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The presence of nanoplastics (NPs) in wastewater poses a considerable risk to ecosystems. Although constructed wetlands (CWs) have the potential to removal NPs, their efficiency is limited by insufficient consideration of ecosystem integrity. Herein, three typical benthic fauna (Corbicula fluminea, Chironomus riparius and Tubifex tubifex) were added to CWs to improve the ecological integrity of CWs, and further enhance the ecological benefits. Results indicated that the addition of C. fluminea, C. riparius and T. tubifex increased NPs removal by 19.14 %, 17.02 %, and 15.76 % than that without benthic faunas, respectively. Based on fluorescence signal analysis, the presence of benthic fauna could intake NPs, and enhanced the adsorption of NPs by plants. The addition of C. fluminea significantly increased catalase (1541.82 ± 41.35 U/g), glutathione S-transferase (0.34 ± 0.02 U/g), and superoxide dismutase (116.33 ± 6.91 U/g) activities (p < 0.05) as a defense mechanism against NPs-induced oxidative stress. Metagenomic analysis revealed that the abundances of key enzymes involved in glycolysis, the tricarboxylic acid cycle, and polystyrene metabolism pathways were increased when C. fluminea was added, corresponding to the microbial degradation of NPs. Overall, the results of this study implied that the benthic fauna can efficiently remove NPs from wastewater in CWs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Iron-rich constructed wetlands (CWs) could promote phenanthrene bioremediation efficiently through biotic and abiotic pathways, which have gained increasing attention. However, the biotic/abiotic transformation mechanisms of trace organic contaminants in iron-rich CW are still ambiguous. Herein, three CWs (i.e., CW-A: Control; CW-B: Iron-rich CW, CW-C: Iron-rich CW + tidal flow) were constructed to investigate the transformation mechanisms of phenanthrene through Mössbauer spectroscopy and metagenomics. Results demonstrated CW-C achieved the highest phenanthrene removal (94.0 %) and bacterial toxicity reduction (92.1 %) due to the optimized degradation pathway, and subsequently achieved the safe transformation of phenanthrene. Surface-bound/low-crystalline iron regulated hydroxyl radical (·OH) production predominantly, and its utilization was promoted in CW-C, which also improved electron transfer capacity. The enhanced electron transfer capacity led to the enrichment of PAH-degrading microorganisms (e.g., Thauera) and keystone species (Sphingobacteriales bacterium 46-32) in CW-C. Additionally, the abundances of phenanthrene transformation (e.g., EC:1.14.12.-) and tricarboxylic-acid-cycle (e.g., EC:2.3.3.1) enzyme were up-regulated in CW-C. Further analysis indicated that the safe transformation of phenanthrene was mainly attributed to the combined effect of abiotic (·OH and surface-bound/low-crystalline iron) and biotic (microbial community and diversity) mechanisms in CW-C, which contributed similarly. Our study revealed the essential role of active iron in the safe transformation of phenanthrene, and was beneficial for enhanced performance of iron-rich CW., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Current echocardiographic risk factors for prognosis in cardiac amyloidosis (CA) do not distinguish between the two main subtypes: transthyretin cardiomyopathy (TTR) and immunoglobulin light chain cardiomyopathy (AL), each of which require distinct diagnostic and therapeutic approaches. Additionally, only traditional parameters have been studied with little data on advanced techniques. Accordingly, we sought to determine whether differences exist in 2D transthoracic echocardiography (2DE) predictors of survival between the CA subtypes using a comprehensive approach., Methods: 220 patients (72±12 years) with confirmed CA (AL=89, TTR=131) who underwent 2DE at the time of CA diagnosis were enrolled. Left ventricular (LV) dimensions, indexed mass (LVMi), global longitudinal strain (LVGLS), apical-sparing ratio (LVASR), diastology, right ventricular (RV) size and function indices including tricuspid annular systolic excursion (TAPSE), RV free-wall (RVFWS) and global (RVGLS) strain, indexed left (LA) and right atrial volumes (LAVi and RAVi), LA strain (reservoir and booster) and RV systolic pressure (RVSP) were measured. A propensity-score weighted stepwise variable selection Cox proportional hazards model derived from NYHA class and renal impairment status at diagnosis was used to determine the associations between 2DE parameters and mortality specific to CA subtype over a median follow-up of 36-months., Results: After adjusting for age, atrial fibrillation and treatment, parameters associated with survival were RVFWS (p=0.003, HR 1.15, 95% CI[1.053,1.245]) and RVSP (p=0.03, HR 1.03, 95% CI[1.004,1.063]) in AL and LVASR (p=0.007, HR 6.68, 95% CI[1.75,25.492]) and RAVi (p=0.049, HR 1.03, 95% CI[1.000,1.052]) in TTR., Conclusions: Echocardiographic prognosticators for survival are specific to cardiac amyloid subtype. These results potentially provide information critical for clinical decision-making and follow-up in these patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karima Addetia reports financial support was provided by Pfizer Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hypertension-related knowledge, attitude and practice (KAP) of hypertensive patients can affect the awareness, treatment and control of hypertension. However, little attention has been paid to the association between the change of hypertension preventive KAP and blood pressure (BP) control in occupational population using longitudinal data. We assess the effectiveness of a workplace-based multicomponent hypertension intervention program on improving the level of KAP of hypertension prevention, and the association between improvement in KAP and BP control during intervention., Methods: From January 2013 to December 2014, workplaces across 20 urban regions in China were randomized to either the intervention group (n = 40) or control group (n = 20) using a cluster randomized control method. All employees in each workplace were asked to complete a cross-sectional survey to screen for hypertension patients. Hypertension patients in the intervention group were given a 2-year workplace-based multicomponent hypertension intervention for BP control. The level of hypertension prevention KAP and BP were assessed before and after intervention in the two groups., Results: Overall, 3331 participants (2658 in the intervention group and 673 in the control group) were included (mean [standard deviation] age, 46.2 [7.7] years; 2723 men [81.7%]). After 2-year intervention, the KAP qualified rate was 63.2% in the intervention groups and 50.1% in the control groups (odds ratio = 1.65, 95% CI, 1.36∼2.00, P < .001). Compared with the control group decreased in the qualified rate of each item of hypertension preventive KAP questionnaire, all the items in the intervention group increased to different degrees. The increase of KAP score was associated with the decrease of BP level after intervention. For 1 point increase in KAP score, systolic blood pressure (SBP) decreased by .28 mmHg and diastolic blood pressure (DBP) decreased by .14 mmHg [SBP: β = -.28, 95%CI: -.48∼-.09, P = .004; DBP: β = -.14, 95%CI: -.26∼-.02, P = .024]. SBP and DBP was significantly in manual labor workers (SBP: β = -.34, 95%CI: -.59∼-.09, P = .008; DBP: β = -.23, 95%CI: -.38∼-.08, P = .003), workers from private enterprise, state-owned enterprise (SOE) (SBP: β = -.40, 95%CI: -.64∼-.16, P = .001; DBP: β = -.21, 95%CI: -.36∼-.06, P = .005) and a workplace with an affiliated hospital (SBP: β = -.31, 95%CI: -.52∼-.11, P = .003; DBP: β = -.16, 95%CI: -.28∼-.03, P = .016). The improvement of knowledge (SBP: β = -.29, 95%CI: -.56∼-.02, P = .038; DBP: β = -.12, 95%CI: -.29∼.05, P = .160), as well as attitude (SBP: β = -.71, 95%CI: -1.25∼-.18, P = .009; DBP: β = .18, 95%CI: -.23∼.59, P = .385) and behavior (SBP: β = -.73, 95%CI: -1.22∼-.23, P = .004; DBP: β = -.65, 95%CI: -.97∼-.33, P < .001) was gradually strengthened in relation to BP control., Conclusion: This study found that workplace-based multicomponent hypertension intervention can effectively improve the level of hypertension preventive KAP among employees, and the improvement of KAP levels were significantly associated with BP control., Trial Registration: Chinese Clinical Trial Registry No. ChiCTR-ECS-14004641., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Traditional PEO electrolyte has high crystallinity which hinders the transmission of Li + , resulting in poor ion conductivity and complicated processing technology. Herein, a polymer electrolyte (p-electrolyte) with a wide electrochemical window and high ionic conductivity is designed, which possesses an amorphous condensed structure. The amorphous structure provides fast transport channels for Li + , so the p-electrolyte possesses an electrochemical window of 4.2 V, and high ionic conductivity of 1.58 × 10 -5  S cm -1 at room temperature, which is 1-2 orders of magnitude higher than that of traditional PEO electrolyte. By using the designed polymer electrolyte as the foundation, an in situ curable composite polymer electrolyte (CPE-L) with multiple Li + transport channels is elaborately constructed. The Cu-BTC MOF stores abundant Li + , which is introduced into the p-electrolyte. The rich unsaturated Cu 2+ coordination sites of Cu-BTC can anchor TFSI - to release Li + , and the pore structure of Cu-BTC MOF cooperates with LLZTO nanoparticles to provide multiple fast transport channel for Li + , resulting in remarkable ionic conductivity (1.02 × 10 -3  S cm -1 ) and Li + transference number (0.58). The Li||CPE-L||Li symmetric battery cycles stably for more than 700 h at 0.1 mA cm -2 , while the specific capacity of full battery is ≈153 mAh g -1 (RT, 0.2 C)., (© 2024 Wiley‐VCH GmbH.)

CO 2 hydrogenation into valuable chemical compounds can effectively address the issues of greenhouse gas emissions and energy scarcity. The activation and dissociation processes of CO 2 are crucial for its reduction reactions, but the effects of *H adatoms on the C-O cleavage are still confusing. This study investigates the H-assisted CO 2 dissociation pathways on the Pd n Pt (4- n ) /In 2 O 3 ( n = 0-4) catalysts via DFT calculation. Initially, the adsorption properties of *H 2 , *COOH, and *HCOO species are calculated. Then, two H-assisted CO 2 dissociation channels, i.e. , *CO 2 + *H → *COOH → *CO + *OH and *CO 2 + *H → *HCOO → *CHO + *O, are studied. Results show that Pt and Pd promote the CO 2 hydrogenation and C-O bond cleavage reactions, respectively. In comparison to CO 2 direct dissociation, the COOH-mediated and HCOO-mediated channels facilitate and impede the C-O bond cleavage, respectively. Overall, the Pd 3 Pt/In 2 O 3 constituent is suggested for the H-assisted CO 2 dissociation reaction. The electronic effects of the Pd n Pt (4- n ) bimetals adjust the stabilities of the intermediates and barriers of the elementary steps, and the interactions between Pd n Pt (4- n ) and In 2 O 3 provide extra sites for the adsorbates and reaction steps. This study reveals the effects of *H on the C-O bond dissociation processes and provides useful insight into designing PdPt/In 2 O 3 catalysts for CO 2 hydrogenation reactions.

Introduction Heart Failure (HF) may induce bowel hypoperfusion, leading to hypoxia of the villa of the bowel wall and the occurrence of Clostridioides difficile infection (CDI). However, the risk factors for the development of CDI in HF patients have yet to be fully illustrated, especially because of a lack of evidence from real-world data., Methods: Clinical data and survival situations of HF patients with CDI admitted to ICU were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. For developing a model that can predict 28-day all-cause mortality in HF patients with CDI, the Recursive Feature Elimination with Cross-Validation (RFE-CV) method was used for feature selection. And nine machine learning (ML) algorithms, including logistic regression (LR), decision tree (DT), bayesian, adaptive boosting (AdaBoost), random forest (RF), gradient boosting decision tree (GBDT), XGBoost, light gradient boosting machine (LightGBM), and categorical boosting (CatBoost) were applied for model construction. After training and hyperparameter optimization of the models through grid search 5-fold cross-validation, the performance of models was evaluated by the area under curve (AUC), accuracy, sensitivity, specificity, precision, negative predictive value, and F1 score. Furthermore, the SHapley Additive exPlanations (SHAP) method was used to interpret the optimal model., Results: A total of 526 HF patients with CDI were included in the study, of whom 99 cases (18.8%) experienced death within 28 days. 18 of the 57 variables were selected for the model construction algorithm for model construction. Among the ML models considered, the RF model emerged as the optimal model achieving the accuracy, F1-score, and AUC values of 0.821, 0.596, and 0.864 respectively. The net benefit of the model surpassed other models at 16%~22% threshold probabilities based on decision curve analysis. According to the importance of features in the RF model, red blood cell distribution width, blood urea nitrogen, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment, and white blood cell count were highlighted as the five most influential variables., Conclusions: We developed ML models to predict 28-day all-cause mortality in HF patients associated with CDI in the ICU, which are more effective than the conventional logistic regression model. The RF model has the best performance among all the ML models employed. It may be useful to help clinicians identify high-risk HF patients with CDI., (S. Karger AG, Basel.)

Management of diabetic chronic wound exudate is a serious challenge in healthcare worldwide since it is related to the speed of diabetic wound healing. However, current foam dressings not only absorb fluid to generate swelling and compress the wound to hinder wound healing but also are very thick and less comfortable to use. Herein, a superabsorbent self-pumping ultrathin dressing is reported to accelerate diabetic wound healing by achieving superior exudate absorption and management in an ultrathin state. The self-pumping dressing is composed of a drainage layer loaded with anthocyanidin and a thermoplastic polyurethane absorbent layer embedded with superabsorbent particles. The dressing realizes the self-pumping process of unidirectional exudate draining to the absorption layer through the drainage layer without significant dressing swelling to compress the diabetic wound. The dressing is experimentally proven to unidirectionally drain excessive exudate with inflammatory factors and modulate the conversion of macrophages from M1 to M2 in diabetic wounds, thereby promoting the healing of diabetic skin ulcers faster than commercial foam dressings. Therefore, the dressing provides a new idea and novel method for accelerating diabetic skin ulcer healing.

Bisphenol A (BPA) and its substitute fluorene-9-bisphenol (BHPF) are used in consumer products; however, their toxic effects on intestinal epithelium remain largely unknown. In this study, we combined intestinal organoids and single-cell RNA sequencing to investigate the impact of BPA and BHPF exposure on intestinal cell composition, differentiation, and function. Both compounds inhibited the growth of small intestinal organoids, with BHPF exhibiting a more potent inhibitory effect. BPA and BHPF did not significantly alter the overall cell type composition; however, they led to different alterations in cell-cell communications. Gene Ontology enrichment analysis showed that BPA and BHPF exposures affected various biological processes, such as glutathione transferase activity, antioxidant activity, and lipid metabolism, in cell type-specific and compound-dependent manners. Trajectory analysis demonstrated that BPA and BHPF altered the differentiation trajectory of the intestinal cells. To further connect the cellular mechanism to the phenotypic impact in vivo, we constructed a mouse model exposed to BPA or BHPF and observed significant alterations in intestinal morphology, including reduced crypt depth and villus length and impaired stem cell proliferation and self-renewal. These results provide novel insights into the cell type-specific effects of BPA and BHPF on the intestinal epithelium and highlight the potential risks of exposure to these compounds. Our findings underscore the importance of evaluating the safety of BPA substitutes and contribute to a better understanding of the effects of environmental chemicals on gut health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews., (© 2024. The Author(s).)

The fate of sulfur (S) was controlled by a complex interaction of abiotic and microbial reactions in constructed wetlands (CWs). Although zero-valent iron (ZVI) was generally considered to promote nitrogen (N) and S cycle by providing electrons, but its binding effect on sulfate (SO 4 2- -S) removal with the rhizosphere oscillating redox conditions had not been determined. This study found that the presence of plants increased SO 4 2-&#95; S removal in Con-CW, while decreased it by 3.93 % in ZVI-CW accompanied by the decrease of S content in the rhizosphere substrates. The enrichment of S oxidation genes (soxA/Y and yedZ), organic S decomposition genes (aslA) and plants radial oxygen loss (ROL) accelerated the transformation of solid-phase S to SO 4 2- -S, resulting in ZVI-CW turn from S sink to S source. Overall, the source-sink transformation provided a theoretical guidance for comprehending S cycling in CWs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Thymosin beta 10 (TMSB10) overexpression is a general characteristic in human carcinogenesis. It is involved in the malignant process of generating multiple cancers. However, there are only a few reports about TMSB10 in colorectal cancer (CRC) and the mechanism of its carcinogenetic effect is still poorly understood. The present study intends to clarify the biological roles and carcinogenic mechanism of TMSB10 in CRC and to explore the possibility whether TMSB10 might be useful as a non-invasive serum tumor biomarker in detecting CRC. Immunohistochemical results showed that TMSB10 protein expression in CRC tissues was generally higher than that in adjacent tissues, and the TMSB10 contents in serum of CRC patients was significantly elevated compared to that of healthy controls. Knockdown-TMSB10 increased apoptosis and induced S-cell cycle arrest, and finally inhibited cell proliferation in vitro and in vivo. Transcriptome sequencing and western blotting analysis revealed that knockdown-TMSB10 increased phosphorylation of p38 and activated the p38 pathway that blocked cell cycle and promoted apoptosis. Taken together, our study indicated that TMSB10 could serve as a minimally invasive serum tumor marker in detecting CRC. At the same time it demonstrates an effective regulatory capacity of TMSB10 on cell proliferation of CRC, suggesting that TMSB10 and downstream effector molecules regulated by TMSB10 could further be applied as an appealing target in clinical post-surgery chemotherapy., Competing Interests: Declaration of competing interest All authors have participated in the research and/or article preparation and agree with submission of this manuscript to Translational Oncology. The material has not been published previously, and will not be submitted for publication elsewhere. None of the authors have potential conflicts of interest with regard to this manuscript to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objectives . Construction worker safety behavior (CWSB) may be affected by a confluence of multilevel and interrelated factors. Cultivating and maintaining CWSB is vital for improving construction safety. Current studies focus on organization-level or individual-level CWSB antecedents. However, few studies have examined the influence of psychological factors on CWSB, thereby reducing the joint effects of multilevel factors on CWSB. Methods. To determine effective strategies for strengthening CWSB, this study adopted the Bayesian network technique to explore the interrelationships between CWSB and its antecedent factors. A Bayesian belief network model was developed and trained with data collected from Chinese construction workers, which connected organizational, individual and psychological factors with CWSB. Results. According to the sensitivity analysis, safety knowledge, safety climate and psychological capital are the three most significant influencing factors for CWSB. A combined strategy that enhances safety knowledge, safety climate and communication competence simultaneously is the most effective option for strengthening CWSB. The validation and robustness of the network showed good accuracy for safety behavior judgment. Conclusion. This study proposes an alternative way to improve safety behavior by identifying its interactive causes and illustrates the importance of initiating systematic safety measures, which may help to mitigate the problem of safety plateau.

The first results of the study of high-energy electron neutrino (ν&#95;{e}) and muon neutrino (ν&#95;{μ}) charged-current interactions in the FASERν emulsion-tungsten detector of the FASER experiment at the LHC are presented. A 128.8 kg subset of the FASERν volume was analyzed after exposure to 9.5  fb^{-1} of sqrt[s]=13.6  TeV pp data. Four (eight) ν&#95;{e} (ν&#95;{μ}) interaction candidate events are observed with a statistical significance of 5.2σ (5.7σ). This is the first direct observation of ν&#95;{e} interactions at a particle collider and includes the highest-energy ν&#95;{e} and ν&#95;{μ} ever detected from an artificial source. The interaction cross section per nucleon σ/E&#95;{ν} is measured over an energy range of 560-1740 GeV (520-1760 GeV) for ν&#95;{e} (ν&#95;{μ}) to be (1.2&#95;{-0.7}^{+0.8})×10^{-38}  cm^{2} GeV^{-1} [(0.5±0.2)×10^{-38}  cm^{2} GeV^{-1}], consistent with standard model predictions. These are the first measurements of neutrino interaction cross sections in those energy ranges.

Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD., (© 2024. The Author(s).)

Abstract: Chimeric antigen receptor T-cell therapy (CAR T) has revolutionized the treatment of hematological cancers. Its production requires a complex logistical process, and the time from leukapheresis to patient infusion (known as the vein-to-vein time [V2VT]) can be long during which a patients clinical condition may deteriorate. This study was designed to estimate the benefits of reduced V2VT for third-line or later (3L+) relapsed/refractory large B-cell lymphoma (R/R LBCL) patients treated with CAR T. A mathematical model was developed to estimate the lifetime outcomes of a hypothetical cohort of patients who had either a long or short V2VT. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were estimated. Scenario analyses were performed to assess the robustness of results to key assumptions. The results of the model show that reducing V2VT from 54 days (tisa-cel median V2VT; JULIET) to 24 days (axi-cel median V2VT; ZUMA-1) led to a 3.2-year gain in life expectancy (4.2 vs 7.7 LYs), and 2.4 additional QALYs (3.2 vs 5.6) per patient. Furthermore, a shorter V2VT was shown to be cost-effective under conventional willingness-to-pay thresholds in the United States. Results are driven by a higher infusion rate and a better efficacy of CAR T for those infused. Scenario analyses using a smaller difference in V2VT (24 vs 36 days) produced consistent results. Our study is the first to quantify lifetime V2VT-related outcomes for 3L+ R/R LBCL patients treated with CAR T utilizing currently available evidence. Shorter V2VTs led to improved outcomes, demonstrating the importance of timely infusion achievable by faster manufacturing times and optimization of hospital delivery., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy., Methods: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317)., Results: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone., Conclusions: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recessive genic male sterility (RGMS) provides an effective approach for the commercial exploitation of heterosis, especially in Brassica crops. Although some artificial RGMS mutants have been reported in B. rapa, no causal genes derived from these natural mutants have been identified so far. In this study, a spontaneous RGMS mutant Bcajh97-01A derived from the 'Aijiaohuang' line traced back to the 1980 s was identified. Genetic analysis revealed that the RGMS trait was controlled by a single locus in the Bcajh97-01A/B system. Bulk segregant analysis (BSA) in combination with linkage analysis was employed to delimit the causal gene to an approximate 129 kb interval on chromosome A02. The integrated information of transcriptional levels and the predicted genes in the target region indicated that the Brmmd1 (BraA02g017420) encoding a PHD-containing nuclear protein was the most likely candidate gene. A 374 bp miniature inverted-repeat transposable element (MITE) was inserted into the first exon to prematurely stop the Brmmd1 gene translation, thus blocking the normal expression of this gene at the tetrad stage in the Bcajh97-01A. Additionally, a co-segregating structure variation (SV) marker was developed to rapidly screen the RGMS progenies from Bcajh97-01A/B system. Our findings reveal that BraA02g017420 is the causal gene responsible for the RGMS trait. This study lays a foundation for marker-assisted selection and further molecular mechanism exploration of pollen development in B. rapa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Tianma-Gouteng Pair (TGP), commonly prescribed as a pair-herbs, can be found in many Chinese medicine formulae to treat brain diseases. However, the neuroprotective effects and molecular mechanisms of TGP remained unexplored., Aim of the Study: This study investigated the difference between the TgCRND8 and 5 × FAD transgenic mice, the anti-AD effects of TGP, and underlying molecular mechanisms of TGP against AD through the two mouse models., Methods: Briefly, three-month-old TgCRND8 and 5 × FAD mice were orally administered with TGP for 4 and 6 months, respectively. Behavioral tests were carried out to determine the neuropsychological functions. Moreover, immunofluorescence and western blotting assays were undertaken to reveal the molecular mechanisms of TGP., Results: Although TgCRND8 and 5 × FAD mice had different beta-amyloid (Aβ) burdens, neuroinflammation status, and cognition impairments, TGP exerted neuroprotective effects against AD in the two models. In detail, behavioral tests revealed that TGP treatment markedly ameliorated the anxiety-like behavior, attenuated the recognition memory deficits, and increased the spatial learning ability as well as the reference memory of TgCRND8 and 5 × FAD mice. Moreover, TGP treatment could regulate the beta-amyloid precursor protein (APP) processing by inhibiting the Aβ production enzymes such as β- and γ-secretases and activating Aβ degrading enzyme to reduce Aβ accumulation. In addition, TGP reduced the Aβ 42 level, the ratio of Aβ 42 /Αβ 40 , Aβ accumulation, and tau hyperphosphorylation in both the 5 × FAD and TgCRND8 mouse models. Furthermore, TGP ameliorated neuroinflammation by decreasing the densities of activated microglia and astrocytes, and inhibiting the production of inflammatory cytokines. TGP upregulated the SIRT1 and AMPK, and downregulated sterol response element binding protein 2 (SREBP2) in the brain of TgCRND8 mice and deactivation of the EPhA4 and c-Abl in the brain tissues of 5 × FAD mice., Conclusion: Our experiments for the first time revealed the neuroprotective effects and molecular mechanism of TGP on 5 × FAD and TgCRND8 transgenic mouse models of different AD stages. TGP decreased the level of Aβ aggregates, improved the tauopathy, and reduced the neuroinflammation by regulation of the SIRT1/AMPK/SREBP2 axis and deactivation of EPhA4/c-Abl signaling pathway in the brains of TgCRND8 and 5 × FAD mice, respectively. All these findings unequivocally confirmed that the TGP would be promising in developing into an anti-AD therapeutic pharmaceutical., Competing Interests: Declaration of competing interest All authors declare that we have no financial and personal relationships with other people or organizations that can inappropriately influent our work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37; 95% CI, 0.22-0.63) and lower complete response rate (OR, 0.57; 95% CI, 0.33-0.97) than NH White patients. NH Black patients also had a shorter progression-free survival vs NH White (HR, 1.41; 95% CI, 1.04-1.90) and NH Asian patients (HR, 1.67; 95% CI, 1.08-2.59). NH Asian patients had a longer duration of response than NH White (HR, 0.56; 95% CI, 0.33-0.94) and Hispanic patients (HR, 0.54; 95% CI, 0.30-0.97). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade immune effector cell-associated neurotoxicity syndrome were observed in NH White patients than in other patients. These results provide important context when treating patients with R/R LBCL with CAR T-cell therapy across different racial and ethnic groups. ZUMA-1 and ZUMA-7 (ClinicalTrials.gov identifiers: #NCT02348216 and #NCT03391466, respectively) are registered on ClinicalTrials.gov., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The study of the outcomes of critically ill patients has been a hard stuff in the field of intensive care. To explore the relationship between changes of severity scores, bioelectrical impedance analysis (BIA) and outcomes of critically ill patients, we enrolled patients (n = 206) admitted to intensive care unit (ICU) in Jinling Hospital from 2018 to 2021 with records of BIA on the days 1- and 3- ICU. Collected BIA and clinical data including simplified acute physiology score II (SAPS II) and sequential organ failure assessment. According to the baseline and change of severity scores or phase angle (PA) values, the patients were divided into: G-G, baseline good status, 3rd day unchanged; G-B, baseline good status, 3rd day deteriorated; B-G, baseline bad status, 3rd day improved; and B-B, baseline bad status, 3rd day unchanged. According to PA, the mortality of group G-G was 8.6%, and it was greater than 50% in group B-B for severity scores. The new score combining PA and severity scores established. Multivariate logistic regression analysis revealed that PA-SAPS II score was the only independent factor for 90-day mortality (P < 0.05). A linear correlation was found between mortality and PA-SAPS II score (prediction equation: Y ( % ) = 16.97 × X - 9.67 , R 2  = 0.96, P < 0.05)., (© 2024. The Author(s).)

Purpose: The significant global burden of endometrial cancer (EC) and the challenges associated with predicting EC recurrence indicate the need for a dynamic prediction model. This study aimed to propose nomograms based on clinicopathological variables to predict recurrence-free survival (RFS) and overall survival (OS) after surgical resection for EC., Methods: This single-institution retrospective cohort study included patients who underwent surgical resection for EC. Web-based nomograms were developed to predict RFS and OS following resection for EC, and their discriminative and calibration abilities were assessed., Results: This study included 289 patients (median age, 56 years). At a median follow-up of 51.1 (range, 4.1-128.3) months, 13.5% (39/289) of patients showed relapse or died, and 10.7% (31/289) had non-endometrioid tumors (median size: 2.8 cm). Positive peritoneal cytology result (hazard ratio [HR], 35.06; 95% confidence interval [CI], 1.12-1095.64; P = 0.0428), age-adjusted Charlson comorbidity index (AACCI) (HR, 52.08; 95% CI, 12.35-219.61; P < 0.001), and FIGO (Federation of Gynecology and Obstetrics) stage IV (HR, 138.33; 95% CI, 17.38-1101.05; P < 0.001) were predictors of RFS. Similarly, depth of myometrial invasion ≥ 1/2 (HR, 1; 95% CI, 0.46-2.19; P = 0.995), AACCI (HR, 93.63; 95% CI, 14.87-589.44; P < 0.001), and FIGO stage IV (HR, 608.26; 95% CI, 73.41-5039.66; P < 0.001) were predictors of OS. The nomograms showed good predictive capability, positive discriminative ability, and calibration (RFS: 0.895 and OS: 0.891)., Conclusion: The nomograms performed well in internal validation when patients were stratified into prognostic groups, offering a personalized approach for risk stratification and treatment decision-making., (© 2024. The Author(s).)

Background: Psoriasis is a long-term inflammatory skin disease. A novel herbal formula containing nine Chinese herbal medicines, named Inflammation Skin Disease Formula (ISDF), has been prescribed in clinics for decades., Aims: To investigate the efficacy and action mechanisms of ISDF on psoriasis using imiquimod (IMQ) and Interleukin-23 (IL-23)-induced models in mice and reveal the pharmacokinetics profile of ISDF in rats., Methods: Topical administration of IMQ and intradermal injection with IL-23 respectively induced skin lesions like psoriasis on the dorsal area of Balb/c and C57 mice. The mice's body weight, skin thickness, and psoriasis area and severity index (PASI) were assessed weekly. SD rats were used in the pharmacokinetics study and the contents of berberine and baicalin were determined., Results: The PASI scores and epidermal thickness of mice were markedly decreased after ISDF treatment in both models. ISDF treatment significantly decreased the contents of IL-17A and IL-22 in the serum of IMQ- and IL-23-treated mice. Importantly, ISDF markedly downregulated IL-4, IL-6, IL-1β, and tumor necrosis factor α (TNF-α) gene expression, and the phosphorylation of NF-κB p65, JNK, ERKs and MAPK p38 in IMQ-treated mice. The protein phosphorylation of Jak1, Jak2, Tyk2 and Stat3 was significantly mitigated in the ISDF-treated groups. The absorption of baicalin and berberine of ISDF through the gastrointestinal tract of rats was limited, and their distribution and metabolism in rats were also very slow, which suggested ISDF could be used in the long-term application., Conclusions: ISDF has a strong anti-psoriatic therapeutic effect on mouse models induced with psoriasis through IMQ and IL-23, which is achieved by inhibiting the activation of the Jak/Stat3-activated IL-23/Th17 axis and the downstream NF-κB signalling and MAPK signalling pathways. ISDF holds great potential to be a therapy for psoriasis and should be further developed for this purpose., (© 2024. The Author(s).)

Introduction: The health impact of retirement is controversial. Most previous studies have been based on self-reported health indicators or the endpoints of some chronic diseases (e.g., morbidity or mortality), but objective physiological indicators (e.g., blood pressure) have rarely been used. The objective of this study is to elucidate the health effects of retirement on blood pressure, thereby offering empirical evidence to facilitate the health of retirees and to optimize retirement policies., Methods: From 2012 to 2015, 84,696 participants of the Chinese Hypertension Survey (CHS) were included in this study. We applied the fuzzy regression discontinuity design (FRDD) to identify retirement's causal effect on systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure. We also explored the heterogeneity in the effects of retirement across different sex and education level groups., Results: Based on the fully adjusted model, we estimated that retirement increased SBP by 5.047 mm Hg (95% CI: -2.628-12.723, P value: 0.197), DBP by 0.614 mm Hg (95% CI: -3.879-5.108, P value: 0.789) and pulse pressure by 4.433 mm Hg (95% CI: -0.985-9.851, P value: 0.109). We found that retirement led to a significant increase in male participants' SBP and pulse pressure as well as a possible decrease in female participants' blood pressure. Additionally, the blood pressure levels of low-educated participants were more vulnerable to the shock of retirement., Conclusion: Retirement is associated with an increase in blood pressure level. There is a causal relationship between the increase in blood pressure levels of men and retirement. Policy-makers should pay extra attention to the health status of men and less educated people when adjusting retirement policies in the future., (© 2024. The Author(s).)

Background: Autophagy is recognized as a promising therapeutic target for traumatic brain injury (TBI). Crocetin is an aglycone of crocin naturally occurring in saffron and has been found to alleviate brain injury diseases. However, whether crocetin affects autophagy after TBI remains unknown. Therefore, we explore crocetin roles in autophagy after TBI., Methods: We used a weight-dropped model to induce TBI in C57BL/6J mice. Neurological severity scoring (NSS) and grip tests were used to evaluate the neurological level of injury. Brain edema, neuronal apoptosis, neuroinflammation and autophagy were detected by measurements of brain water content, TUNEL staining, ELISA kits and western blotting., Results: Crocetin ameliorated neurological dysfunctions and brain edema after TBI. Crocetin reduced neuronal apoptosis and neuroinflammation and enhanced autophagy after TBI., Conclusion: Crocetin alleviates TBI by inhibiting neuronal apoptosis and neuroinflammation and activating autophagy.

Phosphine (PH 3 ) is an important contributor to the phosphorus cycle and is widespread in various environments. However, there are few studies on PH 3 in constructed wetlands (CWs). In this study, lab-scale CWs and batch experiments were conducted to explore the characteristics and mechanisms of PH 3 production in sulfur-based CWs. The results showed that the PH 3 release flux of sulfur-based CWs varied from 0.86±0.04 ng·m -2 ·h -1 to 1.88±0.09 ng·m -2 ·h -1 . The dissolved PH 3 was the main PH 3 form in CWs and varied from 2.73 μg·L -1 to 4.08 μg·L -1 . The matrix-bound PH 3 was a staging reservoir for PH 3 and increased with substrate depth. In addition, the sulfur-based substrates had a significant improvement on PH 3 production. Elemental sulfur is more conducive to PH 3 production than pyrite. Moreover, there was a significant positive correlation between PH 3 production, the dsrB gene, and nicotinamide adenine dinucleotide (NADH). NADH might catalyze the phosphate reduction process. And the final stage of the dissimilatory sulfate reduction pathway driven by the dsrB gene might also provide energy for phosphate reduction. The migration and transformation of PH 3 increased the available P (Resin-P and NaHCO 3 -P) from 35 % to 56 % in sulfur-based CW, and the P adsorption capacity was improved by 12 %. The higher proportion of available P increased the plant uptake rate of P by 17 %. This study improves the understanding of the phosphorus cycle in sulfur-based CW and provides new insight into the long-term stable operation of CWs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Coastal wetlands are the main distribution of blue carbon in coastal zones and well known for their high carbon sequestration capacity. Investigating the variation of carbon budget is crucial for understanding the functionality of coastal wetlands and effectively addressing climate change. In this study, a bibliometric analysis of 4,509 articles was conducted to reveal research progress, hot issues, and emerging trends in the coastal wetland carbon budget field. The number of publications and citations in this field increased exponentially from 1991 to 2022. The leading subject category was Environmental Sciences with 1,844 articles (40.9%). At present, studies have been focused on blue carbon, the effects of climate change and man-made disturbances on carbon cycle, and the restoration of coastal wetlands. Based on the hotspots and trends in this field, the future researches should include (1) exploring the functional mechanisms of various factors affecting carbon cycle and establishing a methodological system for the estimation of blue carbon in coastal wetlands; (2) researching restoration techniques of coastal wetland and constructing wetland restoration evaluation index system; and (3) formulating enforceable carbon trading policy and strengthening international cooperation., Competing Interests: The authors declare there is no conflict., (© 2024 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY-NC-ND 4.0), which permits copying and redistribution for non-commercial purposes with no derivatives, provided the original work is properly cited (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

As a second-order nonlinear optical phenomenon, the bulk photovoltaic (BPV) effect is expected to break through the Shockley-Queisser limit of thermodynamic photoelectron conversion and improve the energy conversion efficiency of photovoltaic cells. Here, we have successfully induced a strong flexo-photovoltaic (FPV) effect, a form of BPV effect, in strained violet phosphorene nanosheets (VPNS) by utilizing strain engineering at the h-BN nanoedge, which was first observed in nontransition metal dichalcogenide (TMD) systems. This BPV effect was found to originate from the disruption of inversion symmetry induced by uniaxial strain applied to VPNS at the h-BN nanoedge. We have revealed the intricate relationship between the bulk photovoltaic effect and strain gradients in VPNS through thickness-dependent photovoltaic response experiments. A bulk photovoltaic coefficient of up to 1.3 × 10 -3 V -1 and a polarization extinction ratio of 21.6 have been achieved by systematically optimizing the height of the h-BN nanoedge and the thickness of VPNS, surpassing those of reported TMD materials (typically less than 3). Our results have revealed the fundamental relationship between the FPV effect and the strain gradients in low-dimensional materials and inspired further exploration of optoelectronic phenomena in strain-gradient engineered materials.

The sensitivity of triboelectric nanogenerators (TENGs) to the surface charge density highlights the significance of triboelectric materials and their modifications. Efforts have been directed toward developing effective strategies for increasing the surface charge density, expanding the potential applications of TENGs. This study proposes the use of irradiation technology for grafting to modify the electron-donating capability of poly(ether sulfone) (PES), thereby affording a dual benefit of enhancing the surface charge density and inducing a shift in the position of PES from negative to positive within the triboelectric series. The TENG based on grafted PES has resulted in a significant 3-fold increase in surface charge density compared to that of pristine PES, reaching 263 μC m -2 . The surface charge density can be further increased to 502 μC m -2 through charge pumping. Notably, irradiation technology presents advantages over chemical grafting methods, particularly in terms of sustainability and environmental friendliness. This innovative approach shows great potential in advancing the domain of TENGs.

Introduction: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated., Methods: MVs of Staphylococcus aureu s USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2-MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor., Results: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 μg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2-MVs (R 2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10 -3 μg. Antares2-MVs can directly target tumor tissues in vivo, and 20 μg/mL Antares2-MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo., Conclusion: S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment., Competing Interests: All authors declare no competing of interests in this work., (© 2024 Li et al.)

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients treated with CIT for R/R LBCL after ≥2 lines of prior therapy were included from SCHOLAR-1 (an international, multicohort, retrospective study). After propensity score matching, at a median follow-up of 24 months for patients receiving axi-cel and 60 months for patients receiving CIT, 12-month overall survival rates were 62% and 28%, respectively (hazard ratio, 0.30 [95% CI, 0.24-0.37]). Objective response rate (ORR) was 76% (complete response [CR] rate 58%) in patients receiving axi-cel versus 28% (CR rate 16%) for those receiving CIT. A 57% difference in ORR (55% difference in CR rate) favoring axi-cel over CIT was observed among patients aged ≥65 years. Increased magnitude of benefit in response rates for axi-cel versus CIT was also observed among patients with ECOG PS = 2. These findings further support the broader use of axi-cel in older patients and patients with ECOG PS = 2 with R/R LBCL., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Bacteria develop tolerance after transient exposure to antibiotics, and tolerance is a significant driver of resistance. The purpose of this study is to evaluate the mechanisms underlying tolerance formation in vancomycin-intermediate Staphylococcus aureus (VISA) strains. VISA strains were cultured with sub-minimum inhibitory concentrations (sub-MICs) of vancomycin. Enhanced vancomycin tolerance was observed in VISA strains with distinct genetic lineages. Western blot revealed that the VISA protein succinylation (Ksucc) levels decreased with the increase in vancomycin exposure. Importantly, Ksucc modification, vancomycin tolerance, and cell wall synthesis were simultaneously affected after deletion of SacobB, which encodes a desuccinylase in S. aureus. Several Ksucc sites were identified in MurA, and vancomycin MIC levels of murA mutant and Ksucc-simulated (MurA(K69E) and MurA(K191E)) mutants were reduced. The vancomycin MIC levels of K65-MurA(K191E) in particular decreased to 1 mg/L, converting VISA strain K65 to a vancomycin-susceptible S. aureus strain. We further demonstrated that the enzymatic activity of MurA was dependent on Ksucc modification. Our data suggested the influence of vancomycin exposure on bacterial tolerance, and protein Ksucc modification is a novel mechanism in regulating vancomycin tolerance., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest to this work., (Copyright © 2024. Published by Elsevier GmbH.)

During the wastewater treatment and resource recovery process by attached microalgae, the chemical oxygen demand (COD) can cause biotic contamination in algal culture systems, which can be mitigated by adding an appropriate dosage of antibiotics. The transport of COD and additive antibiotic (chloramphenicol, CAP) in algal biofilms and their influence on algal physiology were studied. The results showed that COD (60 mg/L) affected key metabolic pathways, such as photosystem II and oxidative phosphorylation, improved biofilm autotrophic and heterotrophic metabolic intensities, increased nutrient demand, and promoted biomass accumulation by 55.9 %, which was the most suitable COD concentration for attached microalgae. CAP (5-10 mg/L) effectively stimulated photosynthetic pigment accumulation and nutrient utilization in pelagic microalgal cells. In conclusion, controlling the COD concentration (approximately 60 mg/L) in the medium and adding the appropriate CAP concentration (5-10 mg/L) are conducive to improving attached microalgal biomass production and resource recovery potential from wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In light of high burden of heart failure (HF) in China, studies of prognostic implication of HF stages are important. We aimed to evaluate the relationship between HF stages and mortality risk in Chinese community populations., Methods: Nationwide representative populations aged ≥35 years (n = 23,284, mean age 56.9 years, women 53.2%) were enrolled from 2012 to 2016. According to the international HF guidelines, participants were divided into stage A, B and C, and those who did not qualify these stages were categorized as apparently-healthy group. Association between HF stages and all-cause, cardiovascular [CV] and non-CV death was evaluated using multivariable-adjusted Cox proportional regression analysis., Findings: During a median follow-up of 4.7 years (109,902.8 person-years), 1314 deaths occurred. Age-adjusted incidence rate of all-cause death was 5.3 in apparently-healthy, 7.8 in stage A, 8.6 in stage B and 24.6 in stage C groups per 1000 person-years. In reference to apparently-healthy group, adjusted hazard ratio for all-cause death was 1.90 (95% CI: 1.47-2.45), 2.43 (95% CI: 1.89-3.13) and 6.40 (95% CI: 4.56-8.99) for stage A, B and C. Advancing HF stages were associated with increasing risks for all-cause, CV and non-CV death ( P -trend <0.05). For all-cause death, population attributable fraction due to stage A, B and C were 21.2%, 33.4% and 4.9%, accounting for 1,933,385, 3,045,993 and 446,867 deaths in China in 2018., Interpretation: Advancing HF stages were associated with increasing risk mortality. Development and implementation of early screening and targeted interventions are urgently needed to reduce HF burdens in China., Funding: This work was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (grant 2017-I2M-1-004), the Projects in the Chinese National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (No.: 2011BAI11B01), and the Project Entrusted by the National Health Commission of the People's Republic of China (NHC2020-609)., Competing Interests: Dr Fonarow has consulted for Abbott, Amgen, AstraZeneca, Bayer, Boehinger Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. The other authors declare that they have no competing interests. Pillar Program during the Twelfth Five-year Plan Period (No.: 2011BAI11B01)., (© 2024 Published by Elsevier Ltd.)

Sepsis is a systemic inflammatory response syndrome caused by pathogen infection, while the current antibiotics mainly utilized in clinical practice to combat infection result in the release of pathogen-associated molecular patterns (PAMPs) in the body. Herein, we provide an innovative strategy for controlling sepsis, namely, capturing active pathogens by means of extracorporeal blood purification. Carbon nanotubes (CNTs) were modified with dimethyldiallylammonium chloride (DDA) through γ-ray irradiation-induced graft polymerization to confer a positive charge. Then, CNT-DDAs are blended with polyurethane (PU) to prepare porous microspheres using the electro-spraying method. The obtained microspheres with a pore diameter of 2 μm served as pathogen traps and are termed as PU-CNT-DDA microspheres. Even at a high flow rate of 50 mL·min -1 , the capture efficiencies of the PU-CNT-DDAs for Escherichia coli and Staphylococcus aureus remained 94.7% and 98.8%, respectively. This approach circumvents pathogen lysis and mortality, significantly curtails the release of PAMPs, and hampers the production of pro-inflammatory cytokines. Therefore, hemoperfusion using porous PU-CNT-DDAs as pathogen traps to capture active pathogens and alleviate inflammation opens a new route for sepsis therapy.

Halomonas bluephagenesis TD serves as an exceptional chassis for next generation industrial biotechnology to produce various products. However, the simultaneous editing of multiple loci in H. bluephagenesis TD remains a significant challenge. Herein, we report the development of a multiple loci genome editing system, named CRISPR-deaminase-assisted base editor (CRISPR-BE) in H. bluephagenesis TD. This system comprises two components: a cytidine (CRISPR-cBE) and an adenosine (CRISPR-aBE) deaminase-based base editor. CRISPR-cBE can introduce a cytidine to thymidine mutation with an efficiency of up to 100 % within a 7-nt editing window in H. bluephagenesis TD. Similarly, CRISPR-aBE demonstrates an efficiency of up to 100 % in converting adenosine to guanosine mutation within a 7-nt editing window. CRISPR-cBE has been further validated and successfully employed for simultaneous multiplexed editing in H. bluephagenesis TD. Our findings reveal that CRISPR-cBE efficiently inactivated all six copies of the IS1086 gene simultaneously by introducing stop codon. This system achieved an editing efficiency of 100 % and 41.67 % in inactivating two genes and three genes, respectively. By substituting the P cas promoter with the inducible promoter P Mmp1 , we optimized CRISPR-cBE system and ultimately achieved 100 % editing efficiency in inactivating three genes. In conclusion, our research offers a robust and efficient method for concurrently modifying multiple loci in H. bluephagenesis TD, opening up vast possibilities for industrial applications in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To explore the distribution of probable causes and clinical characteristics of non-B and non-C (NBNC) primary liver cancer (PLC) patients in the HBV-endemic region., Methods: A total of 86 individuals with biopsy-proven NBNC-PLC were enrolled. NBNC-PLC patients were defined as negative for both anti-HCV antibodies and five serum hepatitis B markers. Patients' characteristics were collected from medical records., Results: Among them, most of the NBNC-PLC patients had intrahepatic cholangiocarcinoma (ICC) (81.4%), and 12.8% had hepatocellular carcinoma (HCC). The NBNC ICC group had more platelet count, GGT, and CA199 levels; approximately two-thirds were female, and it was more often present in patients with biliary inflammatory diseases, especially intrahepatic biliary lithiasis. The NBNC HCC group was older and had a higher proportion of dyslipidemia, obesity, cirrhosis, and AFP levels., Conclusion: Our data revealed that most of the NBNC PLC patients were ICC. Female patients with biliary inflammatory diseases and higher CA199 levels had an increased risk of ICC, and patients with metabolic risk factors and elevated AFP levels were more likely to develop HCC. Additional research should be performed to verify this finding., Competing Interests: The authors declare that they have no financial or non-financial interests with other people or organizations that could inappropriately influence this work., (© 2024 Hu and Zhou.)

Hypoxia is a mounting problem that affects the world's freshwaters, with severe consequence for many species, including death and large economical loss. The hypoxia problem has increased recently due to the combined effects of water eutrophication and global warming. In this study, we investigated the transcriptome atlas for the bony fish Ancherythroculter nigrocauda under hypoxia for 1.5, 3, and 4.5 h and its recovery to normal oxygen levels in heart and brain tissues. We sequenced 21 samples for brain and heart tissues (a total of 42 samples) plus three control samples and obtained an average of 32.40 million raw reads per sample, and 95.24% mapping rate of the filtered clean reads. This robust transcriptome dataset facilitated the discovery of 52,428 new transcripts and 6,609 novel genes. In the heart tissue, the KEGG enrichment analysis showed that genes linked to the Vascular smooth muscle contraction and MAPK and VEGF signaling pathways were notably altered under hypoxia. Re-oxygenation introduced changes in genes associated with abiotic stimulus response and stress regulation. In the heart tissue, weighted gene co-expression network analysis pinpointed a module enriched in insulin receptor pathways that was correlated with hypoxia. Conversely, in the brain tissue, the response to hypoxia was characterized by alterations in the PPAR signaling pathway, and re-oxygenation influenced the mTOR and FoxO signaling pathways. Alternative splicing analysis identified an average of 27,226 and 28,290 events in the heart and brain tissues, respectively, with differential events between control and hypoxia-stressed groups. This study offers a holistic view of transcriptomic adaptations in A. nigrocauda heart and brain tissues under oxygen stress and emphasizes the role of gene expression and alternative splicing in the response mechanisms., Competing Interests: Author BF was employed by Ruibiao (Wuhan) Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Hu, Li, Wang, Wei, Li, Fu and Sun.)

This study aimed to investigate the risk factors related to sleep disorders in patients undergoing hemodialysis using a nomogram model. A cross-sectional survey was conducted in a hospital in Zhejiang province, China from January 1, 2020, to November 31, 2022 among patients undergoing hemodialysis. Dietary intake was assessed applying a Food Frequency Questionnaire. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index. Evaluation of risk factors related to sleep disorders in patients undergoing hemodialysis was using a nomogram model. This study included 201 patients and 87 individuals (43.3%, 87/201) exhibited sleep disorders. The average age of included patients was 51.1 ± 9.0 years, with males accounting for 55.7% (112/201). Results from nomogram model exhibited that potential risk factors for sleep disorders in patients undergoing hemodialysis included female, advanced age, increased creatinine and alanine aminotransferase levels, as well as higher red meat consumption. Inversely, protective factors against sleep disorders in these patients included higher consumption of poultry, fish, vegetables, and dietary fiber. The C-index demonstrated a high level of discriminative ability (0.922). This study found that age, sex, and dietary factors were associated with sleep disorders in hemodialysis patients. Hemodialysis patients with sleep disorders require urgent dietary guidance., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

A novel double spot-ring plane-concave multipass cell (DSPC-MPC) gas sensor was proposed for simultaneous detection of trace gases, which has lower cost and higher mirror utilization than the traditional multipass cell with 129 m, 107 m, 85 m, 63 m and 40 m effective optical path lengths adjustable. The performance of the DSPC-MPC gas sensor was evaluated by measuring CO and CH4 using two narrow linewidth distributed feedback lasers with center wavelengths of 1567 nm and 1653 nm, respectively. An adjustable digital PID laser frequency stabilization system based on LabVIEW platform was developed to continuously stabilize the laser frequency within ∼±30.3 MHz. The Allan deviation results showed that the minimum detection limits for CO and CH4 were 0.07 ppmv and 0.008 ppmv at integration times of 711 s and 245 s, respectively. The proposed concept of DSPC-MPC provides more ideas for the realization of gas detection under different absorption path lengths and the development of multi-component gas sensing systems.

Background: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress., Methods: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-β to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-β with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected., Results: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding., Conclusion: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis., (© 2024. The Author(s).)

Bisphenol A (BPA) in seawater tends to be deposited in coastal sediments. However, its degradation under tidal oscillations has not been explored comprehensively. Hydroxyl radicals (·OH) can be generated through Fe cycling under redox oscillations, which have a strong oxidizing capacity. This study focused on the contribution of Fe-mediated production of ·OH in BPA degradation under darkness. The removal of BPA was investigated by reoxygenating six natural coastal sediments, and three redox cycles were applied to prove the sustainability of the process. The importance of low reactivity Fe(II) in the production of ·OH was investigated, specifically, Fe(II) with carbonate and Fe(II) within goethite, hematite and magnetite. The degradation efficiency of BPA during reoxygenation of sediments was 76.78-94.82%, and the contribution of ·OH ranged from 36.74% to 74.51%. The path coefficient of ·OH on BPA degradation reached 0.6985 and the indirect effect of low reactivity Fe(II) on BPA degradation by mediating ·OH production reached 0.5240 obtained via partial least squares path modeling (PLS-PM). This study emphasizes the importance of low reactivity Fe(II) in ·OH production and provides a new perspective for the role of tidal-induced ·OH on the fate of refractory organic pollutants under darkness., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Manganese oxide (MnO x ) is receiving increased interest in the nutrient removal of constructed wetlands (CWs); however, its service effectiveness for simultaneous greenhouse gas (GHG) emissions reduction is still vague. In this study, three vertical flow CWs, i.e., volcanics (CCW), manganese sand uniformly mixing with volcanics (Mn-CW) and MnO x doped volcanics (MnV-CW), were constructed to investigate the underlying mechanisms of MnO x on nutrient removal enhancement and greenhouse gas (GHG) emissions reduction. The results showed that the MnO x doped volcanics optimized the oxidation-reduction potential surrounding the substrate (-164.0 ∼ +141.1 mv), and resulted in the lowest GHG emissions (CO 2 -equivalent) from MnV-CW, 16.8-36.5 % lower than that of Mn-CW and CCW. This was mainly ascribed to mitigation of N 2 O produced during the NO 3 - -N reduction process, according to results of 15 N stable isotope labeling. Analysis of the microbial community structure revealed that due to the optimized redox conditions through chemical doping of MnO x on volcanics, the abundance of microbe involved in denitrification and Mn-oxidizing process in the MnV-CW was significantly increased at genus level, which led to a higher Mn cycling efficiency between biogenic MnO x and Mn 2+ , and enhanced denitrification efficiency and N 2 O emission reduction. This study would help to understand and provide a preferable reference for future applications for manganese-based CW., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nitrous oxide (N 2 O) and nitrogen oxides (NO x ) (i.e., nitric oxide (NO) and nitrogen dioxide (NO 2 )), which could be produced in wastewater treatment process and result in greenhouse effect and atmospheric pollution, respectively, have been studied limitedly in their emission characteristics and transformation mechanisms. In this study, intelligent oxygen regulation was applied in anoxic/oxic wastewater treatment process (I-A/O), and its effects on regulating NO x and N 2 O transformations were extensively explored by comparing it with conventional A/O process (C-A/O). Results showed that the average emission amounts of N 2 O and NO x in I-A/O were 7.45 ± 0.66 mg and 1.88 ± 0.10 mg, respectively. Satisfactory reduction of N 2 O by 29.28 %-45.08 % was achieved in I-A/O compared to that of C-A/O, but together with increased NO x emission by 83.19 %-120.57 %. Pearson correlation and transcriptional analysis suggested that NO 2 - -N reduction in the anoxic phase dominated N 2 O production, while no significant N 2 O production in the oxic phase was found. Hence, the reduced N 2 O production in I-A/O was mainly attributed to its efficient denitrification process. On the other hand, both the anoxic and oxic phases played important roles in NO production. More importantly, sufficient oxygen in I-A/O promoted the ammonia oxidation process, resulting in higher NO emission in I-A/O in the oxic phase. The imbalance in NO and N 2 O emissions was then amplified by the NOR enzyme, which mediates the conversion of NO to N 2 O in both the anoxic and oxic phases. Besides, carbon emission reduction by 31.32 %-36.50 % was obtained in I-A/O due to aeration consumption savings and greenhouse gas emissions reduction compared to C-A/O. Overall, intelligent oxygen regulation optimized the nitrogen transformation and achieved carbon emission reduction in A/O process, but special attention should be paid to the associated risk caused by increased NO emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Carbon source addition is an important way improving the carbon and nitrogen transformation in aquaculture system; however, its effectiveness of algal-bacterial-based aquaponics (AA) through carbon source addition is still vague. In this study, the influences of organic carbon (OC-AA system) and inorganic carbon (IC-AA system) addition and without carbon source addition (C-AA system) on the operational performance of AA system were investigated. Results showed that 10.1-19.5% increase of algal-bacterial biomass enhanced the purifying effect of ammonia nitrogen in OC-AA system and IC-AA system relative to C-AA system. Moreover, extra electron donor supply in the OC-AA system obtained the lowest NO 3 - -N concentration. However, that was at the cost of aggravated N 2 O conversion ratio, which increased by more than 2.0-folds than other systems, attributing to 2.9-folds increase of nirS gene abundance. In addition, carbon source addition increased the pH and then decreased the fish biomass production of AA system. The results of this study would provide theoretical supports of carbon source addition on the performance of nutrient transformation and greenhouse gas effect in AA system., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Loneliness and isolation are associated with multiple cardiovascular diseases (CVDs), but there is a lack of research on whether they were causally linked. We conducted a Mendelian Randomization (MR) study to explore causal relationships between loneliness and isolation and multiple CVDs., Methods: Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study (GWAS) of 455,364 individuals of European ancestry in the IEU GWAS database. Summary data for 15 CVDs were also obtained from the IEU GWAS database. We used three MR methods including inverse variance weighting, MR-Egger, and weighted median estimation to assess the causal effect of exposure on outcomes. Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy., Results: MR analysis showed that loneliness and isolation were significantly associated with essential hypertension (OR = 1.07, 95% CI: 1.03-1.12), atherosclerotic heart disease (OR = 1.04; 95% CI: 1.02-1.06), myocardial infarction (OR = 1.02; 95% CI: 1-1.04) and angina (OR = 1.04; 95% CI =1.02-1.06). No heterogeneity and pleiotropy effects were found in this study., Conclusions: Causal relationship of loneliness and isolation with CVDs were found in this study., (© 2024 JGC All rights reserved; www.jgc301.com.)

Background: Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established., Results: In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 10 8 colony forming units of S. aureus USA300., Conclusions: Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus., (© 2024. The Author(s).)

The use of iron-manganese oxide (FMO) as a promising amendment for remediating arsenic (As) contamination in soils has gained attention, but its application is limited owing to agglomeration issues. This study aims to address agglomeration using surfactant-modified FMO and investigate their stabilization behavior towards As and resulting environmental changes upon amendments. The results confirmed the efficacy of surfactants and demonstrated that cetyltrimethylammonium-bromide-modified FMO significantly reduced the leaching concentration of As by 92.5 % and effectively suppressed the uptake of As by 85.8 % compared with the control groups. The ratio of the residual fraction increased from 30.5-41.6 % in unamended soil to 67.9-69.2 %. The number of active sites was through the introduction of surfactants and immobilized As via complexation, ion exchange, and redox reactions. The study also revealed that amendments and the concentration of As influenced the soil physicochemical properties and enriched bacteria associated with As and Fe reduction and changed the distribution of C, N, Fe, and As metabolism genes, which promoted the stabilization of As. The interactions among cetyltrimethylammonium bromide, FMO, and microorganisms were found to have the greatest effect on As immobilization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

As a core component of power conversion systems, insulated gate bipolar transistor (IGBT) modules continually suffer from severe thermal damage caused by temperature swings and shear stress, resulting in fatigue failure. Bond wires falling off is one of the failure modes of IGBT modules. Given that the number of fallen-off bond wires is a significant parameter to evaluate the health status of the IGBT modules, this paper proposes an online identification model to recognize the number of fallen-off bond wires during normal operation. Firstly, a database containing datum Vce,on-Tj-IC (collector-emitter on-state voltage Vce,on, chip junction temperature Tj, collector current IC) planes with different fallen-off bond wires is built based on an offline aging test. Secondly, a Foster network model and a special circuit are designed to measure the junction temperature Tj and the collector-emitter on-state voltage Vce,on, respectively. Thirdly, the feature points of the IGBT module represented by Vce,on, Tj, and IC are given to the database to recognize the number of fallen-off bond wires according to the position of the feature points in the datum plane. The experimental results show that the proposed method can determine the fallen-off bond wires under the operation condition.