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Abstract Extremely large magnetoresistance (XMR) is highly applicable in spintronic devices such as magnetic sensors, magnetic memory, and hard drives. Typically, XMR is found in Weyl semimetals characterized by perfect electron–hole symmetry or exceptionally high electric conductivity and mobility. Our study explores this phenomenon in a recently developed graphene moiré system, which demonstrates XMR owing to its topological structure and high-quality crystal formation. We investigate the electronic properties of three-dimensional intertwined twisted graphene spirals (TGS), manipulating the screw dislocation axis to achieve a rotation angle of 7.3°. Notably, at 14 T and 2 K, the magnetoresistance of these structures reaches 1.7 × 107%, accompanied by a metal–insulator transition as the temperature increases. This transition becomes noticeable when the magnetic field exceeds a minimal threshold of approximately 0.1 T. These observations suggest the possible existence of complex, correlated states within the partially filled three-dimensional Landau levels of the 3D TGS system. Our findings open up possibilities for achieving XMR by engineering the topological structure of 2D layered moiré systems.

Abstract The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6’s large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde’s spacing arm, reducing spatial hindrance and enhancing enzyme–substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.

Abstract The influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin–eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure.

To analyze the effect of the composition of ingredients (Sulfur-containing substance, saccharide) on meat flavor derived from high temperature sesame cake protein hydrolysate (HTSPH), the influence of five sulfides such as cysteine (L-Cys), methionine (L-Met), thiamine (VB1) on the sensory evaluation, volatile component, pH, brown intensity and glycosylation degree of the maillard reaction products (MRPs) of HTSPH was first investigated under the constant content of HTSPH and xylose, then the difference in the characteristics of MRPs obtained from the reaction of nine saccharides including xylose, ribose and galactose with L-Cys and HTSPH was compared. Finally, the mixture design was conducted to explore the effects of the composition of L-Cys, xylose and HTSPH on the properties and volatile components of MRPs. Results showed that the volatile components of MRPs formed from various sulfides differed remarkably, the MRPs generated by L-Cys had a prominent meaty flavor and the highest sensory evaluation score (69.32±1.34). Comparison of the properties and composition of MRPs produced from various saccharides revealed that the sensory scores of MRPs prepared from pentoses were significantly higher than those of the MRPs papered with hexoses, and its volatile compounds were rich in meat flavor components. Xylose was the suitable saccharide for preparing meat flavor from HTSPH. Mixture design revealed the composition of L-Cys, xylose and HTSPH dramatically affected the flavor profile of MRPs. 22 key volatile components have been identified though Partial least squares regression. 5-methyl-2-thiophenecarbaldehyde, difurfuryl disulfide, 5-ethylthiophene-2-carbaldehyde, 4,6-dimethyl-1H,3H-thieno[3,4-c]-thiophene, benzaldehyde, 2-furfuryl 2-methyl-3-furyl disulfide, and 2-furfurylthiol were positively correlated with the sensory score of MRPs produced by HTSPH. This study provides theoretical guidance for the preparation of the meat flavor from high-temperature sesame cake meal.

Abstract Aims/Introduction Diabetic cardiomyopathy (DCM) is a prevalent condition among individuals with diabetes, and is associated with a high mortality rate. The anti‐oxidant properties of Jing Huang or Polygonatum sibiricum polysaccharide (PSP) have been extensively used to treat diabetes‐related disorders; however, its potential effectiveness against DCM remains unknown. This study aimed to investigate PSP's therapeutic effects on DCM in an experimental diabetic mouse model. Materials and Methods To induce insulin resistance, mice were fed a high‐fat diet for 3 months, followed by intraperitoneal streptozotocin injection to induce slight hyperglycemia and develop DCM. Both DCM and control mice were given PSP orally for 3 weeks. Western blotting was used to detect the protein expressions of protein kinase G, C/EBP homologous protein, glucose‐regulated protein 78, phosphodiesterase type 5, protein kinase R‐like endoplasmic reticulum (ER) kinase, and phospho‐protein kinase R‐like endoplasmic reticulum kinase in heart tissue. Results The results showed a reduction in bodyweight and blood glucose levels in the PSP therapy group compared with DCM group. PSP also improved cardiac function and had a negligible effect on malondialdehyde activity. Furthermore, the findings showed that PSP alleviated ER and oxidative stress observed in DCM mice hearts, leading to the inhibition of cyclic guanosine monophosphate‐specific phosphodiesterase type 5 and cardiac cyclic guanosine monophosphate reactivation. Phosphodiesterase type 5 inhibition reduced high‐fat diet‐induced cardiac dysfunction and decreased ER stress. Conclusions PSP could effectively protect diabetic myocardium by inhibiting endoplasmic reticulum stress. These findings provide crucial insights into the potential of PSP to ameliorate DCM conditions in diabetic mice by decreasing ER and oxidative stress, and enhancing cyclic guanosine monophosphate protein kinase G signaling.

Abstract Objective To investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome (ASS). Methods This study included 115 anti-Jo-1-positive patients with ASS who were admitted to China-Japan Friendship Hospital between 2009 and 2019. Anti-Jo-1 antibody serum levels at initial admission and follow-up were determined by enzyme-linked immunosorbent assay (ELISA). Global and organ disease activity was assessed at baseline and follow-up according to the International Myositis Assessment and Clinical Studies guidelines. Results Among enrolled patients, 70 (60.9%) patients initially presented with interstitial lung disease (ILD), and 46 (40%) patients presented with with muscle weakness at initial admission. At baseline, patients with ILD had lower levels of anti-Jo-1 antibodies than those without ILD (p = 0.012). Baseline anti-Jo-1 antibody levels were higher in patients with muscle weakness, skin involvement, and arthritis (all p

Abstract Numerous algorithms have been proposed to identify cell types in single-cell RNA sequencing data, yet a fundamental problem remains: determining associations between cells and phenotypes such as cancer. We develop SCIPAC, the first algorithm that quantitatively estimates the association between each cell in single-cell data and a phenotype. SCIPAC also provides a p-value for each association and applies to data with virtually any type of phenotype. We demonstrate SCIPAC’s accuracy in simulated data. On four real cancerous or noncancerous datasets, insights from SCIPAC help interpret the data and generate new hypotheses. SCIPAC requires minimum tuning and is computationally very fast.

Corrosion-erosion performances of Ti-6.5Al–2Zr–1Mo–1V (TA15) alloy fabricated by two laser additive manufacturing technologies, namely selective laser melting (SLM) and laser metal deposition (LMD) were investigated, and compared with those of traditional forged counterpart. Results show that SLM-ed TA15 possesses better corrosion, wear, and tribocorrosion resistances than LMD-ed and forged TA15. This is mainly attributed to the ultrafine-grain αʹ phase in the microstructure of SLM-ed sample, which improves the hardness and thereby enhances the wear and tribocorrosion resistance. Additionally, the complete αʹ phase formed in SLM-ed sample also avoids the galvanic corrosion that occurs at the α+β-type LMD-ed and forged samples.

Abstract Background Patients with congenital myopathies may experience respiratory involvement, resulting in restrictive ventilatory dysfunction and respiratory failure. Pulmonary hypertension (PH) associated with this condition has never been reported in congenital ryanodine receptor type 1(RYR1)-related myopathy. Case presentation A 47-year-old woman was admitted with progressively exacerbated chest tightness and difficulty in neck flexion. She was born prematurely at week 28. Her bilateral lower extremities were edematous and muscle strength was grade IV−. Arterial blood gas analysis revealed hypoventilation syndrome and type II respiratory failure, while lung function test showed restrictive ventilation dysfunction, which were both worse in the supine position. PH was confirmed by right heart catheterization (RHC), without evidence of left heart disease, congenital heart disease, or pulmonary artery obstruction. Polysomnography indicated nocturnal hypoventilation. The ultrasound revealed reduced mobility of bilateral diaphragm. The level of creatine kinase was mildly elevated. Magnetic resonance imaging showed myositis of bilateral thigh muscle. Muscle biopsy of the left biceps brachii suggested muscle malnutrition and congenital muscle disease. Gene testing revealed a missense mutation in the RYR1 gene (exon33 c.C4816T). Finally, she was diagnosed with RYR1-related myopathy and received long-term non-invasive ventilation (NIV) treatment. Her symptoms and cardiopulmonary function have been greatly improved after 10 months. Conclusions We report a case of RYR1-related myopathy exhibiting hypoventilation syndrome, type II respiratory failure and PH associated with restrictive ventilator dysfunction. Pulmonologists should keep congenital myopathies in mind in the differential diagnosis of type II respiratory failure, especially in patients with short stature and muscle weakness.

Abstract Site- and stereoselective C–H functionalization is highly challenging in the synthetic chemistry community. Although the chemistry of vinyl cations has been vigorously studied in C(sp3)–H functionalization reactions, the catalytic enantioselective C(sp3)–H functionalization based on vinyl cations, especially for an unactivated C(sp3)–H bond, has scarcely explored. Here, we report an asymmetric copper-catalyzed tandem diyne cyclization/unactivated C(sp3)–H insertion reaction via a kinetic resolution, affording both chiral polycyclic pyrroles and diynes with generally excellent enantioselectivities and excellent selectivity factors (up to 750). Importantly, this reaction demonstrates a metal-catalyzed enantioselective unactivated C(sp3)–H functionalization via vinyl cation and constitutes a kinetic resolution reaction based on diyne cyclization. Theoretical calculations further support the mechanism of vinyl cation-involved C(sp3)–H insertion reaction and elucidate the origin of enantioselectivity.

Abstract Inflammatory arthritis (IA) is a common rheumatic adverse event following immune checkpoint inhibitors treatment. The clinical disparities between IA and rheumatoid arthritis (RA) imply disease heterogeneity and distinct mechanisms, which remain elusive. Here, we profile CD45+ cells from the peripheral blood or synovial fluid (SF) of patients with PD-1-induced IA (PD-1-IA) or RA using single-cell RNA sequencing. We report the predominant expansion of IL1B hi myeloid cells with enhanced NLRP3 inflammasome activity, in both the SF and peripheral blood of PD-1-IA, but not RA. IL1B hi macrophages in the SF of PD-1-IA shared similar inflammatory signatures and might originate from peripheral IL1B hi monocytes. Exhausted CD8+ T cells (Texs) significantly accumulated in the SF of patients with PD-1-IA. IL1B hi myeloid cells communicated with CD8+ Texs possibly via the CCR1-CCL5/CCL3 and CXCL10-CXCR3 axes. Collectively, these results demonstrate different cellular and molecular pathways in PD-1-IA and RA and highlight IL1B hi macrophages as a possible therapeutic target in PD-1-IA.

Inflammation is a biological response of multicellular organisms caused by injuries, pathogens or irritants. An excessive inflammatory response can lead to tissue damage and various chronic diseases. Chronic inflammation is a common feature of many diseases, making the search for drugs to treat inflammation-related diseases urgent. Scutellarin, a natural flavonoid metabolite, is widely used in the treatment of various inflammation-related diseases for its anti-inflammatory, anti-oxidant and anti-cancer activities. Scutellarin can inhibit key inflammatory pathways (PI3K/Akt, MAPK, and NF-κB, etc.) and activate the anti-oxidant related pathways (Nrf2, ARE, ect.), thereby protecting tissues from inflammation and oxidative stress. Modern extraction technologies, such as microwave-assisted, ultrasound assisted, and supercritical fluid extraction, have been utilized to extract scutellarin from Scutellaria and Erigeron genera. These technologies improve efficiency and retain biological activity, making scutellarin suitable for large-scale production. Scutellarin has significant therapeutic effects in treating osteoarthritis, pulmonary fibrosis, kidney injury, and cardiovascular diseases. However, due to its low bioavailability and short half-life, its clinical application is limited. Researchers are exploring innovative formulations (β-cyclodextrin polymers, triglyceride mimetic active ingredients, and liposome precursors, etc.) to improve stability and absorption rates. Despite these challenges, the potential of scutellarin in anti-inflammatory, anti-oxidant, and anti-cancer applications remains enormous. By optimizing formulations, exploring combination therapies, and conducting in-depth mechanistic research, scutellarin can play an important role in treating various inflammatory diseases, providing patients with more and effective treatment options.

BackgroundPolycyclic aromatic hydrocarbons (PAHs), as organic pollutants widely present in daily environments, have been shown by existing epidemiological studies to be significantly associated with deficits in learning and memory functions in children and adults. However, the association between exposure to PAHs and cognitive function in older adults remains unclear. Additionally, existing related studies have only assessed the association between individual PAH exposures and cognitive assessments, overlooking the risks posed by mixed exposures. This study aims to use three statistical models to investigate the individual and overall effects of mixed PAH exposures on the cognition of older adults in the United States.MethodsThe study cohort was obtained from the NHANES database, which included individuals aged 60 and older from 2011 to 2014. Weighted generalized linear models (GLM), weighted quantile sum (WQS) models, and Bayesian kernel machine regression (BKMR) models were utilized to evaluate the connections between urinary PAH metabolites and the standardized Z-scores of four cognitive tests: Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST).ResultsOur analysis involved 899 individuals aged 60 and above. In the fully adjusted GLM, 2-hydroxynaphthalene (2-OHNa), 3-hydroxyfluorene (3-OHFlu), and 2-hydroxyfluorene (2-OHFlu) demonstrated negative associations with DSST Z-scores. In the WQS model, six urinary PAH metabolites were negatively linked to AFT Z-scores (β (95% confidence intervals [CI]): −0.120 (−0.208, −0.033), p = 0.007) and DSST Z-scores (β (95% CI): −0.182 (−0.262, −0.103), p

Abstract Vasculogenic mimicry (VM) describes a process by which tumor cells formed a novel microcirculation pattern in an endothelial cell‐free manner. Clinically, VM is associated with aggressive phenotype and poor patient survival. However, the current models for investigating VM include 2D monolayer cultures, Matrigel‐based cultures, and animal models, each of which has limitations. Matrigel‐based models often exhibit batch‐to‐batch variations, while in vivo tumor models currently produce insufficient amounts of VM. There is currently no suitable tumor model to discover new therapeutic targets against VM. Herein, we establish an extracellular matrix (ECM)‐based engineered tumor model in vivo and in vitro. In this study, we demonstrate that matrix proteins enhanced the VM formation in the engineered xenograft model. Furthermore, we also investigated the role of collagen/fibronectin (FN) in melanoma progression and VM formation. Compared with cells cultured on TCPS plates, the B16F10 cells cultured on collagen/FN coated plates showed increased proliferation and stemness, and significantly enhanced invasion and formation of VM networks. Molecular mechanism analysis showed that Integrin/VE‐cadherin/EphA2/PI3K/MMP‐2 signaling pathways are responsible for VM formation. Our results indicate that collagen/FN matrix plays an important role in VM formation in melanoma, suggesting that ECM protein is a potential therapeutic target for anti‐VM therapy for melanoma.

Point clouds are sets of points used to visualize three-dimensional (3D) objects. Point clouds can be static or dynamic. Each point is characterized by its 3D geometry coordinates and attributes such as color. High-quality visualizations often require millions of points, resulting in large storage and transmission costs, especially for dynamic point clouds. To address this problem, the moving picture experts group has recently developed a compression standard for dynamic point clouds called video-based point cloud compression (V-PCC). The standard generates two-dimensional videos from the geometry and color information of the point cloud sequence. Each video is then compressed with a video coder, which converts each frame into frequency coefficients and quantizes them using a quantization parameter (QP). Traditionally, the QPs are severely constrained. For example, in the low-delay configuration of the V-PCC reference software, the quantization parameter values of all the frames in a group of pictures are set to be equal. We show that the rate-distortion performance can be improved by relaxing this constraint and treating the QP selection problem as a multi-variable constrained combinatorial optimization problem, where the variables are the QPs. To solve the optimization problem, we propose a variant of the differential evolution (DE) algorithm. Differential evolution is an evolutionary algorithm that has been successfully applied to various optimization problems. In DE, an initial population of randomly generated candidate solutions is iteratively improved. At each iteration, mutants are generated from the population. Crossover between a mutant and a parent produces offspring. If the performance of the offspring is better than that of the parent, the offspring replaces the parent. While DE was initially introduced for continuous unconstrained optimization problems, we adapt it for our constrained combinatorial optimization problem. Also, unlike standard DE, we apply individual mutation to each variable. Furthermore, we use a variable crossover rate to balance exploration and exploitation. Experimental results for the low-delay configuration of the V-PCC reference software show that our method can reduce the average bitrate by up to 43% compared to a method that uses the same QP values for all frames and selects them according to an interior point method.

BackgroundIn recent years, a range of novel smartphone-derived data streams about human mobility have become available on a near–real-time basis. These data have been used, for example, to perform traffic forecasting and epidemic modeling. During the COVID-19 pandemic in particular, human travel behavior has been considered a key component of epidemiological modeling to provide more reliable estimates about the volumes of the pandemic’s importation and transmission routes, or to identify hot spots. However, nearly universally in the literature, the representativeness of these data, how they relate to the underlying real-world human mobility, has been overlooked. This disconnect between data and reality is especially relevant in the case of socially disadvantaged minorities. ObjectiveThe objective of this study is to illustrate the nonrepresentativeness of data on human mobility and the impact of this nonrepresentativeness on modeling dynamics of the epidemic. This study systematically evaluates how real-world travel flows differ from census-based estimations, especially in the case of socially disadvantaged minorities, such as older adults and women, and further measures biases introduced by this difference in epidemiological studies. MethodsTo understand the demographic composition of population movements, a nationwide mobility data set from 318 million mobile phone users in China from January 1 to February 29, 2020, was curated. Specifically, we quantified the disparity in the population composition between actual migrations and resident composition according to census data, and shows how this nonrepresentativeness impacts epidemiological modeling by constructing an age-structured SEIR (Susceptible-Exposed-Infected- Recovered) model of COVID-19 transmission. ResultsWe found a significant difference in the demographic composition between those who travel and the overall population. In the population flows, 59% (n=20,067,526) of travelers are young and 36% (n=12,210,565) of them are middle-aged (P

Abstract Objective This study aims to identify the most effective diagnostic method for distinguishing pathogenic and non-pathogenic Gram-negative bacteria (GNB) in suspected pneumonia cases using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples. Methods The effectiveness of mNGS was assessed on BALF samples collected from 583 patients, and the results were compared with those from microbiological culture and final clinical diagnosis. Three interpretational approaches were evaluated for diagnostic accuracy. Results mNGS outperformed culture significantly. Among the interpretational approaches, Clinical Interpretation (CI) demonstrated the best diagnostic performance with a sensitivity of 87.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 98.3%. CI’s specificity was significantly higher than Simple Interpretation (SI) at 37.9%. Additionally, CI excluded some microorganisms identified as putative pathogens by SI, including Haemophilus parainfluenzae, Haemophilus parahaemolyticus, and Klebsiella aerogenes. Conclusion Proper interpretation of mNGS data is crucial for accurately diagnosing respiratory infections caused by GNB. CI is recommended for this purpose.

Objective: To explore the efficacy and potential mechanisms of the ethanol extract of Abelmoschus manihot (L.) Medic in contrast-induced nephropathy (CIN). Methods: CIN rat models and human renal proximal tubular cells (HK-2) with iopromide-induced injury were employed to mimic CIN conditions. The effect of Abelmoschus manihot extract on the rat models and HK-2 cells was evaluated. In rat models, kidney function, histology, oxidative stress and apoptosis were determined. In HK-2 cells, cell viability, apoptosis, mitochondrial membrane potential, and endoplasmic reticulum stress were assessed. Results: Abelmoschus manihot extract significantly improved structural and functional impairments in the kidneys of CIN rats. Additionally, the extract effectively mitigated the decline in cellular viability and reduced iopromide-induced oxidative stress and lipid peroxidation. Mechanistic investigations revealed that Abelmoschus manihot extract prominently attenuated acute endoplasmic reticulum stress-mediated apoptosis by downregulating GRP78 and CHOP protein levels. Conclusions: Abelmoschus manihot extract can be used as a promising therapeutic and preventive agent in the treatment of CIN.

Abstract This study aimed to develop and validate prognostic nomograms that can estimate the probability of 1-, 3- and 5-year overall survival (OS) as well as cancer-specific survival (CSS) for Intrahepatic cholangiocarcinoma (ICCA) patients. Clinical data of 1446 patients diagnosed with ICCA between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. In both the OS and the CSS group, the training cohort and validation cohort were divided into a 7:3 ratio. Age, sex, AJCC T stage, AJCC N stage, AJCC M stage, surgical status, and tumor grade were selected as independent prognostic risk factors to build the nomograms. To compare the efficacy of predicting 1-, 3-, and 5-year OS and CSS rates of the nomogram with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, we evaluated the Harrell’s index of concordance (C-index), area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) in both cohorts. The results showed the nomogram for 1-, 3-, and 5-year OS and CSS prediction performed better than the AJCC staging system. In the subgroup analysis for patients could not receive surgery as the primary treatment. We developed two nomograms for predicting the 1-, and 2-year OS and CSS rates following the same analysis procedure. Results indicate that the performance of both nomograms, which contained sex, AJCC T stage, AJCC M stage, chemotherapy, and tumor grade and prognostic factors, was also superior to the AJCC staging system. Meanwhile, four dynamic network-based nomograms were published. The survival analysis showed the survival rate of patients classified as high-risk based on the nomogram score was significantly lower compared to those categorized as low-risk (P

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood. Methods: To explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM. Results: Our findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM. Conclusions: Our study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC.

Background: The FXYD domain-containing ion transport regulator 5 (FXYD5) gene is a cancer promoter. However, evidence for an association between FXYD5 and various types of cancer is still lacking. Using multi-omics bioinformatics, our study aimed to reveal the expression distribution, prognostic value, immune infiltration correlation, and molecular functions of FXYD5. Methods: Using pan-cancer multi-omics data (including The Cancer Genome Atlas, PrognoScan, Gene Expression Profiling Interactive Analysis, cBioPortal, Gene Expression Omnibus, TIMER and scTIME Portal), we assessed the differences in the expression and prognostic value of FXYD5 in malignant tumors. Furthermore, at the single-cell level, we analyze the expression distribution of FXYD5 across different cell types within the tumor microenvironment, and its relationship with the immune microenvironment. Finally, focusing on ovarian cancer, we conducted preliminary validation of the above findings using cell and molecular biology techniques. Results: Our results indicated that FXYD5 was up-regulated in various tumor types and was positively associated with tumor progression. We also revealed that FXYD5 was ubiquitously expressed in microenvironmental cells at the single-cell level, and its upregulation was associated with enhanced immune infiltration, cancer-associated fibroblast infiltration, and dysfunction of tumor-infiltrating cytotoxic T lymphocyte. Additionally, its expression was positively correlated with immune checkpoint genes, DNA mismatch repair genes, MSI (microsatellite instability) and TMB (tumor mutational burden) across various cancers. Its higher expression in cytotoxic T lymphocytes attenuated its ability to predict patient survival with PD-L1 (programmed death-ligand 1) blockade therapy, and FXYD5 was found to be a potential regulator of tumor immune escape and resistance to cancer immunotherapies. Based on GSEA (gene set enrichment analysis) and experimental verification, FXYD5 activated TGF‐β/SMAD signaling and drove EMT (epithelial-mesenchymal transition) to promote ovarian cancer progression. Conclusion: In summary, our study revealed that FXYD5-TGFβ axis may coregulate the interaction between tumors, CAFs (carcinoma-associated fibroblasts) and immune cells to reshape the tumor immune microenvironment and promote tumorigenesis and tumor progression. Thus, FXYD5 could be used as an immune-related biomarker for diagnosing and predicting the prognosis of multiple cancer types. Therefore, our findings suggest that targeting FXYD5 in TME (tumor microenvironment) may be a promising therapeutic strategy.

Background: The severity of white matter hyperintensities (WMH) has been shown to be an independent predictor of poor stroke outcome, but the effect of sex on this correlation has not been investigated further. Therefore, the purpose of our study was to assess whether there was a sex difference between the severity of WMH and poor stroke outcome. Methods: This retrospective study included 449 patients with acute ischemic stroke (AIS) who received intravenous thrombolysis. WMH severity was graded based on the Fazekas scale. The association between WMH severity and stroke outcome was explored through multivariable regression analyses in men and women. Results: Among women, when dividing WMH severity into tertiles, T3 (Fazekas scale >3) had a 5.334 times higher risk for unfavorable outcomes than T1 (Fazekas scale

Improvement of sugarcane is hampered due to its narrow genetic base, and the difficulty in synchronizing flowering further hinders the exploitation of the genetic potential of available germplasm resources. Therefore, the continuous evaluation and optimization of flowering control and induction techniques are vital for sugarcane improvement. In view of this, the review was conducted to investigate the current understanding of photoperiodic and lighting treatment effects on sugarcane flowering and its genetic regulation. Photoperiod facilities have made a significant contribution to flowering control in sugarcane; however, inductive photoperiods are still unknown for some genotypes, and some intended crosses are still impossible to produce because of unresponsive varieties. The effectiveness of lower red/far-red ratios in promoting sugarcane flowering has been widely understood. Furthermore, there is vast potential for utilizing blue, red, and far-red light wavelengths in the flowering control of sugarcane. In this context, light-emitting diodes (LEDs) remain efficient sources of light. Therefore, the combined use of photoperiod regimes with different light wavelengths and optimization of such treatment combinations might help to control and induce flowering in sugarcane parental clones. In sugarcane, FLOWERING LOCUS T (ScFT) orthologues from ScFT1 to ScFT13 have been identified, and interestingly, ScFT3 has evidently been identified as a floral inducer in sugarcane. However, independent assessments of different FT-like gene family members are recommended to comprehensively understand their role in the regulation of flowering. Similarly, we believe this review provides substantial information that is vital for the manipulation of flowering and exploitation of germplasm resources in sugarcane breeding.

Summary: Targeting programmed cell death protein 1 (PD-1) is an important component of many immune checkpoint blockade (ICB) therapeutic approaches. However, ICB is not an efficacious strategy in a variety of cancer types, in part due to immunosuppressive metabolites in the tumor microenvironment. Here, we find that αPD-1-resistant cancer cells produce abundant itaconate (ITA) due to enhanced levels of aconitate decarboxylase (Acod1). Acod1 has an important role in the resistance to αPD-1, as decreasing Acod1 levels in αPD-1-resistant cancer cells can sensitize tumors to αPD-1 therapy. Mechanistically, cancer cells with high Acod1 inhibit the proliferation of naive CD8+ T cells through the secretion of inhibitory factors. Surprisingly, inhibition of CD8+ T cell proliferation is not dependent on the secretion of ITA but is instead a consequence of the release of small inhibitory peptides. Our study suggests that strategies to counter the activity of Acod1 in cancer cells may sensitize tumors to ICB therapy.

Objectives To explore the impact of the triglyceride-glucose (TyG) index on the severity of coronary stenosis and the risk of in-hospital mortality in patients with acute ST segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).Design A multicentre retrospective cohort study.Setting Patients with STEMI undergoing PCI from three centres in China from 2015 to 2019.Participants A total of 1491 individuals presenting with STEMI were enrolled.Primary outcome measure The degree of coronary stenosis was quantified by the Gensini score (GS). The association between the TyG index and the severity of coronary stenosis was explored by using a logistic regression analysis. Cox proportional hazards regression analyses were used to investigate the associations between the variables and in-hospital mortality.Results We found a significant correlation between the TyG index and the degree of coronary stenosis in the present study. The TyG index was an independent risk factor for the severity of coronary stenosis (OR 2.003, p

Sugars transported from leaves (source) to stems (sink) energize cell growth, elongation, and maintenance. which are regulated by a variety of genes. This review reflects progress and prospects in the regulatory mechanism for maximum sucrose accumulation, including the role of sucrose metabolizing enzymes, sugar transporters and the elucidation of post-transcriptional control of sucrose-induced regulation of translation (SIRT) in the accumulation of sucrose. The current review suggests that SIRT is emerging as a significant mechanism controlling Scbzip44 activities in response to endogenous sugar signals (via the negative feedback mechanism). Sucrose-controlled upstream open reading frame (SC-uORF) exists at the 5′ leader region of Scbzip44's main ORF, which inhibits sucrose accumulation through post-transcriptional regulatory mechanisms. Sucrose transporters (SWEET1a/4a/4b/13c, TST, SUT1, SUT4 and SUT5) are crucial for sucrose translocation from source to sink. Particularly, SWEET13c was found to be a major contributor to the efflux in the transportation of stems. Tonoplast sugar transporters (TSTs), which import sucrose into the vacuole, suggest their tissue-specific role from source to sink. Sucrose cleavage has generally been linked with invertase isozymes, whereas sucrose synthase (SuSy)-catalyzed metabolism has been associated with biosynthetic processes such as UDP-Glc, cellulose, hemicellulose and other polymers. However, other two key sucrose-metabolizing enzymes, such as sucrose-6-phosphate phosphohydrolase (S6PP) and sucrose phosphate synthase (SPS) isoforms, have been linked with sucrose biosynthesis. These findings suggest that manipulation of genes, such as overexpression of SPS genes and sucrose transporter genes, silencing of the SC-uORF of Scbzip44 (removing the 5′ leader region of the main ORF that is called SIRT-Insensitive) and downregulation of the invertase genes, may lead to maximum sucrose accumulation. This review provides an overview of sugarcane sucrose-regulating systems and baseline information for the development of cultivars with higher sucrose accumulation.

Implant therapy is a well-established clinical treatment, and porous implants are reported to be advantageous, which needs to be confirmed in vivo. In this study, we designed and fabricated titanium implants with the same shape but with different porosities (20 %, 30 %, 40 %, and 50 %, respectively), which produce different elastic moduli based on the results of finite element analysis (FEA). These devices were implanted into the mandibular alveolar bone of miniature swine, and their survival rates, osseointegration, and marginal bone loss were evaluated one, three, and six months after implantation. It was demonstrated that the 30 % porosity implants, which had an elastic modulus similar to that of the cortical bone, exhibited the best survival rate (50 %) and the lowest bone resorption height (1.51 ± 0.33 mm), with almost no inflammation and attachment loss. In vitro analyses indicated that the appropriate pore size is conducive to the extension and cellular communication of cells, which promotes the host cell homing and differentiation functions. Thus, the elastic modulus of the dental implants determines their success rate. Furthermore, the implants with an elastic modulus matching that of the cortical bone of the patient are advantageous in terms of postoperative loading and bone integration.

Dipeptides in sauce-flavor Baijiu Daqu are protein degradation products during the fermentation of Daqu, which are believed to play a crucial role in the flavor and quality of Baijiu. Herein, we integrated dansyl chloride derivatization with ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) for comprehensively profiling dipeptides in Daqu. The derivatization efficiency was higher than 99.1 % for all 17 dipeptide standards under the optimized derivatization conditions. In total, 118 dipeptides were detected in Daqu. The method was validated and the analytical characteristics including the linearity (spanned across 2–4 orders of magnitude), precision (1.2–19.9 %), limit of detection (varied from 1.1 to 53.4 pmol/mL) and the stability (3.6–15.8 %) are satisfactory. The usefulness of the method was examined by studying the distribution characteristics of dipeptides in Daqu under different production conditions. The present method provides an effective and robust strategy for comprehensively analyzing dipeptide compounds in complex biological samples.

Pathogenic Salmonella strains causing gastroenteritis typically can colonize and proliferate in the intestines of multiple host species. They retain the ability to form red dry and rough (rdar) biofilms, as seen in Salmonella enterica serovar Typhimurium. Conversely, Salmonella serovar like Typhi, which can cause systemic infections and exhibit host restriction, are rdar-negative. In this study, duck-derived strains and swine-derived strains of S. Typhimurium locate on independent phylogenetic clades and display relative genomic specificity. The duck isolates appear more closely related to human blood isolates and invasive non-typhoidal Salmonella (iNTS), whereas the swine isolates were more distinct. Phenotypically, compared to duck isolates, swine isolates exhibited enhanced biofilm formation that was unaffected by the temperature. The transcriptomic analysis revealed the upregulation of csgDEFG transcription as the direct cause. This upregulation may be mainly attributed to the enhanced promoter activity caused by the G-to-T substitution at position −44 of the csgD promoter. Swine isolates have created biofilm polymorphisms by altering a conserved base present in Salmonella Typhi, iNTS, and most Salmonella Typhimurium (such as duck isolates). This provides a genomic characteristics perspective for understanding Salmonella transmission cycles and evolution.

Sugarcane, a vital cash crop, contributes significantly to the world’s sugar supply and raw materials for biofuel production, playing a significant role in the global sugar industry. However, sustainable productivity is severely hampered by biotic and abiotic stressors. Genetic engineering has been used to transfer useful genes into sugarcane plants to improve desirable traits and has emerged as a basic and applied research method to maintain growth and productivity under different adverse environmental conditions. However, the use of transgenic approaches remains contentious and requires rigorous experimental methods to address biosafety challenges. Clustered regularly interspaced short palindromic repeat (CRISPR) mediated genome editing technology is growing rapidly and may revolutionize sugarcane production. This review aims to explore innovative genetic engineering techniques and their successful application in developing sugarcane cultivars with enhanced resistance to biotic and abiotic stresses to produce superior sugarcane cultivars.

Stearoyl-CoA desaturase-1 (SCD1) is a key enzyme in the biosynthesis of monounsaturated fatty acids and is considered a candidate gene for improving milk and meat quality traits. Sanger sequencing was employed to investigate the genetic polymorphism of the fifth exon and intron of bovine SCD1, revealing four SNPs, g.21272246 A>G, g.21272306 T>C, g.21272422 C>T, and g.21272529 A>G. Further variance analysis and multiple comparisons were conducted to examine the relationship between variation sites and economic traits in Chinese Simmental cattle, as well as milk production traits in Holstein cows. The findings revealed these four loci exhibited significant associations with carcass traits (carcass weight, carcass length, backfat thickness, and waist meat thickness), meat quality (pH value, rib eye area, and marbling score), adipogenic traits (fat score and carcass fat coverage rate), and fatty acid composition (linoleic acid and α-linolenic acid). Furthermore, these loci were additionally found to be significantly associated with average milk yield and milk fat content in cows. In addition, a haplotype analysis of combinations of SNPs showed that H2H3 has a significant association with adipogenic traits and H2H2 was associated with higher levels of linoleic acid and α-linolenic acid than the other combinations. These results suggest that the four SNPs are expected to be prospective genetic markers for the above economic traits. In addition, the function of SNPs in exon 5 of SCD1 on gene expression and protein structure needs to be explored in the future.

The influence of fluoride ions on electrochemical behavior of lanthanum and neodymium ions in molten LiCl at 1073 K was experimentally investigated. Cyclic voltammetry and square wave voltammetry were conducted using a molybdenum working electrode. Galvanostatic electrolysis using a molybdenum electrode as cathode in molten LiCl-5 mol%LaCl3, LiCl-5 mol%NdCl3, and LiCl-30 mol%LiF-5 mol%NdCl3 were conducted to investigate the influence of fluoride ions. The result indicates that the cathodic process for La3+ in molten LiCl is a one-step reaction, i.e., La3+ + 3e = La. The cathodic process of Nd3+ in molten LiCl is a two-step reaction, including Nd3+ + e = Nd2+ and Nd2+ + 2e = Nd. With the introduction of fluoride ions, however, the current of the first cathodic reaction decreases and when the molar ratio of F− to Nd3+ reaches to 6, the cathodic process of Nd3+ turns to a one-step process: Nd3+ + 3e = Nd. The results indicate that the addition of fluoride ions makes Nd3+ stabler and thus inhibits the reaction to Nd2+ in molten chloride. The deposited neodymium metal was dispersed in the electrolyte in pure chloride melt due to the shuttle of disproportionation and proportionation reactions of neodymium ions. With the addition of enough LiF to melt, the deposited neodymium metal adhered on the cathode. The current efficiency of neodymium electrolysis was remarkably improved and reached the similar value as that for lanthanum electrolysis.

Agricultural drainage from catchment greatly impacts water quality in the hilly area due to high nitrogen concentrations in the central basin of Sichuan Province, China. The original ecological ditches have proven effective in removing associated nutrient loads, but their nitrogen removal efficiency is limited by the elevated nitrogen levels of overland flow and subsurface flow. Field experiments were conducted to optimize the drainage network to enhance the performance of ecological ditches and enhance nitrogen removal efficiency in hilly regions. The results suggested that ecologically permeable dam ditches exhibited superior total nitrogen (TN) and total phosphorus (TP) removal efficiencies compared to single dams, multiple dams, and ecological intercept dams. Specifically, in single, multiple, and ecological intercept dams, TN removal was 20.2 %, 12.7 %, and 2.5 % higher, respectively, while TP removal was 18.2 %, 10.3 %, and 3.7 % higher, respectively. The TN removal efficiency by the Hydrocotyle verticillate and Iris pseudacorus L. ditch was 15.8 % and 2.3 % higher than that of the Myriophyllum verticillatum L. and Hydrocotyle verticillata and Hydrocotyle verticillata and Thalia dealbata Fraser, respectively. The TP removal efficiency in Hydrocotyle verticillata and Thalia dealbata Fraser ditch was 11.4 % and 3.5 % higher than that in Myriophyllum verticillatum L. and Hydrocotyle verticillata and Hydrocotyle verticillate and Iris pseudacorus L., respectively. The soil bed ditch demonstrated superior TN and TP removal efficiencies, with rates of 15.2 % and 11.3 %, respectively, compared to the pebble bed and mudstone bed (2.9 % and 3.4 %, respectively). Therefore, the original ecological ditch was reinforced through a combination of fine-textured soil substrates, native emergent plants with large biomass and ecologically permeable dams to enhance the removal efficiencies of TN and TP in agricultural drainage. Following reinforcement and evaluation in 2020, the removal efficiencies of TN, TP, ammonia nitrogen (AN) and nitrate nitrogen (NN) in the strengthened ecological ditches increased to 58.1 %, 56.5 %, 56.8 % and 54.2 %, respectively. In this study, a scientific foundation for enhancing the efficacy of ecological ditches in mitigating nonpoint source pollution from agricultural drainage in mountainous and hilly regions of subtropical and developing countries is established.

Intense terahertz (THz) radiation in free space has immense potential for regulating material state, accelerating electrons, producing biological effects, and so on. However, the high cost and challenges involved in constructing strong-field THz sources have limited their developments, making it difficult for the potential applications of strong-field THz radiation to be widely adopted. Spintronic THz emitters (STEs) with numerous merits such as high efficiency, ultrabroadband, ease of integration, and low cost have become ubiquitous, but the majority of these emitters require stable operation in the presence of external magnets, limiting their applications, particularly in generating strong fields that necessitate large-sized samples. Here, we demonstrate the feasibility of generating strong-field THz radiation in 4-inch antiferromagnetic material–ferromagnetic metal (IrMn3 [2 nm]/Co20Fe60B20 [2 nm]/W [2 nm]) without external magnetic field driving. Under the excitation of a Ti:sapphire femtosecond laser amplifier with a 35-fs pulse duration and a 1-kHz repetition rate, we obtain strong-field THz radiation from our STEs with a pulse duration of ~110 fs, and a spectrum covering up to ~10 THz. Further scaling up the pump laser energy up to 55 mJ with a pulse duration of ~20 fs and a repetition rate of 100 Hz provided by the Synergetic Extreme Condition User Facility, the radiated THz electric field strength from the external-magnetic-free 4-inch STEs can exceed 242 kV/cm with a pulse duration of ~230 fs, a spectrum covering up to ~14 THz, and a single pulse energy of 8.6 nJ measured by a calibrated pyroelectric detector. Our demonstrated external-magnetic-field-free high-field STEs have some unique applications such as producing sub-cycle ultrashort strong THz fields in huge size emitters under the excitation of high-energy light sources, accelerating the development of THz science and applications.

Terrorism has shown a trend of organizational cooperation in a large number of terrorist attacks around the world, posting a great challenge to counter-terrorism efforts. To investigate the trend and pattern of global terrorist organizational cooperations and to propose effective measures for effectively enforcing and restricting terrorist attacks, based on the Global Terrorism Database and the UN sanctions list of terrorist groups, this study constructs a cooperative evolutionary network of terrorist organizations from 119,803 terrorist attacks that occurred globally between 2001 and 2018. The evolution of worldwide terrorist cooperation is evaluated in terms of network characteristics, including key nodes, cohesion, and motifs. The network keeps expanding, with a large number of new nodes emerging each year. On average, there are 13 additional organizations entering in the collaboration network each year, with a yearly survival rate of about 34.66%, and the rank of node importance iterate and update frequently. Through k-core decomposition, for which the breakdown of the network has increased from three to five partitions, we find that the core of the terrorist organization's cooperation network changes much less frequently than the edges. The dominating modal structure of the network is the "star" motif (90%), and "triadic closed" motif (9%). We conclude that, over time, the cooperative network of terrorist groups has gradually evolved into a cluster of star-shaped networks, with various organizations serving as the centers of the networks and showing core-periphery structure in their individual communities. The core organizations are highly connected and stable, whereas the periphery organizations are loosely connected and highly variable.

BackgroundPrimary gallbladder gastrinoma is an exceptionally uncommon tumor and is a rare form of neuroendocrine neoplasm. Until now, no cases of primary gallbladder gastrinoma and rare cases of primary gastrinoma from the biliary system have been reported.Case presentationWe report a case of a 50-year-old woman with watery diarrhea who intermittently received proton pump inhibitors (PPIs) as treatment. A serum gastrin level of 711 pg/ml was recorded after the withdrawal of PPI over 1 week. Enhanced computed tomography (CT) imaging and octreotide imaging uncovered a solitary tumor at the hepatic hilar region. During the laparoscopic surgery, it was determined that the tumor had its origin in the wall of the gallbladder neck, prompting the implementation of a laparoscopic cholecystectomy. Histological analysis revealed a primary neuroendocrine tumor from the neck of the gallbladder. The patient’s symptoms disappeared after the surgery with a follow-up of 6 months.ConclusionsThis case confirmed that primary gallbladder gastrinoma represents a distinct nosological entity. Immunohistochemical analysis plays a pivotal role in the diagnostic process. Given the limited understanding of primary gallbladder gastrinoma, our objective is to offer novel insights into this rare disease by delivering distinctive information and highlighting the therapeutic significance of surgical intervention.

The toxic metal (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) pollution in 250 agricultural soil samples representing the urban area of Jiaxing was studied to investigate the temporal and spatial variations. Compared to the early 1990s, the pollution level has increased. Industry and urbanization were the main factors causing toxic metal pollution on temporal variation, especially the use of feed containing toxic metals. The soil types and crop cultivation methods are the main factors causing toxic metal pollution on spatial variation. Although the single-factor pollution indices of all the toxic metals were within the safe limits, as per the National Soil Environmental Quality Standard (risk screening value), if the background values of soil elements in Jiaxing City are used as the standard, the pollution index of all the elements surveyed exceeds 1.0, reaching a level of mild pollution. The soil samples investigated were heavily contaminated with toxic metal compounds, and their levels increased over time. This situation poses potential ecological and health risks.

Chemical investigation of marine fungus Nigrospora oryzae SYSU-MS0024 cultured on solid-rice medium led to the isolation of three new alkaloids, including a pair of epimers, nigrosporines A (1) and B (2), and a pair of enantiomers, (+)-nigrosporine C (+)-3, and (−)-nigrosporine C (−)-3, together with eight known compounds (4–11). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses and compared with data in the literature. The absolute configurations of compounds 1–3 were determined by a combination of electronic circular dichroism (ECD) calculations, Mosher’s method, and X-ray single-crystal diffraction technique using Cu Kα radiation. In bioassays, compound 2 exhibited moderate inhibition on NO accumulation induced by lipopolysaccharide (LPS) on BV-2 cells in a dose-dependent manner at 20, 50, and 100 μmol/L and without cytotoxicity in a concentration of 100.0 μmol/L. Moreover, compound 2 also showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values of 103.7 μmol/L. Compound 5 exhibited moderate antioxidant activity with EC50 values of 167.0 μmol/L.

Using zinc oxide (ZnO), tourmaline (TM), and polyethylene terephthalate (PET) as main raw materials, a novel ZnO/TM/PET negative ion functional fiber was created. The rheological properties of a ZnO/TM/PET masterbatch were investigated; the morphology, XRD, and FT-IR of the fibers were observed; and the mechanical properties, thermal properties, and negative ion release properties of the new fiber were tested. The results showed that the average particle size of the ZnO/TM composite is nearly 365 nm, with an increase in negative ion emission efficiency by nearly 50% compared to the original TM. The apparent viscosity of fiber masterbatch decreases with the increase in the addition of the ZnO/TM composite, and the rheological properties of the PET fiber masterbatch are not significantly effected, still showing shear thinning characteristics when the amount of addition reaches 10%. The ZnO/TM composite disperses well in the interior and surface of the ZnO/TM/PET fiber matrix. The prepared ZnO/TM/PET fiber has excellent properties, such as fineness of 1.54 dtex, glass transition temperature of 122.4 °C, fracture strength of 3.31 cN/dtex, and negative ion release of 1640/cm3, which shows great industrialization potential.

Myeloid-derived suppressor cells (MDSCs) play an essential role in suppressing the antitumor activity of T lymphocytes in solid tumors, thus representing an attractive therapeutic target to enhance the efficacy of immunotherapy. However, the differences in protein expression between MDSCs and their physiological counterparts, particularly polymorphonuclear neutrophils (PMNs), remain inadequately characterized, making the specific identification and targeting of MDSCs difficult. PMNs and PMN-MDSCs share markers such as CD11b+CD14−CD15+/CD66b+, and some MDSC-enriched markers are emerging, such as LOX-1 and CD84. More proteomics studies are needed to identify the signature and markers for MDSCs. Recently, we reported the induced differentiation of isogenic PMNs or MDSCs (referred to as iPMNs and iMDSCs, respectively) from the human promyelocytic cell line HL60. Here, we profiled the global proteomics and membrane proteomics of these cells with quantitative mass spectrometry, which identified a 41-protein signature (“cluster 6”) that was upregulated in iMDSCs compared with HL60 and iPMN. We further integrated our cell line-based proteomics data with a published proteomics dataset of normal human primary monocytes and monocyte-derived MDSCs induced by cancer-associated fibroblasts. The analysis identified a 38-protein signature that exhibits an upregulated expression pattern in MDSCs compared with normal monocytes or PMNs. These signatures may provide a hypothesis-generating platform to identify protein biomarkers that phenotypically distinguish MDSCs from their healthy counterparts, as well as potential therapeutic targets that impair MDSCs without harming normal myeloid cells.

Microbial communities inhabiting sedimentary environments in river source regions serve as pivotal indicators of pristine river ecosystems. While the correlation between antibiotic resistome and pathogenicity with core gut bacteria in humans is well established, there exists a significant knowledge gap concerning the interaction of antibiotic resistance genes (ARGs) and human pathogenic bacteria (HPB) with specific microbes in river source basins, often referred to as “terrestrial gut”. Understanding the microbial composition, including bacteria and resident genetic elements such as ARGs, HPB, Mobile Genetic Elements (MGEs), and Virulence Factors (VFs), within natural habitats against the backdrop of global change, is imperative. To address this gap, an enrichment-based culturomics complementary along with metagenomics was conducted in this study to characterize the microbial biobank and provide preliminary ecological insights into profiling the dissemination of ARGs in the Lancang River Source Basin. Based on our findings, in the main stream of the Lancang River Source Basin, 674 strains of bacteria, comprising 540 strains under anaerobic conditions and 124 under aerobic conditions, were successfully isolated. Among these, 98 species were identified as known species, while 4 were potential novel species. Of these 98 species, 30 were HPB relevant to human health. Additionally, bacA and bacitracin emerged as the most abundant ARGs and antibiotics in this river, respectively. Furthermore, the risk assessment of ARGs predominantly indicated the lowest risk rank (Rank Ⅳ) in terms of endangering human health. In summary, enrichment-based culturomics proved effective in isolating rare and unknown bacteria, particularly under anaerobic conditions. The emergence of ARGs showed limited correlation with MGEs, indicating minimal threats to human health within the main stream of the Lancang River Source Basin.

The strength of prestressed steel strands has developed towards high strength, increasing from 1860 MPa to over 2200 MPa. The stress in the prestressed anchorage zone is more concentrated and complex, and the anchor plates for dispersed loads need to be optimized in design. This article proposes a design scheme for adding a middle pressure-bearing step based on the existing anchor plate and then establishes a 1/4 model of the concrete anchoring area of the anchor plate for finite element analysis. Based on the theory of the strut-and-tie model, the position of the middle pressure-bearing step is determined according to the maximum angle of the strut-and-tie model. Then, carry out force transfer tests in the anchorage zone for verification. The research results indicate that after adding a middle pressure bearing step to the anchor plate, the angle between the strut-and-tie model in the anchorage zone increases, and the bearing capacity improves. The position of the middle pressure-bearing step in the anchor plate is different, and the angle between the strut-and-tie models is different. According to the middle step position parameter, λ (the ratio of the effective width of the middle step to the distance from the middle step to the end face of the anchor plate) is 0.533 to optimize the anchor plate, and the bearing capacity of its anchorage zone is relatively high. The main tensile and main compressive stresses of the anchor plate after optimization increased by 6.2% and 5.74%, respectively, compared to the anchor plate before optimization. The main tensile stress of the spiral reinforcement under the anchor plate decreased by 0.59%, the main compressive stress decreased by 2.89%, and the von-Mises stress decreased by 2.32%. The side surface tensile stress of concrete under the anchor plate was reduced by 4.3 percent. Finally, three concrete specimens were poured for force transfer testing in the anchorage zone, verifying the safety and reliability of the optimized anchor plate in the 2200 MPa-level prestressed anchorage zone.

The convergence of cyber and physical systems through cyber–physical systems (CPSs) has been integrated into cyber–physical production systems (CPPSs), leading to a paradigm shift toward intelligent manufacturing. Despite the transformative benefits that CPPS provides, its increased connectivity exposes manufacturers to cyber-attacks through exploitable vulnerabilities. This paper presents a novel approach to CPPS security protection by leveraging digital twin (DT) technology to develop a comprehensive security model. This model enhances asset visibility and supports prioritization in mitigating vulnerable components through DT-based virtual tuning, providing quantitative assessment results for effective mitigation. Our proposed DT security model also serves as an advanced simulation environment, facilitating the evaluation of CPPS vulnerabilities across diverse attack scenarios without disrupting physical operations. The practicality and effectiveness of our approach are illustrated through its application in a human–robot collaborative assembly system, demonstrating the potential of DT technology.

Soilless cultivation of potatoes often utilizes organic coconut peat and inorganic vermiculite as growing substrates. The unique microbial communities and physicochemical characteristics inherent to each substrate significantly influence the microecological environment crucial for potato growth and breeding. This study analyzed environmental factors within each substrate and employed Illumina sequencing alongside bioinformatics tools to examine microbial community structures, their correlation with environmental factors, core microbial functions, and the dynamics of microbial networks across various samples. These included pure coconut peat (CP1) and pure vermiculite (V1), substrates mixed with organic fertilizer for three days (CP2 and V2), and three combinations cultivated with potatoes for 50 days (CP3, V3, and CV3—a 1:1 mix of coconut peat and vermiculite with organic fertilizer). Vermiculite naturally hosts a more diverse microbial community. After mixing with fertilizer and composting for 3 days, and 50 days of potato cultivation, fungal diversity decreased in both substrates. Coconut peat maintains higher bacterial diversity and richness compared to vermiculite, harboring more beneficial bacteria and fungi, resulting in a more complex microbial network. However, vermiculite shows lower bacterial diversity and richness, with an accumulation of pathogenic microorganisms. Among the 11 environmental factors tested, water-soluble nitrogen (WSN), total nitrogen (TN), available potassium (AK), total organic carbon (TOC) and air-filled porosity (AFP) were significantly associated with microbial succession in the substrate.The nutritional type composition and interaction patterns of indigenous microorganisms differ between vermiculite and coconut peat. Adding abundant nutrients significantly affects the stability and interaction of the entire microbial community, even post-potato cultivation. When using vermiculite for soilless cultivation, precise control and adjustment of nutrient addition quantity and frequency are essential.

Metastatic penile squamous cell carcinoma (PSCC) has only a 50% response rate to first-line combination chemotherapies and there are currently no targeted-therapy approaches. Therefore, we have an urgent need in advanced-PSCC treatment to find novel therapies. Approximately half of all PSCC cases are positive for high-risk human papillomavirus (HR-HPV). Our objective was to generate HPV-positive (HPV+) and HPV-negative (HPV−) patient-derived xenograft (PDX) models and to determine the biological differences between HPV+ and HPV− disease. We generated four HPV+ and three HPV− PSCC PDX animal models by directly implanting resected patient tumor tissue into immunocompromised mice. PDX tumor tissue was found to be similar to patient tumor tissue (donor tissue) by histology and short tandem repeat fingerprinting. DNA mutations were mostly preserved in PDX tissues and similar APOBEC (apolipoprotein B mRNA editing catalytic polypeptide) mutational fractions in donor tissue and PDX tissues were noted. A higher APOBEC mutational fraction was found in HPV+ versus HPV− PDX tissues (p = 0.044), and significant transcriptomic and proteomic expression differences based on HPV status included p16 (CDKN2A), RRM2, and CDC25C. These models will allow for the direct testing of targeted therapies in PSCC and determine their response in correlation to HPV status.