Electrocardiogram-based prediction of conduction disturbances after transcatheter aortic valve replacement with convolutional neural network.

Aims: Permanent pacemaker implantation and left bundle branch block are common complications after transcatheter aortic valve replacement (TAVR) and are associated with impaired prognosis. This study aimed to develop an artificial intelligence (AI) model for predicting conduction disturbances after TAVR using pre-procedural 12-lead electrocardiogram (ECG) images. Methods and results: We collected pre-procedural 12-lead ECGs of patients who underwent TAVR at West China Hospital between March 2016 and March 2022. A hold-out testing set comprising 20% of the sample was randomly selected. We developed an AI model using a convolutional neural network, trained it using five-fold cross-validation and tested it on the hold-out testing cohort. We also developed and validated an enhanced model that included additional clinical features. After applying exclusion criteria, we included 1354 ECGs of 718 patients in the study. The AI model predicted conduction disturbances in the hold-out testing cohort with an area under the curve (AUC) of 0.764, accuracy of 0.743, F1 score of 0.752, sensitivity of 0.876, and specificity of 0.624, based solely on pre-procedural ECG images. The performance was better than the Emory score (AUC = 0.704), as well as the logistic (AUC = 0.574) and XGBoost (AUC = 0.520) models built with previously identified high-risk ECG patterns. After adding clinical features, there was an increase in the overall performance with an AUC of 0.779, accuracy of 0.774, F1 score of 0.776, sensitivity of 0.794, and specificity of 0.752. Conclusion: Artificial intelligence-enhanced ECGs may offer better predictive value than traditionally defined high-risk ECG patterns.

Variations in Genetic Diversity of Invasive Species Lithobates catesbeianus in China.

The introduction and subsequent range expansion of the American bullfrog (Lithobates catesbeianus) is part of a rising trend of troublesome biological invasions happening in China. This detrimental amphibious invasive species has strong adaptability. After its introduction and spread, it established its own ecological niche in many provinces of China, and its range has continued to expand to more areas. Previous studies recorded the introduction time of bullfrogs and calculated the changes in their genetic diversity in China using mitochondria, but the specific introduction route in China is still unknown. Expanding upon previous research, we employed whole-genome scans (utilizing 2b-RAD genomic sequencing) to examine single nucleotide polymorphisms (SNPs) and microsatellites within Lithobates catesbeianus to screen the genomes of these invasive amphibian species from eight Chinese provinces and two U.S. states, including Kansas, where bullfrogs originate. A total of 1,336,475 single nucleotide polymorphic loci and 17 microsatellite loci were used to calculate the genetic diversity of bullfrogs and their migration pathways. Our results suggest that the population in Hunan was the first to be introduced and to spread, and there may have been multiple introductions of subpopulations. Additionally, the genetic diversity of both the SNP and microsatellite loci in the Chinese bullfrog population was lower than that of the US population due to bottleneck effects, but the bullfrogs can adapt and spread rapidly. This study will offer crucial insights for preventing and controlling future introductions into the natural habitats in China. Additionally, it will assist in devising more precise strategies to manage the existing populations and curtail their continued expansion, as well as aim to improve clarity and originality while mitigating plagiarism risk.

Cerebral 18F-FDG PET/CT Metabolism as Diagnostic Signature for Central Nervous System Toxicity After Immune Checkpoint Blockade Cancer Treatment.

Our aim was to investigate probable biomarkers specific to immune-related central nervous system toxicity (CNST) in cancer patients treated with immune checkpoint inhibitors (ICI) by analysis of 18F-FDG PET/CT images. Methods: Cancer patients receiving ICI treatment were enrolled in a multicenter observational study that analyzed regional metabolic changes before and during CNST onset from January 2020 to February 2022. In 1:1 propensity score-matched pairs, the regional SUVmean of each bilateral brain lobe of CNST patients (CNST+) was compared with that of patients who had central nervous system infections (CNSIs) and patients without CNST or CNSI (CNST-). In a validation cohort, patients were recruited from February 2022 to July 2023 and followed up for 24 wk after the start of ICI. Early changes in regional SUVmean at 5-6 wk after therapy initiation were evaluated for ability to predict later CNST onset. Results: Of 6,395 ICI-treated patients, 2,387 underwent prognostic 18F-FDG PET/CT and 125 of the scanned patients had CNST (median time from ICI treatment to onset, 9 wk; quartile range, 2-23 wk). Regional 18F-FDG PET/CT SUVmean changes were higher in CNST+ than in CNST- patients (117 patient pairs) but were lower than in CNSI patients (50 pairs). Differentiating analysis reached an area under the curve (AUC) of 0.83 (95% CI, 0.78-0.88) for CNST+ versus CNST- and of 0.80 (95% CI, 0.72-0.89) for CNST+ versus CNSI. Changes in SUVmean were also higher before CNST onset than for CNST- (60 pairs; AUC, 0.74; 95% CI, 0.66-0.83). In a validation cohort of 2,878 patients, preonset changes in SUVmean reached an AUC of 0.86 (95% CI, 0.79-0.94) in predicting later CNST incidence. Conclusion: Brain regional hypermetabolism could be detected during and before CNST clinical onset. CNST may be a distinct pathologic entity versus brain infections defined by 18F-FDG PET/CT brain scans. Regional SUV differences may be translated into early diagnostic tools based on moderate differentiating accuracy in our study.

Pentamethylquercetin attenuates angiotensin II-induced abdominal aortic aneurysm formation by blocking nuclear translocation of C/EBPß at Lys253.

BACKGROUND: Pentamethylquercetin (PMQ) is a natural polymethyl flavonoid that possesses anti-apoptotic and other biological properties. Abdominal aortic aneurysm (AAA), a fatal vascular disease with a high risk of rupture, is associated with phenotypic switching and apoptosis of medial vascular smooth muscle cells (VSMCs). This study aimed to investigate the protective effects of PMQ on the development of AAA and the underlying mechanism. METHODS: ApoE-/- mice were continuously infused with angiotensin II (Ang II) for 4 weeks to develop the AAA model. Intragastric administration of PMQ was initiated 5 days before Ang II infusion and continued for 4 weeks. In vitro, VSMCs were cultured and pretreated with PMQ, stimulated with Ang II. Real-time PCR, western blotting, and immunofluorescence staining were used to examine the roles and mechanisms of PMQ on the phenotypic switching and apoptosis of VSMCs. RESULTS: PMQ dose-dependently reduced the incidence of Ang II-induced AAA, aneurysm diameter enlargement, elastin degradation, VSMCs phenotypic switching and apoptosis. Furthermore, PMQ also inhibited phenotypic switching and apoptosis in Ang II-stimulated VSMCs. PMQ exerted protective effects by regulating the C/EBPß/PTEN/AKT/GSK-3ß axis. AAV-mediated overexpression of PTEN reduced the therapeutic effects of PMQ in the AAA model mice, suggesting that the effects of PMQ on Ang II-mediated AAA formation were related to the PTEN/AKT/GSK-3ß axis. PMQ inhibited VSMCs phenotypic switching and apoptosis by bounding to C/EBPß at Lys253 with hydrogen bond to regulate C/EBPß nuclear translocation and PTEN/AKT/GSK-3ß axis, thereby inhibiting Ang II-induced AAA formation. CONCLUSIONS: Pentamethylquercetin inhibits angiotensin II-induced abdominal aortic aneurysm formation by bounding to C/EBPß at Lys253. Therefore, PMQ prevents the formation of AAA and reduces the incidence of AAA.

Effects of stock enhancement on the macrobenthic community and ecological health in the intertidal zone of the estuarine wetland in Nanhui, China.

Nanhui Dongtan Wetland is an important part of Yangtze Estuary Wetland, and its species diversity has been affected by reclamation in recent years. To increase the diversity of species in reclamation areas, stock enhancement was implemented in the Nanhui Dongtan Wetland in May 2020 as a method of ecological restoration. We investigated macrobenthos before and after release, analysed changes in the macrobenthos and evaluated the ecological health of the sampled area. The diversity index showed species were more abundant and community structure were more diversified after release. Functional groups and redundancy analysis showed that the effects of stock enhancement on macrobenthos in Nanhui Dongtan wetland may be based on changes in secondary productivity. Stock enhancement may promote the resistance of macrobenthic communities to organic pollution without negatively affecting ecological health. As a method of ecological restoration, stock enhancement will play a positive role in the restoration of macrobenthic communities.

Alien range size, habitat breadth, origin location, and domestication of alien species matter to their impact risks.

Invasive alien species are a major driver of biodiversity loss. Currently, the process of biological invasions is experiencing a constant acceleration, foreshadowing a future increase in the threat posed by invasive alien species to global biodiversity. Therefore, it is necessary to assess the impact risks of invasive alien species and related factors. Here, we constructed a dataset of negative environmental impact events to evaluate the impact risks of alien species. We collected information on 1071 established alien terrestrial vertebrates and then gathered negative environmental impacts for 108 of those species. Generalized linear mixed-effects model and phylogenetic generalized least-squares regression model were used to examine the characteristic (including life-history traits, characteristics related to distribution, and introduction event characteristics) correlates of species' impact risks at the global scale for 108 established alien terrestrial vertebrates (mammals, birds, reptiles and amphibians). Our results showed that a total of 3158 negative environmental impacts were reported for 108 harmful species across 71 countries worldwide. Factors associated with impact risks varied slightly among taxa, but alien range size, habitat breadth, origin location, and domestication were significantly correlated with impact risks. Our study aims to identify the characteristics of alien species with high-impact risks to facilitate urgent assessment of alien species and to protect the local ecological environment and biodiversity.

Long-term comparison of Image-guided thermal ablation vs. lobectomy for solitary papillary thyroid microcarcinoma: a multicenter retrospective cohort study.

BACKGROUND: Image-guided thermal ablation has been applied in patients with papillary thyroid microcarcinoma(PTMC) who refuse surgery or active surveillance. However, evidence to support ablation is limited by single-center designs and lack of long-term data. The purpose of this study was to compare long-term outcomes between ablation and lobectomy for patients with solitary PTMC. MATERIALS AND METHODS: This multicenter retrospective study included 1021 consecutive patients with solitary PTMC who underwent ablation(n=444) or lobectomy(n=577) at the four university-affiliated hospitals. The primary outcomes were disease progression(lymph node metastasis[LNM], recurrent tumors, persistent tumors and distant metastasis) and disease-free survival(DFS). Secondary outcomes were complications, hospitalization, procedure time, estimated blood loss and cost. The two groups were compared using propensity score matching. RESULTS: After matching, no significant differences were observed in disease progression (4.7% vs. 3.4%, P=.307), LNM (1.6% vs. 1.6%, P=1.000), recurrent tumors (2.9% vs. 1.8%, P=.269), persistent tumors(0.2% vs. 0%, P=.317) and DFS (95.5% vs. 97.1%, P=.246) between the ablation and lobectomy groups during the median follow-up of 96.5 months. The ablation group had significantly lower complication rates (0.7% vs. 5.2%, P<.001), shorter post-treatment hospitalization (median[IQR], 0 d vs. 4.0[3.0] d, P<.001), shorter procedure time (8.5[2.8] min vs. 90.0[43.8] min, P<.001), reduced estimated blood loss (0 mL vs. 20.0[10.0] mL, P<.001), and lower cost ($1873.2[254.0] vs. $2292.9[797.8], P<.001) than the lobectomy group. CONCLUSIONS: This study revealed comparable disease progression and survival outcomes between ablation and lobectomy for solitary PTMC. Imaged-guided thermal ablation could be effective and safe alternatives to lobectomy for properly selected patients with PTMC.

Chitosan Phytate Nanoparticles: A Synergistic Strategy for Effective Dental Caries Prevention.

Dental caries is a widespread oral disease that poses a significant medical challenge. Traditional caries prevention methods, primarily the application of fluoride, often fall short in effectively destroying biofilms and preventing enamel demineralization, thereby providing limited efficacy in halting the progression of caries over time. To address this issue, we have developed a green and cost-effective synergistic strategy for the prevention of dental caries. By combining natural sodium phytate and chitosan, we have created chitosan-sodium phytate nanoparticles that offer both the antimicrobial properties of chitosan and the enamel demineralization-inhibiting capabilities of sodium phytate. In an ex vivo biofilm model of human teeth, we found that these nanoparticles effectively prevent biofilm buildup and acid damage to the mineralized tissue. Additionally, topical treatment of dental caries in rodent models has shown that these nanoparticles effectively suppress disease progression without negatively impacting oral microbiota diversity or causing harm to the gingival-mucosal tissues, unlike traditional prevention methods.

3D drift correction for super-resolution imaging with a single laser light.

Single-molecule localization microscopy (SMLM) enables three-dimensional (3D) super-resolution imaging of nanoscale structures within biological samples. However, prolonged acquisition introduces a drift between the sample and the imaging system, resulting in artifacts in the reconstructed super-resolution image. Here, we present a novel, to our knowledge, 3D drift correction method that utilizes both the reflected and scattered light from the sample. Our method employs the reflected light of a near-infrared (NIR) laser for focus stabilization while synchronously capturing speckle images to estimate the lateral drift. This approach combines high-precision active compensation in the axial direction with lateral post-processing compensation, achieving the abilities of 3D drift correction with a single laser light. Compared to the popular localization events-based cross correlation method, our approach is much more robust, especially for datasets with sparse localization points.

Ferroelectric Domain Wall Delayer and Low-Dropout Regulator.

A switching-type power converter providing an accurate and stable switching output voltage against line/load variations and power supply ripple is mostly complicated in system-on-chip power management integrated circuits (PMICs) within a limited occupation area. Here we fabricated domain wall (DW) nanodevices using an X-cut LiNbO3 thin film on silicon. The domain switching event occurs after a delay time predicted by Merz's law under the applied voltage. But the output current is irrespective of the applied voltage and can be adjusted by conducting wall width as well as input resistance in the circuit. The regulating currents appear repetitively across the volatile interfacial domains between the nanodevice and electrode under intermittently applied voltages. A wall-current-limited domain switching model is developed to explain the phenomenon. The multifunctional DW nanodevices with smaller occupation areas can serve as compact low-dropout regulators in PMICs, time-domain delayers in energy-efficient neural network systems, and on-chip electrostatic discharge protection besides nonvolatile memories and selectors.

Magnetic Graphene Oxide Nanocomposites Boosts Craniomaxillofacial Bone Regeneration by Modulating circAars/miR-128-3p/SMAD5 Signaling Axis.

Background: The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism. Methods: The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites. Results: We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites. Conclusion: We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.

NCAPH serves as a prognostic factor and promotes the tumor progression in glioma through PI3K/AKT signaling pathway.

Non-SMC (Structural Maintenance of Chromosomes) condensin I complex subunit H (NCAPH) has been shown to facilitate progression and predict adverse prognostic outcome in many cancer types. However, the function of NCAPH in gliomas is still unclear. Series of experiments were taken to uncover the function of NCAPH in glioma. The expression of NCAPH and potential mechanism regulating progression of glioma was verified by bioinformatics analysis. Lentiviral transfection was used for establishment of loss-of-function and gain-of-function cell lines. CCK-8 assay and Colony-formation assay were used to evaluate proliferation. Transwell assay and Cell wound healing assay were used to assess migration and invasion. Cell cycle and apoptosis were measured by flow cytometry. Protein and RNA were quantified by WB and RT-PCR, respectively. The nude mice model of glioma was used to evaluate the effect of NCAPH in vivo. The expression of NCAPH increased significantly in glioma tissues and correlated with WHO grade, IDH wild-type and non-1p/19q codeletion. Glioma patients with high expression of NCAPH had an undesirable prognosis. Functionally, upregulated NCAPH promotes the malignant hallmarks of glioma cells in vivo and in vitro. NCAPH correlated with DNA damage repair ability of glioma cells and facilitated the proliferation, invasion, and migration of glioma cells by promoting the PI3K/AKT signaling pathway. This study identifies the important pro-tumor role of NCAPH in glioma and suggests that NCAPH is a potential therapeutic target.

Regulatory mechanisms of autophagy on DHA and carotenoid accumulation in Crypthecodinium sp. SUN.

BACKGROUND: Autophagy is a crucial process of cellular self-destruction and component reutilization that can affect the accumulation of total fatty acids (TFAs) and carotenoids in microalgae. The regulatory effects of autophagy process in a docosahexaenoic acid (DHA) and carotenoids simultaneously producing microalga, Crypthecodinium sp. SUN, has not been studied. Thus, the autophagy inhibitor (3-methyladenine (MA)) and activator (rapamycin) were used to regulate autophagy in Crypthecodinium sp. SUN. RESULTS: The inhibition of autophagy by 3-MA was verified by transmission electron microscopy, with fewer autophagy vacuoles observed. Besides, 3-MA reduced the glucose absorption and intracellular acetyl-CoA level, which resulting in the decrease of TFA and DHA levels by 15.83 and 26.73% respectively; Surprisingly, 3-MA increased intracellular reactive oxygen species level but decreased the carotenoids level. Comparative transcriptome analysis showed that the downregulation of the glycolysis, pentose phosphate pathway and tricarboxylic acid cycle may underlie the decrease of acetyl-CoA, NADPH and ATP supply for fatty acid biosynthesis; the downregulation of PSY and HMGCR may underlie the decreased carotenoids level. In addition, the class I PI3K-AKT signaling pathway may be crucial for the regulation of carbon and energy metabolism. At last, rapamycin was used to activate autophagy, which significantly enhanced the cell growth and TFA level and eventually resulted in 1.70-fold increase in DHA content. CONCLUSIONS: Our findings indicate the mechanisms of autophagy in Crypthecodinium sp. SUN and highlight a way to manipulate cell metabolism by regulating autophagy. Overall, this study provides valuable insights to guide further research on autophagy-regulated TFA and carotenoids accumulation in Crypthecodinium sp. SUN.

Radiomics for predicting MGMT status in cerebral glioblastoma: comparison of different MRI sequences.

Using radiomics to predict O6-methylguanine-DNA methyltransferase promoter methylation status in patients with newly diagnosed glioblastoma and compare the performances of different MRI sequences. Preoperative MRI scans from 215 patients were included in this retrospective study. After image preprocessing and feature extraction, two kinds of machine-learning models were established and compared for their performances. One kind was established using all MRI sequences (T1-weighted image, T2-weighted image, contrast enhancement, fluid-attenuated inversion recovery, DWI_b_high, DWI_b_low and apparent diffusion coefficient), and the other kind was based on single MRI sequence as listed above. For the machine-learning model based on all sequences, a total of seven radiomic features were selected with the Maximum Relevance and Minimum Redundancy algorithm. The predictive accuracy was 0.993 and 0.750 in the training and validation sets, respectively, and the area under curves were 1.000 and 0.754 in the two sets, respectively. For the machine-learning model based on single sequence, the numbers of selected features were 8, 10, 10, 13, 9, 7 and 6 for T1-weighted image, T2-weighted image, contrast enhancement, fluid-attenuated inversion recovery, DWI_b_high, DWI_b_low and apparent diffusion coefficient, respectively, with predictive accuracies of 0.797-1.000 and 0.583-0.694 in the training and validation sets, respectively, and the area under curves of 0.874-1.000 and 0.538-0.697 in the two sets, respectively. Specifically, T1-weighted image-based model performed best, while contrast enhancement-based model performed worst in the independent validation set. The machine-learning models based on seven different single MRI sequences performed differently in predicting O6-methylguanine-DNA methyltransferase status in glioblastoma, while the machine-learning model based on the combination of all sequences performed best.

Single missing molar with wide mesiodistal length restored using a single or double implant-supported crown: A self-controlled case report and 3D finite element analysis.

PURPOSE: Based on a self-controlled case, this study evaluated the finite element analysis (FEA) results of a single missing molar with wide mesiodistal length (MDL) restored by a single or double implant-supported crown. METHODS: A case of a missing bilateral mandibular first molar with wide MDL was restored using a single or double implant-supported crown. The implant survival and peri-implant bone were compared. FEA was conducted in coordination with the case using eight models with different MDLs (12, 13, 14, and 15 mm). Von Mises stress was calculated in the FEA to evaluate the biomechanical responses of the implants under increasing vertical and lateral loading, including the stress values of the implant, abutment, screw, crown, and cortical bone. RESULTS: The restorations on the left and right sides supported by double implants have been used for 6 and 12 years, respectively, and so far have shown excellent osseointegration radiographically.The von Mises stress calculated in the FEA showed that when the MDL was >14 mm, both the bone and prosthetic components bore more stress in the single implant-supported strategy. The strength was 188.62-201.37 MPa and 201.85-215.9 MPa when the MDL was 14 mm and 15 mm, respectively, which significantly exceeded the allowable yield stress (180 MPa). CONCLUSIONS: Compared with the single implant-supported crown, the double implant-supported crown reduced peri-implant bone stress and produced a more appropriate stress transfer model at the implant-bone interface when the MDL of the single missing molar was ≥14 mm.

Synthesis of a Triangle-Fused Six-Pointed Star and Its Electrocatalytic CO2 Reduction Activity.

As electrocatalysts, molecular catalysts with large aromatic systems (such as terpyridine, porphyrin, or phthalocyanine) have been widely applied in the CO2 reduction reaction (CO2RR). However, these monomeric catalysts tend to aggregate due to strong π-π interactions, resulting in limited accessibility of the active site. In light of these challenges, we present a novel strategy of active site isolation for enhancing the CO2RR. Six Ru(Tpy)2 were integrated into the skeleton of a metallo-organic supramolecule by stepwise self-assembly in order to form a rhombus-fused six-pointed star R1 with active site isolation. The turnover frequency (TOF) of R1 was as high as 10.73 s-1 at -0.6 V versus reversible hydrogen electrode (vs RHE), which is the best reported value so far at the same potential to our knowledge. Furthermore, by increasing the connector density on R1's skeleton, a more stable triangle-fused six-pointed star T1 was successfully synthesized. T1 exhibits exceptional stability up to 126 h at -0.4 V vs RHE and excellent TOF values of CO. The strategy of active site isolation and connector density increment significantly enhanced the catalytic activity by increasing the exposure of the active site. This work provides a starting point for the design of molecular catalysts and facilitates the development of a new generation of catalysts with a high catalytic performance.

Correction: Identification of serum prognostic marker miRNAs and construction of microRNA-mRNA networks of esophageal cancer.

[This corrects the article DOI: 10.1371/journal.pone.0255479.].

Efficient electrosynthesis of HO2- from air for sulfide control in sewers.

Electrochemically in-situ generation of oxygen and caustic soda is promising for sulfide management while suffers from scaling, poor inactivating capacity, hydrogen release and ammonia escape. In this study, the four-compartment electrochemical cell efficiently captured oxygen molecules from the air chamber to produce HO2- without generating toxic by-products. Meanwhile, the catalyst layer surface of PTFE/CB-GDE maintained a relatively balanced gas-liquid micro-environment, enabling the formation of enduring solid-liquid-gas interfaces for efficient HO2- electrosynthesis. A dramatic increase in HO2- generation rate from 453.3 mg L-1 h-1 to 575.4 mg L-1 h-1 was attained by advancement in operation parameters design (flow channels, electrolyte types, flow rates and circulation types). Stability testing resulted in the HO2- generation rate over 15 g L-1 and the current efficiency (CE) exceeding 85%, indicating a robust stable operational capacity. Furthermore, after 120 mg L-1 HO2- treatment, an increase of 11.1% in necrotic and apoptotic cells in the sewer biofilm was observed, higher than that achieved with the addition of NaOH, H2O2 method. The in-situ electrosynthesis strategy for HO2- represents a significance toward the practical implementation of sulfide abatement in sewers, holding the potential to treat various sulfide-containing wastewater.

T Cell Receptor-Directed Bispecific T Cell Engager Targeting MHC-Linked NY-ESO-1 for Tumor Immunotherapy.

Antibody-based bispecific T cell engagers (TCEs) that redirect T cells to kill tumor cells have shown a promising therapeutic effect on hematologic malignancies. However, tumor-specific targeting is still a challenge for TCEs, impeding the development of TCEs for solid tumor therapy. The major histocompatibility complex (MHC) presents almost all intracellular peptides (including tumor-specific peptides) on the cell surface to be scanned by the TCR on T cells. With the premise of choosing optimal peptides, the final complex peptide-MHC could be the tumor-specific target for TCEs. Here, a novel TCR-directed format of a TCE targeting peptide-MHC was designed named IgG-T-TCE, which was modified from the IgG backbone and prepared in a mammalian cell expression system. The recombinant IgG-T-TCE-NY targeting NY-ESO-1157-165/HLA-A*02:01 could be generated in HEK293 cells with a glycosylated TCR and showed potency in T cell activation and redirecting T cells to specifically kill target tumor cells. We also found that the in vitro activity of IgG-T-TCE-NY could be leveraged by various anti-CD3 antibodies and Fc silencing. The IgG-T-TCE-NY efficiently inhibited tumor growth in a tumor-PBMC co-engrafted mouse model without any obvious toxicities.