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Abstract Background Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed. Methods A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA). Results The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin–globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child–pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p

BackgroundAlthough depression symptoms are commonly reported in patients with subcortical vascular mild cognitive impairment (svMCI), their impact on brain functions remains largely unknown, with diagnoses mainly dependent on behavioral assessments.MethodsIn this study, we analyzed resting-state fMRI data from a cohort of 34 svMCI patients, comprising 18 patients with depression symptoms (svMCI+D) and 16 patients without (svMCI-D), along with 34 normal controls (NC). The study used the fraction of the amplitude of low-frequency fluctuations (fALFF), resting-state functional connectivity, correlation analyses, and support vector machine (SVM) techniques.ResultsThe fALFF of the right cerebellum (CERE.R) differed among the svMCI+D, svMCI-D, and NC groups. Specifically, the regional mean fALFF of CERE. R was lower in svMCI-D patients compared to NC but higher in svMCI+D patients compared to svMCI-D patients. Moreover, the adjusted fALFF of CERE. R showed a significant correlation with Montreal Cognitive Assessment (MOCA) scores in svMCI-D patients. The fALFF of the right orbital part of the superior frontal gyrus was significantly correlated with Hamilton Depression Scale scores in svMCI+D patients, whereas the fALFF of the right postcingulate cortex (PCC.R) showed a significant correlation with MOCA scores in svMCI-D patients. Furthermore, RSFC between PCC. R and right precuneus, as well as between CERE. R and the right lingual gyrus (LING.R), was significantly reduced in svMCI-D patients compared to NC. In regional analyses, the adjusted RSFC between PCC. R and PreCUN. R, as well as between CERE. R and LING. R, was decreased in svMCI-D patients compared to NC but increased in svMCI+D patients compared to svMCI-D. Further SVM analyses achieved good performances, with an area under the curve (AUC) of 0.82 for classifying svMCI+D, svMCI-D, and NC; 0.96 for classifying svMCI+D and svMCI-D; 0.82 for classifying svMCI+D and NC; and 0.92 for classifying svMCI-D and NC.ConclusionThe study revealed disruptive effects of cognitive impairment, along with both disruptive and complementary effects of depression symptoms on spontaneous brain activity in svMCI. Moreover, these findings suggest that the identified features might serve as potential biomarkers for distinguishing between svMCI+D, svMCI-D, and NC, thereby guiding clinical treatments such as transcranial magnetic stimulation for svMCI.

To realize nanoscale manufacturing based on laser direct writing technology, objective lenses with high numerical apertures immersed in water or oil are necessary. The use of liquid medium restricts its application in semiconductors. Achieving nanoscale features on silicon by laser direct writing in a low refractive index medium has been a challenge. In this work, a microsphere assisted femtosecond laser far-field induced dewetting approach is proposed. A reduction in the full-width at half-maximum of the focused light spot is realized by modulating tightly focused light through microspheres and achieving a minimum feature size of 9 nm on silicon in ambient air with energy smaller than the ablation threshold. Theoretical analysis and numerical simulation of laser processing are performed based on a two-temperature model. Furthermore, we explored the potential of femtosecond laser-induced dewetting in nanolithography and demonstrated its ability to achieve an arbitrary structure on silicon. Our work enables laser-based far-field sub-10-nm feature etching on a large-scale, providing a novel avenue for nanoscale silicon manufacturing.

BackgroundBasement membranes (BMs) have recently emerged as significant players in cancer progression and metastasis, rendering them promising targets for potential anti-cancer therapies. Here, we aimed to develop a novel signature of basement membrane-related genes (BMRGs) for the prediction of clinical prognosis and tumor microenvironment in hepatocellular carcinoma (HCC).MethodsThe differentially expressed BMRGs were subjected to univariate Cox regression analysis to identify BMRGs with prognostic significance. A six-BMRGs risk score model was constructed using Least Absolute Shrinkage Selection Operator (LASSO) Cox regression. Furthermore, a nomogram incorporating the BMRGs score and other clinicopathological features was developed for accurate prediction of survival rate in patients with HCC.ResultsA total of 121 differentially expressed BMRGs were screened from the TCGA HCC cohort. The functions of these BMRGs were significantly enriched in the extracellular matrix structure and signal transduction. The six-BMRGs risk score, comprising CD151, CTSA, MMP1, ROBO3, ADAMTS5 and MEP1A, was established for the prediction of clinical prognosis, tumor microenvironment characteristics, and immunotherapy response in HCC. Kaplan-Meier analysis revealed that the BMRGs score-high group showed a significantly shorter overall survival than BMRGs score-low group. A nomogram showed that the BMRGs score could be used as a new effective clinical predictor and can be combined with other clinical variables to improve the prognosis of patients with HCC. Furthermore, the high BMRGs score subgroup exhibited an immunosuppressive state characterized by infiltration of macrophages and T-regulatory cells, elevated tumor immune dysfunction and exclusion (TIDE) score, as well as enhanced expression of immune checkpoints including PD-1, PD-L1, CTLA4, PD-L2, HAVCR2, and TIGIT. Finally, a multi-step analysis was conducted to identify two pivotal hub genes, PKM and ITGA3, in the high-scoring group of BMRGs, which exhibited significant associations with an unfavorable prognosis in HCC.ConclusionOur study suggests that the BMRGs score can serve as a robust biomarker for predicting clinical outcomes and evaluating the tumor microenvironment in patients with HCC, thereby facilitating more effective clinical implementation of immunotherapy.

Objective The size of Neogene reservoir formation in rifted basins is closely linked to deep oil and gas accumulation and three-dimensional transport systems. Methods This study examines the differential oil and gas charging issues associated with target traps in Neogene fault basins. Using the eastern steep slope of the Miaoxibei Uplift in the Bohai Sea as an example, we analyze the components of the oil and gas accumulation system in steep slope zones by evaluating fault conduction capability and dividing the dominant injection segments. Subsequently, oil and gas migration simulations are conducted under the control of the fault injection section. Results The research findings are as follows: ① The accumulation system in the steep slope zone consists of deep hydrocarbon accumulative sand bodies, large boundary faults, and late shallow faults. ② The dominant hydrocarbon sinks in the three parts of the accumulation system interact with each other, forming a dominant migration path that is reflected in the overlapping fault charging section with the target trap. The middle section of the main migration fault on the east side of the Miaoxibei Uplift is a strong charging area, while the northern section is a medium charging area. Among the secondary migration faults, faults 4, 6, and 8 have developed strong charging sections, while faults 1, 2, and 11 have developed medium charging sections. ③ Structural migration simulations reveal that the oil and gas accumulation area develops in the middle of the steep slope zone in the east of the Miaoxibei Uplift, with two main migration routes in the east and one in the south. The typical sand traps in fault No. 3 have developed four accumulation zones, with accumulation zone C being the most significant. Conclusion In conclusion, these research findings can serve as a reference for well deployment in target areas, and the technical methods employed can provide support for hydrocarbon accumulation analysis.

Abstract Background Regulatory T cells (Tregs) are involved in the maintenance of immune homeostasis and immune regulation. Clinical trials on the adoptive transfer of Tregs have been ongoing for > 10 years. However, many unresolved issues remain in the production of readymade Treg products and selection of patients. Hence, this study aimed to develop a method to expand off-the-shelf Tregs derived from umbilical cord blood (UCB-Tregs) in vitro without changing their phenotype and inhibitory function. In addition, the study intended to design an approach to precisely select patients who are more likely to benefit from the adoptive Treg transfer therapy. Methods UCB-Tregs were isolated and cultured in a medium containing human recombinant IL-2 and rapamycin and then multiply restimulated with human T-activator CD3/CD28 dynabeads. The phenotype and suppressive capacity of Tregs were assessed on days 18 and 42. The relationship between the suppressive function of UCB-Tregs in vitro and clinical indicators was analyzed, and the ability of the in vitro suppressive capacity to predict the in vivo therapeutic effects was evaluated. Results UCB-Tregs expanded 123-fold and 5,981-fold at 18 and 42 days, respectively. The suppressive function of UCB-Tregs on the proliferation of immune cells at 42 days was not significantly different compared with that of UCB-Tregs obtained at 18 days. The suppression rate of UCB-Tregs to PBMCs was negatively correlated with the course of diabetes. Moreover, the high-suppression group exhibited a better treatment response than the low-suppression group during the 12-month follow-up period. Conclusions Multiply restimulated UCB-Tregs expanded at a large scale without any alterations in their classical phenotypic features and inhibitory functions. The suppressive function of Tregs in vitro was negatively correlated with the disease duration. The present study revealed the possibility of predicting the in vivo therapeutic effects via the in vitro inhibition assay. Thus, these findings provided a method to obtain off-the-shelf Treg products and facilitated the selection of patients who are likely to respond to the treatment, thereby moving toward the goal of precision treatment.

Abstract Background Specific pathogen-free ducks are a valuable laboratory resource for waterfowl disease research and poultry vaccine development. High throughput sequencing allows the systematic identification of structural variants in genomes. Copy number variation (CNV) can explain the variation of important duck genetic traits. Herein, the genome-wide CNVs of the three experimental duck species in China (Jinding ducks (JD), Shaoxing ducks (SX), and Fujian Shanma ducks (SM)) were characterized using resequencing to determine their genetic characteristics and selection signatures. Results We obtained 4,810 CNV regions (CNVRs) by merging 73,012 CNVs, covering 4.2% of the duck genome. Functional analysis revealed that the shared CNVR-harbored genes were significantly enriched for 31 gene ontology terms and 16 Kyoto Encyclopedia of Genes and Genomes pathways (e.g., olfactory transduction and immune system). Based on the genome-wide fixation index for each CNVR, growth (SPAG17 and PTH1R), disease resistance (CATHL3 and DMBT1), and thermoregulation (TRPC4 and SLIT3) candidate genes were identified in strongly selected signatures specific to JD, SM, and SX, respectively. Conclusions In conclusion, we investigated the genome-wide distribution of experimental duck CNVs, providing a reference to establish the genetic basis of different phenotypic traits, thus contributing to the management of experimental animal genetic resources.

It has been shown that deep neural networks can be easily fooled by adversarial examples, which are samples delicately crafted by adding small imperceptible perturbations to the input. Most optimization-based white-box attacks generate adversarial examples by formulating a constrained optimization problem and then solving it using gradient-based iterative methods. During each iteration, the search point is projected back to satisfy the constraints if it falls out of the feasible region. However, this breaks the continuity of the search process, negatively impacting the attacking performance. Additionally, existing methods often employ an identical step size for all dimensions. In this work, to address these problems and improve the performance of constructing adversarial examples, we propose a novel white-box attack capable of generating $\ell _{\infty } $ adversarial examples based on the feasible direction method. In our attack, the step size of each dimension is carefully adjusted to preserve the feasibility and to accelerate the convergence. The efficiency of the proposed method is evaluated on three widely used datasets(MNIST, CIFAR10, and ImageNet). The experimental results show that our method generates adversarial examples at a higher success rate and a faster convergence rate than existing methods. To facilitate reproducing the experiment results presented, we make the source code of our implementation publicly accessible at https://github.com/sjysjy1/Feasible_Direction_Method_Attack.

Abstract Background Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study. Methods HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148’s impact on HBV in vivo was investigated using an established rcccDNA mouse model. Results ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model. Conclusions ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor with a poor prognosis. This study aimed to investigate whether Hemoglobin, Albumin, Lymphocytes, and Platelets (HALP) score and Tumor Burden Score (TBS) serves as independent influencing factors following radical resection in patients with ICC. Furthermore, we sought to evaluate the predictive capacity of the combined HALP and TBS grade, referred to as HTS grade, and to develop a prognostic prediction model. Methods Clinical data for ICC patients who underwent radical resection were retrospectively analyzed. Univariate and multivariate Cox regression analyses were first used to find influencing factors of prognosis for ICC. Receiver operating characteristic (ROC) curves were then used to find the optimal cut-off values for HALP score and TBS and to compare the predictive ability of HALP, TBS, and HTS grade using the area under these curves (AUC). Nomogram prediction models were constructed and validated based on the results of the multivariate analysis. Results Among 423 patients, 234 (55.3%) were male and 202 (47.8) were aged ≥ 60 years. The cut-off value of HALP was found to be 37.1 and for TBS to be 6.3. Our univariate results showed that HALP, TBS, and HTS grade were prognostic factors of ICC patients (all P

Abstract Persistent transcription of HBV covalently closed circular DNA (cccDNA) is critical for chronic HBV infection. Silencing cccDNA transcription through epigenetic mechanisms offers an effective strategy to control HBV. Long non‐coding RNAs (lncRNAs), as important epigenetic regulators, have an unclear role in cccDNA transcription regulation. In this study, lncRNA sequencing (lncRNA seq) is conducted on five pairs of HBV‐positive and HBV‐negative liver tissue. Through analysis, HOXA‐AS2 (HOXA cluster antisense RNA 2) is identified as a significantly upregulated lncRNA in HBV‐infected livers. Further experiments demonstrate that HBV DNA polymerase (DNA pol) induces HOXA‐AS2 after establishing persistent high‐level HBV replication. Functional studies reveal that HOXA‐AS2 physically binds to cccDNA and significantly inhibits its transcription. Mechanistically, HOXA‐AS2 recruits the MTA1‐HDAC1/2 deacetylase complex to cccDNA minichromosome by physically interacting with metastasis associated 1 (MTA1) subunit, resulting in reduced acetylation of histone H3 at lysine 9 (H3K9ac) and lysine 27 (H3K27ac) associated with cccDNA and subsequently suppressing cccDNA transcription. Altogether, the study reveals a mechanism to self‐limit HBV replication, wherein the upregulation of lncRNA HOXA‐AS2, induced by HBV DNA pol, can epigenetically suppress cccDNA transcription.

BackgroundMechanical ventilation (MV) is often required in critically ill patients. However, prolonged mechanical ventilation can lead to Ventilator-induced diaphragmatic dysfunction (VIDD), resulting in difficulty in extubation after tracheal intubation, prolonged ICU stay, and increased mortality. At present, the incidence of diabetes is high in the world, and the prognosis of diabetic patients with mechanical ventilation is generally poor. Therefore, the role of diabetes in the development of VIDD needs to be discovered.MethodsMV modeling was performed on C57 mice and DB mice, and the control group was set up in each group. After 12 h of mechanical ventilation, the muscle strength of the diaphragm was measured, and the muscle fiber immunofluorescence staining was used to verify the successful establishment of the MV model. RNA sequencing (RNA-seq) method was used to detect mRNA expression levels of the diaphragms of each group, and then differential expressed gene analysis, Heatmap analysis, WGCNA analysis, Venn analysis, GO and KEGG enrichment analysis were performed. qRT-PCR was used to verify the expression of the selected mRNAs.ResultsOur results showed that, compared with C57 control mice, the muscle strength and muscle fiber cross-sectional area of mice after mechanical ventilation decreased, and DB mice showed more obvious in this respect. RNA-seq showed that these differential expressed (DE) mRNAs were mainly related to genes such as extracellular matrix, collagen, elastic fiber and Fbxo32. GO and KEGG enrichment analysis showed that the signaling pathways associated with diabetes were mainly as follows: extracellular matrix (ECM), protein digestion and absorption, PI3K-Akt signaling pathway, calcium signaling pathway, MAPK signaling pathway and AGE-RAGE signaling pathway in diabetic complications, etc. ECM has the closest relationship with VIDD in diabetic mice. The key genes determined by WGCNA and Venn analysis were validated by quantitative real-time polymerase chain reaction (qRT-PCR), which exhibited trends similar to those observed by RNA-seq.ConclusionVIDD can be aggravated in diabetic environment. This study provides new evidence for mRNA changes after mechanical ventilation in diabetic mice, suggesting that ECM and collagen may play an important role in the pathophysiological mechanism and progression of VIDD in diabetic mice, and provides some clues for the research, diagnosis, and treatment of VIDD in diabetic context.

Given the development of insects’ resistance and deteriorative ecological environment, the discovery of insecticides with a new mode of action has been proven to be an important tool for comprehensive pest management. Herein, a novel anthranilic diamides containing 3,5-dichloropyridylpyrazole group were designed and synthesized. Their insecticidal potency was assayed against beet armyworm (Spodoptera exigua). Moreover, the structure-activity relationship of these new compounds was also discussed. Of them, compound 15g exhibited potential insecticidal activity. Because of the excellent efficacy against a series of Lepidoptera and low toxicity to mammals, compound 15g, namely tetrachlorantraniliprole, has been developed and launched into the market as an insecticide.

It has been reported that selenium (Se) can reduce hepatopancreas lipid accumulation induced by high-fat diet. However, its mechanism is still unknown. This study aims to investigate the specific mechanisms by which Se alleviates high-fat diet-induced lipid accumulation. Grass carp were fed control diet (4.8% lipid, Con), high-fat diet (8.8% lipid, HFD) or HFD supplemented with 0.3 mg/kg nano-Se (HSe0.3) for 10 weeks. Growth performance, Se deposition, lipid accumulation, hepatic ultrastructure, and gene and protein expression levels associated with autophagy were examined. Furthermore, oleic acid (OA) was used to incubate the grass carp hepatocytes (L8824) for 24 h, and then the L8824 were incubated with sodium selenite in presence or absence of an autophagy inhibitor for 24 h. L8824 was analyzed for triglyceride concentration, immunofluorescence, and gene and protein expression levels associated with autophagy. We found that dietary nano-Se improved the growth of fish fed HFD and also decreased hepatosomatic index and intraperitoneal fat ratio of fish fed HFD (P

AbstractContext Dolichos trilobus Linn (Leguminosae) is often used in Yi ethnic medicine to treat pain, fracture, and rheumatism.Objective To explore the therapeutic potential of doliroside B (DB) from D. trilobus and its disodium salt (DBDS) and the underlying mechanism in pain.Materials and methods In the writhing test, Kunming mice were orally treated with DB and DBDS at doses of 0.31, 0.62, 1.25, 2.5, and 5 mg/kg. Vehicle, morphine, indomethacin, and acetylsalicylic acid were used as negative and positive control on the nociception-induced models, respectively. In the hot plate test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the formalin test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the meanwhile, lipopolysaccharide-induced inflammatory model in RAW264.7 macrophages was adopted to study the mechanism of pain alleviation for DBDS.Results DBDS (5 mg/kg) inhibited the writhing number by 80.2%, which exhibited the highest antinociceptive activity in pain models. DBDS could selectively inhibite the activity of COX-1. Meanwhile, it also reduced the production of NO, iNOS, and IL-6 by 55.8%, 69.0%, and 49.9% inhibition, respectively. It was found that DBDS also positively modulated the function of GABAA1 receptor.Discussion and conclusions DBDS displayed antinociceptive activity by acting on both the peripheral and central nervous systems, which may act on multitargets. Further work is warranted for developing DBDS into a potential drug for the treatment of pain.

BackgroundNormal hepatic functional reserve is the key to avoiding liver failure after liver surgery. This study investigated the assessment of hepatic functional reserve using liver shear wave velocity (LSWV) combined with biochemical indicators, tumor volume, and portal vein diameter.MethodsIn this single-center prospective study, a total of 123 patients with hepatocellular carcinoma (HCC) were divided into a test group (n=92) and a validation group (n=31). All patients were Child-Pugh grade A. The indocyanine green retention rate at 15 min (ICG-R15), liver shear wave velocity (LSWV), portal vein diameter (Dpv), alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), albumin (ALB), prothrombin time (PT), and also liver tumor volume (maximum diameter ≤5 cm) were measured. In the test group, multiple parameters were used to evaluate hepatic functional reserve, and the multiparametric model was established. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic performance of the multiparametric model. In the validation group, the predictive effectiveness of the multiparametric model was analyzed using consistency tests.ResultsIt was revealed that LSWV, ALB, and PT were statistically significant in evaluation of the hepatic functional reserve (P

Accounting for over 40% of the total energy consumption, the global building sector is pivotal for achieving carbon peak and neutrality objectives. The intricate nature of building carbon emissions, influenced by spatial, temporal, and multifactor coupling, poses challenges on implementing carbon-neutral technologies and conservation strategies. This study focuses on nearly zero energy buildings in China and employs system dynamics to predict energy consumption and carbon emissions according to various scenarios, unveiling influencing patterns and viable emission reduction pathways. The results highlight the substantial impact of enhancing energy conservation awareness as this leads to a 36.4% reduction in energy consumption and a 44.2% reduction in carbon emissions. To attain energy efficiency and carbon reduction goals, a comprehensive approach is essential, encompassing improved building performance, heightened resident energy awareness, increased renewable energy use, and energy landscape adjustments. These findings inform future building energy and carbon emission regulations and offer valuable policy insights.

Abstract Flexible pressure sensors based on micro‐/nanostructures can be integrated into robots to achieve sensitive tactile perception. However, conventional symmetric structures, such as pyramids or hemispheres, can sense only the magnitude of a force and not its direction. In this study, a capacitive flexible tactile sensor inspired by skin structures and based on an asymmetric microhair structure array to perceive directional shear force is designed. Asymmetric microhair structures are obtained by two‐photon polymerization (TPP) and replication. Owing to the features of asymmetric microhair structures, different shear force directions result in different deformations. The designed device can determine the directions of both static and dynamic shear forces. Additionally, it exhibits large response scales ranging from 30 Pa to 300 kPa and maintains high stability even after 5000 cycles; the final relative capacitive change (ΔC/C0) is

Summary: Gestational diabetes mellitus (GDM), the most prevalent metabolic disorder during pregnancy, has long-term risks of metabolic diseases in offspring. However, the underlying mechanisms remain unclear. Here, we analyzed single-cell transcriptional data of cord blood mononuclear cells (CBMCs) from fetuses of healthy and GDM mothers, peripheral blood mononuclear cells from children and adolescents, and coronary plaques myeloid cells from atherosclerosis. Our results demonstrated that monocytes in cord blood were characterized with down-regulated proinflammatory-related pathways and up-regulated proliferation-related pathways. And monocytes in cord blood from GDM mothers were featured with expanded CXCL8+IL1B+ subclusters, enhanced crosstalk with neutrophil granulocytes and augmented adhesive and phagocytic abilities. Interestingly, CXCL8+IL1B+ monocytes influenced by GDM had transcriptome similarity with those of coronary plaques myeloid cells from individuals with atherosclerotic cardiovascular disease. Collectively, our data reveal adverse impact of maternal GDM environment on fetal monocytes and propose potential mechanisms between maternal GDM and offspring atherosclerosis.

Abstract Autophagy plays an important role in the development of diabetic cardiomyopathy. Cellular repressor of E1A-stimulated genes 1 (CREG1) is an important myocardial protective factor. The aim of this study was to investigate the effects and mechanisms of CREG1 in diabetic cardiomyopathy. Male C57BL/6 J mice, Creg1 transgenic mice and cardiac-specific knockout mice were used to establish a type 2 diabetes model. Small animal ultrasound, Masson’s staining and western blotting were used to evaluate cardiac function, myocardial fibrosis and autophagy. Neonatal mouse cardiomyocytes (NMCMs) were stimulated with palmitate, and the effects of CREG1 on NMCMs autophagy were examined. CREG1 deficiency exacerbated cardiac dysfunction, cardiac hypertrophy and fibrosis in mice with diabetic cardiomyopathy, which was accompanied by exacerbated autophagy dysfunction. CREG1 overexpression improved cardiac function and ameliorated cardiac hypertrophy and fibrosis in diabetic cardiomyopathy by improving autophagy. CREG1 protein expression was decreased in palmitate-induced NMCMs. CREG1 knockdown exacerbated cardiomyocyte hypertrophy and inhibited autophagy. CREG1 overexpression inhibited cardiomyocyte hypertrophy and improved autophagy. LAMP2 overexpression reversed the effect of CREG1 knockdown on palmitate-induced inhibition of cardiomyocyte autophagy. CREG1 inhibited LAMP2 protein degradation by inhibiting the protein expression of F-box protein 27 (FBXO27). Our findings indicate new roles of CREG1 in the development of diabetic cardiomyopathy.

Abstract Surrogate-assisted evolutionary algorithm (SAEA) prevails in the optimization of computationally expensive problems. However, existing SAEAs confront low efficiency in the resolution of high-dimensional problems characterized by multiple local optima and multivariate coupling. To this end, this paper offers a dual-drive collaboration surrogate-assisted evolutionary algorithm (DDCSAEA) by coupling feature reduction and reconstruction, which coordinates two unsupervised feature learning techniques, i.e., principal component analysis and autoencoder, in tandem. DDCSAEA creates a low-dimensional solution space by downscaling the target high-dimensional space via principal component analysis and collects promising candidates in the reduced space by collaborating a surrogate-assisted evolutionary sampling with differential mutation. An autoencoder is used to perform the feature reconstruction on the collected candidates for infill-sampling in the target high-dimensional space to sequentially refine the neighborhood landscapes of the optimal solution. Experimental results reveal that DDCSAEA has stronger convergence performance and optimization efficiency against eight state-of-the-art SAEAs on high-dimensional benchmark problems within 200 dimensions.

Amidst escalating global policy uncertainties and the painful transformation phase of the Chinese economy, studying the time-varying characteristics of risk spillover among the real economy, real estate market, and financial system holds substantial practical relevance for preventing and resolving significant systemic risks. This paper employs the TVP-VAR-DY model, selects indices from the real sectors to construct a risk spillover index for the real economy, and incorporates indices from the real estate and financial sectors to develop a trivariate SV-TVP-VAR model for empirically analyzing the time-varying nature of risk spillover relationships among these variables. This study reveals that risk spillover among different sectors of the real economy exhibits asymmetry and volatility, with the industrial sector experiencing the highest degree of risk spillover. The prosperity of the real estate market consistently aligns with that of the financial system; however, shocks during periods of risk accumulation in the real estate market significantly amplify risks in the real economy. The financial system serves the real economy, which suffers lesser impacts. Nonetheless, post-2008, the financial system’s support for the real estate market has gradually diminished. Crises exacerbate the extent of risk spillover, but the causative factors and socio-economic context create heterogeneity in fluctuations. Based on these findings, in response to the current real estate shock, the Chinese government should discuss the real economy, the real estate industry, and the financial system within the same research framework. Policies should primarily focus on fiscal measures to promote the recovery of the real economy more rapidly. Additionally, by allowing local governments to implement tailored policies based on local conditions, potential homebuying demand has been effectively stimulated.

Abstract The artificial bee colony algorithm (ABC) struggles in handling complex optimization problems with high dimensions in light of its search operators’ strong exploration and weak exploitation properties. To tackle this situation, in this study, we propose a bi-preference linkage-driven ABC algorithm with multi-operator fusion, named BPLABC. BPLABC couples a preference-free stochastic search operator with a global best-guided search operator in the employed bee phase to maintain the population diversity while enhancing the population quality. During the onlooker bee phase, a tailored bi-type elite-guided exploitation mechanism is employed to regulate the exploitation intensity of the promising elite nectar sources selected via a new roulette selection probability calculation paradigm. To discourage the onlooker bees from slipping into local traps, after the scout bee phase, an auxiliary adversarial search operator is assembled to tug certain promising elite solutions away from the present pseudo-global best solution. To illustrate the effectiveness and efficiency of BPLABC, two sets of test suits consisting of 23 benchmark problems, 30 complex CEC2014 functions, and two real-world problems are picked for testing. Experimental results showed that BPLABC can achieve superior or equivalent performance to several representative ABC variants on the majority of the tested problems.

Lung cancer is the main cause of cancer-related deaths, and non-small cell lung cancer (NSCLC) is the most common type. Understanding the potential mechanisms, prognosis, and treatment aspects of NSCLC is essential. This study systematically analyzed the correlation between mitophagy and NSCLC. Six mitophagy-related feature genes (SRC, UBB, PINK1, FUNDC1, MAP1LC3B, and CSNK2A1) were selected through machine learning and used to construct a diagnostic model for NSCLC. These feature genes are closely associated with the occurrence and development of NSCLC. Additionally, NSCLC was divided into two subtypes using unsupervised consensus clustering, and their differences in clinical characteristics, immune infiltration, and immunotherapy were systematically analyzed. Furthermore, the interaction between mitophagy-related genes (MRGs) and immune cells was analyzed using single-cell sequencing data. The findings of this study will contribute to the development of potential diagnostic biomarkers for NSCLC and the advancement of personalized treatment strategies.

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

The tree-fruit industry is extremely vulnerable to climate change. We are already seeing that global warming is increasing the incidence and severity of extreme high temperature weather. This means fruit trees are more often experiencing damage due to high temperatures which upsets their growth and development. Heat stress disturbs not only cellular homeostasis but also a fruit’s normal physiological and metabolic processes. Together these effects are proving to be a major adverse factor that compromise both fruit yield and fruit quality. Hence, a better understanding of the response mechanisms of fruit trees to repeated incidences of high temperature is hugely significant for the sustainability of tree-fruit production, justifying this research as one of the main focuses of fruit biology today. In this review, we summarize the physiological and molecular mechanisms through which high temperatures affect tree-fruit species and discuss possible new directions for future study.

Measuring the distribution of atmospheric aerosol concentration is of great significance for accurately assessing the scale of explosions and fires, the evolution of atmospheric environment, and so on. Due to the effect of atmospheric diffusion and other complex meteorological conditions, the distribution of aerosol concentration will change significantly in a short period of time, which puts higher requirements on the speed of aerosol concentration measurement. The existing measurement technology mainly uses LIDAR for intensive sampling of aerosol in a region. Although lidar can achieve accurate measurement of the average concentration of atmospheric aerosol more conveniently, due to longer data processing time and more measurement sampling times, the timeliness of lidar remote sensing has decreased, resulting in the problem of difficult to capture the shape of atmospheric smoke and clouds in a timely manner. Therefore, this study proposes a fast reconstruction deep network model of aerosol extinction coefficient for lidar remote sensing from the perspective of sparse sampling-reconstruction. This model eliminates the feature distribution difference between lidar return signals under sparse sampling and conventional dense sampling by using unsupervised generative adversarial networks from the perspective of transfer learning. Then, the extinction coefficient reconstruction network with the encoding-decoding structure maps the low-dimensional abstract features of aerosol concentration distribution back to the high-dimensional extinction coefficient representation space. This model greatly reduces the sampling number of lidar, thereby reducing the total time required for aerosol extinction coefficient inversion. Experimental measurements of smoke and clouds above a thermal power plant show that the proposed deep network model can reduce more than 50% of the lidar sampling times within the allowable error range. This indicates that the model has the ability to significantly improve the remote sensing measurement efficiency of lidar for atmospheric aerosols.

Learning from work failures is not only beneficial for individual development but also crucial for improving organizational performance and achieving sustainable development. We hypothesize that leader bottom-line mentality, which is commonly used by leaders to prevent profit and performance losses, may reduce subordinates learning from work failures. Drawing on social information processing theory, this paper examines how and when leader bottom-line mentality negatively affects subordinates learning from work failures. We tested our hypotheses through a three-wave survey of 245 employees from several high-tech companies in China. For data analysis, we used SPSS 26.0 and Mplus 8.0 to test the theoretical model and research hypotheses. The results indicated that leader bottom-line mentality has a negative indirect effect on subordinates learning from work failures through the mediating role of subordinates’ psychological availability. In addition, subordinate self-compassion can mitigate this negative mediating mechanism. The present study has several theoretical and practical implications for the current literature.

We developed the Stem Cell Educator therapy among multiple clinical trials based on the immune modulations of multipotent cord blood-derived stem cells (CB-SCs) on different compartments of immune cells, such as T cells and monocytes/macrophages, in type 1 diabetes and other autoimmune diseases. However, the effects of CB-SCs on the B cells remained unclear. To better understand the molecular mechanisms underlying the immune education of CB-SCs, we explored the modulations of CB-SCs on human B cells. CB-SCs were isolated from human cord blood units and confirmed by flow cytometry with different markers for their purity. B cells were purified by using anti-CD19 immunomagnetic beads from human peripheral blood mononuclear cells (PBMCs). Next, the activated B cells were treated in the presence or absence of coculture with CB-SCs for 7 days before undergoing flow cytometry analysis of phenotypic changes with different markers. Reverse transcription-polymerase chain reaction (RT-PCR) was utilized to evaluate the levels of galectin expressions on CB-SCs with or without treatment of activated B cells in order to find the key galectin that was contributing to the B-cell modulation. Flow cytometry demonstrated that the proliferation of activated B cells was markedly suppressed in the presence of CB-SCs, leading to the downregulation of immunoglobulin production from the activated B cells. Phenotypic analysis revealed that treatment with CB-SCs increased the percentage of IgD+CD27− naïve B cells, but decreased the percentage of IgD−CD27+ switched B cells. The transwell assay showed that the immune suppression of CB-SCs on B cells was dependent on the galectin-9 molecule, as confirmed by the blocking experiment with the anti-galectin-9 monoclonal antibody. Mechanistic studies demonstrated that both calcium levels of cytoplasm and mitochondria were downregulated after the treatment with CB-SCs, causing the decline in mitochondrial membrane potential in the activated B cells. Western blot exhibited that the levels of phosphorylated Akt and Erk1/2 signaling proteins in the activated B cells were also markedly reduced in the presence of CB-SCs. CB-SCs displayed multiple immune modulations on B cells through the galectin-9-mediated mechanism and calcium flux/Akt/Erk1/2 signaling pathways. The data advance our current understanding of the molecular mechanisms underlying the Stem Cell Educator therapy to treat autoimmune diseases in clinics.

The recovery of the ozone layer relies on decreasing atmospheric mixing ratios of ozone-depleting substances (ODSs), including chlorofluorocarbons (CFCs). A significant decline in the mixing ratio of trichlorofluoromethane (CFC-11 or $\mathrm{CCl_3F}$ ), the second most abundant CFC, has been observed since the mid-1990s. However, a slowdown in the decline after 2012 indicates a rise in emissions, particularly in Eastern Asia. Ground-based observations are lacking in southeastern China, limiting a thorough evaluation of CFC-11 levels and emissions in this region. A new Advanced Global Atmospheric Gases Experiment background station was established at Xichong (XCG), Shenzhen, China, to provide high-frequency continuous in situ observations. The annual mean CFC-11 mixing ratio, recorded from May 2022 to April 2023, is 221.64 ± 2.29 ppt. When compared with a monthly (MHD) or daily (MLO) observation, this value is found to be 0.45% to 5.36% higher than the northern hemispheric background. With the inverse modeling and interspecies correlation method, we estimate CFC-11 emissions in southeastern China between 1.23 ± 0.25 Gg yr ^−1 and 1.58 ± 0.21 Gg yr ^−1 , in line with the bottom-up estimation of 1.50 Gg yr ^−1 . Results indicate that CFC-11 emissions in the Pearl River Delta region have returned to levels before 2010, aligning with regional and global trends. Observations from XCG would compensate for the deficiency of CFC-11 measurements in southeastern China, paving the road for ODS studies in this region and beyond.

BackgroundThe degree of inflammation and immune status is widely recognized to be associated with intrahepatic cholangiocarcinoma (ICC) and is closely linked to poor postoperative survival. The purpose of this study was to evaluate whether the systemic immune-inflammatory index (SII) and the albumin bilirubin (ALBI) grade together exhibit better predictive strength compared to SII and ALBI separately in patients with ICC undergoing curative surgical resection.MethodsA retrospective analysis was performed on a cohort of 374 patients with histologically confirmed ICC who underwent curative surgical resection from January 2016 to January 2020 at three medical centers. The cohort was divided into a training set comprising 258 patients and a validation set consisting of 116 patients. Subsequently, the prognostic predictive abilities of three indicators, namely SII, ALBI, and SII+ALBI grade, were evaluated. Independent risk factors were identified through univariate and multivariate analyses. The identified independent risk factors were then utilized to construct a nomogram prediction model, and the predictive strength of the nomogram prediction model was assessed through Receiver Operating Characteristic (ROC) survival curves and calibration curves.ResultsUnivariate analysis of the training set, consisting of 258 eligible patients with ICC, revealed that SII, ALBI, and SII+ALBI grade were significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) (p < 0.05). Multivariate analysis revealed the independent significance of SII+ALBI grade as a risk factor for postoperative OS and RFS (p < 0.05). Furthermore, we conducted an analysis of the correlation between SII, ALBI, SII+ALBI grade, and clinical features, indicating that SII+ALBI grade exhibited stronger associations with clinical and pathological characteristics compared to SII and ALBI. We constructed a predictive model for postoperative survival in ICC based on SII+ALBI grade, as determined by the results of multivariate analysis. Evaluation of the model’s predictive strength was performed through ROC survival curves and calibration curves in the training set and validation set, revealing favorable predictive performance.ConclusionThe SII+ALBI grade, a novel classification based on inflammatory and immune status, serves as a reliable prognostic indicator for postoperative OS and RFS in patients with ICC.

Human cord blood–endothelial progenitor cells (hCB-EPCs) isolated from the human umbilical cord can be used to repair damaged arteries. In this study, we used an animal model with pathological changes that mimics artery wall damage caused by stent retrievers in humans. We injected hCB-EPCs to investigate their effect on endothelial hyperplasia and dysfunction during intimal repair. Four groups were established based on the length of reperfusion (3 and 28 days), as well as the presence or absence of hCB-EPC therapy. Damage to the internal carotid artery was evaluated by hematoxylin-eosin and immunohistochemical staining. Stroke volume was not significantly different between non-EPC and EPC groups although EPC treatment alleviated intimal hyperplasia 28 days after intimal damage. Vascular endothelial growth factor (VEGF) and eNOS expression were significantly higher in the EPC-treated group than in the non-EPC group 3 days after intimal damage. In addition, MMP9 and 4HNE expression in the EPC-treated group was significantly lower than in the non-EPC group. Ultimately, this study found that venous transplantation of hCB-EPCs could inhibit neointimal hyperplasia, alleviate endothelial dysfunction, suppress intimal inflammation, and reduce oxidative stress during healing of intimal damage.

ABSTRACT: Specific pathogen-free ducks are important high-grade laboratory animals, with a key role in research related to poultry biosecurity, production, and breeding. However, the genetic characteristics of experimental duck varieties remain poorly explored. Herein we performed whole-genome resequencing to construct a single nucleotide polymorphism genetic map of the genomes of 3 experimental duck varieties [Jinding ducks (JD), Shaoxing ducks (SX), and Fujian Shanma ducks (SM)] to determine their genetic characteristics and identify selection signatures. Subsequent analyses of population structure and genetic diversity revealed that each duck variety formed a monophyletic group, with SM showing richer genetic diversity than JD and SX. Further, on exploring shared selection signatures, we found 2 overlapping genomic regions on chromosome Z of all experimental ducks, which comprised immune response-related genes (IL7R and IL6ST). Moreover, growth and skeletal development (IGF1R and GDF5), meat quality (FoxO1), and stress resistance (HSP90B1 and Gpx8-b) candidate gene loci were identified in strongly selected signatures specific to JD, SM, and SX, respectively. Our results identified the population genetic basis of experimental ducks at the whole-genome level, providing a framework for future molecular investigations of genetic variations and phenotypic changes. We believe that such studies will eventually contribute to the management of experimental animal resources.

Circular RNA (circRNA) has been confirmed to be the key regulators of diabetic nephropathy (DN) progression. However, the role of circ_0114428 in the DN progression remains unclear. Glomerular mesangial cells (GMCs) were treated with high glucose (HG) to mimic DN cell models in vitro. The expression levels of circ_0114428, microRNA (miR)-185-5p, and SMAD3 mRNA were examined by quantitative real-time PCR. Cell proliferation ability was detected by MTT assay, EdU staining and flow cytometry. The protein levels of proliferation marker, fibrosis markers, epithelial-mesenchymal transition (EMT) markers and SMAD3 were measured by western blot assay. The interaction between miR-185-5p and circ_0114428 or SMAD3 was confirmed via dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Our data showed that circ_0114428 was upregulated in HG-induced GMCs. Circ_0114428 overexpression could aggravate the promotion effect of HG on the proliferation, fibrosis and EMT process of GMCs, while its knockdown had an opposite effect. In the terms of mechanisms, circ_0114428 could sponge miR-185-5p to regulate SMAD3. MiR-185-5p inhibitor could reverse the suppressive effect of circ_0114428 knockdown on the proliferation, fibrosis and EMT process in HG-induced GMCs. Also, SMAD3 overexpression abolished the inhibition of miR-185-5p on the proliferation, fibrosis and EMT process in HG-induced GMCs. Taken together, our data suggested that circ_0114428 might promote DN progression by regulating the miR-185-5p/SMAD3 axis.

Redβ annealase catalyses single-strand annealing homologous DNA recombination. Here, the authors present a cryo-EM structure of a Redβ annealing intermediate bound to two complementary 27mer oligonucleotides.

Abstract Background Major depressive disorder (MDD) is a common mental illness, characterized by persistent depression, sadness, despair, etc., troubling people’s daily life and work seriously. Methods In this work, we present a novel automatic MDD detection framework based on EEG signals. First of all, we derive highly MDD-correlated features, calculating the ratio of extracted features from EEG signals at frequency bands between $$\beta$$ β and $$\alpha$$ α . Then, a two-stage feature selection method named PAR is presented with the sequential combination of Pearson correlation coefficient (PCC) and recursive feature elimination (RFE), where the advantages lie in minimizing the feature searching space. Finally, we employ widely used machine learning methods of support vector machine (SVM), logistic regression (LR), and linear regression (LNR) for MDD detection with the merit of feature interpretability. Results Experiment results show that our proposed MDD detection framework achieves competitive results. The accuracy and $$F_{1}$$ F 1 score are up to 0.9895 and 0.9846, respectively. Meanwhile, the regression determination coefficient $$R^2$$ R 2 for MDD severity assessment is up to 0.9479. Compared with existing MDD detection methods with the best accuracy of 0.9840 and $$F_1$$ F 1 score of 0.97, our proposed framework achieves the state-of-the-art MDD detection performance. Conclusions Development of this MDD detection framework can be potentially deployed into a medical system to aid physicians to screen out MDD patients.

BackgroundFunctional magnetic resonance imaging (fMRI) has been widely used to investigate the brain effect of acupuncture point Stomach 36 (ST36, Zusanli). However, inconsistent results have hindered our understanding of the neural mechanisms of acupuncture at ST36.ObjectiveTo perform a meta-analysis of fMRI studies on acupuncture at ST36 to assess the brain atlas of acupuncture at ST36 from available studies.MethodBased on a preregistered protocol in PROSPERO (CRD42019119553), a large set of databases was searched up to August 9, 2021, without language restrictions. Peak coordinates were extracted from clusters that showed significant signal differences before and after acupuncture treatment. A meta-analysis was performed using seed-based d mapping with permutation of subject images (SDM-PSI), a newly improved meta-analytic method.ResultsA total of 27 studies (27 ST36) were included. This meta-analysis found that ST36 could activate the left cerebellum, the bilateral Rolandic operculum, the right supramarginal gyrus, and the right cerebellum. Functional characterizations showed that acupuncture at ST36 was mainly associated with action and perception.ConclusionOur results provide a brain atlas for acupuncture at ST36, which, besides offering a better understanding of the underlying neural mechanisms, also provides the possibility of future precision therapies.

BackgroundSurgery is an important means for patients with colorectal liver metastases (CRLM) to improve their long-term survival, and accurate screening of high-risk factors is crucial to guiding postoperative monitoring and treatment. With this in mind, the aim of this study was to investigate the expression levels and prognostic roles of Mismatch Repair (MMR), Ki67, and Lymphovascular invasion(LVI) in the tumor tissues of colorectal of CRLM.Methods85 Patients with CRLM who received surgical treatment for liver metastases after colorectal cancer resection from June, 2017 and Jan, 2020 were included in this study. Independent risk factors affecting the survival of patients with CRLM were investigated using a Cox regression model and the Kaplan-Meier method, and a nomogram for predicting the OS of patients with CRLM was established according to a Cox multivariate regression model. Calibration plots and Kaplan-Meier curves were used to assess the performance of the nomogram.ResultsThe median survival time was 39 months (95% CI: 32.05-45.950), and MMR, Ki67 and LVI were significantly correlated with prognosis. Univariate analysis indicated that larger metastasis size (p=0.028), more than one liver metastases (p=0.001),higher serum CA199 (p

ObjectiveThis study aimed to analyze the changes in structure and function in amygdala sub-regions in patients with postpartum depression (PPD) before and after acupuncture.MethodsA total of 52 patients with PPD (All-PPD group) were included in this trial, 22 of which completed 8 weeks of acupuncture treatment (Acu-PPD group). An age-matched control group of 24 healthy postpartum women (HPW) from the hospital and community were also included. Results from the 17-Hamilton Depression Scale (17-HAMD) and the Edinburgh Postnatal Depression Scale (EPDS) were evaluated, and resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed at baseline and after the acupuncture treatment. Sub-regions of the amygdala were used as seed regions to measure gray matter volume (GMV) and analyzed for resting-state functional connectivity (RSFC) values separately. Finally, correlation analyses were performed on all patients with PPD to evaluate association values between the clinical scale scores, GMV, and RSFC values, while controlling for age and education. Pearson's correlation analyses were conducted to investigate the relevance between GMV and RSFC values of brain regions that differed before and after acupuncture treatment and clinical scale scores in Acu-PPD patients.ResultsThe HAMD scores for Acu-PPD were reduced after acupuncture treatment (P < 0.05), suggesting the positive effects of acupuncture on depression symptoms. Structurally, the All-PPD group showed significantly decreased GMV in the left lateral part of the amygdala (lAMG.L) and the right lateral part of the amygdala (lAMG.R) compared to the HPW group (P < 0.05). In addition, the GMV of lAMG.R was marginally increased in the Acu-PPD group after acupuncture (P < 0.05). Functionally, the Acu-PPD group showed a significantly enhanced RSFC between the left medial part of the amygdala (mAMG.L) and the left vermis_6, an increased RSFC between the right medial part of the amygdala (mAMG.R) and left vermis_6, and an increased RSFC between the lAMG.R and left cerebelum_crus1 (P < 0.05). Moreover, correlation studies revealed that the GMV in the lAMG.R was significantly related to the EPDS scores in the All-PPD group (P < 0.05).ConclusionOur findings demonstrated that the structure of amygdala sub-regions is impaired in patients with PPD. Acupuncture may improve depressive symptoms in patients with PPD, and the mechanism may be attributed to changes in the amygdala sub-region structure and the functional connections of brain areas linked to the processing of negative emotions. The fMRI-based technique can provide comprehensive neuroimaging evidence to visualize the central mechanism of action of acupuncture in PPD.

Abstract Pathological cardiac hypertrophy is a process of abnormal remodeling of cardiomyocytes in response to pressure overload or other stress stimuli, resulting in myocardial injury, which is a major risk factor for heart failure, leading to increased morbidity and mortality. General control nonrepressed protein 5 (GCN5)/lysine acetyltransferase 2 A, a member of the histone acetyltransferase and lysine acetyltransferase families, regulates a variety of physiological and pathological events. However, the function of GCN5 in pathological cardiac hypertrophy remains unclear. This study aimed to explore the role of GCN5 in the development of pathological cardiac hypertrophy. GCN5 expression was increased in isolated neonatal rat cardiomyocytes (NRCMs) and mouse hearts of a hypertrophic mouse model. GCN5 overexpression aggravated the cardiac hypertrophy triggered by transverse aortic constriction surgery. In contrast, inhibition of GCN5 impairs the development of pathological cardiac hypertrophy. Similar results were obtained upon stimulation of NRCMs (having GCN5 overexpressed or knocked down) with phenylephrine. Mechanistically, our results indicate that GCN5 exacerbates cardiac hypertrophy via excessive activation of the transforming growth factor β-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK)/p38 signaling pathway. Using a TAK1-specific inhibitor in rescue experiments confirmed that the activation of TAK1 is essential for GCN5-mediated cardiac hypertrophy. In summary, the current study elucidated the role of GCN5 in promotion of cardiac hypertrophy, thereby implying it to be a potential target for treatment.

Abstract Background Hereditary spherocytosis (HS) complicated by splenic infarction is very rare, and it is even rarer to develop splenic infarction after infectious mononucleosis (IM) as a result of Epstein–Barr virus (EBV) infection. Therefore, misdiagnosis or missed diagnosis is prone to occur. Case presentation A 19-year-old Chinese female previously diagnosed with HS was admitted to our institution with persistent high fever and icterus. On admission, the physical examination showed anemia, jaundice, marked splenomegaly, obvious tenderness in the left upper abdomen (LUA). Peripheral blood film shows that spherical red blood cells accounted for about 6%, and Immunoglobulin M (IgM) antibodies specific to Epstein–Barr virus (EBV) viral capsid antigen were detected. An abdominal CT scan revealed a splenic infarction. The patient was diagnosed with HS with splenic infarction following EBV infection and underwent an emergency laparoscopic splenectomy (LS). Pathological analysis showed a splenic infarction with red pulp expansion, white pulp atrophy and a splenic sinus filled with red blood cells. After two months of follow-up visits, the patient showed no signs of relapse. Conclusions HS complicated by splenic infarction is very rare and mostly occurs in men under 20 years of age and is often accompanied by other diseases, such as sickle cell traits (SCT) or IM. Although symptomatic management may be sufficient, emergency laparoscopic splenectomy may be safe and effective when conservative treatment is ineffective.

Radiomics was proposed by Lambin et al. in 2012 and since then there has been an explosion of related research. There has been significant interest in developing high-throughput methods that can automatically extract a large number of quantitative image features from medical images for better diagnostic or predictive performance. There have also been numerous radiomics investigations on intrahepatic cholangiocarcinoma in recent years, but no pertinent review materials are readily available. This work discusses the modeling analysis of radiomics for the prediction of lymph node metastasis, microvascular invasion, and early recurrence of intrahepatic cholangiocarcinoma, as well as the use of deep learning. This paper briefly reviews the current status of radiomics research to provide a reference for future studies.

IntroductionCollege students have become a high prevalence group and vulnerable group of depression. The present study aims to explore the effect of perceived stress on depression in a sample of Chinese college students and proposes that both emotion regulation and positive psychological capital play a moderating role between the two, so as to provide rational intervention for the prevention of potential depression among college students.MethodIn this study, 1,267 college students (46.4% female) from a university in western China were selected for the study using a whole-group convenience sampling method.ResultsAfter controlling for gender, this study found that both cognitive reappraisal and positive psychological capital positively moderated the relationship between perceived stress and depression, and both significantly inhibited depression in high and low stress perceivers, and the inhibitory effect was more pronounced in high stress perceivers, but expression inhibition did not moderate the relationship between perceived stress and depression.DiscussionThe results suggest that college students can be helped to cope with the negative effects of perceived stress on depression by increasing the frequency of their use of cognitive reappraisal strategies and encouraging the accumulation of positive psychological capital. This study provides theoretical and practical implications for rational interventions for depression among college students.

Abstract By exploiting versatile P450 enzymes, whole‐cell biocatalysis can be performed to synthesize valuable compounds in Escherichia coli. However, the insufficient supply of heme limits the whole‐cell P450 biocatalytic activity. Here a strategy for improving intracellular heme biosynthesis to enhance the catalytic efficiencies of P450s is reported. After comparing the effects of improving heme transport and biosynthesis on P450 activities, intracellular heme biosynthesis is optimized through the integrated expression of necessary synthetic genes at proper ratios and the assembly of rate‐limiting enzymes using DNA‐guided scaffolds. The intracellular heme level is fine‐tuned by the combined use of mutated heme‐sensitive biosensors and small regulatory RNA systems. The catalytic efficiencies of three different P450s, BM3, sca‐2, and CYP105D7, are enhanced through fine‐tuning heme biosynthesis for the synthesis of hydroquinone, pravastatin, and 7,3′,4′‐trihydroxyisoflavone as example products of chemical intermediate, drug, and natural product, respectively. This strategy of fine‐tuned heme biosynthesis will be generally useful for developing whole‐cell biocatalysts involving hemoproteins.

IntroductionThe study assesses the moderated mediation effect of sense of hope on the mental health of secondary school students.MethodsThe Adult Dispositional Hope Scale (ADHS), Connor-Davidson Resilience Scale (CD-RISC), and the Symptom Check List 90 (SCL-90) were used to conduct a questionnaire survey on 1776 secondary school students.ResultsThe results showed that total mental health scores of secondary school students were significantly negatively correlated with sense of hope and psychological resilience; sense of hope was significantly positively correlated with psychological resilience; sense of hope significantly and positively predicted the level of mental health of secondary school students, and psychological resilience played a mediating role in it; gender plays a moderating role in the relationship between sense of hope and psychological resilience.DiscussionThe study further revealed the mechanism of the effect of sense of hope on secondary school students’ mental health, and provided suggestions for cultivating positive psychological qualities and promoting the mental health development of secondary school students.