Placebo immune-related adverse events (irAEs): A neglected phenomenon in cancer immunotherapy trials.

PURPOSE: This study aims to investigate the underexplored prevalence of placebo-reported immune-related adverse events (irAEs) in immune checkpoint inhibitor (ICI) trials. METHODS: We searched public databases for randomized clinical trials (RCTs) involving ICI versus placebo treatments in patients with malignancies. Study characteristics and irAEs occurrences were extracted for meta-analyses using a random-effects model. MAIN OUTCOMES: Proportions of patients reported to experience any grade and grade 3 to 5 placebo irAEs; the risk ratio (RR) of reporting 'false' irAEs in the experiment arm (defined as 'false-irAE ratio', calculated by dividing the proportion of patients documented with irAEs in the placebo arm by that in the experimental arm). RESULTS: 47 RCTs with 30,119 patients were analyzed. The pooled proportion of patients reported to experience any grade and grade 3 to 5 irAEs among placebo participants was 22.85 % (17.33 %-29.50 %) and 3.40 % (2.35 %-4.63 %), respectively. The pooled proportion of placebo-treated patients who experienced serious irAEs was 0.67 % (0.03 %-1.91 %). Treatment discontinuation and death due to placebo irAEs occurred in 0.69 % (<0.01 %-1.30 %) and 0.12 % (<0.01 %-0.40 %) of patients, respectively. The false-irAE ratio for any grade and grade 3 to 5 irAEs were 0.49 and 0.28. The false-irAE ratio was significantly higher in RCTs with control arms of placebo plus non-immunotherapy than in those with placebo alone (any grade: 0.57 vs. 0.32, P < 0.001; grade 3 to 5: 0.36 vs. 0.12, P = 0.009). CONCLUSION: Our analyses of placebo-treated participants in ICI RCTs document the common occurrence of placebo irAEs. These findings are important for interpreting irAE profiles, avoiding inappropriate therapeutic interventions.

ReMAR: a preoperative CT angiography guided metal artifact reduction framework designed for follow-up CTA of endovascular coiling.

Objective. Follow-up computed tomography angiography (CTA) is necessary for ensuring occlusion effect of endovascular coiling. However, the implanted metal coil will introduce artifacts that have a negative spillover into radiologic assessment.Method. A framework named ReMAR is proposed in this paper for metal artifacts reduction (MARs) from follow-up CTA of patients with coiled aneurysms. It employs preoperative CTA to provide the prior knowledge of the aneurysm and the expected position of the coil as a guidance thus balances the metal artifacts removal performance and clinical feasibility. The ReMAR is composed of three modules: segmentation, registration and MAR module. The segmentation and registration modules obtain the metal coil knowledge via implementing aneurysms delineation on preoperative CTA and alignment of follow-up CTA. The MAR module consisting of hybrid convolutional neural network- and transformer- architectures is utilized to restore sinogram and remove the artifact from reconstructed image. Both image quality and vessel rendering effect after metal artifacts removal are assessed in order to responding clinical concerns.Main results. A total of 137 patients undergone endovascular coiling have been enrolled in the study: 13 of them have complete diagnosis/follow-up records for end-to-end validation, while the rest lacked of follow-up records are used for model training. Quantitative metrics show ReMAR significantly reduced the metal-artifact burden in follow-up CTA. Qualitative ranks show ReMAR could preserve the morphology of blood vessels during artifact removal as desired by doctors.Significance. The ReMAR could significantly remove the artifacts caused by implanted metal coil in the follow-up CTA. It can be used to enhance the overall image quality and convince CTA an alternative to invasive follow-up in treated intracranial aneurysm.

Miniaturized 3D-printed hand-operable dispersive sample pretreatment device with replaceable chitosan/polydopamine thin film metal sorbent for enhanced metal analysis.

To address the increasing demand for sensitive and selective sample preparation methods for metal analysis; preconcentration of intended analyte from complex sample matrices before analysis is required to improve the performance of analysis instruments. In this study, we have engineered a sustainable and portable syringe-based hand-operable three-dimensionally (3D) printed sample pretreatment apparatus equipped with a replaceable bio-based thin- film metal sorbent. This device effectively addresses the challenges of sample matrix interference in metal analysis. A metal sorbent film composed of chitosan (CS) and polydopamine (PDA) leveraged the diverse functional groups in the CS/PDA matrix to significantly enhance the extraction efficiency for various metals. Our approach demonstrated excellent analytical performance, with coefficients of determination (R2) of 0.9982 for copper (Cu) and 0.996 for chromium (Cr). The method achieved low limits of detection (LOD) of 0.3 µg L-1 for Cr and 0.7 µg L-1 for Cu. Precision and practicality assessments using actual urine samples yielded satisfactory relative standard deviations (RSD%) ranging from of 1.6 %-8.5 % for both metals, indicating minimal interference from the sample matrix. Moreover, our approach exhibited robust performance even after seven consecutive extraction and desorption cycles, highlighting its sustainability and practical applicability for laboratory and on-site sample pretreatment.

Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection.

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors.

Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition.

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.

Leveraging FAM features to predict the prognosis of LGG patients and immunotherapy outcome.

Heterogeneity at biological and transcriptomic levels poses a challenge in defining and typing low-grade glioma (LGG), leading to a critical need for specific molecular signatures to enhance diagnosis, therapy, and prognostic evaluation of LGG. This study focused on fatty acid metabolism (FAM) related genes and prognostic features to investigate the mechanisms and treatment strategies for LGG cell metastasis and invasion. By screening 158 FAM-related genes and clustering 512 LGG samples into two subtypes (C1 and C2), differential gene expression analysis and functional enrichment were performed. The immune cell scores and prognosis were compared between the two subtypes, with C1 showing poorer outcomes and higher immune scores. A four-gene signature (PHEX, SHANK2, HOPX, and LGALS1) was identified and validated across different datasets, demonstrating a stable predictive effect. Cellular experiments confirmed the roles of LGALS1 and HOPX in promoting tumor cell proliferation, migration, and invasion, while SHANK2 exhibited a suppressive effect. This four-gene signature based on FAM-related genes offers valuable insights for understanding the pathogenesis and clinical management of LGG.

Single-cell transcriptomic reveals a cell atlas and diversity of chicken amygdala responded to social hierarchy.

Amygdala serves as a highly cellular, heterogeneous brain region containing excitatory and inhibitory neurons and is involved in the dopamine and serotoninergic neuron systems. An increasing number of studies have revealed the underpinned mechanism mediating social hierarchy in mammal and vertebrate, however, there are rare studies conducted on how amygdala on social hierarchy in poultry. In this study, we conducted food competition tests and determined the social hierarchy of the rooster. We performed cross-species analysis with mammalian amygdala, and found that cell types of human and rhesus monkeys were more closely related and that of chickens were more distant. We identified 26 clusters and divided them into 10 main clusters, of which GABAergic and glutamatergic neurons were associated with social behaviors. In conclusion, our results provide to serve the developmental studies of the amygdala neuron system and new insights into the underpinned mechanism of social hierarchy in roosters.

Neuroimaging and clinical features of bilateral Wallerian degeneration of middle cerebellar peduncles subsequent to pontine infarction.

OBJECTIVE: Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its infrequency, there is limited research on its characteristics. METHODS: This study aims to present three cases of WD of MCPs following pontine infarction and to analyze the prognosis, clinical manifestations, and neuroimaging features by amalgamating our cases with previously reported ones. RESULTS: The cohort consisted of 25 cases, comprising 18 men and 7 women aged 29 to 77 years (mean age: 66.2 years). The majority of patients (94%) exhibit risk factors for cerebrovascular disease, with hypertension being the primary risk factor. Magnetic resonance imaging (MRI) can detect WD of MCPs within a range of 21 days to 12 months following pontine infarction. This degeneration is characterized by bilateral symmetric hyperintensities on T2/FLAIR-weighted images (WI) lesions in the MCPs. Moreover, restricted diffusion, with hyperintensity on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) signal intensity may be observed as early as 21 days after the infarction. Upon detection of WD, it was observed that 20 patients (80%) remained asymptomatic during subsequent clinic visits, while four (16%) experienced a worsening of pre-existing symptoms. CONCLUSIONS: These findings underscore the importance of neurologists enhancing their understanding of this condition by gaining fresh insights into the neuroimaging characteristics, clinical manifestations, and prognosis of individuals with WD of bilateral MCPs.

Cardiac autonomic regulation following a 246-km mountain ultra-marathon: An observational study.

Physical exercise requires integrated autonomic and cardiovascular adjustments to maintain homeostasis. We aimed to observe acute posture-related changes in blood pressure, and apply a portable noninvasive monitor to measure the heart index for detecting arrhythmia among elite participants of a 246-km mountain ultra-marathon. Nine experienced ultra-marathoners (8 males and 1 female) participating in the Run Across Taiwan Ultra-marathon in 2018 were enrolled. The runners' Heart Spectrum Blood Pressure Monitor measurements were obtained in the standing and supine positions before and immediately after the race. Their high-sensitivity troponin T and N-terminal proB-type natriuretic peptide levels were analyzed 1 week before and immediately after the event. Heart rate was differed significantly in the immediate postrace assessment compared to the prerace assessment, in both the standing (P = .011; d = 1.19) and supine positions (P = .008; d = 1.35). Postural hypotension occurred in 4 (44.4%) individuals immediately postrace. In 3 out of 9 (33.3%) recruited finishers, the occurrence of premature ventricular complex signals in the standing position was detected; premature ventricular complex signal effect was observed in the supine position postrace in only 1 participant (11.1%). Premature ventricular complex signal was positively correlated with running speed (P = .037). Of the 6 individuals who completed the biochemical tests postrace, 2 (33.3%) had high-sensitivity troponin T and 6 (100%) had N-terminal proB-type natriuretic peptide values above the reference interval. A statistically significant increase was observed in both the high-sensitivity troponin T (P = .028; d = 1.97), and N-terminal proB-type natriuretic peptide (P = .028; d = 2.91) levels postrace compared to prerace. In conclusion, significant alterations in blood pressure and heart rate were observed in the standing position, and postexercise (postural) hypotension occurred among ultra-marathoners. The incidence of premature ventricular complexes was higher after the race than before.

Combined detection of serum EFNA1 and MMP13 as diagnostic biomarker for gastric cancer.

We previously identified that serum EFNA1 and MMP13 were potential biomarker for early detection of esophageal squamous cell carcinoma. In this study, our aim is to explore the diagnostic value of serum EFNA1 and MMP13 for gastric cancer. We used enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of serum EFNA1 and MMP13 in 210 GCs and 223 normal controls. The diagnostic value of EFNA1 and MMP13 was evaluated in an independent cohorts of GC patients and normal controls (n = 238 and 195, respectively). Receiver operating characteristics were used to calculate diagnostic accuracy. In training and validation cohorts, serum EFNA1 and MMP13 levels in the GC groups were significantly higher than those in the normal controls (P < 0.001). The area under the curve (AUC) of the combined detection of serum EFNA1 and MMP13 for GC was improved (0.794), compared with single biomarker used. Similar results were observed in the validation cohort. Importantly, the combined measurement of serum EFNA1 and MMP13 to detect early-stage GC also had acceptable diagnostic accuracy in training and validation cohort. Combined detection of serum EFNA1 and MMP13 could help identify early-stage GC, suggesting that it may be a promising tool for the early detection of GC.

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

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

Development and validation of a preoperative radiomics-based nomogram to identify patients who can benefit from splenic hilar lymphadenectomy: a pooled analysis of three prospective trials.

BACKGROUND: We aimed to use preoperative computed tomography images to develop a radiomic nomogram to select patients who would benefit from spleen-preserving splenic hilar (No.10) lymphadenectomy (SPSHL). METHODS: A pooled analysis of three distinct prospective studies was performed. The splenic hilar lymph node (SHLN) ratio (sLNR) was established as the quotient of the number of metastatic SHLN to the total number of SHLN. Radiomic features reflecting the phenotypes of the primary tumor (RS1) and SHLN region (RS2) were extracted and used as predictive factors for sLNR. RESULTS: This study included 733 patients: 301 in the D2 group and 432 in the D2+No.10 group. The optimal sLNR cutoff value was set at 0.4, and the D2+No.10 group was divided into three groups: sLNR=0, sLNR≤0.4, and sLNR>0.4. Patients in the D2+No. 10 group were randomly divided into the training (n=302) and validation (n=130) cohorts. The AUCs value of the nomogram, including RS1 and RS2, were 0.952 in the training cohort and 0.888 in the validation cohort. The entire cohort was divided into three groups based on the nomogram scores: low, moderate and high SHLN metastasis burden groups (LMB, MMB and HMB, respectively). A similar 5-year OS rate was found between the D2 and D2+No. 10 groups in the LMB and HMB groups. In the MMB group, the 5-year OS of the D2+No. 10 group (73.4%) was significantly higher than that of the D2 group (37.6%) (P<0.001). CONCLUSIONS: The nomogram showed good predictive ability for distinguishing patients with various SHLN metastasis burdens. It can accurately identify patients who would benefit from SPSHL.

Indolent CD8-positive T-LPD of the peripheral nervous system in a 19-year-old man.

A 19-year-old man presented with recurrent intermittent fever, progressive limbs weakness, numbness, and atrophy for 5 years. Biopsy of the sural nerve, spleen, lymph nodes, bone marrow and labial gland revealed that monomorphic small lymphoid cells infiltrated diffusely and that there was severe loss of large myelinated nerve fibers. Immunohistochemically, these cells were mainly CD8-positive T cells and were positive for CD3 and CD57. This patient was diagnosed as indolent CD8-positive T lymphoproliferative disorder (indolent CD8-positive T-LPD), emphasizing the need for a broad differential diagnosis under these conditions, and nerve biopsy should be performed.

Real-ambient bedroom light at night increases systemic inflammation and disrupts circadian rhythm of inflammatory markers.

BACKGROUND: Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human inflammation. OBJECTIVES: To examine the association between real-ambient bedroom LAN exposure with systemic inflammation and circadian rhythm of inflammatory markers. METHODS: Using data from a prospective cohort study of Chinese young adults. At baseline, bedroom LAN exposure was measured with a portable illuminance meter; fasting blood sample for high-sensitivity C-reactive protein (hs-CRP) assay was collected. At 3-year follow-up, 20 healthy young adults (10 LANavg < 5 lx, 10 LANavg ≥ 5 lx) were recruited from the same cohort; time-series venous blood samples were sampled every 4 h over a 24 h-cycle for the detection of 8 inflammatory markers. Circadian rhythm of inflammatory markers was assessed using cosinor analysis. RESULTS: At baseline, the average age of the 276 participants was 18.7 years, and 33.3 % were male. Higher levels of bedroom LAN exposure were significantly associated with increased hs-CRP levels. The association between bedroom LAN exposure and systemic inflammation was only significant in the inactive group (MVPA < 2 h/d) but not in the physically active group (MVPA ≥ 2 h/d). In addition, exposure to higher levels of nighttime light (LANavg ≥ 5 lx) disrupted circadian rhythms (including rhythmic expression, circadian amplitude and circadian phase) of some inflammatory cytokines and inflammatory balance indicators. CONCLUSION: Exposure to bedroom nighttime light increases systemic inflammation and disrupts circadian rhythm of inflammatory markers. Keep bedroom darkness at night may represent important strategies for the prevention of chronic inflammation. Additionally, for people living a community with higher nighttime light pollution, regular physical activity may be a viable option to counteract the negative impacts of LAN exposure on chronic inflammation.

Tumor microenvironment characteristics of lipid metabolism reprogramming related to ferroptosis and EndMT influencing prognosis in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a refractory malignant tumor with high tumor heterogeneity, a low rate of early diagnosis, and poor patient prognosis. Lipid metabolism reprogramming plays a critical role in tumorigenesis and progression, but its prognostic role and regulatory mechanism in GC are rarely studied. Thus, the identification of signatures related to lipid metabolism is necessary and may present a new avenue for improving the overall prognosis of GC. METHODS: Lipid metabolism-associated genes (LMAGs) with differential expression in tumor and tumor-adjacent tissue were acquired to identify lipid metabolism-associated subtypes. The differentially expressed genes (DEGs) between the two clusters were then utilized for prognostic analysis and signature construction. Additionally, pathway enrichment analysis and immune cell infiltration analysis were employed to identify the characteristics of the prognostic model. Further analyses were conducted at the single-cell level to better understand the model's prognostic mechanism. Finally, the prediction of immunotherapy response was used to suggest potential treatments. RESULTS: Two lipid metabolism-associated subtypes were identified and 9 prognosis-related genes from the DEGs between the two clusters were collected for the construction of the prognostic model named lipid metabolism-associated signature (LMAS). Then we found the low LMAS patients with favorable prognoses were more sensitive to ferroptosis in the Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD). Meanwhile, the tumor cells exhibiting high levels of lipid peroxidation and accumulation of reactive oxygen species (ROS) in single-cell levels were primarily enriched in the low LMAS group, which was more likely to induce ferroptosis. In addition, endothelial cells and cancer-associated fibroblasts (CAFs) facilitated tumor angiogenesis, proliferation, invasion, and metastasis through endothelial-mesenchymal transition (EndMT), affecting the prognosis of the patients with high LMAS scores. Moreover, CD1C- CD141- dendritic cells (DCs) also secreted pro-tumorigenic cytokines to regulate the function of endothelial cells and CAFs. Finally, the patients with low LMAS scores might have better efficacy in immunotherapy. CONCLUSIONS: A LMAS was constructed to guide GC prognosis and therapy. Meanwhile, a novel anti-tumor effect was found in lipid metabolism reprogramming of GC which improved patients' prognosis by regulating the sensitivity of tumor cells to ferroptosis. Moreover, EndMT may have a negative impact on GC prognosis.

Dynamic volume-outcome association for esophagectomies: Do current volume thresholds still apply?

BACKGROUND: It is unknown if the current minimum case volume recommendation of 20 cases per year per hospital is applicable to contemporary practice. METHODS: Patients undergoing esophageal resection between 2005 and 2015 were identified in the National Cancer Database. High, medium, and low-volume hospital strata were defined by quartiles. Adjusted odds ratios and adjusted 30-day mortality between low-, medium-, and high-volume hospitals were calculated using logistic regression analyses and trended over time. RESULTS: Only 1.1% of hospitals had ≥20 annual cases. The unadjusted 30-day mortality for esophagectomy was 3.8% overall. Unadjusted and adjusted 30-day mortality trended down for all three strata between 2005 and 2015, with disproportionate decreases for low-volume and medium-volume versus high-volume hospitals. By 2015, adjusted 30-day mortality was similar in medium- and high-volume hospitals (odds ratio 1.35, 95% confidence interval 0.96-1.91). For hospitals with 20 or more annual cases the adjusted 30-day mortality was 2.7% overall. To achieve this same 30-day mortality the minimum volume threshold had lowered to 7 annual cases by 2015. CONCLUSION: Only 1.1% of hospitals meet current volume recommendations for esophagectomy. Differential improvements in postoperative mortality at low- and medium- versus high-volume hospitals have led to 7 cases in 2015 achieving the same adjusted 30-day mortality as 20 cases in the overall cohort. Lowering volume thresholds for esophagectomy in contemporary practice would potentially increase the proportion of hospitals able to meet volume standards and increase access to quality care without sacrificing quality.

Uptake, subcellular distribution, and fate of tetracycline in two wetland plants supplemented with microbial agents: Effect and mechanism.

The use of wetland plants in the context of phytoremediation is effective in the removal of antibiotics from contaminated water. However, the effectiveness and efficiency of many of these plants in the removal of antibiotics remain undetermined. In this study, the effectiveness of two plants-Phragmites australis and Iris pseudacorus-in the removal of tetracycline (TC) in hydroponic systems was investigated. The uptake of TC at the roots of I. pseudacorus and P. australis occurred at concentrations of 588.78 and 106.70 µg/g, respectively, after 7-day exposure. The higher uptake of TC in the root of I. pseudacorus may be attributed to its higher secretion of root exudates, which facilitate conditions conducive to the reproduction of microorganisms. These rhizosphere-linked microorganisms then drove the TC uptake, which was higher than that in the roots of P. australis. By elucidating the mechanisms underlying these uptake-linked outcomes, we found that the uptake of TC for both plants was significantly suppressed by metabolic and aquaporin inhibition, suggesting uptake and transport of TC were active (energy-dependent) and passive (aquaporin-dominated) processes, respectively. The subcellular distribution patterns of I. pseudacorus and P. australis in the roots were different, as expressed by differences in organelles, cell wall concentration levels, and transport-related dynamics. Additionally, the microbe-driven enhancement of the remediation capacities of the plants was studied comprehensively via a combined microbial-phytoremediation hydroponic system. We confirmed that the microbial agents increased the secretion of root exudates, promoting the variation of TC chemical speciation and thus enhancing the active transport of TC. These results contribute toward the improved application of wetland plants in the context of antibiotic phytoremediation.

P-N Heterojunction formation: Metal Sulfide@Metal Oxide Chemiresistor for ppb H2S Detection from Exhaled Breath and Food Spoilage at Flexible Room Temperature.

The development of a portable, low-cost sensor capable of accurately detecting H2S gas in exhaled human breath at room temperature is highly anticipated in the fields of human health assessment and food spoilage evaluation. However, achieving outstanding gas sensing performance and applicability for flexible room-temperature operation with parts per billion H2S gas sensors still poses technical challenges. To address this issue, this study involves the in situ growth of MoS2 nanosheets on the surface of In2O3 fibers to construct a p-n heterojunction. The In2O3@MoS2-2 sensor exhibits a high response of 460.61 to 50 ppm of H2S gas at room temperature, which is 19.5 times higher than that of the pure In2O3 sensor and 322.1 times higher than that of pure MoS2. The In2O3@MoS2-2 also demonstrates a minimum detection limit of 3 ppb and maintains a stable response to H2S gas even after being bent 50 times at a 60° angle. These exceptional gas sensing properties are attributed to the increase in oxygen vacancies and chemisorbed oxygen on In2O3@MoS2-2 nanofibers as well as the formation of the p-n heterojunction, which modulates the heterojunction barrier. Furthermore, in this study, we successfully applied the In2O3@MoS2-2 sensor for oral disease and detection of food spoilage conditions, thereby providing new design insights for the development of portable exhaled gas sensors and gas sensors for evaluating food spoilage conditions at room temperature.

Laurocapram, a transdermal enhancer, boosts cephalosporin's antibacterial activity against Methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA), a notorious bacterium with high drug resistance and easy recurrence after surgery, has posed significant clinical treatment challenges. In the current scarcity of new antibiotics, the identification of adjuvants to existing antibiotics is a promising approach to combat infections caused by multidrug-resistant Gram-positive bacteria. The in vitro synergy test, which included a MIC assay, time-kill curve, antimicrobial susceptibility testing, and live/dead bacteria staining assay, revealed that laurocapram, a widely used chemical transdermal enhancer, could potentiate the antibacterial activity of cephalosporins against MRSA. In vitro, laurocapram combined with cefixime showed an excellent synergistic activity against MRSA (FICI = 0.28 ±â€¯0.00). In addition, the combination of laurocapram and cefixime may inhibited the formation of MRSA biofilm and caused cell membrane damage. Following that, we discovered that combining laurocapram with cefixime could alleviate the symptoms of mice in the MRSA skin infection model and the MRSA pneumonia model. In conclusion, laurocapram is a promising and low-cost antibacterial adjuvant, providing a new strategy for further exploring the use of lower doses of cephalosporins to combat MRSA infection.

Counterion docking: a general approach to reducing energetic disorder in doped polymeric semiconductors.

Molecular doping plays an important role in controlling the carrier concentration of organic semiconductors. However, the introduction of dopant counterions often results in increased energetic disorder and traps due to the molecular packing disruption and Coulomb potential wells. To date, no general strategy has been proposed to reduce the counterion-induced structural and energetic disorder. Here, we demonstrate the critical role of non-covalent interactions (NCIs) between counterions and polymers. Employing a computer-aided approach, we identified the optimal counterions and discovered that NCIs determine their docking positions, which significantly affect the counterion-induced energetic disorder. With the optimal counterions, we successfully reduced the energetic disorder to levels even lower than that of the undoped polymer. As a result, we achieved a high n-doped electrical conductivity of over 200 S cm-1 and an eight-fold increase in the thermoelectric power factor. We found that the NCIs have substantial effects on doping efficiency, polymer backbone planarity, and Coulomb potential landscape. Our work not only provides a general strategy for identifying the most suitable counterions but also deepens our understanding of the counterion effects on doped polymeric semiconductors.