) with p = 0.0262, and individuals who did not have fundus arteriosclerosis were used as a reference in the total population. Fundus arteriosclerosis was associated with the incidence of carotid atherosclerosis in males (p = 0.0005) but not in females (p = 0.0746). Conclusions Fundus arteriosclerosis was closely associated with carotid atherosclerosis in the Chinese population. This association was found in males but not in females.

Abstract Background Meningiomas are common primary brain tumours, with macrophages playing a crucial role in their development and progression. This study aims to identify module genes correlated with meningioma‐associated macrophages and analyse their correlation with clinical features and immune infiltration. Methods We analysed single‐cell RNA sequencing (scRNA‐seq) data from two paired meningioma and normal meninges to identify meningioma‐associated macrophages. High‐dimensional weighted gene co‐expression network analysis (hdWGCNA) was employed to identify module genes linked to these macrophages, followed by functional enrichment and pseudotime trajectory analyses. A machine learning‐based model using the module genes was developed to predict tumour grades. Finally, meningiomas were classified into two molecular subtypes based on the module genes, followed by a comparison of clinical characteristics and immune cell infiltration. Results Meningiomas exhibited a significantly higher proportion of macrophages than normal meninges, including novel macrophage clusters referred to as meningioma‐associated macrophages. The hdWGCNA analysis of macrophages within meningiomas unveiled 12 distinct modules, with the blue, black, and turquoise modules closely correlated with the meningioma‐associated macrophages. Hub genes within these modules were enriched in immune regulation, cellular communication, and metabolism pathways. Machine learning analysis identified 13 module genes (RSBN1, TIPRL, ATIC, SPP1, MALSU1, CDK1, MGP, DDIT3, SUPT16H, NFKBIA, SRSF5, ATXN2L, and UBB) strongly correlated with meningioma grade and constructed a predictive model with high accuracy and robustness. Based on the module genes, meningiomas were classified into two subtypes with distinct clinical and tumour microenvironment characteristics. Conclusions Our findings provide insights into the molecular characteristics underlying macrophage infiltration in meningiomas. The molecular signatures of macrophages demonstrate correlations with clinical features and immune cell infiltration in meningiomas.

Abstract Background The original weight loss grading system (WLGS) was developed in western population, which did not perform effectively in cancer patients from China. This study aimed to develop and validate the modified WLGS (mWLGS) in the prognostic assessment of cancer patients in China. Methods A prospective multicentre real‐world cohort study involving 16 842 patients diagnosed with cancer was conducted. Cox regression was used to calculate the hazard ratios for overall survival. Logistic linear regression was used to assess the odds ratio for 90‐day outcomes. Results We calculated survival risks for the 25 mWLGS groups and clustered the approximate survival risks. Finally, we revised the prognostic grading system for mWLGS to include five grades of 0–4. Compared with the original WLGS, the mWLGS had a better prognostic differentiation effect in predicting the prognosis of patients with cancer. The survival rate gradually deteriorated with increasing grade of mWLGS, with the survival rate of grade 0 decreasing from 76.4% to 48.2% for grade 4 (76.4 vs. 72.8 vs. 66.1 vs. 57.0 vs. 48.2%, respectively). The mWLGS provides effective prognostic stratification for most site‐specific cancers, especially lung and gastrointestinal cancers. High‐grade mWLGS is independently associated with an increased risk of poor quality of life and adverse 90‐day outcomes. Multivariate Cox regression analysis showed that the mWLGS was an independent prognostic factor for cancer patients in the validation cohorts. Conclusions Compared with the original WLGS, the mWLGS can better stratify the prognosis of cancer patients. mWLGS is a useful tool for predicting survival, 90‐day outcomes, and quality of life in patients with cancer. These analyses may provide new insights into the application of WLGS in cancer patients in China.

It is discovered that activated caspase-3 tends to induce apoptosis in gasdermin E (GSDME)-deficient cells, but pyroptosis in GSDME-sufficient cells. The high GSDME expression and apoptosis resistance of pancreatic ductal adenocarcinoma (PDAC) cells shed light on another attractive strategy for PDAC treatment by promoting pyroptosis. Here we report a hGLuc-hGSDME-PCA system for high-throughput screening of potential GSDME activators against PDAC. This screening system neatly quantifies the oligomerization of GSDME-N to characterize whether pyroptosis occurs under the stimulation of chemotherapy drugs. Based on this system, ponatinib and perifosine are screened out from the FDA-approved anti-cancer drug library containing 106 compounds. Concretely, they exhibit the most potent luminescent activity and cause drastic pyroptosis in PDAC cells. Further, we demonstrate that perifosine suppresses pancreatic cancer by promoting pyroptosis via caspase-3/GSDME pathway both in vitro and in vivo. Collectively, this study reveals the great significance of hGLuc-hGSDME-PCA in identifying compounds triggering GSDME-dependent pyroptosis and developing promising therapeutic agents for PDAC.

Cytokinins (CKs) are a group of phytohormones that are involved in plant growth, development, and disease resistance. The isopentenyl transferase (IPT) and cytokinin oxidase/dehydrogenase (CKX) families comprise key enzymes controlling CK biosynthesis and degradation. However, an integrated analysis of these two gene families in radish has not yet been explored. In this study, 13 RsIPT and 12 RsCKX genes were identified and characterized, most of which had four copies in Brassica napus and two copies in radish and other diploid Brassica species. Promoter analysis indicated that the genes contained at least one phytohormone or defense and stress responsiveness cis-acting element. RsIPTs and RsCKXs were expanded through segmental duplication. Moreover, strong purifying selection drove the evolution of the two gene families. The expression of the RsIPT and RsCKX genes distinctly showed diversity in different tissues and developmental stages of the root. Expression profiling showed that RsCKX1-1/1-2/1-3 was significantly upregulated in club-resistant materials during primary infection, suggesting their vital function in clubroot resistance. The interaction network of CKX proteins with similar 3D structures also reflected the important role of RsCKX genes in disease resistance. This study provides a foundation for further functional study on the IPT and CKX genes for clubroot resistance improvement in Raphanus.

Existing research in the shipbuilding field tends to focus on isolated single aspects of Industry 4.0 (I4.0) without a full picture. To address this gap, this paper seeks to offer a thorough and in-depth examination of the concepts and technologies necessary to integrate I4.0 into the design, construction, maintenance, and other stages throughout the entire life cycle of a ship. This paper will firstly examine the recent developments and identify the gaps in I4.0 application within shipbuilding. By conducting a systematic literature review on 68 publications through an appropriate review methodology, we synthesize the current state of I4.0 research in the shipbuilding industry, propose a framework for the application of I4.0 in shipbuilding to analyze the progression and research agenda of I4.0 in the shipbuilding sector, and discuss its implications. The Shipbuilding 4.0 framework proposed comprises five main components: concepts, value chain, smart factory, smart manufacturing, infrastructure, and technologies. The proposed framework aims to enhance the understanding of both academics and practitioners regarding the specific needs of the shipbuilding industry and the role I4.0 can and should play in its advancement.

With increasing research, the sirtuin (SIRT) protein family has become increasingly understood. Studies have demonstrated that SIRTs can aid in metabolism and affect various physiological processes, such as atherosclerosis, heart failure (HF), hypertension, type 2 diabetes, and other related disorders. Although the pathogenesis of HF with preserved ejection fraction (HFpEF) has not yet been clarified, SIRTs have a role in its development. Therefore, SIRTs may offer a fresh approach to the diagnosis, treatment, and prevention of HFpEF as a novel therapeutic intervention target.

Valorization of food processing effluent (FPE) by microalgae cultivation for astaxanthin production is regarded as a potential strategy to solve the environmental pollution of food processing industry and promote the development of eco-friendly agriculture. In this review paper, microalgal species which have the potential to be employed for astaxanthin in FPE were identified. Additionally, in terms of CO2 emission, the performances of microalgae cultivation and traditional methods for FPE remediation were compared. Thirdly, an in-depth discussion of some innovative technologies, which may be employed to lower the total cost, improve the nutrient profile of FPE, and enhance the astaxanthin synthesis, was provided. Finally, specific effects of dietary supplementation of algal astaxanthin on the growth rate, immune response, and pigmentation of animals were discussed. Based on the discussion of this work, the cultivation of microalgae in FPE for astaxanthin production is a value-adding process which can bring environmental benefits and ecological benefits to the food processing industry and agriculture. Particularly, technological innovations in recent years are promoting the shift of this new idea from academic research to practical application. In the coming future, with the reduction of the total cost of algal astaxanthin, policy support from the governments, and further improvement of the innovative technologies, the concept of growing microalgae in FPE for astaxanthin will be more applicable in the industry.

This study evaluates the value of ecological products in the Yellow River Basin, China within the “Two Mountains” theory framework prioritizing ecological conservation and quality growth. Major basin cities were analyzed to quantify ecological product value flows from 2011 to 2020 using an entropy approach assessing rural dynamics, financing, governance, manufacturing, and economic structuring. Entropy valuations of datasets from 38 basin municipalities showed aggregated ecological product values increased from ¥5.73 trillion in 2011 to ¥6.54 trillion in 2020. Spatial disparities were observed with mid-upper basin regions exhibiting significantly higher valuations than lower basinal areas. The novel entropy valuation methodology provides localized quantification of ecological product values aligned with China's sustainability initiatives. The multivariate panel regression model shows that while rural development and agricultural fiscal support negatively impact ecological product value, environmental regulation and advanced industrial structures have a strong positive influence. Furthermore, quantile regression analysis reveals heterogeneities in the distribution of explanatory variables across different quantiles of ecological product value. This offers a comprehensive view of the various factors and dynamics influencing ecological product values in the Yellow River Basin. The study concludes by emphasizing the importance of balancing ecological value realization with economic growth, particularly in coastal cities of the Basin. These findings provide valuable insights for optimizing ecological value and advancing environmental protection and high-quality development in the Yellow River Basin.

In this paper, the objective was to evaluated the impact of germination of chickpea cultivars (Muying1, Y2-514 and YZ-364) on the bioactivity, volatiles and functional properties. The results showed that the Vitamin C content of Muying1, Y2-514 and YZ-364 after germination significantly increased (p

A recently developed Integral Suspension Pressure (ISP) sedimentation-based particle size analysis technique was tested as an alternative to the hydrometer method. The ISP method determines the particle size distribution using an electronic device, namely the PARIO meter. The PARIO meter provides an alternative to collecting manual readings with the hydrometer, by automatically recording differences in suspension pressure during a settling period of up to 24 h at a depth of 18 cm below the surface of the test suspension. The particle size distribution of the samples is then determined by inverse modeling the recorded pressure data. The objective of this study was to validate the accuracy of the ISP method compared to the hydrometer method using a number of soil mixtures manufactured from materials with known particle size composition. Nine soil mixtures with known reference values were analysed by the hydrometer and ISP methods. Statistical comparison of the results revealed that both measurement methods overestimated clay content and underestimated silt content, the hydrometer method providing more accurate results compared to the ISP method. Thirty-eight mixtures of soil were tested using the ISP method to further validate the accuracy. The results indicated that the accuracy of the ISP method depends on the mass of clay-sized particles and the species composition of the clay minerals in suspension. The ISP method obtained more accurate results for soil mixtures containing expandable clay minerals than to those containing non-expandable clays.

Background: Currently, there is no recommended standard third-line chemotherapy for metastatic gastric cancer. Objectives: In this study, we aimed to evaluate irinotecan’s efficacy and safety in treating metastatic gastric cancer after the failure of first- and second-line chemotherapy. Design: Prospective single-arm, two-center, phase II trial. Methods: Patients were aged 18–70 years, with histologically confirmed gastric adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0–1, progressed during or within 3 months following the last administration of second-line chemotherapy and had no other severe hematologic, cardiac, pulmonary, hepatic, or renal functional abnormalities or immunodeficiency diseases. Eligible patients received 28-day cycles of irinotecan (180 mg/m 2 intravenously, days 1 and 15) and were assessed according to the RECIST 1.1 criteria every two cycles. Patients who discontinued treatment for any reason were followed up every 2 months until death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results: A total of 98 eligible patients were enrolled in this study. In the intention-to-treat population, the median OS was 7.17 months, the median PFS was 3.47 months, and the ORR and DCR were 4.08% and 47.96%, respectively. In the per-protocol population, the median OS was 7.77 months, the median PFS was 3.47 months, and the ORR and DCR were 4.82% and 50.60%, respectively. The incidence of grade 3 or 4 hematological and non-hematological toxicities was 19.4%, and none of the patients died owing to adverse events. Cox regression analysis revealed neutropenia and baseline thrombocyte levels were independently correlated with PFS and OS. Conclusion: Irinotecan monotherapy is an efficient, well-tolerated, and economical third-line treatment for patients with metastatic gastric cancer as a third-line treatment. Trial registration: ClinicalTrials.gov identifier: NCT02662959.

Droop control is widely used in multi-terminal flexible DC (VSC-MTDC) transmission systems by virtue of the advantage of multi-station cooperative unbalanced power dissipation, however, the essence of the droop control strategy is to change the DC current to realize the unbalanced power dissipation, and the resulting DC voltage deviation will affect the normal operation of the system. Firstly, this paper theoretically analyses the working characteristics of the conventional droop control and proposes a control method to realize the quasi-differential-free regulation of DC voltage by translating the droop curve. Second, according to the power margin of the converter station, the feedforward compensation amount of each converter station is reasonably set to avoid the power impact on the converter station. Finally, for the problem that the actual value of DC voltage still deviates from the rated value, a control strategy containing secondary regulation of DC voltage is proposed to further restore the DC voltage to the initial value on the basis of ensuring the effect of power regulation, which improves the stability of the operation of the VSC-MTDC system. The final simulation results verify the effectiveness of the proposed method.

Abstract The photothermal conversion capacity of pristine organic phase change materials (PCMs) is inherently insufficient in solar energy utilization. To upgrade their photothermal conversion capacity, we developed bimetallic zeolitic imidazolate framework (ZIF) derived Co/N co‐doped flower‐like carbon (Co/N‐FLC)‐based composite PCMs toward solar energy harvesting. 3D interconnected carbon framework with low interfacial thermal resistance, abundant carbon defects and high content of nitrogen doping, excellent localized surface plasmon resonance (LSPR) effect of Co nanoparticles, and light absorber Co3ZnC in Co/N‐FLC synergistically upgrade the photothermal capacity of (polyethylene glycol) PEG@Co/N‐FLC composite PCMs with an ultrahigh photothermal conversion efficiency of 94.8% under 0.16 W/cm2. Uniformly anchored Co and Co3ZnC nanoparticles in carbon framework guarantee excellent photon capture ability. Bridging carbon nanotubes (CNTs) in 2D carbon nanosheets further accelerate the rapid transport of phonons by constructing cross‐connected heat transfer paths. Additionally, PEG@Co/N‐FLC exhibits a thermal energy storage density of 100.69 J/g and excellent thermal stability and durable reliability. Therefore, PEG@Co/N‐FLC composite PCMs are promising candidates to accelerate the efficient utilization of solar energy.

Jieyu Anshen Granules (JY) is a traditional Chinese medicine formula commonly used as an adjuvant treatment for Alzheimer's disease (AD) complicated with depression. However, the specific underlying mechanisms and therapeutic targets of JY remain unclear. We used the TCMSP, TCMID, BATMAN-TCM, and other databases to screen the components and assumed targets of JY. Next, the GEO and DisGeNET databases were used to identify the related targets of both AD and Major Depressive Disorder (MDD). Enrichment analyses of core targets were performed, and the main components and core targets of JY for the comorbidity of AD and MDD were identified via protein–protein interaction (PPI) network construction and machine learning algorithms. Lastly, we verified binding affinity using the AutoDock software and molecular docking was performed. A total of 171 components were identified from JY, and 979 targets were obtained from the screening process. Bioinformatics analysis displayed 397 differentially expressed genes (DEGs) were shared by AD and MDD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis revealed significant enrichment of genes associated with neurotransmitter receptor activity, G protein-coupled amine receptor activity, as well as signaling pathways such as the cAMP signaling pathway, PI3K-Akt signaling pathway, and cholinergic synapses. Through the PPI network and machine learning, we identified three hub genes (Ataxia telangiectasia-mutated gene [ATM], Colony stimulating factor 1 receptor [CSF1R], EPH receptor B2 [EPHB2]) as potential therapeutic targets. Molecular docking confirmed that the components of JY (Mairin, Hederagenin, 3-Epioleanolic Acid) could effectively bind to multiple key targets. This study revealed the effective components and potential mechanisms associated with JY treatment regarding AD and MDD comorbidities, offering valuable insights into promising therapeutic targets for subsequent studies.

BackgroundThe novel International Association for the Study of Lung Cancer (IASLC) grading system suggests that poorly differentiated invasive pulmonary adenocarcinoma (IPA) has a worse prognosis. Therefore, prediction of poorly differentiated IPA before treatment can provide an essential reference for therapeutic modality and personalized follow-up strategy. This study intended to train a nomogram based on CT intratumoral and peritumoral radiomics features combined with clinical semantic features, which predicted poorly differentiated IPA and was tested in independent data cohorts regarding models’ generalization ability.MethodsWe retrospectively recruited 480 patients with IPA appearing as subsolid or solid lesions, confirmed by surgical pathology from two medical centers and collected their CT images and clinical information. Patients from the first center (n =363) were randomly assigned to the development cohort (n = 254) and internal testing cohort (n = 109) in a 7:3 ratio; patients (n = 117) from the second center served as the external testing cohort. Feature selection was performed by univariate analysis, multivariate analysis, Spearman correlation analysis, minimum redundancy maximum relevance, and least absolute shrinkage and selection operator. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the model performance.ResultsThe AUCs of the combined model based on intratumoral and peritumoral radiomics signatures in internal testing cohort and external testing cohort were 0.906 and 0.886, respectively. The AUCs of the nomogram that integrated clinical semantic features and combined radiomics signatures in internal testing cohort and external testing cohort were 0.921 and 0.887, respectively. The Delong test showed that the AUCs of the nomogram were significantly higher than that of the clinical semantic model in both the internal testing cohort(0.921 vs 0.789, p< 0.05) and external testing cohort(0.887 vs 0.829, p< 0.05).ConclusionThe nomogram based on CT intratumoral and peritumoral radiomics signatures with clinical semantic features has the potential to predict poorly differentiated IPA manifesting as subsolid or solid lesions preoperatively.

Objective: Paclitaxel (P) is a standard second-line chemotherapy in the treatment of advanced gastric cancer. This study compared the clinical outcome of a paclitaxel plus raltitrexed (RP) regimen as second-line treatment in metastatic gastric cancer (MGC) patients. Methods: An open, randomized, multi-center phase II clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP [raltitrexed (3 mg/m2 on day 1) and paclitaxel (135 mg/m2 on day 1 every 3 weeks)] or P [paclitaxel (135 mg/m2 on day 1 every 3 weeks)] as 2nd-line chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the overall response rate (ORR), overall survival (OS), and safety. Results: PFS had a tendency to be prolonged with RP compared to P (2.7 months vs. 1.7 months; P = 0.148). OS was also prolonged with RP compared to P (10.2 months vs. 6.1 months; P = 0.140). The ORR was equal in the RP and P groups (6.8% and 4.0%; P = 0.72). The disease control rate (DCR) in the RP and P groups was 56.2% and 36.0%, respectively. Grade 3-4 treatment-related adverse events occurred in 36.2% (RP) and 28.2% (P) of patients. Frequent grade 3-4 toxicities for RP and P were neutropenia (11.0% and 4.0%), anemia (1.4% and 4.0%), and thrombocytopenia (1.4% and 5.3%), and all grades of peripheral neurotoxicity (12.3% vs. 17.3%). All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels (27.4% and 14.1%). Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement, the OS of the RP regimen was longer (P = 0.05). Conclusions: Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS, especially among patients with ascites or peritoneal involvement, which warrants confirmation using larger sample studies.

Abstract Background Solid papillary carcinoma (SPC) is a rare breast papillary tumor variant. The main histological features of SPC consist of neoplastic cell-rich nodules with thin fibrovascular cores, often accompanied by mucous secretion and neuroendocrine differentiation. Infiltrative solid papillary carcinoma (ISPC) tumor cells have an invasive, map-like growth pattern with serrated irregular growth. Due to its unique clinicopathological features, SPC is classified as two pathological tissue types based on the 2019 WHO classification of breast tumors: SPC in situ and ISPC. Case presentation We report a case of a 55-year-old female patient who was admitted to the hospital due to a painless left breast mass that had persisted for two years. Mammography suggested a mass in the left upper outer quadrant (BI-RADS 4B), and ultrasound of the breast demonstrated a cystic mass of the left breast (US_BI_RADS 4 C) with multiple enlarged lymph nodes in the left axilla. Postoperative pathology revealed ISPC with one lymph node metastasis in the left breast. Modified radical mastectomy was performed on the left breast. Subsequently, the patient received letrozole endocrine therapy, epirubicin hydrochloride and cyclophosphamide chemotherapy, and radiotherapy of the left chest wall and left upper and lower clavicular regions. After 17 months of follow-up, there was no evidence of recurrence or distant metastasis. Conclusions SPC is a group of heterogeneous tumors. SPC in situ has a good prognosis. In contrast, ISPC has a unique histological morphology and growth pattern with invasive biological behavior that can lead to lymph node and distant metastases.

Abstract Purpose Metastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established. Materials and Methods We retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022. Results Overall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p

Abstract Background Melanoma frequently harbors BRAF, NRAS, or KIT mutations which influence both tumor development and treatment strategies. For example, it is still controversial whether adjuvant anti‐PD‐1 monotherapy or BRAF/MEK inhibitors may better improve the survival for resected BRAF‐mutant melanoma. Furthermore, outcomes for melanoma with NRAS and KIT mutation receiving adjuvant immunotherapy remain unclear. Methods One hundred seventy‐four stage III melanoma patients who underwent radical surgery in Fudan University Shanghai Cancer Center (FUSCC) during January 2017 to December 2021 were included in this real‐world study. Patients were followed up until death or May 30th, 2022. Pearson's chi‐squared test or Fisher's exact test was performed for univariable analysis of the different category groups. Log‐rank analysis was used to identify the prognostic factors for disease‐free survival (DFS). Results There were 41 (23.6%) patients with BRAF mutation, 31 (17.8%) with NRAS mutation, 17 (9.8%) with KIT mutation, and 85 (48.9%) wild‐type patients without either genomic alteration of those three genes. Most ( n = 118, 67.8%) of them were acral melanoma, while 45 (25.9%) were cutaneous subtype, and 11 were (6.3%) primary unknown. Among them, 115 (66.1%) patients received pembrolizumab or toripalimab monotherapy as adjuvant therapy; 22 (12.6%) patients received high‐dose interferon (IFN), and 37 (21.3%) patients were just for observation. There was no statistical difference in clinicopathologic factors between anti‐PD‐1 group and IFN/OBS group. Of all the enrolled patients, anti‐PD‐1 group had a better DFS than IFN/OBS group ( p = 0.039). In anti‐PD‐1 group, patients with BRAF or NRAS mutations had poorer DFS than wild‐type group. No survival difference was found among patients harboring different gene mutations in IFN/OBS group. In wild‐type patients, anti‐PD‐1 group had a better DFS than IFN/OBS group ( p = 0.003), while no survival benefits were found for patients with BRAF, NRAS, or KIT mutations. Conclusion Although anti‐PD‐1 adjuvant therapy provides a better DFS in the general population and in wild‐type patients, patients with BRAF, KIT or, especially, NRAS mutation may not benefit further from immunotherapy than conventional IFN treatment or observation.

Abstract The precision of the weak equivalence principle (WEP) test using atom interferometers (AIs) is expected to be extremely high in microgravity environment. The microgravity scientific laboratory cabinet (MSLC) in the China Space Station (CSS) can provide a higher-level microgravity than the CSS itself, which provides a good experimental environment for scientific experiments that require high microgravity. We designed and realized a payload of a dual-species cold rubidium atom interferometer. The payload is highly integrated and has a size of $$460\,{\rm{mm}}\times 330\,{\rm{mm}}\times 260\,{\rm{mm}}$$ 460 mm × 330 mm × 260 mm . It will be installed in the MSLC to carry out high-precision WEP test experiment. In this article, we introduce the constraints and guidelines of the payload design, the compositions and functions of the scientific payload, the expected test precision in space, and some results of the ground test experiments.

Abstract Reliable and comparable estimates of biodiversity are the foundation for understanding ecological systems and informing policy and decision‐making, especially in an era of massive anthropogenic impacts on biodiversity. Environmental DNA (eDNA) metabarcoding is at the forefront of technological advances in biodiversity monitoring, and the last few years have seen major progress and solutions to technical challenges from the laboratory to bioinformatics. Water eDNA has been shown to allow the fast and efficient recovery of biodiversity signals, but the rapid pace of technological development has meant that some important principles regarding sampling design, which are well established in traditional biodiversity inventories, have been neglected. Using a spatially explicit river flow model, we illustrate how sampling must be adjusted to the size of the watercourse to increase the quality of the biodiversity signal recovered. We additionally investigate the effect of sampling parameters (volume, number of sites, sequencing depth) on detection probability in an empirical data set. Based on traditional sampling principles, we propose that aquatic eDNA sampling replication and volume must be scaled to match the organisms' and ecosystems' properties to provide reliable biodiversity estimates. We present a generalizable conceptual equation describing sampling features as a function of the size of the ecosystem monitored, the abundance of target organisms, and the properties of the sequencing procedure. The aim of this formalization is to enhance the standardization of critical steps in the design of biodiversity inventory studies using eDNA. More robust sampling standards will generate more comparable biodiversity data from eDNA, which is necessary for the method's long‐term plausibility and comparability.

Abstract Training a deep-learning text classification model usually requires a large amount of labeled data, yet labeling data are usually labor-intensive and time-consuming. Few-shot text classification focuses on predicting unknown samples using only a few labeled samples. Recently, metric-based meta-learning methods have achieved promising results in few-shot text classification. They use episodic training in labeled samples to enhance the model’s generalization ability. However, existing models only focus on learning from a few labeled samples but neglect to learn from a large number of unlabeled samples. In this paper, we exploit the knowledge learned by the model in unlabeled samples to improve the generalization performance of the meta-network. Specifically, we introduce a novel knowledge distillation method that expands and enriches the meta-learning representation with self-supervised information. Meanwhile, we design a graph aggregation method that efficiently interacts the query set information with the support set information in each task and outputs a more discriminative representation. We conducted experiments on three public few-shot text classification datasets. The experimental results show that our model performs better than the state-of-the-art models in 5-way 1-shot and 5-way 5-shot cases.

Subspace clustering algorithms have demonstrated remarkable success across diverse fields, including object segmentation, gene clustering, and recommendation systems. However, they often face challenges, such as omitting cluster information and the neglect of higher-order neighbor relationships within the data. To address these issues, a novel subspace clustering method named Markov-Embedded Affinity Learning with Connectivity Constraints for Subspace Clustering is proposed. This method seamlessly embeds Markov transition probability information into the self-expression, leveraging a fine-grained neighbor matrix to uncover latent data structures. This matrix preserves crucial high-order local information and complementary details, ensuring a comprehensive understanding of the data. To effectively handle complex nonlinear relationships, the method learns the underlying manifold structure from a cross-order local neighbor graph. Additionally, connectivity constraints are applied to the affinity matrix, enhancing the group structure and further improving the clustering performance. Extensive experiments demonstrate the superiority of this novel method over baseline approaches, validating its effectiveness and practical utility.

Abstract Introduction Acute postoperative pain is a major concern among surgical patients. Thus, this study established a new acute pain management model and compared the effects of the acute pain service (APS) model in 2020 and the virtual pain unit (VPU) model in 2021 on postoperative analgesia quality. Methods This retrospective, single-center clinical study involved 21,281 patients from 2020 to 2021. First, the patients were grouped on the basis of their pain management model (APS and VPU). The incidence of moderate to severe postoperative pain (MSPP) [numeric rating scale (NRS) score ≥ 5], postoperative nausea and vomiting (PONV), and postoperative dizziness were recorded. Results The VPU group recorded significantly lower MSPP incidence (1–12 months), PONV, and postoperative dizziness (1–10 months and 12 months) compared with the APS group. In addition, the annual average incidence of MSPP, PONV, and postoperative dizziness in the VPU group was significantly lower than in the APS group. Conclusions The VPU model reduces the incidence of moderate to severe postoperative pain, nausea, vomiting, and dizziness; hence, it is a promising acute pain management model.

Abstract Introduction Intracerebral hemorrhage is a high-risk pathological event that is associated with formidable morality rates. Here, our objective was to perform a retrospective study to determine the best timing for drainage using physiological data on patients who received drainage at different timings. Methods In this retrospective study, we reviewed 198 patients with hypertensive cerebral hemorrhage who underwent stereotactic drainage at the conventional timing (surgery within 12 h of admission; control group) and 216 patients who underwent stereotactic drainage at a customized surgical timing (elective group). Follow-ups were performed at 3 and 6 months after surgery. Results The clinical indicators, including prognosis, hematoma clearance, recurrent hemorrhage, intracerebral infection, pulmonary infection, deep venous thrombosis, gastrointestinal hemorrhage, National Institutes of Health Stroke Scale scores, and matrix metallopeptidase 2 and 9 levels, were compared between the control and elective groups. Our data indicated that the elective group had significantly better prognosis compared to the control group (p = 0.021), with a higher rate of hematoma clearance (p = 0.004) and a lower rate of recurrent hemorrhage (p = 0.018). The total occurrence rate of post-surgery complications was also lower for the elective group (p = 0.026). NIHSS scores and serum MMP2/9 levels of the elective group were lower than those of the control group. Conclusions Customized timing of stereotactic drainage may be superior to conventional fixed timing (within 12 h post-hemorrhage) in reducing post-surgery complications and promoting recovery, which supports the potential use of customized timing of stereotactic minimally invasive drainage as a new convention in clinics.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3–MDM2–SLUG–SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

Abstract Background Hyaluronic acid (HA) injection has become a burgeoning method to treat premature ejaculation (PE) due to its high biocompatibility and structural properties. Purpose In this study, we proposed a modified technique: injecting hyaluronic acid around coronal sulcus to treat PE, aiming to decrease the complications of hyaluronic acid injection in penis while achieving similar effects. Method A total of 85 patients who had HA injection from January 2018 to December 2019 were analyzed retrospectively in our study. 31 patients received injection at glans penis and 54 patients received injection around coronal sulcus. Intravaginal ejaculation latency time (IELT) was mainly measured to estimate the efficacy and the severity of complications was assessed between two groups. Results The mean IELT was 123.0 ± 37.28 s of all patients, 124.7 ± 39.01 s of patients injecting at glans penis and 121.9 ± 36.58 s of patients injecting around coronal sulcus. IELT of all patients increased to 482.1 ± 121.7 s at 1 month, 331.2 ± 81.2 s at 3 month and 280 ± 80.4 s at 6 month. In the group of injecting at glans penis, the incidence of complications is 25.8% and it is 1.9% in the group of injecting around coronal sulcus. No severe complication was reported in both groups. Conclusion The modified technique of injecting around coronal sulcus decreases complications and it has the potential to become a new injectable technique for treating premature ejaculation.

Abstract Background Systemic inflammation, the most representative tumour–host interaction, plays a crucial role in disease progression and prognosis in patients with non‐small cell lung cancer (NSCLC). Few studies have compared the performance of existing haematological systemic inflammation biomarkers in predicting the prognosis of NSCLC patients. The purpose of this study was to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with NSCLC through a multicentre prospective study. Methods The predictive accuracy of systemic inflammation biomarkers for prognostic assessment in NSCLC was assessed using C‐statistics. Inter‐group differences in survival were assessed using the log‐rank test and visualized using the Kaplan–Meier method. A restricted cubic spline (RCS) curve was used to explore the association between the biomarkers and survival. Independent prognostic biomarkers for overall survival were determined using multivariable Cox proportional hazards regression analysis. Logistic regression analysis was used to determine independent predictors of 90‐day outcomes, length of hospitalization, hospitalization expenses and cachexia. Results The inflammatory burden index (IBI) had the highest C‐statistic for predicting the prognosis of patients with NSCLC, reaching 0.640 (0.617, 0.663). Patients with a high IBI had significantly worse outcomes than those with a low IBI (35.46% vs. 57.22%; log‐rank P

In order to study the effects of stress change and adaptability of the overrun hydraulic stent under impact load, the rigid–flexible coupling numerical model of the stent is established using multi-body dynamics simulation software ADAMS. In the model, the stent is flexibilized using the HyperMesh module, and the column and jack are equivalently replaced with a spring damping system. By applying impact loads to different positions above the front roof beam of the stent, the dynamic response characteristics of the column and the articulation point are obtained at different positions with different strengths. The results show that when the impact load is applied to different positions of the front roof beam, the steady-state response force of the column shows an overall “M" distribution, and along the length direction of the roof beam, the steady-state response force of the column shows an upward trend, and the maximum steady-state response force of the column is 547 kN at point (1, 6); when the impact load is applied to both sides of the front roof beam, the response at the articulation point is greater, resulting in a higher maximum simple harmonic response at that articulation point. When the impact load acts on both sides of the front roof beam, the response of the articulation point is greater, with a maximum simple harmonic response coefficient of 0.75 and a maximum excitation response coefficient of 0.28; when the impact loads of different strengths act on the whole front roof beam, the force acting on the column and pin shaft at the articulation point will produce a large impact, reducing its adaptability. To address this, we can consider changing the top plate stress conditions using methods like high-pressure injection of water and control the gradual and slow release of the top plate stresses. The results of the study provide a reference for the structural strength design and reliability analysis of the hydraulic support, which is of practical significance and value for improving the safe mining of the coal mining face.

Abstract Extensive research has demonstrated the critical role of selenium (Se) and selenoproteins in brain function and cognition. However, the impact of Se on brain cortical structure remains enigmatic. Therefore, this study used Mendelian randomization (MR) analysis to investigate the causal effect between Se levels and brain cortical structure. Methods This study utilizes 11 genetic variants associated with Se level variations, extracted from a large‐scale genome‐wide association study (GWAS) encompassed circulating Se levels (n = 5477) and toenail Se levels (n = 4162) in the European population. Outcome data were sourced from the summary statistics of the ENIGMA Consortium, comprising GWAS data from 51,666 individuals. The variables include cortical surface area (SA), thickness (TH) at the global level, and 34 functional cortical regions evaluated by magnetic resonance imaging. The inverse‐variance‐weighted method was used as the primary estimate. Additionally, sensitivity analyses were conducted to detect potential violations of assumptions underlying MR. Results At the global level, Se levels were not correlated with SA but showed a significant negative correlation with TH (β = −0.00485 mm, SE = 0.00192, p = .0115). Heterogeneity was observed across different brain regions, with positive correlations found between Se levels and the TH of the parahippocampal gyrus, superior frontal gyrus, and frontal pole, whereas negative correlations were found with the TH of the inferior parietal lobe and middle temporal lobe. Regarding SA, Se levels exhibit positive correlations with the pars triangularis, caudal anterior cingulate, inferior parietal lobe, and banks of the superior temporal sulcus. Conversely, negative correlations were observed with the medial orbitofrontal cortex, posterior cingulate gyrus, insula, and the middle, superior, and transverse gyrus of the temporal lobe. No pleiotropy was detected. Results This MR study indicated that Se levels causally influence the brain cortical structure.

IntroductionThe design of high-pressure optical windows is one of the key tasks in deep-sea exploration, as it directly determines the reliability and maximum operating depth of underwater optical equipment.MethodIn this paper, mechanical modeling and finite element analysis methods are employed to study optical windows.Results and discussionResults show that changes in boundary conditions during loading significantly affect the stress distribution of the window. Based on this conclusion, an optimization design method is proposed, which involves the use of transition materials to reduce the impact of base deformation on the window. The study further analyzes the effects of the transition material’s Young’s modulus, Poisson’s ratio, thickness, and friction coefficient on the stress of the optical window. A calculation method for material selection criteria is proposed to select appropriate transition materials, and actual materials are used for verification. Finally, the reliability of the optimization design scheme based on transition materials is confirmed through high-pressure experiments.

Abstract Aronia melanocarpa is rich in anthocyanin, among which cyanidin‐3‐galactoside (C3G) is the most abundant. Here, we established an experimental model of mice and alveolar macrophage cell line MH‐S exposed to PM10, and C3G was administered to explore the underlying mechanism of C3G exerting protective effects on PM10‐induced lung inflammation. The results showed C3G alleviated PM10‐induced lung inflammation by reducing matrix metalloproteinases production at both gene and protein levels as well as pro‐inflammatory cytokine levels. Autophagy was activated in PM10‐injured alveolar macrophages (AMs), and C3G promoted autophagy indicated by LC3, BECN1, Atg5, Bcl‐2, and P62 expression, and C3G further resisted PM10‐induced AMs apoptosis. Besides, C3G could promote Pink1/Parkin‐mediated mitochondrial autophagy of AMs to alleviate the overexpression of mitochondrial reactive oxygen species (ROS) so that maintain mitochondrial membrane potential and ATP productions to restrict the distribution of Cyt‐c and further reduce the increasing of caspase 3/7 activity. Therefore, C3G enhanced the clearance of PM10‐damaged mitochondria by promoting AMs mitophagy, thereby reducing the activation of mitochondria‐dependent apoptosis pathway and the production of excess ROS, which reduced AMs apoptosis and secretion of pro‐inflammatory factors to ameliorate PM10‐induced pulmonary inflammation, suggesting that C3G may be as a functional food ingredient with the potential to improve lung health.

Background and objectives: The heterogeneity of pulmonary fibroblasts, a critical aspect of both murine and human models under physiological and pathological conditions, is well-documented. Yet, consensus remains elusive on the subtypes, lineage, biological attributes, signal transduction pathways, and plasticity of these fibroblasts. This ambiguity significantly impedes our understanding of the fibrotic processes that transpire in lung tissue during aging. This study aims to elucidate the transcriptional profiles, differentiation pathways, and potential roles of fibroblasts within aging pulmonary tissue.Methods: We employed single-cell transcriptomic sequencing via the 10x Genomics platform. The downstream data were processed and analyzed using R packages, including Seurat. Trajectory and stemness of differentiation analyses were conducted using the Monocle2 and CytoTRACE R packages, respectively. Cell interactions were deciphered using the CellChat R package, and the formation of collagen and muscle fibers was identified through Masson and Van Geison staining techniques.Results: Our analysis captured a total of 22,826 cells, leading to the identification of fibroblasts and various immune cells. We observed a shift in fibroblasts from lipogenic and immune-competent to fibrotic and myofibroblast-like phenotype during the aging process. In the aged stage, fibroblasts exhibited a diminished capacity to express chemokines for immune cells. Experimental validation confirmed an increase of collagen and muscle fiber in the aged compared to young lung tissues. Furthermore, we showed that TGFβ treatment induced a fibrotic, immunodeficient and lipodystrophic transcriptional phenotype in young pulmonary fibroblasts.Conclusion: We present a comprehensive single-cell transcriptomic landscape of lung tissue from aging mice at various stages, revealing the differentiation trajectory of fibroblasts during aging. Our findings underscore the pivotal role of fibroblasts in the regulation of immune cells, and provide insights into why age increases the risk of pulmonary fibrosis.

BackgroundFunctional restoration of hemiplegic upper limbs is a difficult area in the field of neurological rehabilitation. Electrical stimulation is one of the treatments that has shown promising advancements and functional improvements. Most of the electrical stimulations used in clinical practice are surface stimulations. In this case, we aimed to investigate the feasibility of a minimally invasive, ultrasound-guided median nerve electrical stimulation (UG-MNES) in improving the upper limb motor function and activity of a patient with right-sided hemiparesis.Case presentationA 65-year-old male recovering from a left massive intracerebral hemorrhage after open debridement hematoma removal had impaired right limb movement, right hemianesthesia, motor aphasia, dysphagia, and complete dependence on his daily living ability. After receiving 3 months of conventional rehabilitation therapy, his cognitive, speech, and swallowing significantly improved but the Brunnstrom Motor Staging (BMS) of his right upper limb and hand was at stage I-I. UG-MNES was applied on the right upper limb for four sessions, once per week, together with conventional rehabilitation. Immediate improvement in the upper limb function was observed after the first treatment. To determine the effect of UG-MNES on long-term functional recovery, assessments were conducted a week after the second and fourth intervention sessions, and motor function recovery was observed after 4-week of rehabilitation. After completing the full rehabilitation course, his BMS was at stage V-IV, the completion time of Jebsen Hand Function Test (JHFT) was shortened, and the scores of Fugl-Meyer Assessment for upper extremity (FMA-UE) and Modified Barthel Index (MBI) were increased. Overall, the motor function of the hemiplegic upper limb had significantly improved, and the right hand was the utility hand. Electromyography (EMG) and nerve conduction velocity (NCV) tests were normal before and after treatment.ConclusionThe minimally invasive, UG-MNES could be a new alternative treatment in stroke rehabilitation for functional recovery of the upper limbs.

Abstract Comprehensive and accurate assessments of fish composition and diversity are essential for understanding fish ecology and resource management. Traditional fish surveys generally involve capturing organisms, which is invasive for the biological community under study and conflicts with the original intention of biodiversity conservation. Environmental DNA (eDNA) metabarcoding has become an integrated method for monitoring fish species without disturbing ecosystems. However, due to the serious nonspecific amplification of primers in eDNA‐based monitoring, many non‐fish sequences, usually human sequences, are also amplified, which results in serious data wastage and an increase in monitoring costs. We designed new universal primers for freshwater fish by analyzing the whole mitochondrial genome of Chinese freshwater fish. The performance of the primers was compared using an in silico polymerase chain reaction, followed by an in vitro metabarcoding analysis using eDNA from the Yangtze River, which is the third largest river in the world and harbors many freshwater fish species. We found that the mitochondrial 12S region is the most suitable metabarcoding gene marker for both Chinese and other freshwater fish. The minor change at the 3′‐end of the primer can greatly reduce the nonspecific amplification and improve the effectiveness of eDNA metabarcoding. Even small changes in primers may have qualitative and quantitative effects on the detected biodiversity, which should be considered in experimental design and data interpretation. These results will help with primer design and selection for eDNA‐based fish surveys, and consequently support the conservation of freshwater biodiversity.

Abstract Ibrutinib, a Bruton's tyrosine kinase inhibitor, is often used as first‐line (1L) treatment of chronic lymphocytic leukaemia (CLL); however, it is associated with an increased risk for cardiovascular adverse events (CVAEs). This real‐world study adds to existing literature by simultaneously investigating the correlation between pre‐existing CV risk factors and the relative cardiotoxicity of ibrutinib vs other therapies in CLL/small lymphocytic lymphoma (SLL). Using a real‐world database, the risk of subsequent CVAEs (any CVAE, atrial fibrillation [AF], or hypertension) were compared among patients who received 1L ibrutinib monotherapy or another type of non‐ibrutinib therapy, grouped as intensive (IT) or non‐intensive therapy (NIT). Each patient's baseline CV risk was estimated using the Framingham risk score. Inverse probability treatment weighting was incorporated into a logistic regression model to reduce baseline imbalance. Results showed ibrutinib was significantly associated with higher risk of CVAEs regardless of baseline CV risk. Compared with IT, odds ratios of any CVAE, hypertension, or AF were 2.61, 3.66, and 3.02, respectively vs 1.88, 2.13, and 2.46, respectively, with NIT. Sensitivity analyses confirmed the findings were robust. These results suggest clinical caution should be taken when selecting ibrutinib for patients with CLL/SLL, especially in those with high baseline CV risk.

Abstract Background Systemic inflammation and handgrip weakness have been used to predict mortality in many cancers. The purpose of current study was to evaluate the association of co‐occurrence of inflammation indicators and handgrip weakness with overall survival (OS) of lung cancer (LC) patients with good performance status. Methods The cutoff points for handgrip strength (HGS) and the four inflammation indicators were calculated using Maxstat. The time‐dependent receiver operating characteristic curve and C‐index were used to select optimal inflammation indicator for predicting OS of LC patients. The Cox proportional hazard regression model was used to calculate the hazard ratio (HR) of mortality. Kaplan–Meier curves were constructed to evaluate the association of indicators and the OS of LC patients. Results Among the 1951 patients, the mean ± standard deviation (SD) age was 60.6 ± 9.9 years, and 1300 (66.6%) patients were male. In patients with good performance status (PS), handgrip weakness (HR, 1.49; 95% confidence interval [95% CI], 1.30–1.70, p

Abstract Insoluble plant cell walls are a main source of dietary fiber. Both chemical and physical fiber structures create distinct niches for gut bacterial utilization. Here, we have taken key fermentable solubilized polysaccharides of plant cell walls and fabricated them back into cell wall-like film forms to understand how fiber physical structure directs gut bacterial fermentation outcomes. Solubilized corn bran arabinoxylan (Cax), extracted to retain some ferulate residues, was covalently linked using laccase to form an insoluble cell wall-like film (Cax-F) that was further embedded with pectin (CaxP-F). In vitro fecal fermentation using gut microbiota from three donors was performed on the films and soluble fibers. Depending on the donor, CaxP-F led to higher relative abundance of recognized beneficial bacteria and/or butyrate producers—Akkermansia, Bifidobacterium, Eubacterium halii, unassigned Lachnospiraceae, Blautia, and Anaerostipes—than free pectin and Cax, and Cax-F. Thus, physical form and location of fibers within cell walls form niches for some health-related gut bacteria. This work brings a new understanding of the importance of insoluble cell wall-associated fibers and shows that targeted fiber materials can be fabricated to support important gut microbiota taxa and metabolites of health significance.

DC voltage stability and power balance are the key conditions for stable operation of DC transmission systems. The droop control does not depend on inter-station communication and has the advantage of multi-station cooperative unbalanced power dissipation, which has been widely used in the voltage source converter based multi-terminal direct current (VSC-MTDC) system. However, its control will cause DC voltage deviation, and there are a series of problems such as unstable system control and overload operation of the VSC-station due to improper setting of droop coefficient. In this paper, the infeasibility of DC voltage error-free correction under droop control mode is theoretically analyzed, and a VSC-MTDC cooperative optimization droop control strategy with DC voltage "quasi-error-free" adjustment ability is proposed. The strategy adjusts the droop coefficient in real-time by monitoring the DC voltage deviation and the power margin of the VSC-station to solve the problem of voltage deviation caused by unbalanced power consumption. At the same time, an additional DC voltage stabilizer is designed to automatically adjust the power reference value and restore the DC voltage. Finally, a five-terminal VSC-MTDC system is built under PSCAD/EMTDC to verify the feasibility of the proposed strategy.

Objective: In this study, we aim to investigate the safety and feasibility of robot-assisted kidney transplantation (RAKT) in children by reporting our initial experience. Methods: Using the Da Vinci robotic system, we performed a successful RAKT on a 12-year-old child who had been on hemodialysis for 27 months. Results: The total operative time for the RAKT procedure was 245 min. The vascular anastomosis took 41 min, while the ureterovesical anastomosis lasted 18 min. The estimated blood loss during the surgery was 100.0 ml. Following the removal of the arterial and venous clamp, the kidney was well perfused, and no perioperative complications were observed. Conclusion: This study presents the first pediatric RAKT in China, proving the safety and feasibility of the robot-assisted technique for children awaiting kidney transplantation.

Depression is a severe psychiatric illness that causes emotional and cognitive impairment and has a considerable impact on patients’ thoughts, behaviors, feelings and well-being. Moreover, methods for recognizing and treating depression are lacking in clinical practice. Electroencephalogram (EEG) signals, which objectively reflect the internal workings of the brain, is a promising and objective tool for recognizing and diagnosing of depression and enhancing clinical effects. However, previous EEG feature extraction methods have not performed well when exploring the intrinsic characteristics of highly complex and nonstationary EEG signals. To address this issue, we propose a regularization parameter-based improved intrinsic feature extraction method of EEG signals via empirical mode decomposition (EMD), which mines the intrinsic patterns in EEG signals, for depression recognition. Furthermore, our method can effectively solve the problem that EMD fails to extract intrinsic features. In this method, we first select an appropriate regularization parameter to generate the regularization matrix. Next, we calculate the sum of the matrix products of the IMFs and the regularization matrix and leverage the inverse of this matrix to extract the intrinsic features. The classification results of our method on four EEG datasets reached 0.8750, 0.8850, 0.8485 and 0.7768, respectively. In addition, compared with the iEMD method, our method requires less computational costs. These results support our claim that our method can effectively strengthen the depression recognition performance, and our method outperforms state-of-the-art feature extraction approaches.

Abstract Background Chronic endometritis (CE) is a disease of continuous and subtle inflammation occurring in the endometrial stromal area, which is often asymptomatic or present with non-specific clinical symptoms. Methods This study investigated the composition and distribution of the intrauterine microbiota of 71 patients who underwent hysteroscopy during the routine clinical inspection of infertility. Among them, patients who were diagnosed with chronic endometritis (CE) were allocated into CE group (n = 29) and others into non-CE group (n = 42). There was no significant difference in average age between the two groups (P = 0.19). Uterine flushing fluid was collected by the self-developed cervical trocar uterine cavity sampler and 16S rRNA sequencing was performed. Results The alpha diversity in the CE group was significantly higher than that in the non-CE group (P

Crystal monochromators are indispensable optical components for the majority of beamlines at synchrotron radiation facilities. Channel-cut monochromators are sometimes chosen to filter monochromatic X-ray beams by virtue of their ultrahigh angular stability. Nevertheless, high-accuracy polishing on the inner diffracting surfaces remains challenging, thus hampering their performance in preserving the coherence or wavefront of the photon beam. Herein, a magnetically controlled chemical–mechanical polishing (MC-CMP) approach has been successfully developed for fine polishing of the inner surfaces of channel-cut crystals. This MC-CMP process relieves the constraints of narrow working space dictated by small offset requirements and achieves near-perfect polishing on the surface of the crystals. Using this method, a high-quality surface with roughness of 0.614 nm (root mean square, r.m.s.) is obtained in a channel-cut crystal with 7 mm gap designed for beamlines at the High Energy Photon Source, a fourth-generation synchrotron radiation source under construction. On-line X-ray topography and rocking-curve measurements indicate that the stress residual layer on the crystal surface was removed. Firstly, the measured rocking-curve width is in good agreement with the theoretical value. Secondly, the peak reflectivity is very close to theoretical values. Thirdly, topographic images of the optics after polishing were uniform without any speckle or scratches. Only a nearly 2.5 nm-thick SiO2 layer was observed on the perfect crystalline matrix from high-resolution transmission electron microscopy photographs, indicating that the structure of the bulk material is defect- and dislocation-free. Future development of MC-CMP is promising for fabricating wavefront-preserving and ultra-stable channel-cut monochromators, which are crucial to exploit the merits of fourth-generation synchrotron radiation sources or hard X-ray free-electron lasers.