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Abstract Upregulation of vascular endothelial growth factor (VEGF) and enhanced angiogenesis have been implicated in the severe progression of age-related macular degeneration (AMD). Abnormal arachidonate 5-lipoxygenase (ALOX5) is associated with AMD pathogenesis. However, no reports have shown the causal role of ALOX5 in angiogenesis during AMD. In the present study, ARPE-19 cells were exposed to hypoxia, an inducer of VEGF expression. Potential proteins implicated in AMD progression were predicted using bioinformatics. RNA affinity antisense purification-mass spectrometry (RAP-MS) was applied to identify the binding proteins of ALOX5 3′UTR. Expression of ALOX5 and YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1) was detected by qRT-PCR and western blotting. VEGF expression and secretion were assessed by immunofluorescence and ELISA, respectively. The chicken embryo chorioallantoic membrane (CAM) was used to analyze the effect of ALOX5 on angiogenesis. RNA stability was assayed using the Actinomycin D assay. The results show that hypoxia promoted cell growth and increased VEGF expression in ARPE-19 cells. ALOX5 was associated with AMD progression, and hypoxia upregulated ALOX5 expression in ARPE-19 cells. ALOX5 silencing reduced VEGF expression induced by hypoxia in ARPE-19 cells. Moreover, the conditioned medium of ALOX5-silenced ARPE-19 cells could suppress the viability and migration of HUVECs and diminish angiogenesis in the CAM. Furthermore, YTHDF1 was validated to bind to ALOX5 3′UTR, and YTHDF1 promoted ALOX5 expression by elevating the stability of ALOX5 mRNA. In conclusion, our findings demonstrate that YTHDF1-regulated ALOX5 increases VEGF expression in hypoxia-exposed ARPE-19 cells and enhances the viability, migration, and angiogenesis of vascular endothelial cells.

Abstract Wooden buildings represent a unique aspect of China’s architectural heritage. However, over time, these buildings have suffered varying degrees of structural damage, particularly those located in China’s mountainous regions. Frequent natural disasters and inconvenient transportation further exacerbate the vulnerability of these structures. This study focuses on the typical wooden stilt houses found in the Wuling Mountain area of southwest Hubei. The different forms of columns and beams, as well as the overall structural symmetry of the stilt houses, were classified into five common structural types. Precise digital models were established via real photos and collected dimensional data, and these five models were evaluated for static, buckling, utilization, and ultimate limit states. The results indicate that: (1) overall symmetrical structures perform better than asymmetrical ones; (2) structures where all columns are grounded and act as support columns exhibit the best overall mechanical performance; and (3) transverse-tie beams(chuanfang) primarily serve a connecting role rather than a load-bearing role, thus an excess of transverse-tie beams(chuanfang) can reduce the stability of the building structure. Based on the analysis results, targeted protective measures and recommendations were proposed and verified through structural evaluations. These initiatives provide new methods and insights for the protection of architectural heritage.

Abstract Background Breast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets. Methods Bioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes. Results The analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells. Conclusion This study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

Abstract Renal cell carcinoma (RCC) is considered a “metabolic disease” characterized by elevated glycolysis in patients with advanced RCC. Tyrosine kinase inhibitor (TKI) therapy is currently an important treatment option for advanced RCC, but drug resistance may develop in some patients. Combining TKI with targeted metabolic therapy may provide a more effective approach for patients with advanced RCC. An analysis of 14 RCC patients (including three needle biopsy samples with TKI resistance) revealed by sing-cell RNA sequencing (scRNA-seq) that glycolysis played a crucial role in poor prognosis and drug resistance in RCC. TCGA-KIRC and glycolysis gene set analysis identified DEPDC1 as a target associated with malignant progression and drug resistance in KIRC. Subsequent experiments demonstrated that DEPDC1 promoted malignant progression and glycolysis of RCC, and knockdown DEPDC1 could reverse TKI resistance in RCC cell lines. Bulk RNA sequencing (RNA-seq) and non-targeted metabolomics sequencing suggested that DEPDC1 may regulate RCC glycolysis via AKT/mTOR/HIF1α pathway, a finding supported by protein-level analysis. Clinical tissue samples from 98 RCC patients demonstrated that DEPDC1 was associated with poor prognosis and predicted RCC metastasis. In conclusion, this multi-omics analysis suggests that DEPDC1 could serve as a novel target for TKI combined with targeted metabolic therapy in advanced RCC patients with TKI resistance.

Abstract Immunotherapy exhibited potential effects for advanced hepatocellular carcinoma, unfortunately, the clinical benefits are often countered by cancer adaptive immune suppressive response. Uncovering the mechanism how cancer cells evade immune surveillance would help to develop new immunotherapy approaches and combination therapy. In this article, by analyzing the transcriptional factors which modulate the differentially expressed genes between T cell infiltration high group and low group, we identified oncoprotein B cell lymphoma 6 (BCL6) suppresses the infiltration and activation of tumor infiltrating T lymphocytes, thus correlated with poorer clinical outcome. By using antibody deletion experiment, we further demonstrated that CD4+T cells but not CD8+T cells are the main lymphocyte population suppressed by Bcl6 to promote HCC development. Mechanistically, BCL6 decreases cancer cell expression of pro-inflammatory cytokines and T lymphocyte chemokines such as IL6, IL1F6, and CCL5. Moreover, BCL6 upregulates Endothelial cell-specific molecule 1 (ESM1) to inhibit T lymphocyte recruitment and activation possibly through ICAM-1/LFA-1 signaling pathway. Our findings uncovered an unappreciated paracrine mechanism how cancer cell-derived BCL6 assists cancer cell immune evasion, and highlighted the role of CD4+T cells in HCC immune surveillance.

Abstract The Daling River Basin is an important ecological functional area in the western region of Liaoning with outstanding environmental problems. The monitoring of ecological and environmental quality in the basin and the analysis of driving factors are of great importance for the protection of the ecological environment and the improvement of economic quality. In this paper, the three periods of Landsat remote sensing images in 1995, 2010 and 2020 are used as the basic data, and platforms and technical means such as RS and GIS are used to decipher and extract the three periods of land use information, and to construct the land use type transfer matrix. The remote sensing ecological index (RSEI) was improved, and the principal component analysis method was applied to construct the improved remote sensing ecological index (IRSEI) model based on the greenness (NDVI), moisture (WET), heat (LST) and new dryness (N-NDBSI), so as to realize the dynamic monitoring of ecological and environmental quality in the study area. Based on the land use change, combined with the trend of improved remote sensing ecological index (IRSEI) of Daling River Basin, thus achieving the purpose of rapid and efficient dynamic monitoring of ecological quality of Daling River Basin from 1995 to 2020. A geoprobe model was then used to systematically assess the drivers of ecological quality in the catchment. The results show that the improved remote sensing ecological index (IRSEI) can efficiently and accurately obtain the spatial distribution pattern and temporal variation trend of IRSEI in the study area, which is more in line with the characteristics of indicators in this study area. The IRSEI in the study area showed an increasing trend from 1995 to 2020, from 0.4794 to 0.5615, and the proportion of benign ecological classes increased year by year during the period. Among the evaluation indicators, NDVI and N-NDBSI are the main factors affecting the environmental and ecological quality of the Daling River Basin, and the increase of vegetation cover, climate regulation and human activities have obvious promoting effects on the improvement of the ecological environment of the Daling River Basin. This study provides a scientific theoretical basis for the implementation of further ecological environmental protection measures.

Abstract Background This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. Methods By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. Results The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P

Abstract Chemotherapy is an important therapuetic strategy for colorectal cancer (CRC), but chemoresistance severely affects its efficacy, and the underlying mechanism has not been fully elucidated. Increasing evidence suggests that lipid peroxidation imbalance-mediated ferroptosis is closely associated with chemoresistance. Hence, targeting ferroptosis pathways or modulating the tolerance to oxidative stress might be an effective strategy to reverse tumor chemoresistance. HtrA serine protease 1 (HTRA1) was screened out as a CRC progression- and chemoresistance-related gene. It is highly expressed in CRC cells and negatively correlated with the prognosis of CRC patients. Gain- and loss-of-function analyses demonstrated a stimulatory role of HTRA1 on the proliferation of CRC cells. The enrichment analysis of HTRA1-interacting proteins indicated the involvement of ferroptosis in the HTRA1-mediated chemoresistance. Moreover, electron microscope analysis, as well as the ROS and MDA levels in CRC cells also confirmed the effect of HTRA1 on ferroptosis. We also verified that HTRA1 could interact with SLC7A11 through its Kazal structural domain and up-regulate the expression of SLC7A11, which in turn inhibited the ferroptosis and leaded to the chemoresistance of CRC cells to 5-FU/L-OHP. Hence, we propose that HTRA1 may be a potential therapeutic target and a prognostic indicator in CRC.

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors, and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor progression. Herein, we demonstrated that salvianic acid A (SAA) played a pivotal role in contributing to vascular normalization in the tumor-bearing mice, thereby improving delivery and effectiveness of the chemotherapeutic agent. SAA was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells (HUVECs) exposed to hypoxia. Mechanistically, SAA was inclined to directly bind to the glycolytic enzyme PKM2, leading to a dramatic decrease in endothelial glycolysis. More importantly, SAA improved the endothelial integrity via activating the β-Catenin/Claudin-5 signaling axis in a PKM2-dependent manner. Our findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

IntroductionThe eating sounds of largemouth black bass (Micropterus salmoides) are primarily categorized into swallowing and chewing sounds, both intensities of which are closely correlated with fish density and feeding desire. Therefore, accurate recognition of these two sounds is of significant importance for studying fish feeding behavior.MethodsIn this study, we propose a method based on low-dimensional acoustic features for the recognition of swallowing and chewing sounds in fish. Initially, utilizing synchronous audio-visual means, we collect feeding sound signals and image signals of largemouth black bass. By analyzing the time-frequency domain features of the sound signals, we identify 15 key acoustic features across four categories including short-time average energy, average Mel-frequency cepstral coefficients, power spectral peak, and center frequency. Subsequently, employing nine dimensionality reduction algorithms, we select the Top-6 features from the 15-dimensional acoustic features and compare their precision in recognizing swallowing and chewing sounds using four machine learning models.ResultsExperimental results indicate that supervised feature pre-screening positively enhances the accuracy of largemouth black bass feeding feature recognition. Extracted acoustic features demonstrate global correlation and linear characteristics. When considering feature dimensionality and classification performance, the combination of feature dimensionality reduction and recognition model based on the random forest model exhibits the best performance, achieving an identification accuracy of 98.63%.DiscussionThe proposed method offers higher assessment accuracy of swallowing and chewing sounds with lower computational complexity, thus providing effective technical support for the research on precise feeding technology in fish farming.

Abstract Engineering a catalytic membrane capable of efficiently removing emerging organic microcontaminants under ultrahigh flux conditions is of significance for water purification. Herein, drawing inspiration from the functional attributes of lymphatic vessels involved in immunosurveillance and fluid transport with minimal energy consumption, a novel hierarchical porous catalytic membrane is engineered. This membrane, based on an innovative nitrogen‐rich conjugated microporous polymer (polytripheneamine, PTPA), is synthesized using an electrospinning coupled in situ polymerization approach. The resulting bioinspired membrane with hierarchical channels comprises a thin layer (≈1.7 µm) of crosslinked PTPA nanoparticles covering the interconnected electrospun nanofibers. This unique design creates an intrinsic microporous angstrom‐confined system capable of activating peroxymonosulfate (PMS) to generate 98.7% singlet oxygen (1O2), enabling durable and highly efficient degradation of microcontaminants. Additionally, the presence of a thin layer of mesoporous structure between PTPA nanoparticles and macroporous channels within the interwoven nanofibers enhances mass transfer efficiency and facilitates high flux rates. Notably, the prepared hierarchical porous organic catalytic membrane demonstrates enduring high‐efficiency degradation performance with a superior permeance (>95% and >2500 L m−2 h−1 bar−1) sustained over 100 h. This work introduces an innovative pathway for the design of high‐performance catalytic membranes for the removal of emerging organic microcontaminants.

Summary: A major obstacle to exploiting industrial flue gas for microalgae cultivation is the unfavorable acidic environment. We previously identified three upregulated genes in the low-pH-adapted model diatom Phaeodactylum tricornutum: ferredoxin (PtFDX), cation/proton antiporter (PtCPA), and HCO3− transporter (PtSCL4-2). Here, we individually overexpressed these genes in P. tricornutum to investigate their respective roles in resisting acidic stress (pH 5.0). The genetic modifications enabled positive growths of transgenic strains under acidic stress that completely inhibited the growth of the wild-type strain. Physiological studies indicated improved photosynthesis and reduced oxidative stress in the transgenic strains. Transcriptomes of the PtCPA- and PtSCL4-2-overexpressing transgenics showed widespread upregulation of various transmembrane transporters, which could help counteract excessive external protons. This work highlights ion/electron carrier genes’ role in enhancing diatom resistance to acidic stress, providing insights into phytoplankton adaptation to ocean acidification and a strategy for biological carbon capture and industrial flue gas CO2 utilization.

As autonomous vehicles and the other supporting infrastructures (e.g., smart cities and intelligent transportation systems) become more commonplace, the Internet of Vehicles (IoV) is getting increasingly prevalent. There have been attempts to utilize Digital Twins (DTs) to facilitate the design, evaluation, and deployment of IoV-based systems, for example by supporting high-fidelity modeling, real-time monitoring, and advanced predictive capabilities. However, the literature review undertaken in this paper suggests that integrating DTs into IoV-based system design and deployment remains an understudied topic. In addition, this paper explains how DTs can benefit IoV system designers and implementers, as well as describes several challenges and opportunities for future researchers.

Abstract Clustering algorithm is the primary technology used in target clustering and group status analysis which are key features of the Unmanned Aerial Vehicles (UAVs) control system. Due to variable application environment, the stability of the algorithm in the UAVs control system needs to be considered. K‐means clustering is a widely used method in intelligent systems. However, K‐means algorithm is susceptible to the local optimum due to the influence of the initial centroid. For this problem, the predecessors have proposed various effective solutions. These algorithms perform better on real and large‐scale datasets, but they are unable to achieve optimum results with unbalanced datasets. Herein, a simpler and more effective algorithm for seed initialization is proposed, it has a better accuracy rate than the alternative algorithms.Moreover, after running tests multiple times with each algorithm independently, it has the highest stability and the lowest overall volatility. With unbalanced datasets, the proposed algorithm performs significantly better than several other algorithms and therefore can solve the problems that other algorithms have with unbalanced datasets.

Manipulating the thermal emission in the infrared (IR) range significantly impacts both fundamental scientific research and various technological applications, including IR thermal camouflage, information encryption, and radiative cooling. While prior research has put forth numerous materials and structures for these objectives, the significant challenge lies in attaining spatially resolved and dynamically multilevel control over their thermal emissions. In this study, a one-step ultrafast laser writing technique is experimentally demonstrated to achieve position-selective control over thermal emission based on the phase-change material Ge2Sb2Te5 (GST). Ultrafast laser writing technique enables direct fabrication and manipulation of laser-induced crystalline micro/nano-structures on GST films. Thermal emission can be precisely controlled by adjusting the pulse energy of the ultrafast laser, achieving a high thermal emissivity modulation precision of 0.0014. By controlling thermal emission, the ultrafast laser writing technique enables multilevel patterned processing. This provides a promising approach for multilevel IR thermal camouflage, which is demonstrated with emissivity-modulated GST emitters. Remarkably, ultrafast laser-induced crystalline micro/nano-structures display geometric grating features, resulting in a diffraction-based structural color effect. This study demonstrates the effective use of laser-printed patterns for storing information in both visible and infrared spectrum.

Abstract Objective The objective of this research was to create a deep learning network that utilizes multiscale images for the classification of follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) through preoperative US. Methods This retrospective study involved the collection of ultrasound images from 279 patients at two tertiary level hospitals. To address the issue of false positives caused by small nodules, we introduced a multi-rescale fusion network (MRF-Net). Four different deep learning models, namely MobileNet V3, ResNet50, DenseNet121 and MRF-Net, were studied based on the feature information extracted from ultrasound images. The performance of each model was evaluated using various metrics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, F1 value, receiver operating curve (ROC), area under the curve (AUC), decision curve analysis (DCA), and confusion matrix. Results Out of the total nodules examined, 193 were identified as FTA and 86 were confirmed as FTC. Among the deep learning models evaluated, MRF-Net exhibited the highest accuracy and area under the curve (AUC) with values of 85.3% and 84.8%, respectively. Additionally, MRF-Net demonstrated superior sensitivity and specificity compared to other models. Notably, MRF-Net achieved an impressive F1 value of 83.08%. The curve of DCA revealed that MRF-Net consistently outperformed the other models, yielding higher net benefits across various decision thresholds. Conclusion The utilization of MRF-Net enables more precise discrimination between benign and malignant thyroid follicular tumors utilizing preoperative US.

Abstract Previous studies of neuronal survival have primarily focused on identifying intrinsic mechanisms controlling the process. This study explored how intercellular communication contributes to retinal ganglion cell (RGC) survival following optic nerve crush based on single-cell RNA-seq analysis. We observed transcriptomic changes in retinal cells in response to the injury, with astrocytes and Müller glia having the most interactions with RGCs. By comparing RGC subclasses characterized by distinct resilience to cell death, we found that the high-survival RGCs tend to have more ligand-receptor interactions with neighboring cells. We identified 47 interactions stronger in high-survival RGCs, likely mediating neuroprotective effects. We validated one identified target, the μ-opioid receptor (Oprm1), to be neuroprotective in three retinal injury models. Although the endogenous Oprm1 is preferentially expressed in intrinsically photosensitive RGCs, its neuroprotective effect can be transferred to other subclasses by pan-RGC overexpression of Oprm1. Lastly, manipulating the Oprm1 activity improved visual functions in mice.

Abstract Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment. However, it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain. In this study, we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2 (PGE2) concentration in response to mechanical loading. Bone PGE2 levels are in proportion to their weight bearing. When weight bearing changes in the tail-suspension mice, the PGE2 concentrations in bones change in line with their weight bearing changes. Deletion of cyclooxygenase-2 (COX2) in the osteoblast lineage cells or knockout of receptor 4 (EP4) in sensory nerve blunts bone formation in response to mechanical loading. Moreover, knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation. Moreover, mechanical loading induces cAMP-response element binding protein (CREB) phosphorylation in the hypothalamic arcuate nucleus (ARC) to inhibit sympathetic tyrosine hydroxylase (TH) expression in the paraventricular nucleus (PVN) for osteogenesis. Finally, we show that elevated PGE2 is associated with ankle osteoarthritis (AOA) and pain. Together, our data demonstrate that in response to mechanical loading, skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis, while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.

A comprehensive and comparative study of the thermal-oxygen aging and tribological properties of antioxidant 6PPD synergized with carbon nanotubes (CNTs) and graphene (GE)-reinforced hydrogenated nitrile rubber (HNBR) composites was performed using molecular simulations and experiments. The results indicated that GE exhibits superior capabilities in inhibiting the volatilization and migration of the antioxidant 6PPD compared to CNTs and enhancing the thermal and oxygen aging resistance of HNBR. The surface morphology of the HNBR composites was characterized using scanning electron microscopy (SEM) and X-ray spectroscopy (XPS), which revealed the different enhancement mechanisms of CNTs and GE. The mechanical and tribological properties of the HNBR composites were experimentally investigated before and after the thermal-oxygen aging. The results revealed that the tensile and tear strengths of the 6PPD/HNBR composites with added GE increased by approximately 4% compared to those of the 6PPD/HNBR composites with added CNTs. The coefficient of friction decreased by approximately 7%. Finally, the wear surface morphologies of the HNBR composites were characterized using SEM and energy dispersive spectrometer (EDS). These results further indicate that the larger specific surface area of GE can be better combined with HNBR, improving its overall thermal-oxygen aging and tribological properties.

Congenital fibroblast growth factor 23 (FGF23)‐related hypophosphatemic rickets/osteomalacia is a rare bone metabolism disorder characterized by hypophosphatemia and caused by genetic abnormalities that result in excessive secretion of FGF23. Hyp mice are a model of X‐linked hypophosphatemia (XLH) caused by deletion of the PHEX gene and excessive production of FGF23. The purpose of this study was to investigate the potential of TM5614 as a therapeutic agent for the treatment of congenital FGF23‐related hypophosphatemic rickets and osteomalacia in humans by administering TM5614 to Hyp mice and examining its curative effect on hypophosphatemia. After a single oral administration of TM5614 10 mg·kg−1 to female Hyp mice starting at 17 weeks of age, the serum phosphate concentration increased with a peak at 6 h after administration. ELISA confirmed that TM5614 administration decreased the intact FGF23 concentration in the blood. Expression of 25‐hydroxyvitamin D‐1α‐hydroxylase protein encoded by Cyp27b1 mRNA in the kidney was suppressed in Hyp mice, and treatment with 10 mg·kg−1 of TM5614 normalized the expression of 25‐hydroxyvitamin D‐1α‐hydroxylase protein and Cyp27b1 mRNA in the kidneys of these mice. Our data indicate that oral administration of TM5614 ameliorates hypophosphatemia in Hyp mice, suggesting that TM5614 may be an effective treatment for congenital FGF23‐related hypophosphatemic rickets and osteomalacia.

Introduction: Ovarian cancer is the most malignant gynecological tumor. Previous studies have demonstrated that chimeric antigen receptor (CAR)-engineered NK-92 cells targeting folate receptor α (αFR) (NK-92-αFR-CAR) can specifically kill αFR-positive ovarian cancer cells. However, the migration barrier restricts antitumor effects of CAR-engineered cells. Objectives: To elucidate the mechanism by which NK-92-αFR-CAR cells induce the secretion of chemokine CXCL10 during killing ovarian cancer cells. It is speculated that NK-92-αFR-CAR-CXCR3A can target αFR and have chemotaxis of CXCL10, and they may have stronger killing effect of ovarian cancer. Methods: Study the mechanism of CXCL10 expression strongly induced by TNF-α and IFN-γ combined stimulation in ovarian cancer cells. Construct the fourth generation of NK-92-αFR-CAR-CXCR3A cells, which were co-expressed CXCR3A and αFR-CAR. Evaluate the killing and migration effects of NK-92-αFR-CAR-CXCR3A in vitro and in vivo. Results: RNA sequencing (RNA-seq) first revealed that the expression level of the chemokine CXCL10 was most significantly increased in ovarian cancer cells co-cultured with NK-92-αFR-CAR. Secondly, cytokine stimulation experiments confirmed that IFN-γ and TNF-α secreted by NK-92-αFR-CAR synergistically induced high CXCL10 expression in ovarian cancer cells. Further signaling pathway experiments showed that IFN-γ and TNF-α enhanced the activation level of the IFN-γ-IFNGR-JAK1/2-STAT1-CXCL10 signaling axis. Cytotoxicity experiments showed that NK-92-αFR-CAR-CXCR3A cells could not only efficiently kill αFR-positive ovarian cancer cells in vitro but also secrete IFN-γ and TNF-α. Higher migration than that of NK-92-αFR-CAR was detected in NK-92-αFR-CAR-CXCR3A using transwell assay. NK-92-αFR-CAR-CXCR3A effectively killed tumor cells in different mouse xenograft models of ovarian cancer and increased infiltration into tumor tissue. Conclusion: This study confirmed that IFN-γ and TNF-α secreted by αFR-CAR-engineered NK cells can synergistically induce high expression of CXCL10 in ovarian cancer cells and constructed self-driving αFR-CAR-engineered NK cells that can break through migration barriers based on CXCL10, which may provide a new therapeutic weapon for ovarian cancer.

ABSTRACTObjective It was to assess the efficacy of preoperative guidance using cone beam computed tomography (CBCT) and the application of autologous concentrated growth factors (CGF) for implantation in maxillary teeth with inadequate bone mass.Methods An eigenvector-based multimodal elasticity algorithm was developed. Eighty patients with insufficient bone mass in the maxillary dental region were rolled into control group (n = 40, Bio-Oss bone powder treatment) and observation group (n = 40, autologous CGF and Bio-Oss bone powder treatment). The scale-invariant feature transform (SIFT) algorithm and the hierarchical attribute matching mechanism for elastic registration (HAMMER) were introduced, whose registration time and mutual information value were compared. Therapeutic outcomes of patients were also compared.Results The eigenvector-based multimodal elastic algorithm exhibited a significantly shorter registration time versus SIFT and HAMMER algorithms, and superior accuracy, sensitivity, and specificity (p

End-stage renal disease is a worldwide health burden, but the pathogenesis of uremia-associated cognitive impairment (CI) is poorly recognized. We hypothesized that uremia brings about deficiency of thiamin and folic acid and causes CI by inducing oxidative stress. Therefore, 24 Sprague-Dawley rats were randomly divided into two groups: a 5/6 nephrectomy group (n = 12) and a sham-operated group (n = 12). The Morris water maze was used to assess the cognitive function eight weeks post-surgery, and serum levels of thiamin, folic acid and homocysteine were detected subsequently. Brain and kidney tissues were collected for pathological examination and 8-Hydroxy-2’-deoxyguanosine (8-OHdG) immunochemistry staining. Results showed that the escape latency on training days 1-2 was longer, and the time in quadrant IV on experimental day 6 was significantly shorter in 5/6 nephrectomy group. Meanwhile, the uremic rats showed decreased thiamin, folic acid and increased homocysteine. We also found the time in quadrant IV was positively correlated with thiamin and folic acid level, while negatively correlated with the blood urea nitrogen and 8-OHdG positive cell proportion. Furthermore, in 5/6 nephrectomy group, the hippocampal neuron count was significantly reduced, and a greater proportion of 8-OHdG positive cells were detected. Pretreating LPS-stimulated rat microglial cells with thiamin or folic acid in vitro alleviated the inflammatory impairment in terms of cell viability and oxidative stress. In summary, we applied a uremic rat model and proved that uremia causes serum thiamin and folic acid deficiency, homocysteine elevation, along with neuron reduction and severe oxidative stress in hippocampus, finally leading to CI.

Summary: The emergence of novel Omicron subvariants has raised concerns regarding the efficacy of immunity induced by prior Omicron subvariants breakthrough infection (BTI) or reinfection against current circulating Omicron subvariants. Here, we prospectively investigated the durability of antibody and T cell responses in individuals post Omicron BA.2.2 BTI, with or without subsequent Omicron BA.5 reinfection. Our findings reveal that the emerging Omicron subvariants, including CH.1.1, XBB, and JN.1, exhibit extensive immune evasion induced by previous infections. Notably, the level of IgG and neutralizing antibodies were found to correlate with subsequent Omicron BA.5 reinfection. Fortunately, T cell responses recognizing both Omicron BA.2 and CH.1.1 peptides were observed. Furthermore, Omicron BA.5 reinfection may alleviate immune imprinting induced by WT-vaccination, bolster virus-specific ICS+ T cell responses, and promote the phenotypic differentiation of virus-specific memory CD8+ T cells. Antigen-updated or T cell-conserved vaccines are needed to control the transmission of diverse emerging SARS-CoV-2 variants.

Abstract Liver fibrosis is a major risk factor for hepatocellular carcinoma origin, and its progression not only correlates with oxidative stress and inflammation, but also is encouraged by autophagy hold‐up. Therefore, new solutions to effectively attenuate oxidative stress and inflammation and coincidently favor autophagy are highly demanded to reverse liver fibrosis, and even hamper its escalation into hepatocellular carcinoma. Herein, the porous manganese‐substituted Prussian blue (PMPB) analogs are harnessed to activate autophagy, scavenge reactive oxygen species (ROS), and suppress inflammation for liver fibrosis therapy. PMPB can effectively inhibit macrophage activation, facilitate macrophage autophagy, eradicate ROS, and blockade cellular cross‐talk, thus impeding further inflammation progression. Moreover, the favorable spontaneous capture of PMPB by Kupffer cells allows more PMPB accumulation in liver to significantly attenuate liver injury and collagen deposition, thereby inhibiting the progression of liver fibrosis. PMPB‐based nanomedicine shows great potentials in promoting autophagy activation, eliminating ROS, inhibiting inflammation, and protecting hepatocytes from oxidative stress‐arised damages, which eventually attenuate the extent of liver fibrosis, holding great promise in clinical translation for treating liver fibrosis.

Transparent conductive oxide (TCO) films, known for their role as carrier transport layers in solar cells, can be adversely affected by hydrolysis products from encapsulants. In this study, we explored the morphology, optical-electrical properties, and deterioration mechanisms of In2O3-based TCO films under acetic acid stress. A reduction in film thickness and carrier concentration due to acid-induced corrosion was observed. X-ray photoelectron spectroscopy and inductively coupled plasma emission spectrometry analyses revealed that TCOs doped with less-reactive metals exhibited enhanced corrosion resistance. The efficiency of silicon heterojunction (SHJ) solar cells with tin-doped indium oxide, titanium-doped indium oxide, and zinc-doped indium oxide films decreased by 10%, 26%, and 100%, respectively, after 200 ​h of corrosion. We also found that tungsten-doped indium oxide could effectively safeguard SHJ solar cells against acetic acid corrosion, which offers a potential option for achieving long-term stability and lower levelized cost of solar cell systems. This research provides essential insights into selecting TCO films for solar cells and highlights the implications of ethylene-vinyl acetate hydrolysis for photovoltaic modules.

Building communication links among multiple users in a scalable and robust way is a key objective in achieving large-scale quantum networks. In a realistic scenario, noise from the coexisting classical light is inevitable and can ultimately disrupt the entanglement. The previous significant fully connected multiuser entanglement distribution experiments are conducted using dark fiber links, and there is no explicit relation between the entanglement degradations induced by classical noise and its error rate. Here, a semiconductor chip with a high figure-of-merit modal overlap is fabricated to directly generate broadband polarization entanglement. The monolithic source maintains the polarization entanglement fidelity of above 96% for 42 nm bandwidth, with a brightness of 1.2 × 107 Hz mW−1. A continuously working quantum entanglement distribution are performed among three users coexisting with classical light. Under finite-key analysis, secure keys are established and images encryption are enabled as well as quantum secret sharing between users. This work paves the way for practical multiparty quantum communication with integrated photonic architecture compatible with real-world fiber optical communication network.

In this work, the effect of annealing temperature of Ti552 titanium alloy is systematically investigated based on mechanical property tests, electrochemical tests and static immersion tests. The results show that after the annealing treatment, the microstructure morphology of the α-phase transforms from striated to equiaxed, and the intergranular β-phase gradually increases. As the annealing temperature increases, the grain size gradually increases and the volume fraction of α-phase gradually decreases. The tensile strength and Vickers hardness are the maximum and the elongation is the minimum in the hot-rolled condition. With increasing annealing temperature, the strength and Vickers hardness of Ti552 alloy gradually decrease, while the elongation gradually increases. In 3.5 wt% NaCl solution, Ti552 alloy has similar corrosion behavior at different annealing temperatures, although its corrosion resistance varies. In potentiodynamic polarization and EIS testing, the annealed Ti552 alloy shows a low corrosion current density (10-6 A/cm2) and a high polarization impedance (106 Ω·cm2), indicating the formation of a dense and stable oxide film. Under annealing at 800 °C, the corrosion resistance is at its highest and the corrosion rate is the lowest, according to electrochemical and static immersion studies. The comprehensive analysis suggests that the corrosion behavior of Ti552 alloy in NaCl solution may be a result of the combined effect of the volume fraction of the β-phase and the grain size of the α-phase.

Abstract The field of environmental DNA (eDNA) has rapidly advanced in recent years, providing a non‐invasive and time‐saving method for assessing biodiversity. The First International Environmental DNA (eDNA) Workshop in Hong Kong was held from 16 to 27 October 2023 and provided early career professionals with hands‐on training and collaboration opportunities in eDNA research. With support from The Croucher Foundation Limited (Hong Kong), the workshop covered all stages of an eDNA‐based research project, including study design, field sampling, eDNA extraction, library preparation, bioinformatics, statistical data analysis, and ethics in scientific research. Participants gained insights into the principles and practical applications of eDNA technology, emphasizing the importance of careful experimental design and data interpretation. The workshop also highlighted the need for standardized protocols, comprehensive and local DNA reference databases, and careful selection of primer sets to overcome current issues and limitations. Workshop participants expressed enthusiasm for the potential of eDNA metabarcoding as a valuable tool for ecological monitoring, biodiversity assessment, and conservation decision‐making. The future of eDNA research looks promising overall, with continued advancements in technology, collaboration among researchers, and the integration of eDNA into large‐scale ecological monitoring. Future iterations of the Hong Kong International eDNA workshop will continue to provide hands‐on training and collaboration opportunities for early career professionals interested in eDNA research, focusing on addressing current limitations and challenges in the field.

Summary: This study systematically reviewed the application of large language models (LLMs) in medicine, analyzing 550 selected studies from a vast literature search. LLMs like ChatGPT transformed healthcare by enhancing diagnostics, medical writing, education, and project management. They assisted in drafting medical documents, creating training simulations, and streamlining research processes. Despite their growing utility in assisted diagnosis and improving doctor-patient communication, challenges persisted, including limitations in contextual understanding and the risk of over-reliance. The surge in LLM-related research indicated a focus on medical writing, diagnostics, and patient communication, but highlighted the need for careful integration, considering validation, ethical concerns, and the balance with traditional medical practice. Future research directions suggested a focus on multimodal LLMs, deeper algorithmic understanding, and ensuring responsible, effective use in healthcare.

Rosa rugosa is a deciduous shrub of the rosa family having ecological, economical, and ornamental values. In this study, the cutting seedlings of wild R. rugosa and five cultivated varieties were treated with polyethylene glycol-6000 (PEG-6000) solution to mimic drought stress. The leaf transpiration rate (Tr), photosynthetic rate (Pn), stomatal conductance (Gs), and the relative water content (RWC) of all genotypes decreased under drought stress. Importantly, the Tr in wild R. rugosa (W) was decreased by 29.42% under 5% PEG treatment, whereas that in other varieties was decreased by 57.63%–74.54%. Similarly, the Pn and Gs of genotype W were significantly higher in W than in other genotypes under 5% PEG treatment. The malondialdehyde (MDA) contents in five cultivated varieties were significantly increased under 5%–10% PEG treatments, and that in W was increased under 15% PEG treatment. In summary, the drought resistance of wild R. rugosa was the strongest, followed by that of ZZ, S, and P, and the drought resistance of ZD and F was the poorest. To explore the adaptation characteristics of R. rugosa leaves to drought stress, the leaf surface and microstructure of six genotypes were observed. The characteristics of the wild leaves such as sunken stomata, developed palisade tissue, and low stomatal density may reduce the water loss, resulting in significantly higher drought tolerance than the other five cultivated varieties. This study elucidated the difference of drought resistance among the six R. rugosa genotypes, and enhanced the understanding of the regulatory mechanisms of drought tolerance.

Abstract Background Parkinson’s disease (PD) affects 1% of people over 60, and long-term levodopa treatment can cause side effects. Early diagnosis is of great significance in slowing down the pathological process of PD. Multiple pieces of evidence showed that non-coding RNAs (ncRNAs) could participate in the progression of PD pathology. Pyroptosis is known to be regulated by ncRNAs as a key pathological feature of PD. Therefore, evaluating ncRNAs and pyroptosis-related proteins in serum could be worthy biomarkers for early diagnosis of PD. Methods NcRNAs and pyroptosis/inflammation mRNA levels were measured with reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Luciferase assays were performed to confirm GSDME as a target of miR-675-5p and HMGB1 as a target of miR-1247-5p. In the serum of healthy controls (n = 106) and PD patients (n = 104), RT-qPCR was utilized to assess miR-675-5p, miR-1247-5p, and two related ncRNAs (circSLC8A1and lncH19) levels. The enzyme-linked immunosorbent assay measured serum levels of pyroptosis-related proteins in controls (n = 54) and PD patients (n = 70). Results Our data demonstrated that miR-675-5p and miR-1247-5p significantly changed in PD neuron and animal models. Overexpressed miR-675-5p or downregulated miR-1247-5p could regulate pyroptosis and inflammation in PD neuron models. Using the random forest algorithm, we constructed a classifier based on PD neuron-pyroptosis pathology (four ncRNAs and six proteins) having better predictive power than single biomarkers (AUC = 92%). Additionally, we verified the performance of the classifier in early-stage PD patients (AUC ≥ 88%). Conclusion Serum pyroptosis-related ncRNAs and proteins could serve as reliable, inexpensive, and non-invasive diagnostic biomarkers for PD. Limitations All participants were from the same region. Additionally, longitudinal studies in the aged population are required to explore the practical application value of the classifier.

Abstract Developing facile and efficient methods to obtain circularly polarized luminescence (CPL) materials with a large luminescence dissymmetry factor (g lum) and fluorescence quantum yield (Φ Y) is attractive but still challenging. Herein, supramolecular polymerization of styrylpyrenes (R/S-PEB) is utilized to attain this aim, which can self-assemble into helical nanoribbons. Benefiting from the dominant CH-π interactions between the chromophores, the supramolecular solution of S-PEB shows remarkable blue-color CPL property (g lum: 0.011, Φ Y: 69%). From supramolecular solution to gel, the emission color (blue to yellow-green) and handedness of CPL (g lum: –0.011 to +0.005) are concurrently manipulated, while the corresponding supramolecular chirality maintains unchanged, representing the rare example of color-dependent CPL materials. Thanks to the supramolecular confine effect, the [2 + 2] cycloaddition reaction rate of the supramolecular solution is 10.5 times higher than that of the monomeric solution. In contrast, no cycloaddition reaction occurs for the gel and assembled solid samples. Our findings provide a vision for fabricating multi-modal and high-performance CPL-active materials, paving the way for the development of advanced photo-responsive chiral systems.

Understanding migratory routes is crucial for the conservation of birds and their habitats. Zhejiang is a crucial stopover and wintering area for birds in the East Asian–Australasian Flyway; however, detailed information on this area, and particularly on connections between coastal areas, is limited. By synthesizing ringed and recapture records from local bird-ringing projects and re-sighting community science data (208 records of 35 species), we established migratory connectivity between the Zhejiang coast and nine countries (i.e., Russia, Mongolia, the United States, Korea, Japan, Malaysia, Singapore, Thailand, and Australia), as well as eleven sites within China, and established its crucial role in this flyway. Stopover fidelity was verified by some species with high recapture frequency (seven species exceeded 1%) and species with duplicated re-sighted records (seven Black-faced Spoonbill, one Dalmatian Pelican, and two Spoon-billed Sandpiper individuals). We identified six areas—Hangzhou Bay, Aiwan Bay, Xuanmen National Park, Wenzhou Bay, the reclaimed area between the Ou and Feiyun Rivers, and the Wenzhou Jiangnan Reclamation Area—as crucial stopovers and wintering refuges for waterbirds. Notably, in Xuanmen National Park and the coastal regions along Wenzhou, there were many recovery records for flagship species, such as the Black-faced Spoonbill and Spoon-billed Sandpiper. There were several cases of the recovery of the same individual studied across the years. These findings indicate that these unprotected wetlands require particular attention. Broadly, our findings highlight the feasibility of integrating comprehensive ringing projects with citizen science data to formulate effective conservation strategies and underscore the critical importance of the Zhejiang Coast for migratory waterbirds, particularly those with high conservation concerns, emphasizing the need to mitigate the threats faced by these vulnerable populations.

As a promising technology for high-power and high-temperature power electronics packaging, nanocopper (nanoCu) paste sintering has recently received increasing attention as a die-attachment. The high-temperature deformation of sintered nanoCu paste and its underlying mechanisms challenge the reliability of high-power electronics packaging. In this study, the tensile deformation behaviors of sintered nanoCu paste were firstly characterized by high-temperature tensile tests performed at various temperatures and strain rates ranging from 180 °C to 360 °C, 1 × 10−4 s−1 to 1 × 10−3 s−1 respectively. It was found that the elastic modulus and tensile strength decreased at the higher tensile temperature while the ductility increased accordingly. The highest elastic modulus and tensile strength results were 12.15 GPa and 46.97 MPa, respectively. Second, failure analysis was conducted based on the fracture surface after tensile testing. Recrystallization was revealed as the main factor for ductility improvement. Subsequently, an Anand model was fitted by stress-strain curves to describe the tensile constitutive behavior of the sintered nanoCu paste. Multi-scale modelling techniques also investigated the impact of tensile temperature and strain rate on the tensile response. Molecular dynamics simulation was implemented using a hemispherical Cu nanoparticle model to reveal the properties from an atomistic perspective. In addition, a two-dimensional equivalent model was further established by using a stochastically distributed void morphology. The multi-scale modelling techniques successfully describe the evolution of tensile response to the different tensile temperatures and strain rates. Besides, the equivalent model with random void morphology was demonstrated as the finite element simulation results were highly consistent with the high-temperature tensile experiments.

Abstract Background Renal cell carcinoma (RCC) is a hypermetabolic disease. Abnormal up-regulation of glycolytic signaling promotes tumor growth, and glycolytic metabolism is closely related to immunotherapy of renal cancer. The aim of the present study was to determine whether and how the glycolysis-related biomarker TCIRG1 affects aerobic glycolysis, the tumor microenvironment (TME) and malignant progression of clear cell renal cell carcinoma (ccRCC). Methods Based on The Cancer Genome Atlas (TCGA, n = 533) and the glycolysis-related gene set from MSigDB, we identified the glycolysis-related gene TCIRG1 by bioinformatics analysis, analyzed its immunological properties in ccRCC and observed how it affected the biological function and glycolytic metabolism using online databases such as TIMER 2.0, UALCAN, LinkedOmics and in vitro experiments. Results It was found that the expression of TCIRG1, was significantly increased in ccRCC tissue, and that high TCIRG1 expression was associated with poor overall survival (OS) and short progression-free interval (PFI). In addition, TCIRG1 expression was highly correlated with the infiltration immune cells, especially CD4+T cell Th1, CD8+T cell, NK cell, and M1 macrophage, and positively correlated with PDCD1, CTLA4 and other immunoinhibitors, CCL5, CXCR3 and other chemokines and chemokine receptors. More importantly, TCIRG1 may regulate aerobic glycolysis in ccRCC via the AKT/mTOR signaling pathway, thereby affecting the malignant progression of ccRCC cell lines. Conclusions Our results demonstrate that the glycolysis-related biomarker TCIRG1 is a tumor-promoting factor by affecting aerobic glycolysis and tumor immune microenvironment in ccRCC, and this finding may provide a new idea for the treatment of ccRCC by combination of metabolic intervention and immunotherapy.

Membrane-based pervaporation (PV) for organic solvent dehydration is of great significance in the chemical and petrochemical industries. In this work, high-aluminum ZSM-5 zeolite membranes were synthesized by a fluoride-assisted secondary growth on α-alumina tubular supports using mordenite framework inverted (MFI) nanoseeds (~110 nm) and a template-free synthesis solution with a low Si/Al ratio of 10. Characterization by XRD, EDX, and SEM revealed that the prepared membrane was a pure-phase ZSM-5 zeolite membrane with a Si/Al ratio of 3.8 and a thickness of 2.8 µm. Subsequently, two categories of PV performance parameters (i.e., flux versus separation factor and permeance versus selectivity) were used to systematically examine the effects of operating conditions on the PV dehydration performance of different organic solvents (methanol, ethanol, n-propanol, and isopropanol), and their PV mechanisms were explored. Employing permeance and selectivity effectively disentangles the influence of operating conditions on PV performance, thereby elucidating the inherent contribution of membranes to separation performance. The results show that the mass transfer during PV dehydration of organic solvents was mainly dominated by the adsorption–diffusion mechanism. Furthermore, the diffusion of highly polar water and methanol molecules within membrane pores had a strong mutual slowing-down effect, resulting in significantly lower permeance than other binary systems. However, the mass transfer process for water/low-polar organic solvent (ethanol, n-propanol, and isopropanol) mixtures was mainly controlled by competitive adsorption caused by affinity differences. In addition, the high-aluminum ZSM-5 zeolite membrane exhibited superior PV dehydration performance for water/isopropanol mixtures.

Irrigation refers to supplying water to soil through pipes, pumps, and spraying systems to ensure even distribution across the field. In traditional farming or gardening, the setup and usage of an agricultural irrigation system solely rely on the personal experience of farmers. The Food and Agriculture Organization of the United Nations (UN) has projected that by 2030, developing countries will expand their irrigated areas by 34%, while water consumption will only be up 14%. This discrepancy highlights the importance of accurately monitoring water flow and volume rather than people’s rough estimations. The smart irrigation systems, a key subsystem of smart agriculture known as the cyber–physical system (CPS) in the agriculture domain, automate the administration of water flow, volume, and timing via using cutting-edge technologies, especially the Internet of Things (IoT) technology, to solve the challenges. This study explores a comprehensive three-dimensional problem space to thoroughly analyze the IoT’s applications in irrigation systems. Our framework encompasses several critical domains in smart irrigation systems. These domains include soil science, sensor technology, communication protocols, data analysis techniques, and the practical implementations of automated irrigation systems, such as remote monitoring, autonomous operation, and intelligent decision-making processes. Finally, we discuss a few challenges and outline future research directions in this promising field.

Hepatocellular carcinoma (HCC) has become the fourth leading cause of cancer-related deaths worldwide; annually, approximately 830,000 deaths related to liver cancer are diagnosed globally. Since early-stage HCC is clinically asymptomatic, traditional treatment modalities, including surgical ablation, are usually not applicable or result in recurrence. Immunotherapy, particularly immune checkpoint blockade (ICB), provides new hope for cancer therapy; however, immune evasion mechanisms counteract its efficiency. In addition to viral exposure and alcohol addiction, nonalcoholic steatohepatitis (NASH) has become a major cause of HCC. Owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance, NASH-associated HCC patients respond much less efficiently to ICB treatment than do patients with other etiologies. In addition, abnormal inflammation contributes to NASH progression and NASH–HCC transition, as well as to HCC immune evasion. Therefore, uncovering the detailed mechanism governing how NASH-associated immune cells contribute to NASH progression would benefit HCC prevention and improve HCC immunotherapy efficiency. In the following review, we focused our attention on summarizing the current knowledge of the role of CD4+T cells in NASH and HCC progression, and discuss potential therapeutic strategies involving the targeting of CD4+T cells for the treatment of NASH and HCC.

An integrated and high-throughput device for pathogen detection is crucial in point-of-care testing (POCT), especially for early diagnosis of infectious diseases and preventing the spread of infection. We developed an on-site testing platform that utilizes a centrifugal microfluidic chip and automated device to achieve high-throughput detection. The low-power (E. coli, our platform achieves a limit of detection (LOD) of 102 CFU/mL in 60 min. In summary, our active centrifugal microfluidic platform provides a solution for the integration of complex biological assays on turntables, with great potential in the application of point-of-care diagnosis.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectures of ccRCC tissues using imaging mass cytometry (IMC) and explored their associations with clinical outcome and therapeutic response. Methods Using IMC, we profiled the TME landscape of ccRCC and paracancerous tissue by measuring 17 markers involved in tissue architecture, immune cell and immune activation. In the ccRCC tissue, we identified distinct immune architectures of ccRCC tissue based on the mix score and performed cellular neighborhood (CN) analysis to subdivide TME phenotypes. Moreover, we assessed the relationship between the different TME phenotypes and ccRCC patient survival, clinical features and treatment response. Results We found that ccRCC tissues had higher levels of CD8+ T cells, CD163− macrophages, Treg cells, endothelial cells, and fibroblasts than paracancerous tissues. Immune infiltrates in ccRCC tissues distinctly showed clustered and scattered patterns. Within the clustered pattern, we identified two subtypes with different clinical outcomes based on CN analysis. The TLS-like phenotype had cell communities resembling tertiary lymphoid structures, characterized by cell–cell interactions of CD8+ T cells-B cells and GZMB+CD8+ T cells-B cells, which exhibited anti-tumor features and favorable outcomes, while the Macrophage/T-clustered phenotype with macrophage- or T cell-dominated cell communities had a poor prognosis. Patients with scattered immune architecture could be further divided into scattered-CN-hot and scattered-CN-cold phenotypes based on the presence or absence of immune CNs, but both had a better prognosis than the macrophage/T-clustered phenotype. We further analyzed the relationship between the TME phenotypes and treatment response in five metastatic ccRCC patients treated with sunitinib, and found that all three responders were scattered-CN-hot phenotype while both non-responders were macrophage/T-clustered phenotype. Conclusion Our study revealed the structural heterogeneity of TME in ccRCC and its impact on clinical outcome and personalized treatment. These findings highlight the potential of IMC and CN analysis for characterizing TME structural units in cancer research.

Reconfigurable battery systems (RBSs) provide a promising alternative to traditional battery systems due to their flexible and dynamically changeable topological structures that can be adapted to different battery charging and discharging strategies. A critical system parameter known as the maximum allowable current (MAC) is pivotal to RBS operation. This parameter is instrumental in maintaining the current of each individual battery within a safe range and serves as a guiding indicator for the system’s reconfiguration, ensuring its safety and reliability. This paper proposes a method for calculating the MAC of an arbitrary RBS using a greedy algorithm in conjunction with a directed graph model of the RBS. Using the shortest path of the battery, the greedy algorithm transforms the exhaustion of the switch states in the brute-force algorithm or variable search without utilizing structures in the heuristic algorithms in the combination of the shortest paths. The directed graph model, based on an equivalent circuit, provides a specific method for calculating the MAC of a given structure. The proposed method is validated using 2 previously published RBS structures and an additional one with a more complex structure. The results are the same as those from the brute-force algorithm, but the proposed method substantially improves the computational efficiency, being theoretically Ns2Ns − Nblog10Nb times faster than the brute-force algorithm for an RBS with Nb batteries and Ns switches. Another advantage of the proposed method is its ability to calculate the MAC of RBSs with arbitrary structures and variable batteries, even in scenarios with random isolated batteries.

Tumor cell extravasation across endothelial barrier has been recognized as a pivotal event in orchestrating metastasis formation. This event is initiated by the interactions of extravasating tumor cells with endothelial cells (ECs). Therefore, targeting the crosstalk between tumor cells and ECs might be a promising therapeutic strategy to prevent metastasis. In this study, we demonstrated that Rh1, one of the main ingredients of ginseng, hindered the invasion of breast cancer (BC) cells as well as diminished the permeability of ECs both in vitro and in vivo, which was responsible for the attenuated tumor cell extravasation across endothelium. Noteworthily, we showed that ECs were capable of inducing the epithelial-mesenchymal transition (EMT) and invadopodia of BC cells that are essential for tumor cell migration and invasion through limiting the nuclear translocation of hematopoietically expressed homeobox (HHEX). The decreased nuclear HHEX paved the way for initiating the CCL20/CCR6 signaling axis, which in turn contributed to damaged endothelial junctions, uncovering a new crosstalk mode between tumor cells and ECs. Intriguingly, Rh1 inhibited the kinase activity of casein kinase II subunit alpha (CK2α) and further promoted the nuclear translocation of HHEX in the BC cells, which resulted in the disrupted crosstalk between chemokine (C-C motif) ligand 20 (CCL20) in the BC cells and chemokine (C-C motif) receptor 6 (CCR6) in the ECs. The prohibited CCL20-CCR6 axis by Rh1 enhanced vascular integrity and diminished tumor cell motility. Taken together, our data suggest that Rh1 serves as an effective natural CK2α inhibitor that can be further optimized to be a therapeutic agent for reducing tumor cell extravasation.

Purpose To evaluate the efficacy and safety of ultrasound-guided femoral nerve block (FNB) in treating great saphenous vein (GSV) insufficiency by endovenous radiofrequency ablation (EVRA) combined with punctate stripping (PS). Methods This was a single-center, retrospective cohort study. A total of 135 patients were divided into Group A (59 patients) and Group B (76 patients). All patients received tumescent anesthesia during the operation, and group A received an additional ultrasound-guided FNB before the procedure. Intraoperative and postoperative pain score, the volume of tumescent anesthesia solution (TAS), and other indicators were compared in two groups. Results Group A had a significantly lower intraoperative pain visual analog scale than group B (2.7 ± 1.2 vs 5.2 ± 1.5, P

Blood vessels are a key target for cancer therapy. Compared with the healthy vasculature, tumor blood vessels are extremely immature, highly permeable, and deficient in pericytes. The aberrantly vascularized tumor microenvironment is characterized by hypoxia, low pH, high interstitial pressure, and immunosuppression. The efficacy of chemotherapy, radiotherapy, and immunotherapy is affected by abnormal blood vessels. Some anti-angiogenic drugs show vascular normalization effects in addition to targeting angiogenesis. Reversing the abnormal state of blood vessels creates a normal microenvironment, essential for various cancer treatments, specifically immunotherapy. In addition, immune cells and molecules are involved in the regulation of angiogenesis. Therefore, combining vascular normalization with immunotherapy may increase the efficacy of immunotherapy and reduce the risk of adverse reactions. In this review, we discussed the structure, function, and formation of abnormal vessels. In addition, we elaborated on the role of the immunosuppressive microenvironment in the formation of abnormal vessels. Finally, we described the clinical challenges associated with the combination of immunotherapy with vascular normalization, and highlighted future research directions in this therapeutic area.

Attribution of high-impact weather events to anthropogenic climate change is important for disentangling long-term trends from natural variability and estimating potential future impacts. Up to this point, most attribution studies have focused on univariate drivers, despite the fact that many impacts are related to multiple compounding weather and climate drivers. For instance, co-occurring climate extremes in neighbouring regions can lead to very large combined impacts. Yet, attribution of spatially compounding events with different hazards poses a great challenge. Here, we present a comprehensive framework for compound event attribution to disentangle the effects of natural variability and anthropogenic climate change on the event. Taking the 2020 spatially compounding heavy precipitation and heatwave event in China as a showcase, we find that the respective dynamic and thermodynamic contributions to the intensity of this event are 51% (35–67%) and 39% (18–59%), and anthropogenic climate change has increased the occurrence probability of similar events at least 10-fold. We estimate that compared to the current climate, such events will become 10 times and 14 times more likely until the middle and end of the 21st century, respectively, under a high-emissions scenario. This increase in likelihood can be substantially reduced (to seven times more likely) under a low-emissions scenario. Our study demonstrates the effect of anthropogenic climate change on high-impact compound extreme events and highlights the urgent need to reduce greenhouse gas emissions.

Abstract Edible rose is one of the main cash crops in Yunnan, China. Due to the high degree of lignification of rose stalks which is difficult to cut, and roses can only be pruned by hand after picking. Most of Yunnan Province is hilly landscape. Therefore, it is necessary to design an efficient small rose pruner for hills. Based on the experimental results of the physical and mechanical properties of rose stems, a simulation experiment of three different cutting methods was conducted to determine the optimal scheme. The results showed that single disc cutter is the best cutting method. An improved disc cutter with variable sliding angle is designed. In order to study the effects of the different structure parameters on the performance of the pruning machine and get the optimal combination of parameters, the orthogonal test was conducted. Forward speed, rotational speed of cutter, number of blades, cutting angle and knife-edge angle as factors, and the quality of pruning was selected as the evaluation index. The experiment results indicated that the working performance of machine was the highest when the number of blades was 6, rotational speed of cutter was 2000 rpm, cutting angle was 20°, knife-edge angle was 10°, forward speed was 0.5 m s−1. The average quality of pruning index, miss cutting index and tearing index were 90.6%, 5.68% and 3.72%, respectively. The designed machine can meet the agronomic requirements of Yunnan edible rose pruning operation. The research provides a reference for the design and extending of the pruning machine for edible rose.

Abstract Objective To explore the association of delivery mode and the number of pregnancies with anorectal manometry data in patients with postpartum constipation. Methods This retrospective study included women with postpartum constipation treated at the pelvic floor rehabilitation department of Huzhou Maternity & Child Health Care Hospital between January 2018 and December 2019. Results Among 127 patients included, 55 (43.3%) had one pregnancy, 72 (56.7%) had two pregnancies, 96 (75.6%) delivered spontaneously, 25 (16.7%) underwent Cesarean section, and six (4.7%) needed a Cesarean section despite spontaneous labor. The median duration of constipation was 12 months (range, 6–12). There were no differences between the two groups for any manometry parameters (all P > 0.05). The patients with a spontaneous delivery had a lower change in maximal contracting sphincter pressure compared with those with Cesarean section (14.3 (4.5–25.0) vs. 19.6 (13.4–40.0), P = 0.023). Only the delivery mode (Cesarean vs. spontaneous) independently affected the changes in contracting sphincter pressure (B = 10.32, 95%CI: 2.95–17.69, P = 0.006); age (P = 0.201), number of pregnancies (P = 0.190), and constipation duration (P = 0.161) were not associated. Conclusion The patients with a spontaneous delivery had a lower change in maximal contracting sphincter pressure compared with those with a Cesarean section, suggesting that patients with Cesarean may retain a better “push” function during defecation.

Ti and its alloys are widely used in the aerospace, chemical equipment, and other fields due to their excellent comprehensive properties. Ti-0.3Mo-0.8Ni (TA10) alloy is a type of near-α Ti alloy with good corrosion resistance. The addition of Al element can improve the effect of solution strengthening in Ti alloy, thus, it can improve the strength of Ti alloy. The strength, corrosion resistance, and heat resistance can be further improved by the addition of Zr element. Therefore, a new Near-α Ti alloy (Ti-0.3Mo-0.8Ni-0.5Al-0.5Zr) was developed in the basis of TA10 alloy to enhance the mechanical properties of the alloy. In this study, the deformation mechanism and constitutive model of the new alloy were investigated. The results demonstrate that the extent of flow-softening phenomenon was obvious when deformed in the α+β phase field, and the extent was weakened when deformed in the single β phase field which exhibited a near steady-state flow. The primary mechanism of softening was DRX and DRV when deformed in the α+β phase field, and the DRV would be the main flow-softening mechanism when deformed in the single β phase field. The hot processing map was established based on Prasad's instability criterion, and the unsuitable processing parameters were 780–870 °C and 1-10 s−1.