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Differential Privacy (DP) stands as a secure and efficient mechanism for privacy preservation, offering enhanced data utility without compromising computational complexity. Its adaptability is evidenced by its integration into blockchain-based Internet of Things (IoT) contexts, including smart wearables, smart homes, etc. Nevertheless, a notable vulnerability surfaces in decentralized environments where existing DP mechanisms falter in withstanding collusion attacks. This vulnerability stems from the absence of an efficient strategy to synchronize the privacy budget consumption and historical query information among all network participants. Adversaries can exploit this weakness, collaborating to inject a substantial volume of queries simultaneously into disparate blockchain nodes to extract more precise results. To address this issue, we propose a novel dual response DP mechanism to preserve privacy in blockchain-based IoT scenarios. It encompasses both direct and indirect response strategies, enabling an adaptive response to external queries, aiming to provide better data utility while preserving privacy. Additionally, this mechanism can synchronize historical query information and privacy budget consumption within the blockchain network to prevent privacy leakage. We employ Relative Error (RE), Mean Square Error (MSE), and privacy budget consumption as evaluation metrics to measure the performance of the proposed mechanism. Experimental outcomes substantiate that the proposed mechanism can adapt to blockchain networks well, affirming its capacity for privacy and great utility.

Plant lead (Pb) tolerance and accumulation are key characteristics affecting phytoremediation efficiency. Bermudagrass is an excellent candidate for the remediation of Pb-polluted soil, and it needs to be mowed regularly. Here, we explored the effect of different mowing frequencies on the remediation of Pb-contaminated soil using bermudagrass. Mowing was found to decrease the biomass and photosynthetic efficiency of bermudagrass under Pb stress, thereby inhibiting its growth. Although mowing exacerbated membrane peroxidation, successive mowing treatments alleviated peroxidation damage by regulating enzymatic and nonenzymatic systems. A comprehensive evaluation of Pb tolerance revealed that all the mowing treatments reduced the Pb tolerance of bermudagrass, and a once-per-month mowing frequency had a less negative effect on Pb tolerance than did more frequent mowing. In terms of Pb enrichment, mowing significantly increased the Pb concentration, total Pb accumulation, translocation factor (TF), and bioenrichment factor (BCF) of bermudagrass. The total Pb accumulation was greatest under the once-a-month treatment, while the TF and BCF values were greatest under the three-times-a-month mowing treatment. Additionally, the decrease in soil pH and DOC were significantly correlated with the soil available Pb content and plant Pb accumulation parameters. The results showed that changes in the rhizosphere are crucial factors regulating Pb uptake in bermudagrass during mowing. Overall, once-a-month mowing minimally affects Pb tolerance and maximizes Pb accumulation, making it the optimal mowing frequency for soil Pb remediation by bermudagrass. This study provides a novel approach for the remediation of Pb-contaminated soil with bermudagrass based on mowing.

WADED Al-Mg and Al-Mg-Sc-Zr aluminium alloy thin-wall components were produced. Heat treatment (350°C aging for 4 h) was further conducted. The effects of Sc/Zr addition on porosity, microstructure, mechanical properties and corrosion behaviour were investigated. With Sc/Zr adding, pore area fraction decreased from 0.208 to 0.005% and grain size decreased from 84.34 to 19.54 μm. In WADED Al-Mg-Sc-Zr component, microstructure showed refined equiaxed grains. Mechanical properties were improved with 360 MPa ultimate tensile strength (UTS), 185 MPa yield strength, and 23.31% elongation. After heat treatment, UTS increased to 388 MPa with good ductility (22.53%) maintained. The grain refinement and Al3(Sc, Zr) particles were the key factors for mechanical property improvement. The corrosion behaviour was improved with introduced Sc/Zr and further optimised after heat treatment. The corrosion exhibited layered characteristics due to the distribution of primary Al3(Sc, Zr) while minor-size secondary Al3(Sc, Zr) along grain boundaries improved the corrosion behaviour.

RNA-binding proteins (RBPs) bind to RNAs and are crucial for regulating RNA splicing, stability, translation, and transport. Among these proteins, the CUGBP Elav-like family (CELF) is a highly conserved group crucial for posttranscriptional regulation by binding to CUG repeats. Comprising CELF1–6, this family exhibits diverse expression patterns and functions. Dysregulation of CELF has been implicated in various neural disorders, encompassing both neurodegenerative and neurodevelopmental conditions, such as Alzheimer's disease and autism. This article aims to provide a comprehensive summary of the CELF family's role in neurodevelopment and neurodevelopmental disorders. Understanding CELF's mechanisms may offer clues for potential therapeutic strategies by regulating their targets in neurodevelopmental disorders.

Abstract Fast spin-flipping is the key to exploit the triplet excitons in thermally activated delayed fluorescence based organic light-emitting diodes toward high efficiency, low efficiency roll-off and long operating lifetime. In common donor-acceptor type thermally activated delayed fluorescence molecules, the distribution of dihedral angles in the film state would have significant influence on the photo-physical properties, which are usually neglected by researches. Herein, we find that the excited state lifetimes of thermally activated delayed fluorescence emitters are subjected to conformation distributions in the host-guest system. Acridine-type flexible donors have a broad conformation distribution or bimodal distribution, in which some conformers feature large singlet-triplet energy gap, leading to long excited state lifetime. Utilization of rigid donors with steric hindrance can restrict the conformation distributions in the film to achieve degenerate singlet and triplet states, which is beneficial to efficient reverse intersystem crossing. Based on this principle, three prototype thermally activated delayed fluorescence emitters with confined conformation distributions are developed, achieving high reverse intersystem crossing rate constants greater than 106 s−1, which enable highly efficient solution-processed organic light-emitting diodes with suppressed efficiency roll-off.

Abstract Background The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40–45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. Methods The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a protein‒protein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1β and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8+ T cells were performed using flow cytometry. Results Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8+ T cells. Experiments with both clinical samples and mice indicated that infiltration of IL-1β-driven MDSCs and inactivation of CD8+ T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. Conclusions CD8+ T cells and IL-1β were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Infiltration of IL-1β-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. IL-1β antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.

Objective: The aim of this study is to investigate the association between Cathepsin B and Parkinson’s Disease (PD), with a particular focus on determining the role of N-acetylaspartate as a potential mediator. Methods: We used summary-level data from Genome-Wide Association Studies (GWAS) for a two-sample Mendelian randomization (MR) analysis, exploring the association between Cathepsin B (3301 cases) and PD (4681 cases). A sequential two-step MR approach was applied (8148 cases) to study the role of N-acetylaspartate. Results: The MR analysis yielded that genetically predicted elevated Cathepsin B levels correlated with a reduced risk of developing PD (p = 0.0133, OR: 0.9171, 95% CI: 0.8563–0.9821). On the other hand, the analysis provided insufficient evidence to determine that PD affected Cathepsin B levels (p = 0.8567, OR: 1.0035, 95% CI: 0.9666–1.0418). The estimated effect of N-acetylaspartate in this process was 7.52% (95% CI = −3.65% to 18.69%). Conclusions: This study suggested that elevated Cathepsin B levels decreased the risk of developing PD, with the mediation effect of N-acetylaspartate. Further research is needed to better understand this relationship.

IntroductionClear cell renal cell carcinoma (ccRCC) is a prevalent subtype of kidney cancer that exhibits a complex tumor microenvironment, which significantly influences tumor progression and immunotherapy response. In recent years, emerging evidence has underscored the involvement of tumor-infiltrating B lymphocytes (TIL-Bs), a crucial component of adaptive immunity, and their roles in ccRCC as compared to other tumors. Therefore, the present study endeavors to systematically explore the prognostic and molecular features of TIL-Bs in ccRCC.MethodsInitially, xCell algorithm was used to predict TIL-Bs in TCGA-KIRC and other ccRCC transcriptomic datasets. The Log-Rank test and Cox regression were applied to explore the relationship of B-cells with ccRCC survival. Then, we used WGCNA method to identify important modules related to TIL-Bs combining Consensus subcluster and scRNA-seq data analysis. To narrow down the prospective biomarkers, a prognostic signature was proposed. Next, we explored the feature of the signature individual genes and the risk-score. Finally, the potential associations of signature with clinical phenotypes and drugs were investigated.ResultsPreliminary, we found ccRCC survival was negatively associated with TIL-Bs, which was confirmed by other datasets. Afterwards, ten co-expression modules were identified and a distinct ccRCC cluster was subsequently detected. Moreover, we assessed the transcriptomic alteration of B-cell in ccRCC and a relevant B-cell subtype was also pinpointed. Based on two core modules (brown, red), a 10-gene signature (TNFSF13B, SHARPIN, B3GAT3, IL2RG, TBC1D10C, STAC3, MICB, LAG3, SMIM29, CTLA4) was developed in train set and validated in test sets. These biomarkers were further investigated with regards to their differential expression and correlation with immune characteristics, along with risk-score related mutations and pathways. Lastly, we established a nomogram combined tumor grade and discovered underlying drugs according to their sensitivity response.DiscussionIn our research, we elucidated the remarkable association between ccRCC and B-cells. Then, we detected several key gene modules, together with close patient subcluster and B-cell subtype,which could be responsible for the TIL-Bs in ccRCC. Moreover, we proposed a 10-gene signature and investigated its molecular features from multiple perspectives. Overall, understanding the roles of TIL-Bs could aid in the immunotherapeutic approaches for ccRCC, which deserve further research to clarify the implications for patient prognosis and treatment.

ObjectiveExamine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR).MethodsLARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded.ResultsTwenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs.ConclusionNeoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT.

With the deepening and expansion of semiconductor technology and research, in order to continuously optimize the structure and performance of semiconductor detectors, a high-precision hexagonal spiral silicon drift detector (SDD) is proposed in this paper. In order to obtain a more accurate spiral ring structure, this paper goes beyond the first-order formula in the Taylor expansion for calculating the radius of the spiral ring. Based on the first-order formula, the second-order formula for calculating the radius of the spiral ring is further developed and derived. The point coordinates are obtained by combining the radius, angle, and ring spacing change formula to obtain a more accurate spiral ring structure. The actual number of turns is more accurate than that obtained from first-order approximation, which better solves the problem of accurate calculation of the number of spiral rings and the structure of the spiral SDD in the existing technology, that is, the accurate calculation of the radius of the spiral ring. In order to verify the abovementioned theory, we model this new structure and use Technology Computer-Aided Design to system simulate and study its electrical properties, including potential distribution, electric field distribution, and electron concentration distribution. According to the simulation results, compared with the first-order formula, the second-order formula has better electrical properties; more uniform distribution of potential, electric field, and electron concentration; and a clearer electron drift channel.

Hematopoietic stem cells (HSCs) developing from mesoderm during embryogenesis are important for the blood circulatory system and immune system. Many factors such as genetic factors, chemical exposure, physical radiation, and viral infection, can lead to the dysfunction of HSCs. Hematological malignancies (involving leukemia, lymphoma, and myeloma) were diagnosed in more than 1.3 million people globally in 2021, taking up 7% of total newly-diagnosed cancer patients. Although many treatments like chemotherapy, bone marrow transplantation, and stem cell transplantation have been applied in clinical therapeutics, the average 5-year survival rate for leukemia, lymphoma, and myeloma is about 65%, 72%, and 54% respectively. Small non-coding RNAs play key roles in a variety of biological processes, including cell division and proliferation, immunological response and cell death. With the development of technologies in high-throughput sequencing and bioinformatic analysis, there is emerging research about modifications on small non-coding RNAs, as well as their functions in hematopoiesis and related diseases. In this study, we summarize the updated information of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis, which sheds lights into the future application of HSCs into the treatment of blood diseases.

Among the 3D electrode Si detectors for high energy particle and X-ray detection, the traditional 3D-Trench electrode Si detector is a semiconductor detector that is widely used and discussed. Aiming at removing the shortcomings of the traditional 3D-Trench electrode Si detectors such as uneven electric field distribution, asymmetric electric potential, and the existence of some dead zone, we propose a new type 3D-Spherical Electrode Detectors and carry out extensive and systematic studies of their physical properties. We simulated detector electric field, electric potential, electron concentration distribution, full depletion voltage, leakage current, capacitance, the incident particle induced transient current and the weighting field. We systematically studied and analyzed detector’s electrical characteristics. By comparing with the traditional 3D-Trench electrode Si detectors, the new detector structure has more uniform electric field and potential, and less depletion voltage, leakage current and capacitance.

Background: Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of death worldwide. Seriously threatens human life and health. Previous studies have identified that inhibin βA (INHBA) could induce tumorgenesis and progression of CRC through the regulation of the TGF-β/Smad signal axis. The abnormal expression of INHBA is related to the poor prognosis of patients. The aim of this study was to identify the molecular mechanism of HNF1A-AS1 and miR-214 regulating INHBA and carcinogenesis through bioinformatics combined with experiments. Methods: The expression of HNF1A-AS1, miRNA-214-5p, INHBA in pan-cancer and CRC were investigated in the Cancer Genome Atlas (TCGA). The correlation between HNF1A-AS1 and immune-related genes or miRNAs was explored via the Gene Expression Profiling Interactive Analysis (GEPIA) and volcano plots, respectively. The association between HNF1A-AS1 and differentially expressed miRNAs was constructed by TargetScan. The miRDB, miRWalk, and TargetScan databases were utilized to predict the target genes of hsa-miR-214. The expression of INHBA in tissues and cell lines of CRC was examined by RT-qPCR and western blot assay. Results: The INHBA and HNF1A-AS1 expressions were increased in Colon adenocarcinoma (COAD) and Rectum adenocarcinoma (READ) of the TCGA database. Hsa-miR-214 was relatively less expressed in CRC tissues compared with para-cancer tissues. The expression of HNF1A-AS1 was negatively correlated with hsa-miR-214. INHBA was one of the target genes of hsa-miR-214 based on miRDB, miRWalk, and TargetScan databases. The specific binding sites of INHBA-3’UTR and miR-214-5p were identified by starBase. The expression level of INHBA was positively correlated with the T stage of tumor and negatively correlated with overall survival (OS) and disease-free survival (DFS) in CRC patients. The results of RT-qPCR and western blot indicated that the expression of INHBA in tissues and cell lines in CRC was higher than those in para-carcinoma tissues and normal colon cell lines, respectively. Conclusions: These findings suggested that HNF1A-AS1 and miRNA-214-5p were key upstream non-coding RNAs of INHBA. The HNF1A-AS1/miR-214/INHBA signal axis plays a significant role in the tumorgenesis and progression of CRC. By interfering with HNF1A-AS1 and INHBA genes on HT29 and SW480 cells, it was found that HNF1A-AS1 and INHBA genes may be important target genes in CRC.

Lead (Pb) is one of the most harmful, toxic pollutants to the ecological environment and humans. Centipedegrass, a fast-growing warm-season turfgrass, is excellent for Pb pollution remediation. Exogenous low-molecular-weight organic acid (LMWOA) treatment is a promising approach for assisted phytoremediation. However, the effects of this treatment on the tolerance and Pb accumulation of centipedegrass are unclear. This study investigated these effects on the physiological growth response and Pb accumulation distribution characteristics of centipedegrass. Applications of 400 μM citric acid (CA), malic acid (MA) and tartaric acid (TA) significantly reduced membrane lipid peroxidation levels of leaves and improved biomass production of Pb-stressed plants. These treatments mainly increased peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) activities and enhanced free protein (Pro), ascorbic acid (AsA) and phytochelatins (PCs) contents, ultimately improving the Pb tolerance of centipedegrass. Their promoting effects decreased as follows: TA>CA>MA. All the treatments decreased root Pb concentrations and increased stem and leaf Pb concentrations, thus increasing total Pb accumulation and TF values. MA had the best and worst effects on Pb accumulation and Pb transportation, respectively. CA had the best and worst effects on Pb transportation and Pb accumulation, respectively. TA exhibited strong effects on both Pb accumulation and transport. Furthermore, all treatments changed the subcellular Pb distribution patterns and distribution models of the chemical forms of Pb in each tissue. The root Pb concentration was more highly correlated with the Pb subcellular fraction distribution pattern, while the stem and leaf Pb concentrations were more highly correlated with the distribution models of the chemical forms of Pb. Overall, TA improved plant Pb tolerance best and promoted both Pb absorption and transportation well and is considered the best candidate for Pb-contaminated soil remediation with centipedegrass. This study provides a new idea for Pb-contaminated soil remediation with centipedegrass combined with LMWOAs.

ObjectiveTo explore the efficacy and safety of single-agent programmed cell death protein-1 (PD-1) inhibitor in the neoadjuvant treatment of patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer (LACRC) through single-center large⁃sample analysis based on real⁃world data in China.MethodsThis study was a retrospective, single-center, case series study. 33 colorectal cancer (CRC) patients with clinical stage of T3~4N0~2M0 treated in Yunnan Cancer Hospital from June 2019 to June 2021 were analyzed retrospectively. Among them, 32 patients were dMMR or MSI-H or both dMMR and MSI-H, and one patient was both dMMR and microsatellite stability (MSS) (excluded in the final analysis). All 32 patients received neoadjuvant immunotherapy (nIT) with single-agent PD⁃1 inhibitor.ResultsAmong the 32 patients, 8 (25%) were locally advanced rectal cancer (LARC) and 24 (75%) were locally advanced colon cancer (LACC); 4 (12.55%) were stage II and 28 (87.5%) were stage III. The median number of cycles of 32 patients with dMMR/MSI-H LACRC receiving nIT with single-agent PD-1 blockade was 6 (4~10), and the median number of cycles to achieve partial response (PR) was 3 (2~4). Among them, three LARC patients achieved clinical complete response (cCR) and adopted the watch-and-wait (W&W) strategy. The objective response rate (ORR) of the other 29 patients with radical surgery was 100% (29/29), the pathological response rate was 100% (29/29), the rate of major pathological response (MPR) was 86.2% (25/29), and the rate of pathological complete response (pCR) was 75.9% (22/29). The incidence of immune-related adverse events (irAEs) in 32 patients during nIT was 37.5% (12/32), while the incidence of irAEs in 22 patients with operation during adjuvant immunotherapy was 27.3% (6/22), all of which were grade 1~2. No grade 3 or above irAEs were occured. The median time from the last nIT to surgery was 27 (16~42) days. There were no delayed radical resection due to irAEs in these patients. All 29 patients achieved R0 resection. The incidence of surgical-related adverse events (srAEs) in perioperative period was 10.3% (3/29).ConclusionsNeoadjuvant monoimmunotherapy with PD-1 inhibitor has favorable ORR and pCR rate, and relatively low incidences of irAEs and srAEs for patients with dMMR/MSI-H LACRC, suggesting that this nIT regimen of single-agent PD-1 inhibitor is significantly effective and sufficiently safe.

The world is still following an unsustainable development pathway, facing great challenges in global CO2 emissions reduction in the coming decades. In this study, we used Kaya identity model to project CO2 emissions. We considered three main scenarios (business-as-usual, BAU; post-Copenhagen-Paris, PCP; deglobalization (COVID-19), DGC), which explored different pathways for CO2 emissions of fuel combustion to 2050 from global to national level. The results show that industrialized countries have been the largest contributors to global CO2 emissions, but some emerging economies are now among the top emitters in absolute terms. For countries at all stages of development, it's going to be important to reduce the trajectory of global greenhouse gas emissions and boost resilience to mounting climate impacts. Among the global, regional, the United States and China CO2 emissions reduction scenarios, the PCP scenario is the best CO2 emissions reduction pathway, in this scenario global CO2 emissions will reach a peak by 2029 (31.813 Gt). Renewable energy leads the transition to a lower-carbon energy mix. The COVID-19 pandemic resulted in the largest-ever decline in global emissions.

China is the largest producer and consumer of plastics worldwide. Microplastic (MP) pollution has been a recent research hotspot in environmental science and ecology. This study collects and analyzes the statistical data for microplastics (MPs) 86 lakes in entire China’s lake ecosystems in past five years (2016–2020), their range in area is 0.056–4543.000 km2 (average: 566.045 km2), and the water storage varies from 0.162 × 108 to 1050.000 × 108 m3 (average: 77.884 ×108 m3). The results showed (1) The MP abundance in lake surface water is significantly correlated with lake area (ρ = −0.562, p ＜0.01), provincial GDP (Gross Domestic Product, GDP) (ρ = 0.377, p = 0.002), GDP per capita (ρ = 0.346, p = 0.006), urban waste water discharge and ratio of agricultural land area (ρ = 0.369, p = 0.003). (2) The MP abundance in lake sediment is significantly correlated with per capita domestic volume of garbage disposal (ρ = −0.536, p ＜0.001), per capita urban waste water discharge (ρ = −0.544, p ＜0.001) and ratio of agricultural land area (ρ = 0.635, p ＜0.001). (3) Irrespective of whether the samples were from surface water or sediment, MPs were primarily transparent, and the dominant types were fragments, films, and fibers. In addition, the size of MPs samples was mostly less than 2 mm, and the major polymers were polyethylene (PE), polypropylene (PP), and polystyrene (PS). (4) The degree of MP pollution in organisms was related to the degree of environmental pollution. These findings could provide a theoretical basis for the control and management of MP pollution in China’s lake ecosystems.

Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit. However, patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). The 2015 KEYNOTE-016 trial identified MSI-H/dMMR as a biomarker indicative of immunotherapy efficacy, and pointed to the potential use of immune checkpoint inhibitors (ICIs). In 2017, the FDA approved two ICIs (pembrolizumab and nivolumab) for treatment of MSI-H/dMMR metastatic CRC (mCRC). In 2018, the CheckMate-142 trial demonstrated successful treatment of mCRC based on “double immunity” provided by nivolumab with ipilimumab, a regimen that may become a standard first-line treatment for MSI-H mCRC. In 2018, the FDA approved nivolumab alone or with ipilimumab for patients who progressed to MSI-H/dMMR mCRC after standard chemotherapy. The FDA then approved pembrolizumab alone as a first-line treatment for patients with MSI-H/dMMR CRC that was unresectable or metastatic. There is now interest in using these drugs in neoadjuvant immunotherapy (nIT) for patients with MSI-H/dMMR non-mCRC. In 2020, the NICHE trial marked the start of using nIT for CRC. This novel treatment of MSI-H/dMMR LACRC may change the approaches used for neoadjuvant therapy of other cancers. Our review of immunotherapy for CRC covers diagnosis and treatment, clinical prognostic characteristics, the mechanism of nIT, analysis of completed prospective and retrospective studies, and ongoing clinical trials, and the clinical practice of using nIT for MSI-H/dMMR LACRC. Our team also proposes a new organ-preservation strategy for patients with MSI-H/dMMR low LARC.

A new type of 3D electrode detector, named here as the Implanted-Epi Silicon 3D-Spherical Electrode Detector, is proposed in this work. Epitaxial and ion implantation processes can be used in this new detector, allowing bowl-shaped electrodes to penetrate the silicon completely. The distance between the bowl cathode and the central collection electrode is basically the same, thus the total depletion voltage of Implanted-Epi Silicon 3D-Spherical Electrode Detectors is no longer directively correlated with the thickness of the silicon wafer, but only related to the electrode spacing. In this work, we model the device physics of this new structure and use a simulation program to conduct a systematic 3D simulation of its electrical characteristics, including electric potential and electric field distributions, electron concentration profile, leakage current, and capacitance, and compare it to the traditional 3D detectors. The theoretical and simulation study found that the internal electric potential of the new detector was smooth and no potential saddle point was found. The electric field is also uniform, and there is no zero field and a low electric field area. Compared with the traditional silicon 3D electrode detectors, the full depletion voltage is greatly reduced and the charge collection efficiency is improved. As a large electrode spacing (up to 500 μm) can be realized in the Implanted-Epi Silicon 3D-Spherical Electrode Detector thanks to their advantage of a greatly reduced full depletion voltage, detectors with large pixel cells (and thus small dead volume) can be developed for applications in photon science (X-ray, among others).

Since the advent of semiconductor detectors, they have been developed for several generations, and their performance has been continuously improved. In this paper, we propose a new silicon drift detector structure that is different from the traditional spiral SDD structure that has a gap between the cathode ring and the width of cathode ring, increasing gradually with the increase of the radius of the cathode ring. Our new structure of spiral SDD structure has equal cathode ring gap and a given surface electric field, which has many advantages compared with the traditional structure. The novel SDD structure controllably reduces the area of silicon oxide between the spiral rings, which in turn reduces the surface leakage current due to the reduction of total oxide charge in the silicon oxide and electronic states on the silicon/silicon oxide interface. Moreover, it has better controllability to adjust this spiral ring cathode gap to achieve better surface electric field distribution, thus realizing the optimal carrier drift electric field and achieving the optimal detector performance. In order to verify this theory, we have modeled this new structure and simulated its electrical properties using the Sentaurus TCAD tool. We have also analyzed and compared different spiral ring cathode gap structures (from 10 µm to 25 µm for the gap). According to the simulation results of potential, electric field, and electron concentration, we have obtained that a spiral ring cathode gap of 10 µm has the best electrical characteristics, more uniform distribution of potential and surface electric field, and a more smooth and straight electron drift channel.

Dwarf bamboos are clonal plants with potential applications in the remediation of heavy metal-polluted soils, although their pollution adaptation strategies are unknown. This study examined the biomass allocation strategies and lead (Pb) enrichment characteristics of various dwarf bamboo tissues by the end of the growing season and explored their potential for phytoremediation of Pb stress in the soils. Six dwarf bamboo genotypes were treated with three levels (0, 300, and 1500 mg kg–1) of soil Pb stress. The majority of the bamboos adopted two biomass allocation strategies to adapt to Pb stress, namely, “reducing biomass allocation into new bamboo growth” and “increasing/stabilizing biomass allocation into rhizomes”. Pb accumulation was highest in the roots, rhizomes, and old stems and showed the following trend: rhizomes/old stems> new roots/old roots> old leaves> new leaves> new stems among various tissues. Moreover, the six bamboos used three different Pb-enrichment strategies, as follows: (i) “rhizome domination and old stem synergy” (Sasaella glabra (Nakai) f. albo-striata Muroi, Sasa auricoma (Mitford) E.G. Camus, Sasa fortunei (Van Houtte) Fiori, and Shibataea lanceifolia C.H. Hu); (ii) “old stem domination and rhizome synergy” (Indocalamus decorus Q.H. Dai); and (iii) “old stem domination and new root synergy” (Sasa argenteostriata (Regel) E.G. Camus). In Pb-contaminated soils, genotypes with TFs greater than 1 were Sasa fortunei (Van Houtte) Fiori, Sasa argenteostriata (Regel) E.G. Camus, and Indocalamus decorus Q.H. Dai; in addition, only S. argenteostriata had BCF values greater than 1. Furthermore, this study provides the first evidence that S. argenteostriata can extract 0.22 and 0.58 mgplant−1 of Pb ions in soil polluted with 300 and 1500 mg kg−1 Pb, respectively. S. argenteostriata showed the greatest potential for phytoremediation among the bamboo genotypes in both Pb-contaminated urban and mining sites.

The design of orange-light emitting, thermally activated, delayed fluorescence (TADF) materials is necessary and important for the development and application of organic light-emitting diodes (OLEDs). Herein, two donor–acceptor–donor (D–A–D)-type orange TADF materials based on fluorenone and acridine, namely 2,7-bis(9,9-dimethylacridin-10(9H)-yl)-9H-fluoren-9-one (27DACRFT, 1) and 3,6-bis(9,9-dimethylacridin-10(9H)-yl)-9H-fluoren-9-one (36DACRFT, 2), were successfully synthetized and characterized. The studies on their structure–property relationship show that the different configurations have a serious effect on the photoluminescence and electroluminescence performance according to the change in singlet–triplet splitting energy (ΔEST) and excited state geometry. This indicates that a better configuration design can reduce internal conversion and improve triplet exciton utilization of TADF materials. Importantly, OLEDs based on 2 exhibited a maximum external quantum efficiency of 8.9%, which is higher than the theoretical efficiency of the OLEDs based on conventional fluorescent materials.

Abstract Organic light‐emitting diodes (OLEDs) employing exciplex cohosts have gained attractive interest due to the promising high efficiency, low driving voltage, and potential low cost in future solid‐state lighting sources and full‐color displays. However, their device lifetime is still the most challenging weakness and rarely studied, which is regarded as a time consuming and complicated work. Therefore, a simplified but effective and comprehensive approach is demonstrated to give prediction for the exciplex cohosts operating lifespan and analyze their possible degradation mechanisms by considering molecular dissociated activation energy with internal exciton dynamics correlations. As a consequence, strong chemical bond stability for the hole transport moieties and rapid reactive exciton relaxation have the intrinsic talent to access potentially long‐lived exciplex cohosts, achieving an extended lifetime of 10169 h for the predicted long‐lived exciplex cohost OLEDs. Degradation behaviors further confirm that the deteriorated source is attributed to the formation of exciton quenchers and hole traps from excited states and charged‐excited states, respectively. The current findings establish a universal technique to screen the stable exciplex cohost candidates with economic time consumption and expenses.

As one of the three primary colors that are indispensable in full-color displays, the development of red emitters is far behind the blue and green ones. Here, three novel orange-yellow to near-infrared (NIR) emitters based on 5,6-difluorobenzo[c][1,2,5]thiadiazole (BTDF) namely BTDF-TPA, BTDF-TTPA, and BTDF-TtTPA were designed and synthesized. Density functional theory analysis and photophysical characterization reveal that these three materials possess hybridized local and charge-transfer (HLCT) state feature and a feasible reverse intersystem crossing (RISC) from the high-lying triplet state to the singlet state may conduce to an exciton utilization exceeding the limit of 25% of traditional fluorescence materials under electrical excitation. The insertion of thiophene with small steric hindrance as π-bridge between the electron-donating (D) moiety triphenylamine (TPA) and the electron-accepting (A) moiety BTDF not only results in a remarkable 67 nm red-shift of the emission peak but also brings about a large overlap of frontier molecular orbitals to guarantee high radiative transition rate that is of great significance to obtain high photoluminescence quantum yield (PLQY) in the “energy-gap law” dominated long-wavelength emission region. Consequently, an attractive high maximum external quantum efficiency (EQE) of 5.75% was achieved for the doped devices based on these thiophene π-bridged emitters, giving a deep-red emission with small efficiency roll-off. Remarkably, NIR emission could be obtained for the non-doped devices, achieving an excellent maximum EQE of 1.44% and Commission Internationale de l'Éclairage (CIE) coordinates of (0.71, 0.29). These results are among the highest efficiencies in the reported deep-red to NIR fluorescent OLEDs and offer a new π-bridge design strategy in D-π-A and D-π-A-π-D red emitter design.

Introduction: Clear cell renal cell carcinoma (ccRCC) is a prevalent subtype of kidney cancer that exhibits a complex tumor microenvironment, which significantly influences tumor progression and immunotherapy response. In recent years, emerging evidence has underscored the involvement of tumorinfiltrating B lymphocytes (TIL-Bs), a crucial component of adaptive immunity, and their roles in ccRCC as compared to other tumors. Therefore, the present study endeavors to systematically explore the prognostic and molecular features of TIL-Bs in ccRCC. Methods: Initially, xCell algorithm was used to predict TIL-Bs in TCGA-KIRC and other ccRCC transcriptomic datasets. The Log-Rank test and Cox regression were applied to explore the relationship of B-cells with ccRCC survival. Then, we used WGCNA method to identify important modules related to TIL-Bs combining Consensus subcluster and scRNA-seq data analysis. To narrow down the prospective biomarkers, a prognostic signature was proposed. Next, we explored the feature of the signature individual genes and the risk-score. Finally, the potential associations of signature with clinical phenotypes and drugs were investigated. Results: Preliminary, we found ccRCC survival was negatively associated with TIL-Bs, which was confirmed by other datasets. Afterwards, ten co-expression modules were identified and a distinct ccRCC cluster was subsequently detected. Moreover, we assessed the transcriptomic alteration of B-cell in ccRCC and a relevant B-cell subtype was also pinpointed. Based on two core modules (brown, red), a 10-gene signature (TNFSF13B, SHARPIN, B3GAT3, IL2RG, TBC1D10C, STAC3, MICB, LAG3, SMIM29, CTLA4) was developed in train set and validated in test sets. These biomarkers were further investigated with regards to their differential expression and correlation with immune characteristics, along with risk-score related mutations and pathways. Lastly, we established a nomogram combined tumor grade and discovered underlying drugs according to their sensitivity response. Discussion: In our research, we elucidated the remarkable association between ccRCC and B-cells. Then, we detected several key gene modules, together with close patient subcluster and B-cell subtype, which could be responsible for the TIL-Bs in ccRCC. Moreover, we proposed a 10-gene signature and investigated its molecular features from multiple perspectives. Overall, understanding the roles of TIL-Bs could aid in the immunotherapeutic approaches for ccRCC, which deserve further research to clarify the implications for patient prognosis and treatment. [ABSTRACT FROM AUTHOR]