Search

Summary: Background: The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms. Methods: We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts). Findings: The ICI benefit group was enriched for propionate (P = 0.01) and butyrate/isobutyrate (P = 0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P

Abstract Radical substitution is a useful method to functionalize heterocycles, as in the venerable Minisci reaction. Empirically observed regiochemistries indicate that the CF2H radical has a nucleophilic character similar to alkyl radicals, but the CF3 radical is electrophilic. While the difference between •CH3 and •CF3 is well understood, the reason that one and two Fs make little difference but the third has a large effect is puzzling. DFT calculations with M06-2X both reproduce experimental selectivities and also lead to an explanation of this difference. Theoretical methods reveal how the F inductive withdrawal and conjugative donation alter radical properties, but only CF3 becomes decidedly electrophilic toward heterocycles. Here, we show a simple model to explain the radical orbital energy trends and resulting nucleophilicity or electrophilicity of fluorinated radicals.

Abstract Disease activity evaluation is important in Crohn's disease (CD). We aimed to establish new disease activity indices for CD based on noninvasive parameters. The data of 110 patients with CD were retrospectively analyzed. Parameters from bowel ultrasound and biomarkers were measured to select the variables included in the models by univariate analysis. Logistic regression analysis was performed to predict mucosal and transmural activities defined by ileocolonoscopy or computed tomography enterography, respectively. The models' performance was measured by the area under the receiver operating characteristic (ROC) curve (AUC). Leave‐one‐out cross validation (LOOCV) was applied to adjust for overconfidence in the newly established score models. To predict mucosal activity, erythrocyte sedimentation rate (ESR) and (LimG × BWT)‐SUM (the sum of the product of Limberg grade [LimG] and bowel wall thickness [BWT] of each bowel segment) were selected for model A, and the equation was A = 2 × ESR + 9.3 × (LimG × BWT)‐SUM. The AUC of ROC, sensitivity, and specificity were 0.927%, 89.8%, and 86.4%, respectively. The AUC of the ROC curve verified by LOOCV was 0.913. To predict transmural activity, albumin (ALB) and LimG‐SUM (the sum of the LimG of all the bowel segments) were selected for model B, which was established as B = −1.3 × ALB +1.7 × LimG‐SUM. The AUC of ROC, sensitivity, and specificity were 0.851%, 78.0%, and 84.2%, respectively. The AUC of the ROC curve verified by LOOCV was 0.833. Nomograms were developed for two score models. New score models based on noninvasive parameters established in this study showed good abilities in detecting active disease and performed well in the validation phase.

In response to the trend of drug−resistant and super bacteria, the existing single antibacterial methods are not sufficient to kill bacteria, and the development of multifunctional antibacterial nanomaterials is urgent. Our study aims to construct copper−doped polydopamine−coated Ti3C2Tx (CuPDA@Ti3C2Tx) with an enhanced photothermal property and Fenton−like activity. The nanocomposite hydrogel consisting of CuPDA@Ti3C2Tx and alginate can improve the antioxidant activity of two−dimensional MXene nanosheets by coating them with a thin layer of PDA nanofilm. Meanwhile, Cu ions are adsorbed through the coordination of PDA−rich oxygen−containing functional groups and amino groups. Calcium ions were further used to crosslink sodium alginate to obtain antibacterial hydrogel materials with combined chemotherapy and photothermal therapy properties. The photothermal conversion efficiency of CuPDA@Ti3C2Tx is as high as 57.7% and the antibacterial rate of Escherichia coli reaches 96.12%. The photothermal effect leads to oxidative stress in bacteria, increases cell membrane permeability, and a high amount of ROS and copper ions enter the interior of the bacteria, causing protein denaturation and DNA damage, synergistically leading to bacterial death. Our study involves a multifunctional synergistic antibacterial nanodrug platform, which is conducive to the development of high−performance antibacterial agents and provides important research ideas for solving the problem of drug−resistant bacteria.

Sn-based materials are promising candidates for lithium storage but suffer generally from huge volume change during the (de)lithiation processes. Sn-organic materials with monodispersed Sn centers surrounded by lithium active ligands can alleviate the volume change of anode materials based on reversible (de)lithiation processes. However, the structural factors governing the kinetics of lithium storage and utilization efficiency of active sites are not well understood to date. Herein, we report three two-dimensional Sn-organic materials with enhanced lithium storage performance by manipulation of π-aromatic conjugation of the ligands. The increasing π-aromatic conjugation plays a key role in promoting efficient lithium storage, and the volume expansion during the (de)lithiation reaction is suppressed in these Sn-organic materials. This work reveals that the π-aromatic conjugation of the ligand is crucial for improving the kinetics of lithium storage and the utilization of active sites in metal-organic materials with minimised volume expansion.

BackgroundImmune checkpoint inhibitors (ICIs) have been a breakthrough in cancer immunotherapy, but secondary resistance (SR) and immune-related adverse events (irAEs) are significant clinical dilemmas. Although the gut microbiota is associated with ICI efficacy and irAEs, the knowledge of longitudinal gut microbiota dynamics during SR and irAE development is still quite limited.MethodsThis was a prospective observational cohort study of cancer patients initially receiving anti-programmed cell death-1 (PD-1) treatment between May 2020 and October 2022. Clinical information was collected to evaluate therapy response and AEs. Patients were divided into a secondary resistance (SR) group, a non-secondary resistance (NSR) group, and an irAE group. Fecal samples were longitudinally obtained from baseline across multiple timepoints and analyzed with 16S rRNA sequencing.ResultsThirty-five patients were enrolled, and 29 were evaluable. After a median follow-up of 13.3 months, NSR patients had a favorable progression-free survival (PFS) compared with SR (457.9 IQR 241.0-674.0 days vs. 141.2 IQR 116.9-165.4 days, P=0.003) and irAE patients (457.9 IQR 241.0-674.0 days vs. 269.9, IQR 103.2-436.5 days, P=0.053). There were no significant differences in the microbiota between groups at baseline. Several previously reported beneficial microbiomes for ICI efficacy including Lachnospiraceae, Ruminococcaceae, Agathobacter, and Faecalibacterium showed decreasing trends as secondary resistance developed, yet not achieved significance (P>0.05). Significant changes in butyrate-producing bacteria were also presented in the SR cohort (P=0.043) with a decreasing trend upon secondary resistance occurrence (P=0.078). While the abundance of IgA-coated bacteria was stable in the SR cohort, there was a temporary decrease upon ICI treatment initiation and reestablishment after continuation of ICI treatment in the NSR cohort (primary ICI response: 0.06, IQR 0.04-0.10; durable ICI response: 0.11, IQR 0.07-0.14; P=0.042). Bacteroides contributed most to the difference between baseline and irAE occurrence, which decreased after irAE occurrence (Baseline: 0.10 IQR 0.07-0.36; irAE occurrence: 0.08 IQR 0.06-0.12) and was restored upon irAE remission to a comparable level as baseline (irAE remission: 0.10 IQR 0.09-0.18).ConclusionsThe development of SR and irAEs is related to the longitudinal dynamics of the intestinal microbiota. The investigation into the preventative and protective effects of enteric microbe manipulation strategies is further required.

Driven by growing applications that use computer screens as interfaces for daily remote interactions, almost all current video coding standards have included screen content coding (SCC) tools. Recently, an efficient SCC tool called intra string copy (ISC) has been adopted in the third-generation of audio video coding standard in China (AVS3). ISC has two coding unit (CU) level sub-modes: fully-matching-string and partially-matching-string based string prediction (FPSP) sub-mode and equal-value-string, unit-basis-vector-string, and unmatched-pixel-string based string prediction (EUSP) sub-mode. To further improve the coding efficiency of SCC, this paper proposes four enhancement techniques of ISC (EISC), including CU partition improvements, point vector (PV) relocation and reactivation, line-based overlapping string prediction, and an optimized coding method for string length in the EUSP sub-mode. Compared with the latest AVS3 reference software HPM with EISC disabled, using AVS3 SCC common test condition and YUV test sequences in text and graphics with motion and mixed content categories, the proposed technique achieves an average Y BD-rate reduction of 2.39% and 1.49% for all intra (AI) and low-delay B (LDB) configurations, respectively, with low additional encoding complexity and almost no additional decoding complexity. All proposed ISC enhancement techniques have been adopted in AVS3.

Semantic communication has witnessed a great progress with the development of natural language processing (NLP) and deep learning (DL). Although existing semantic communication technologies can effectively reduce errors in semantic interpretation, most of these solutions adopt a fixed bit length structure, along with a rigid transmission scheme, which is inefficient and lacks scalability faced with different meanings and signal-to-noise ratio (SNR) conditions. In this paper, we explore the impact of adaptive bit lengths on semantic coding (SC) under various channel conditions. First, we propose progressive semantic hybrid automatic repeat request (HARQ) schemes that utilize incremental knowledge (IK) to simultaneously reduce the communication cost and semantic error. On top of this, we design a novel semantic encoding solution with multi-bit length selection. In this fashion, the transmitter employs a policy network to decide the appropriate coding rate, so as to secure the correct information delivery at the cost of minimal bits. Moreover, a specific denoiser is further introduced to reduce the semantic errors encountered in the transmission process according to the semantic characteristics of context. Extensive simulation results have been conducted to verify the effectiveness of the proposed solution.

IntroductionThe gut microbiota is implicated in the occurrence and severity of immune-related adverse events (irAEs), but the role it plays as well as its causal relationship with irAEs has yet to be established.MethodsFrom May 2020 to August 2021, 93 fecal samples were prospectively collected from 37 patients with advanced thoracic cancers treated with anti-PD-1 therapy, and 61 samples were collected from 33 patients with various cancers developing different irAEs. 16S rDNA amplicon sequencing was performed. Antibiotic-treated mice underwent fecal microbiota transplantation (FMT) with samples from patients with and without colitic irAEs.ResultsMicrobiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs (P=0.003). Bifidobacterium, Faecalibacterium, and Agathobacter were less abundant and Erysipelatoclostridium more abundant in irAE patients, while Bacteroides and Bifidobacterium were less abundant and Enterococcus more abundant in colitis-type irAE patients. Major butyrate-producing bacteria were also less abundant in patients with irAEs than those without (P=0.007) and in colitic vs. non-colitic irAE patients (P=0.018). An irAE prediction model had an AUC of 86.4% in training and 91.7% in testing. Immune-related colitis was more common in colitic-irAE-FMT (3/9) than non-irAE-FMT mice (0/9).ConclusionsThe gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.

To improve the output power of the polydimethylsiloxane (PDMS)-based triboelectric nanogenerators (TENGs), we fabricated an asymmetric TiO2/PDMS composite film in which a pure PDMS thin film was deposited as a capping layer on a TiO2 nanoparticles (NPs)-embedded PDMS composite film. Although in the absence of the capping layer, the output power decreased when the content of TiO2 NPs exceeded a certain value, the asymmetric TiO2/PDMS composite films showed that the output power increased with increasing content. The maximum output power density was approximately 0.28 W/m2 at a TiO2 content of 20 vol.%. The capping layer could be responsible not only for maintaining the high dielectric constant of the composite film but also for suppressing interfacial recombination. To further improve the output power, we applied a corona discharge treatment to the asymmetric film and measured the output power at a measurement frequency of 5 Hz. The maximum output power density was approximately 78 W/m2. The idea of the asymmetric geometry of the composite film should be applicable to various combinations of materials for TENGs.

Background and Aim: The aim was to assess non-invasive factors among clinical features, laboratory, and bowel ultrasound (BUS) characteristics and to develop a scoring system to predict endoscopic activities for ulcerative colitis (UC) patients. Methods: We performed a retrospective study collecting UC patients between January 2015 to September 2020. Logistic regression was performed to predict moderate-to-severe endoscopic activities, defined as endoscopic Mayo score ⩾2. Model performance was described with discrimination and calibration ability and validated by internal and external methods. Results: A total of 103 and 29 patients were enrolled in the modeling and validation groups, respectively. Stool frequency ⩾5 times/day, hematochezia, erythrocyte sedimentation rate (ESR), and colonic wall flow in BUS were included into two predictive models for endoscopic activities, both with good discrimination ability [Area under curve (AUC) 0.879 and 0.882, p < 0.001] and a sensitivity of 76.7% and specificity of 92.3%, which showed an adequate calibration ability by using the Hosmer–Lemeshow test ( p = 0.14 and 0.07). The external validation displayed consistent results with the above mentioned. Nomograms were also established for these models. Conclusion: We developed predictive models for endoscopic disease activities by using noninvasive factors based on stool frequency, hematochezia, ESR, and colonic wall blood flow in BUS. These models performed well in the internal and external validation.

Background Human brucellosis imposes a heavy burden on the health and economy of endemic regions. Since 2011, China has reported at least 35,000 human brucellosis cases annually, with more than 90% of these cases reported in the northern. Given the alarmingly high incidence and variation in the geographical distribution of human brucellosis cases, there is an urgent need to decipher the causes of such variation in geographical distribution. Method We conducted a retrospective epidemiological study in Shaanxi Province from January 1, 2005 to December 31, 2018 to investigate the association between meteorological factors and transmission of human brucellosis according to differences in geographical distribution and seasonal fluctuation in northwestern China for the first time. Results Human brucellosis cases were mainly distributed in the Shaanbei upland plateau before 2008 and then slowly extended towards the southern region with significant seasonal fluctuation. The results of quasi-Poisson generalized additive mixed model (GAMM) indicated that air temperature, sunshine duration, rainfall, relative humidity, and evaporation with maximum lag time within 7 months played crucial roles in the transmission of human brucellosis with seasonal fluctuation. Compared with the Shaanbei upland plateau, Guanzhong basin had more obvious fluctuations in the occurrence of human brucellosis due to changes in meteorological factors. Additionally, the established GAMM model showed high accuracy in predicting the occurrence of human brucellosis based on the meteorological factors. Conclusion These findings may be used to predict the seasonal fluctuations of human brucellosis and to develop reliable and cost-effective prevention strategies in Shaanxi Province and other areas with similar environmental conditions.

The existing safety helmet detection methods are mainly based on one-stage object detection algorithms with high detection speed to reach the real-time detection requirements, but they can't accurately detect small objects and objects with obstructions. Therefore, we propose a helmet detection algorithm based on the attention mechanism (AT-YOLO). First of all, a channel attention module is added to the YOLOv3 backbone network, which can adaptively calibrate the channel features of the direction to improve the feature utilization, and a spatial attentionmodule is added to the neck of theYOLOv3 network to capture the correlation between any positions in the feature map so that to increase the receptive field of the network. Secondly, we use DIoU (Distance Intersection over Union) bounding box regression loss function, it not only improving the measurement of bounding box regression loss but also increases the normalized distance loss between the prediction boxes and the target boxes, which makes the network more accurate in detecting small objects and faster in convergence. Finally, we explore the training strategy of the network model, which improves network performance without increasing the inference cost. Experiments show that the mAP of the proposed method reaches 96.5%, and the detection speed can reach 27 fps. Compared with other existing methods, it has better performance in detection accuracy and speed. [ABSTRACT FROM AUTHOR]

Common perceptions of the former Eastern Bloc often characterize the socialist societies as overly oppressive, where stringent political censorship categorically denied freedom of expression. Nevertheless, a closer examination of the socialist public sphere reveals more nuanced patterns. This essay examines how cinema functioned as a unique space where citizens of the former German Democratic Republic (GDR) could critically reflect on their everyday experiences in manners that departed from the dominant ideology prescribed by the state. I start by critiquing models of the socialist public sphere previously proposed by David Bathrick and Michael Meyen and offer an alternative model in which popular cinema plays an indispensable role in articulating authentic daily experiences of ordinary GDR citizens. Through an analysis of Heiner Carow's cult film "The Legend of Paul and Paula" ("Die Legende von Paul und Paula," 1973), I argue that the East German state studio DEFA (Deutsche Film-Aktiengesellschaft) offered filmmakers a certain degree of artistic license despite frameworks of limitation, and that the film serves as a space for discussion where individualist desires find expression despite official constraints on the fulfillment of such wishes. [ABSTRACT FROM AUTHOR]

Copyright of Focus on German Studies is the property of University of Cincinnati Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bioleaching is a promising technology for removal of metals from sludge and improvement of its dewaterability. Most of the previous studies of bioleaching were focused on removal of metals; bioleaching in cold environments has not been studied extensively. In this study, Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans were acclimated at 15 °C and co-inoculated to explore the optimal conditions for improvement of sludge dewaterability and removal of metals by the sequencing batch reactors. The data show after 6 days of bioleaching at 15 °C, 89.6% of Zn, 72.8% of Cu and 39.4% of Pb were removed and the specific resistance to filtration (SRF) was reduced to ~12%. In addition, the best conditions for bioleaching are an initial pH of 6, a 15% (v/v) inoculum concentration, and A. thiooxidans and A. ferrooxidans mixed in a ratio of 4:1. We found that bioleaching of heavy metals is closely related to final pH, while the sludge SRF is dominated by other factors. Bioleaching can be completed in 6 days, and the sludge dewaterability and removal of metals at 15 °C meet the requirements of most sewage treatment plants. [ABSTRACT FROM AUTHOR]