How the secrets behind photocurrents are revealed in Ag-TiO2 heterostructures-based plasmonic photoelectrochemical systems: A collaborative approach of EC-SERS and photoelectrochemical methods.

Plasmon-mediated chemical reactions (PMCR) have garnered growing interest as a promising concept for photocatalysis. However, in electrochemical systems at solid-liquid interfaces, the photo-induced charge transfer on the surface of metal-semiconductor heterostructures involves complex processes and mechanisms, which are still poorly understood. We explore the plasmon-mediated carrier transfer mechanism and the synergistic effect of light and electric fields on Ag-TiO2 heterostructures, through a combination of electrochemical surface-enhanced Raman spectroscopy and photoelectrochemical methods, with para-aminothiophenol (PATP) serving as a probe molecule. The results show that photocurrent responses are dependent on not only excitation wavelengths and applied potentials, but also the irreversibility of redox. The relationship between photocurrent responses and the chemical transformation between PATP and 4,4'-dimercaptoazobenzene is established, reflecting the photo-induced charge transfer of the heterostructures. The collaboration of spectroscopic and photoelectrochemical methods provide valuable insights into the chemical transformation and kinetic information of adsorbed molecules on the heterostructure during PMCR, offering opportunities for modulating of photocatalytic activities of hot carriers.

Multi-gene phylogenetic analyses revealed two novel species and one new record of Trichobotrys (Pleosporales, Dictyosporiaceae) from China.

The rotting wood in freshwater is a unique eco-environment favoring various fungi. During our investigation of freshwater fungi on decaying wood, three hyphomycetes were collected from Jiangxi and Guangxi Provinces, China. Based on the morphological observations and phylogenetic analysis of a combined DNA data containing ITS, LSU, SSU and tef1-α sequences, two new Trichobotrys species, T.meilingensis and T.yunjushanensis, as well as a new record of T.effusa, were introduced. Additionally, a comprehensive description of the genus with both morphological and molecular data was first provided.

Surgical outcomes of patients with genetically refractory epilepsy: A systematic review and meta-analysis.

OBJECTIVE: To summarize the surgical outcomes of genetically refractory epilepsy and identify prognostic factors for these outcomes. METHODS: A literature search of the PubMed, Web of Science, and Embase databases for relevant studies, published between January 1, 2002 and December 31, 2023, was performed using specific search terms. All studies addressing surgical outcomes and follow-up of genetically refractory epilepsy were included. All statistical analyses were performed using STATA software (StataCorp LLC, College Station, TX, USA). This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020 (i.e., "PRISMA") reporting guidelines. RESULTS: Of the 3833 studies retrieved, 55 fulfilled the inclusion criteria. Eight studies were eligible for meta-analysis at the study level. Pooled outcomes revealed that 74 % of patients who underwent resective surgery (95 % confidence interval [CI] 0.55-0.89; z = 9.47, p < 0.05) achieved Engel I status at the last follow-up. In the study level analysis, pooled outcomes revealed that 9 % of patients who underwent vagus nerve stimulation achieved seizure-free status (95 % CI 0.00-0.31; z = 1.74, p < 0.05), and 61 % (95 % CI 0.55-0.89; z = 11.96, p < 0.05) achieved a 50 % reduction in seizure frequency at the last follow-up. Fifty-three studies comprising 249 patients were included in an individual-level analysis. Among patients who underwent lesion resection or lobectomy/multilobar resection, 65 % (100/153) achieved Engel I status at the last follow-up. Univariate analysis indicated that female sex, somatic mutations, and presenting with focal seizure symptoms were associated with better prognosis (p < 0.05). Additionally, 75 % (21/28) of patients who underwent hemispherectomy/hemispherotomy achieved Engel I status at the last follow-up. In the individual-level analysis, among patients treated with vagus nerve stimulation, 21 % (10/47) were seizure-free and 64 % (30/47) experienced >50 % reduction in seizure frequency compared with baseline. CONCLUSION: Meticulous presurgical evaluation and selection of appropriate surgical procedures can, to a certain extent, effectively control seizures. Therefore, various surgical procedures should be considered when treating patients with genetically refractory epilepsy.

Enhanced Interfacial Electron Transfer in Photocatalyst-Natural Enzyme Coupled Artificial Photosynthesis System: Tuning Strategies and Molecular Simulations.

Laccase is capable of catalyzing a vast array of reactions, but its low redox potential limits its potential applications. The use of photocatalytic materials offers a solution to this problem by converting absorbed visible light into electrons to facilitate enzyme catalysis. Herein, MIL-53(Fe) and NH2-MIL-53(Fe) serve as both light absorbers and enzyme immobilization carriers, and laccase is employed for solar-driven chemical conversion. Electron spin resonance spectroscopy results confirm that visible light irradiation causes rapid transfer of photogenerated electrons from MOF excitation to T1 Cu(II) of laccase, significantly increasing the degradation rate constant of tetracycline (TC) from 0.0062 to 0.0127 min-1. Conversely, there is only minimal or no electron transfer between MOF and laccase in the physical mixture state. Theoretical calculations demonstrate that the immobilization of laccase's active site and its covalent binding to the metal-organic framework surface augment the coupled system's activity, reducing the active site accessible from 27.8 to 18.1 Å. The constructed photo-enzyme coupled system successfully combines enzyme catalysis' selectivity with photocatalysis's high reactivity, providing a promising solution for solar energy use.

Mining the interpretable prognostic features from pathological image of intrahepatic cholangiocarcinoma using multi-modal deep learning.

BACKGROUND: The advances in deep learning-based pathological image analysis have invoked tremendous insights into cancer prognostication. Still, lack of interpretability remains a significant barrier to clinical application. METHODS: We established an integrative prognostic neural network for intrahepatic cholangiocarcinoma (iCCA), towards a comprehensive evaluation of both architectural and fine-grained information from whole-slide images. Then, leveraging on multi-modal data, we conducted extensive interrogative approaches to the models, to extract and visualize the morphological features that most correlated with clinical outcome and underlying molecular alterations. RESULTS: The models were developed and optimized on 373 iCCA patients from our center and demonstrated consistent accuracy and robustness on both internal (n = 213) and external (n = 168) cohorts. The occlusion sensitivity map revealed that the distribution of tertiary lymphoid structures, the geometric traits of the invasive margin, the relative composition of tumor parenchyma and stroma, the extent of necrosis, the presence of the disseminated foci, and the tumor-adjacent micro-vessels were the determining architectural features that impacted on prognosis. Quantifiable morphological vector extracted by CellProfiler demonstrated that tumor nuclei from high-risk patients exhibited significant larger size, more distorted shape, with less prominent nuclear envelope and textural contrast. The multi-omics data (n = 187) further revealed key molecular alterations left morphological imprints that could be attended by the network, including glycolysis, hypoxia, apical junction, mTORC1 signaling, and immune infiltration. CONCLUSIONS: We proposed an interpretable deep-learning framework to gain insights into the biological behavior of iCCA. Most of the significant morphological prognosticators perceived by the network are comprehensible to human minds.

Synthesis of Long-Chain Polyamides via Main-Chain Modification of Polyethyleneketones.

Long-chain polyamides (polyethyleneamides) were prepared from polyethylenes bearing in-chain carbonyl groups (polyethyleneketones) by the oxime formation and successive Beckmann rearrangement. (Diethylamino)sulfur trifluoride (DAST) was utilized as a promoter, which allowed mild conversion of the oxime group in spite of low solubility of the polymers. The polyethyleneamide exhibited different tensile property compared to a commercial HDPE.

Cerebral cortex functional reorganization in preschool children with congenital sensorineural hearing loss: a resting-state fMRI study.

Purpose: How cortical functional reorganization occurs after hearing loss in preschool children with congenital sensorineural hearing loss (CSNHL) is poorly understood. Therefore, we used resting-state functional MRI (rs-fMRI) to explore the characteristics of cortical reorganization in these patents. Methods: Sixty-three preschool children with CSNHL and 32 healthy controls (HCs) were recruited, and the Categories of Auditory Performance (CAP) scores were determined at the 6-month follow-up after cochlear implantation (CI). First, rs-fMRI data were preprocessed, and amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated. Second, whole-brain functional connectivity (FC) analysis was performed using bilateral primary auditory cortex as seed points. Finally, Spearman correlation analysis was performed between the differential ALFF, ReHo and FC values and the CAP score. Results: ALFF analysis showed that preschool children with CSNHL had lower ALFF values in the bilateral prefrontal cortex and superior temporal gyrus than HCs, but higher ALFF values in the bilateral thalamus and calcarine gyrus. And correlation analysis showed that some abnormal brain regions were weak negatively correlated with CAP score (p < 0.05). The ReHo values in the bilateral superior temporal gyrus, part of the prefrontal cortex and left insular gyrus were lower, whereas ReHo values in the bilateral thalamus, right caudate nucleus and right precentral gyrus were higher, in children with CSNHL than HCs. However, there was no correlation between ReHo values and the CAP scores (p < 0.05). Using primary auditory cortex (PAC) as seed-based FC further analysis revealed enhanced FC in the visual cortex, proprioceptive cortex and motor cortex. And there were weak negative correlations between the FC values in the bilateral superior temporal gyrus, occipital lobe, left postcentral gyrus and right thalamus were weakly negatively correlated and the CAP score (p < 0.05). Conclusion: After auditory deprivation in preschool children with CSNHL, the local functions of auditory cortex, visual cortex, prefrontal cortex and somatic motor cortex are changed, and the prefrontal cortex plays a regulatory role in this process. There is functional reorganization or compensation between children's hearing and these areas, which may not be conducive to auditory language recovery after CI in deaf children.

SIGLEC15, negatively correlated with PD-L1 in HCC, could induce CD8+ T cell apoptosis to promote immune evasion.

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and Jurkat cells, flow cytometry analysis of tumor infiltrated immune cells and further sequencing analyses were performed to investigate how SIGLEC15 could affect T cells in vitro and in vivo. We found SIGLEC15 was increased in HCC tumor tissues and was negatively correlated with PD-L1 in HCC samples. In vitro and in vivo models demonstrated inhibition of SIGLEC15 did not directly influence tumor proliferation. However, SIGLEC15 could promoted HCC immune evasion in immune competent mouse models. Knock-out of Siglec15 could inhibit tumor growth and reinvigorate CD8+ T cell cytotoxicity. Anti-SIGLEC15 treatment could effectively inhibit tumor growth in mouse models with or without mononuclear phagocyte deletion. Bulk and single-cell RNA sequencing data of treated mouse tumors demonstrated SIGLEC15 could interfere CD8+ T cell viability and induce cell apoptosis. In all, SIGLEC15 was negatively correlated with PD-L1 in HCC and mainly promote HCC immune evasion through inhibition of CD8+ T cell viability and cytotoxicity.

Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury.

ABSTRACT: The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro. Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Achieving consistency of flexible surface acoustic wave sensors with artificial intelligence.

Flexible surface acoustic wave technology has garnered significant attention for wearable electronics and sensing applications. However, the mechanical strains induced by random deformation of these flexible SAWs during sensing often significantly alter the specific sensing signals, causing critical issues such as inconsistency of the sensing results on a curved/flexible surface. To address this challenge, we first developed high-performance AlScN piezoelectric film-based flexible SAW sensors, investigated their response characteristics both theoretically and experimentally under various bending strains and UV illumination conditions, and achieved a high UV sensitivity of 1.71 KHz/(mW/cm²). To ensure reliable and consistent UV detection and eliminate the interference of bending strain on SAW sensors, we proposed using key features within the response signals of a single flexible SAW device to establish a regression model based on machine learning algorithms for precise UV detection under dynamic strain disturbances, successfully decoupling the interference of bending strain from target UV detection. The results indicate that under strain interferences from 0 to 1160 µÎµ the model based on the extreme gradient boosting algorithm exhibits optimal UV prediction performance. As a demonstration for practical applications, flexible SAW sensors were adhered to four different locations on spacecraft model surfaces, including flat and three curved surfaces with radii of curvature of 14.5, 11.5, and 5.8 cm. These flexible SAW sensors demonstrated high reliability and consistency in terms of UV sensing performance under random bending conditions, with results consistent with those on a flat surface.

The association between weight change patterns and obesity-related complex multimorbidity: evidence from NHANES.

Objective: Obesity is a major risk factor for non-communicable diseases (NCDs), which has been the leading cause of death nowadays. The aim of this study is to examine the association between total changes in body mass index (BMI) across adulthood and the risk of obesity-related complex multimorbidity in elderly, characterizing the capacity of BMI waves in predicting major chronic diseases. Methods: In this retrospective study, 15,520 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999 and 2018. BMI was categorized as obesity (≥30.0 kg/m²), overweight (25.0-29.9 kg/m²), normal weight (18.5-24.9 kg/m²), and underweight (<18.5 kg/m²). Odds ratios (ORs) with 95% confidence interval (CIs) for the relationship between BMI change patterns and major health outcomes included hypertension, cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes, and population attributable fractions (PAFs) of BMI were evaluated. Results: In comparison with participants who remained non-obese, those who are stable obese showed the highest risks of developing at least one chronic disease in later life, with odds ratios of 2.76 (95% CI: 2.20 to 3.45) from age 25 years to 10 years before baseline, 2.90 (2.28 to 3.68) from age 25 years to baseline, and 2.49 (2.11 to 2.95) in the 10-year period before baseline. Moving from non-obese to obese weight-change pattern in all periods (from age 25 years to 10 years before baseline: OR = 1.82; 95% CI, 1.57 to 2.11; from age 25 years to baseline: OR = 1.87; 95% CI, 1.59 to 2.19; from 10 years before baseline to baseline: OR = 1.62; 95% CI, 1.26 to 2.08) and moving from obese to non-obese, the 10-year period before baseline (OR = 1.89; 95% CI, 1.39 to 2.57) was associated with increased risk of chronic diseases. Midlife obesity status can explain the 8.6% risk of occurrence of the chronic diseases in elderly. Conclusions: Maintaining a stable healthy weight and losing weight in early adulthood and midlife are important for better life quality during the aging process. More effective strategies and policies to reduce the prevalence of obesity are needed.

Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

Mechanisms of conjugative transfer of antibiotic resistance genes induced by extracellular polymeric substances: Insights into molecular diversities and electron transfer properties.

Dissemination of antibiotic resistance genes (ARGs) has become a critical threat to public health. Activated sludge, rich in extracellular polymeric substances (EPS), is an important pool of ARGs. In this study, mechanisms of conjugation transfer of ARGs induced by EPS, including tightly bound EPS (TBEPS), soluble EPS (SEPS), and loosely bound EPS (LBEPS), were explored in terms of molecular diversities and electron transfer properties of EPS. Conjugation transfer frequency was increased by 9.98-folds (SEPS), 4.21-folds (LBEPS), and 15.75-folds (TBEPS) versus the control, respectively. Conjugation-related core genes involving SOS responses (9 genes), membrane permeability (18 genes), intercellular contact (17 genes), and energy metabolism pathways (13 genes) were all upregulated, especially in the presence of TBEPS. Carbohydrates and aliphatic substances in SEPS and LBEPS were contributors to ARG transfer, via influencing reactive oxygen species (ROS) formation (SEPS) and ROS and adenosine triphosphate (ATP) production (LBEPS). TBEPS had the highest redox potential and greatest lability and facilitated electron transfer and alternated respiration between cells, thus promoting ARG transfer by producing ATP. Generally, the chemical molecular characteristics and redox properties of EPS facilitated ARG transfer mainly by influencing lipid peroxidation and ATP, respectively.

[Improvement of the mastication function of orthodontics combined with restoration in the treatment of deep overbite with severe lower anterior teeth attrition].

PURPOSE: To observe the effect of orthodontics combined with restoration on masticatory function in deep overbite patients with severe lower anterior teeth attrition. METHODS: From January 2018 to January 2022, a total of 164 deep overbite patients with severe lower anterior teeth attrition were collected and divided into two groups according to different treatment plans: control group(72 patients, with restoration treatment) and experimental group(92 patients, with orthodontics combined with restoration treatment). The chewing efficiency of the two groups was evaluated, temporomandibular joint dysfunction index (DI), muscle palpation index (PI) and cranio-mandibular index (CMI) were calculated. The satisfaction with facial esthetic, the Chinese version of Oral Health Impact Scale-14(OHIP-14) and the repair satisfaction score were evaluated, the occurrence of adverse events between the two groups was compared. SPSS 23.0 software package was used for statistical analysis. RESULTS: After treatment, the chewing efficiency of the experimental group was significantly improved compared to the control group, while the DI, PI, and CMI were significantly reduced compared to the control group(P＜0.05). Compared with the control group, the satisfaction degree with facial esthetic and restoration in the experimental group was significantly higher, while the OHIP-14 score was significantly lower after treatment(P＜0.05). The incidence of adverse events in the experimental group was significantly decreased compared with the control group (6.52% vs 25.00%, P＜0.05). CONCLUSIONS: Combination of orthodontics and restoration treatment can enhance the effectiveness of restoration treatment for deep overbite with severe lower anterior teeth attrition, improve the mastication function and temporomandibular joint balance,satisfaction and quality of life of patients, as well as reduce the risk of adverse events.

Complexation with Metal Ions Affects Chlorination Reactivity of Dissolved Organic Matter: Structural Reactomics of Emerging Disinfection Byproducts.

Metal ions are liable to form metal-dissolved organic matter [dissolved organic matter (DOM)] complexes, changing the chemistry and chlorine reactivity of DOM. Herein, the impacts of iron and zinc ions (Fe3+ and Zn2+) on the formation of unknown chlorinated disinfection byproducts (Cl-DBPs) were investigated in a chlorination system. Fe3+ preferentially complexed with hydroxyl and carboxyl functional groups, while Zn2+ favored the amine functional groups in DOM. As a consequence, electron-rich reaction centers were created by the C-O-metal bonding bridge, which facilitated the electrophilic attack of α-C in metal-DOM complexes. Size-reactivity continuum networks were constructed in the chlorination system, revealing that highly aromatic small molecules were generated during the oxidation and decarbonization of metal-DOM complexes. Molecular transformation related to C-R (R represents complex sites) loss was promoted via metal complexation, including decarboxylation and deamination. Consequently, complexation with Fe3+ and Zn2+ promoted hydroxylation by the C-O-metal bonding bridge, thereby increasing the abundances of unknown polychlorinated Cl-DBPs by 9.6 and 14.2%, respectively. The study provides new insights into the regulation of DOM chemistry and chlorine reactivity by metal ions in chlorination systems, emphasizing that metals increase the potential health risks of drinking water and more scientific control standards for metals are needed.

Deep Brain Stimulation Inhibits Epileptic Seizures via Increase of Adenosine Release and Inhibition of ENT1, CD39, and CD73 Expression.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8 weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.

Photo-responsive anti-fouling polyzwitterionic brushes: a mesoscopic simulation.

The antifouling effects of a toothbrush-shaped photo-responsive polyzwitterionic membrane were studied via dissipative particle dynamics simulations in this work. The results reveal that the membrane modified by spiropyran methacrylate brushes displays photo-switchable and antifouling capability due to the photo-induced ring-opening reaction. Namely, surface morphology and hydrophilicity change in response to visible or UV light irradiation, which can be observed visually by protein adsorption and desorption. Further study indicates that: (1) brush-modification density can influence the structure and properties of the membrane. With low modification density, systems cannot establish an intact selective layer, which hinders the antifouling ability; as the modification density increases, the intact selective layer can be formed, which is conducive to the expression of photo-responsiveness and antifouling capability. (2) Factors of toothbrush-hair length and grafting ratio can influence the establishment of a light-responsive surface: as the grafting ratio and toothbrush-hair length increase, the light-responsive surface is gradually formed, meanwhile, the antifouling ability can be continuously reinforced under UV light irradiation. (3) As the brushes switch into a zwitterionic merocyanine state under UV exposure, the selective layer swelling becomes stronger than that with a hydrophobic spiropyran state under visible exposure. This is owing to the enhanced interaction between zwitterionic brushes and water, which is the root of the antifouling effect. The present work is expected to provide some guidelines for the design and development of novel antifouling membrane surfaces.

Overexpression of RpKTI2 from Robinia pseudoacacia Affects the Photosynthetic Physiology and Endogenous Hormones of Tobacco.

Kunitz trypsin inhibitor genes play important roles in stress resistance. In this study, we investigated RpKTI2 cloned from Robinia pseudoacacia and its effect on tobacco. RpKTI2 was introduced into the tobacco cultivar NC89 using Agrobacterium-mediated transformation. Six RpKTI2-overexpressing lines were obtained. Transgenic and wild-type tobacco plants were then compared for photosynthetic characteristics and endogenous hormone levels. Transgenic tobacco showed minor changes in chlorophyll content, fluorescence, and photosynthetic functions. However, the maximum photochemical efficiency (Fv/Fm) increased significantly while intercellular CO2 concentration (Ci) decreased significantly. Stomatal size and hormone content (indole-3-acetic acid, zeatin riboside, gibberellin, and indole-3-propionic acid) were reduced, while brassinosteroid content increased. Random forest regression revealed that RpKTI2 overexpression had the biggest impact on carotenoid content, initial fluorescence, Ci, stomatal area, and indole-3-acetic acid. Overall, RpKTI2 overexpression minimally affected chlorophyll synthesis and photosynthetic system characteristics but influenced stomatal development and likely enhanced the antioxidant capacity of tobacco. These findings provide a basis for future in-depth research on RpKTI2.

Effects of the subtypes of apolipoprotein E on immune inhibition and prognosis in patients with Hepatocellular Carcinoma.

PURPOSE: To investigate whether prognosis of patients with hepatocellular carcinoma (HCC) is affected by the abundance and subgroups of myeloid-derived suppressor cells (MDSCs) as well as subtypes and expression of apolipoprotein E (apoE). METHODS: 31 HCC patients were divided into three groups according to blood total apoE level for detecting the abundance of immunoregulatory cells by flow cytometry. Tumour tissue microarrays from 360 HCC patients were evaluated about the abundance and subgroups of MDSCs and the expression of apoE2, apoE3, apoE4 by immunofluorescence staining and immunohistochemistry staining. Survival analysis by means of univariate, multivariate COX regression and Kaplan-Meier methods of the 360 patients was performed based on clinical and pathological examinations along with 10 years' follow-up data. RESULTS: The lower apoE group presented higher abundance of MDSCs in the peripheral blood of HCC patients than higher apoE group. The abundance of monocyte-like MDSCs (M-MDSCs) was higher in the apoE low level group than high level group (p = 0.0399). Lower H-score of apoE2 (HR = 6.140, p = 0.00005) and higher H-score of apoE4 (HR = 7.001, p = 0.009) in tumour tissue were significantly associated with shorter overall survival (OS). The higher infiltration of polymorphonuclear granulocyte-like MDSCs (PMN-MDSCs, HR = 3.762, p = 0.000009) and smaller proportion of M-MDSCs of total cells (HR = 0.454, p = 0.006) in tumour tissue were independent risk factors for shorter recurrence-free survival (RFS). CONCLUSION: The abundance of MDSCs in HCC patients' plasma negatively correlates with the level of apoE. The expression of apoE4 in HCC tissue indicated a poor prognosis while apoE2 might be a potential protective factor.

Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA. METHODS: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody. RESULTS: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3ß/ß-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells. CONCLUSIONS: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response.