Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm.

Tumor heterogeneity presents a challenge for inferring clonal evolution and driver gene identification. Here, we describe a method for analyzing the cancer genome at a single-cell nucleotide level. To perform our analyses, we first devised and validated a high-throughput whole-genome single-cell sequencing method using two lymphoblastoid cell line single cells. We then carried out whole-exome single-cell sequencing of 90 cells from a JAK2-negative myeloproliferative neoplasm patient. The sequencing data from 58 cells passed our quality control criteria, and these data indicated that this neoplasm represented a monoclonal evolution. We further identified essential thrombocythemia (ET)-related candidate mutations such as SESN2 and NTRK1, which may be involved in neoplasm progression. This pilot study allowed the initial characterization of the disease-related genetic architecture at the single-cell nucleotide level. Further, we established a single-cell sequencing method that opens the way for detailed analyses of a variety of tumor types, including those with high genetic complex between patients.

C-terminal glutamine acts as a C-degron targeted by E3 ubiquitin ligase TRIM7.

The exposed N-terminal or C-terminal residues of proteins can act, in cognate sequence contexts, as degradation signals (degrons) that are targeted by specific E3 ubiquitin ligases for proteasome-dependent degradation by N-degron or C-degron pathways. Here, we discovered a distinct C-degron pathway, termed the Gln/C-degron pathway, in which the B30.2 domain of E3 ubiquitin ligase TRIM7 (TRIM7B30.2) mediates the recognition of proteins bearing a C-terminal glutamine. By determining crystal structures of TRIM7B30.2 in complexes with various peptides, we show that TRIM7B30.2 forms a positively charged binding pocket to engage the "U"-shaped Gln/C-degron. The four C-terminal residues of a substrate play an important role in C-degron recognition, with C-terminal glutamine as the principal determinant. In vitro biochemical and cellular experiments were used to further analyze the substrate specificity and selective degradation of the Gln/C-degron by TRIM7.

Programmable Ferroelectricity in Hf0.5Zr0.5O2 Enabled by Oxygen Defect Engineering.

Ferroelectricity, especially the Si-compatible type recently observed in hafnia-based materials, is technologically useful for modern memory and logic applications, but it is challenging to differentiate intrinsic ferroelectric polarization from the polar phase and oxygen vacancy. Here, we report electrically controllable ferroelectricity in a Hf0.5Zr0.5O2-based heterostructure with Sr-doped LaMnO3, a mixed ionic-electronic conductor, as an electrode. Electrically reversible extraction and insertion of an oxygen vacancy into Hf0.5Zr0.5O2 are macroscopically characterized and atomically imaged in situ. Utilizing this reversible process, we achieved multilevel polarization states modulated by the electric field. Our study demonstrates the usefulness of the mixed conductor to repair, create, manipulate, and utilize advanced ferroelectric functionality. Furthermore, the programmed ferroelectric heterostructures with Si-compatible doped hafnia are desirable for the development of future ferroelectric electronics.

ECDEP: identifying essential proteins based on evolutionary community discovery and subcellular localization.

BACKGROUND: In cellular activities, essential proteins play a vital role and are instrumental in comprehending fundamental biological necessities and identifying pathogenic genes. Current deep learning approaches for predicting essential proteins underutilize the potential of gene expression data and are inadequate for the exploration of dynamic networks with limited evaluation across diverse species. RESULTS: We introduce ECDEP, an essential protein identification model based on evolutionary community discovery. ECDEP integrates temporal gene expression data with a protein-protein interaction (PPI) network and employs the 3-Sigma rule to eliminate outliers at each time point, constructing a dynamic network. Next, we utilize edge birth and death information to establish an interaction streaming source to feed into the evolutionary community discovery algorithm and then identify overlapping communities during the evolution of the dynamic network. SVM recursive feature elimination (RFE) is applied to extract the most informative communities, which are combined with subcellular localization data for classification predictions. We assess the performance of ECDEP by comparing it against ten centrality methods, four shallow machine learning methods with RFE, and two deep learning methods that incorporate multiple biological data sources on Saccharomyces. Cerevisiae (S. cerevisiae), Homo sapiens (H. sapiens), Mus musculus, and Caenorhabditis elegans. ECDEP achieves an AP value of 0.86 on the H. sapiens dataset and the contribution ratio of community features in classification reaches 0.54 on the S. cerevisiae (Krogan) dataset. CONCLUSIONS: Our proposed method adeptly integrates network dynamics and yields outstanding results across various datasets. Furthermore, the incorporation of evolutionary community discovery algorithms amplifies the capacity of gene expression data in classification.

Membranous translocation of murine double minute 2 promotes the increased renal tubular immunogenicity in ischemia-reperfusion-induced acute kidney injury.

Kidneys from donors with prolonged warm and cold ischemia are prone to post-transplant T cell-mediated rejection (TCMR) due to ischemia-reperfusion injury (IRI). However, the precise mechanisms still remain obscure. Renal tubular epithelial cells (TECs) are the main target during IRI. Meanwhile, we reported previously that murine double minute 2 (MDM2) actively participates in TEC homeostasis during IRI. In this study, we established a murine model of renal IRI and a cell model of hypoxia/reoxygenation by culturing immortalized rat renal proximal tubule cells (NRK-52E) in a hypoxic environment for different time points followed by 24 hours of reoxygenation or incubating NRK-52E cells in a chemical anoxia/recovery environment. We found that during renal IRI, MDM2 expression increased on the membrane of TECs and aggregated mainly on the basolateral side. This process was accompanied by a reduction of a transmembrane protein programmed death-ligand 1 (PD-L1), a co-inhibitory second signal for T cells in TECs. By using mutant plasmids of MDM2 to anchor MDM2 on the cell membrane or nuclei, we found that the upregulation of membrane MDM2 could promote the ubiquitination of PD-L1 and lead to its ubiquitination-proteasome degradation. Lastly, we set up a co-culture system of TECs and CD4+ T cells in vitro; our results revealed that the immunogenicity of TECs was enhanced during IRI. In conclusion, our findings suggest that the increased immunogenicity of TECs during IRI may be related to ubiquitinated degradation of PD-L1 by increased MDM2 on the cell membrane, which consequently results in T cell activation and TCMR.

Novel quantitative immunohistochemistry method using histone H3, family 3B as the internal reference standard for measuring human epidermal growth factor receptor 2 expression in breast cancer.

BACKGROUND: Immunohistochemistry (IHC) is an essential technique in surgical and clinical pathology for detecting diagnostic, prognostic, and predictive biomarkers for personalized cancer therapy. However, the lack of standardization and reference controls results in poor reproducibility, and a reliable tool for IHC quantification is urgently required. The objective of this study was to describe a novel approach in which H3F3B (histone H3, family 3B) can be used as an internal reference standard to quantify protein expression levels using IHC. METHODS: The authors enrolled 89 patients who had human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). They used a novel IHC-based assay to measure protein expression using H3F3B as the internal reference standard. H3F3B was uniformly expressed at the protein level in all tumor regions in cancer tissues. HER2 expression levels were measured with the H-score using HALO software. RESULTS: Kaplan-Meier analysis indicated that, among patients who had HER2-positive BC in The Cancer Genome Atlas data set and the authors' data set, the subgroup with low HER2 expression had a significantly better prognosis than the subgroup with high HER2 expression. Furthermore, the authors observed that HER2 expression levels were precisely evaluated using the proposed method, which can classify patients who are at higher risk of HER2-positive BC to receive trastuzumab-based adjuvant therapy. Dual-color IHC with H3F3B is an excellent tool for internal and external quality control of HER2 expression assays. CONCLUSIONS: The proposed IHC-based quantification method accurately assesses HER2 expression levels and provides insights for predicting clinical prognosis in patients with HER2-positive BC who receive trastuzumab-based adjuvant therapy.

The effect of fecal microbiota transplantation on antibiotic-associated diarrhea and its impact on gut microbiota.

BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut. METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT. RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-α before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased. CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.

Chiral-at-Ruthenium Catalysts for Nitrene-Mediated Asymmetric C-H Functionalizations.

ConspectusAsymmetric transition metal catalysis is an indispensable tool used both in academia and industry for forging chiral molecules in an enantioselective fashion. Its advancement relies in large part on the design and discovery of new chiral catalysts. In contrast to conventional endeavors of generating chiral transition metal catalysts from carefully tailored chiral ligands, the development of chiral transition metal catalysts containing solely achiral ligands (chiral-at-metal catalysts) has been neglected. This Account presents our recent work on the synthesis and catalytic applications of a new class of C2-symmetric chiral-at-ruthenium catalysts. These octahedral ruthenium(II) complexes are constructed from two achiral bidentate N-(2-pyridyl)-substituted N-heterocyclic carbene (PyNHC) ligands and two monodentate acetonitriles, and the dicationic complexes are typically complemented with two hexafluorophosphate anions. The chirality of these complexes originates from the helical cis-arrangement of the bidentate ligands, thereby generating a stereogenic metal center as the exclusive stereocenter in these complexes. The strong σ donor and π acceptor properties of the PyNHC ligands provide a strong ligand field that ensures a high constitutional and configurational inertness of the helical Ru(PyNHC)2 core, while at the same time, the trans-effect exerted by the σ-donating NHC ligands results in high lability of the MeCN ligands and, therefore, provides high catalytic activity. As a result, this chiral-at-ruthenium catalyst scaffold combines formidable structural robustness with high catalytic activity in a unique fashion. Asymmetric nitrene C-H insertion constitutes an efficient strategy for accessing chiral amines. The direct conversion of C(sp3)-H bonds into amine functionality circumvents the need for using functionalized starting materials. Our C2-symmetric chiral-at-ruthenium complexes display exceptionally high catalytic activity and excellent stereocontrol for various asymmetric nitrene C(sp3)-H insertion reactions. The ruthenium nitrene species can be generated from nitrene precursors, such as organic azides and hydroxylamine derivatives, which undergo ring-closing C-H aminations to afford chiral cyclic pyrrolidines, ureas, and carbamates in high yields and with excellent enantioselectivities at low catalyst loadings. Mechanistically, the turnover-determining C-H insertion is proposed to proceed in a concerted or stepwise fashion, depending on the nature of intermediate ruthenium nitrenes (singlet or triplet). Computational studies revealed that the stereocontrol originates from a better steric fit in combination with favorable catalyst/substrate π-π stacking effects for aminations at benzylic C-H bonds. In addition, we also present our research for exploring novel reaction patterns and reactivities of intermediate transition metal nitrenes. First, we discovered a novel chiral-at-ruthenium-catalyzed 1,3-migratory nitrene C(sp3)-H insertion to convert azanyl esters into nonracemic α-amino acids. Second, we found a chiral-at-ruthenium-catalyzed intramolecular C(sp3)-H oxygenation, thereby allowing for the construction of chiral cyclic carbonates and lactones via nitrene chemistry. We expect that our research program on catalyst development and reaction discovery will inspire the creation of novel types of chiral-at-metal catalysts and drive the development of new applications for nitrene-mediated asymmetric C-H functionalization reactions.

Preliminary study of finger temperature recovery in patients with diabetes mellitus following cold stimulation.

OBJECTIVE: To explore the difference in temperature recovery following cold stimulation between participants with and without diabetes mellitus (DM). MATERIALS AND METHODS: The participants without (control group; n = 25) and with (DM group; n = 26) DM were subjected to local cold stimulation (10º C for 90 s). The thermal images of their hands were continuously captured using a thermal camera within 7 min following cold stimulation, and the highest temperature of each fingertip was calculated. According to the temperature values at different timepoints, the temperature recovery curves were drawn, and the baseline temperature (T-base), initial temperature after cooling (T0), temperature decline amplitude (T-range), and area under the temperature recovery curve > T0 (S) were calculated. Finally, symmetry differences between the two groups were analysed. RESULTS: No statistical differences in the T-base, T0, and T-range were observed between the DM and control groups. After drawing the rewarming curve according to the temperature of the fingertips of the patients following cold stimulation, the S in the DM group was significantly lower than that in the control group (p < 0.05). Furthermore, the asymmetry of the base temperature of the hand was observed in the DM group. CONCLUSIONS: Following cold stimulation, the patients with DM exhibited a different rewarming pattern than those without DM. Thus, cold stimulation tests under infrared thermography may contribute to the early screening of diabetic peripheral neuropathy in future.

A promising electrochemical sensor based on PVP-induced shape control of a hydrothermally synthesized layered structured vanadium disulfide for the sensitive detection of a sulfamethoxazole antibiotic.

The presence of sulfamethoxazole (SMX) in natural waters has become a significant concern recently because of its detrimental effects on human health and the ecological environment. To address this issue, it is of utmost urgency to develop a reliable method that can determine SMX at ultra-low levels. In our research, we utilized PVP-induced shape control of a hydrothermal synthesis method to fabricate layer-like structured VS2, and employed it as an electrode modification material to prepare an electrochemical sensor for the sensitive determination of SMX. Thus, our prepared VS2 electrodes exhibited a linear range of 0.06-10.0 µM and a limit of detection (LOD) as low as 47.0 nM (S/N = 3) towards SMX detection. Additionally, the electrochemical sensor presented good agreement with the HPLC method, and afforded perfect recovery results (97.4-106.8%) in the practical analysis. The results validated the detection accuracy of VS2 electrodes, and demonstrated their successful applicability toward the sensitive determination of SMX in natural waters. In conclusion, this research provides a promising approach for the development of electrochemical sensors based on VS2 composite materials.

Exploration of rich-club reorganization in facial synkinesis: insights from structural and functional brain network analysis.

Facial palsy therapies based on cortical plasticity are in development, but facial synkinesis progress is limited. Studying neural plasticity characteristics, especially network organization and its constitutive elements (nodes/edges), is the key to overcome the bottleneck. We studied 55 participants (33 facial synkinesis patients, 22 healthy controls) with clinical assessments, functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI). We analyzed rich-club organization and metrics of structural brain networks (rich-club coefficients, strength, degree, density, and efficiency). Functional brain network metrics, including functional connectivity and its coupling with the structural network, were also computed. Patients displayed reduced strength and density of rich-club nodes and edges, as well as decreased global efficiency. All nodes exhibited decreased nodal efficiency in patients. Patients had significantly increased functional connectivity and decreased structural-functional coupling strength in rich-club nodes, rich-club edges, and feeder edges. Our study indicates that facial synkinesis patients have weakened structural connections but enhanced functional transmission from rich-club nodes. The loss of connections and efficiency in structural network may trigger compensatory increases in functional connectivity of rich-club nodes. Two potential biomarkers, rich-club edge density and structural-functional coupling strength, may serve as indicators of disease outcome. These findings provide valuable insights into synkinesis mechanisms and offer potential targets for cortical intervention.

Jianpi-Tiaoqi decoction inhibits tumour proliferation and lung metastasis in tumour-bearing mice with triple-negative breast cancer.

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.

Period measurement of a periodic structure by using a heterodyne grating interferometer.

This paper proposes an alternative method for grating period measurement based on heterodyne grating interferometry. The optical configurations for measuring the period of reflection/transmission gratings were demonstrated, and four commercially available gratings were used to evaluate the effectiveness of the proposed method. Based on the phase-lock technique, the grating period could be obtained immediately through the phase wrapped/unwrapped process. Under precise measurement conditions, the grating period measurement error of the proposed method was better than 1 nm, and the grating period difference between product specifications was less than 1%. In addition, the measurement results of the proposed method also exhibited high similarity with optical microscopy measurements.

First Report of Ilyonectria coprosmae Causing Root Rot of Bletilla striata in Yunnan province of China.

Bletilla striata is a valuable medicine in China, belonging to the Orchidaceae family, and is used for treating various ailments such as hemoptysis, pyocutaneous disease, and anal fissure by preventing blood flow, reducing swelling, and promoting granulation. In June 2022, a disease with symptoms similar to root rot was observed on B. striata in the pineland (the area was 0.4 hectare) of Lancang County (22°48'17" N, 99°46'58"22 E), Yunnan Province, China. The root rot incidence rate reached 16% (Table S1). The root rot incidence was calculated as follows: root rot incidence (%) = (number of root rot seedlings/total number of seedlings investigated) × 100. In May 2023, the similar symptoms were observed in the field, and the disease incidence was 17% (Table S1). Initially, there were no obvious symptoms on the leaves. Subsequently, the leaves wilted and brown spots appeared. Later, the entire leaf browned, withered and eventually died (Fig. S1A, B). The roots were brown and the browning spread from the root edge to the center, causing vascular bundle browning and dead lignified fibers in the cortex (Fig. S1C, D). To isolate the causal pathogen, 20 symptomatic root tissues were collected from 20 plants. Cutting the diseased tissues into small pieces (0.5 × 0.5 cm). After surface sterilization (30s with 75% ethanol and 3 min with 2% sodium hypochlorite, rinsed three times with sterile water), the disinfected root tissues were plated onto potato dextrose agar (PDA) and incubated at 25℃ for 4 to 6 days with 12 h light/dark photoperiod. A total of 10 single-spore isolates with similar morphology and conidial characteristics were obtained. one representative isolate BJG6 was selected for identification and further study. The fungal colony was reddish-brown or orange-white on PDA after 8 days of incubation at 25℃. The mycelium was like carpet or cotton, and the edge of colony was uniform (Fig. S1E). Large conidia were formed on simple conidial peduncles (Fig. S1F, G). The conidia with 1~3 septates and 1 mostly, with cylindrical shapes and narrow tops but sharp bases (Fig. S1H-J). Conidia with 1 septate measured as 5.5 (4.3-6.7) × 20.7 (16.0-25.4) µm (n=30), while those with 2 septates measured as 6.6 (5.8-7.4) × 26.5 (21.7-31.3) µm (n=30), and those with 3 septates was 6.9 (6.2-7.8) × 31.8 (29.3-34.3) µm (n=30). Ellipsoidal microconidia could be formed on conidiophore and measured as 2.4 (1.9-2.9) × 4.9 (5.9-3.9) µm to 2.7 (2.2-3.2) × 5.4 (4.3-6.5) µm (n=30). Spherical or subspherical chlamydospores were produced on low-nutrient agar, with an average size of 5.8(5.0-6.6) µm×5.3 (4.4-6.2) µm (n=30) (Fig. S1K, L). According to the morphology and conidial features, the pathogen was consistent with the description of Ilyonectria coprosmae (Cabral et al. 2012). The total genomic DNA was extracted, and primer pairs ITS4/ITS5 were used to amplify and sequence the rDNA-ITS region (ITS1-5.8 S rRNA-ITS2 gene regions) (White et al. 1990). The sequences were deposited in GenBank (SUB13905750 for ITS). BLAST searches revealed BJG6 showed 98% homology with corresponding sequences of Ilyonectria coprosmae in GenBank (JF735260). A phylogenetic tree (MEGA 7.0) was constructed using maximum-likelihood methods (Fig. S2). To identify pathogenicity, a cultured medium in a size of 6mm containing isolate BJG6 was inoculated onto ten healthy roots of B. striata, PDA plugs alone were used as the uninoculated controls. All samples were placed in a dark inoculation chamber at 25℃. The pathogenicity test was replicated three times. After two weeks, all inoculated roots appeared similar symptoms identical to those observed on field plants (Fig. S1M, N-P), while control plants remained healthy (Fig. S1Q, R). The same pathogenic fungus was reisolated from the symptomatic root rot, and the characteristics of colony and conidia were the same as the original isolates (Fig. S1S, T). These results confirmed I. coprosmae as the causal pathogen of root rot disease on B. striata in China by Koch's postulates tests for the first time. Further exploration should be conducted to understand the occurrence and migration of this disease, so as to develop specific and efficient disease management strategies in the future.

Advancements in Polymer-Assisted Layer-by-Layer Fabrication of Wearable Sensors for Health Monitoring.

Recent advancements in polymer-assisted layer-by-layer (LbL) fabrication have revolutionized the development of wearable sensors for health monitoring. LbL self-assembly has emerged as a powerful and versatile technique for creating conformal, flexible, and multi-functional films on various substrates, making it particularly suitable for fabricating wearable sensors. The incorporation of polymers, both natural and synthetic, has played a crucial role in enhancing the performance, stability, and biocompatibility of these sensors. This review provides a comprehensive overview of the principles of LbL self-assembly, the role of polymers in sensor fabrication, and the various types of LbL-fabricated wearable sensors for physical, chemical, and biological sensing. The applications of these sensors in continuous health monitoring, disease diagnosis, and management are discussed in detail, highlighting their potential to revolutionize personalized healthcare. Despite significant progress, challenges related to long-term stability, biocompatibility, data acquisition, and large-scale manufacturing are still to be addressed, providing insights into future research directions. With continued advancements in polymer-assisted LbL fabrication and related fields, wearable sensors are poised to improve the quality of life for individuals worldwide.

Prognostic impact and immunotherapeutic implications of NETosis-related gene signature in gastric cancer patients.

The role of NETosis and its related molecules remains unclear in gastric cancer. The data used in this study was directly downloaded from the Cancer Genome Atlas (TCGA) database. All analysis and plots are completed in R software using diverse R packages. In our study, we collected the list of NETosis-related genes from previous publications. Based on the list and expression profile of gastric cancer patients from the TCGA database, we identified the NETosis-related genes significantly correlated with patients survival. Then, CLEC6A, BST1 and TLR7 were identified through LASSO regression and multivariate Cox regression analysis for prognosis model construction. This prognosis model showed great predictive efficiency in both training and validation cohorts. We noticed that the high-risk patients might have a worse survival performance. Next, we explored the biological enrichment difference between high- and low-risk patients and found that many carcinogenic pathways were upregulated in the high-risk patients. Meanwhile, we investigated the genomic instability, mutation burden and immune microenvironment difference between high- and low-risk patients. Moreover, we noticed that low-risk patients were more sensitive to immunotherapy (85.95% vs. 56.22%). High-risk patients were more sensitive to some small molecules compounds like camptothecin_1003, cisplatin_1005, cytarabine_1006, nutlin-3a (-)_1047, gemcitabine_1190, WZ4003_1614, selumetinib_1736 and mitoxantrone_1810. In summary, our study comprehensively explored the role of NETosis-related genes in gastric cancer, which can provide direction for relevant studies.

Charge Recombination Deceleration by Lateral Transfer of Electrons in Dye-Sensitized NiO Photocathode.

Control of charge separation and recombination is critical for dye-sensitized solar cells and photoelectrochemical cells, and for p-type cells, the latter process limits their photovoltaic performance. We speculated that the lateral electron hopping between dyes on a p-type semiconductor surface can effectively separate electrons and holes in space and retard recombination. Thus, device designs where lateral electron hopping is promoted can lead to enhanced cell performance. Herein, we present an indirect proof by involving a second dye to monitor the effect of electron hopping after hole injection into the semiconductor. In mesoporous NiO films sensitized with peryleneimide (PMI) or naphthalene diimide (NDI) dyes, dye excitation led to ultrafast hole injection into NiO from either excited PMI* (τ < 200 fs) or NDI* (τ = 1.2 ps). In cosensitized films, surface electron transfer from PMI- to NDI was rapid (τ = 24 ps). Interestingly, the subsequent charge recombination (ps-µs) with NiO holes was much slower when NDI- was generated by electron transfer from PMI- than when NDI was excited directly. We therefore indicate that the charge recombination is slowed down after the charge hopping from the original PMI sites to the NDI sites. The experimental results supported our hypothesis and revealed important information on the charge carrier kinetics for the dye-sensitized NiO photoelectrode system.

Global Analysis of Aggregation Profiles of Three Kinds of Immuno-Oncology mAb Drug Products Using Flow Cytometry.

Accurately quantifying the protein particles in both subvisible (1-100 µm) and submicron (≤1 µm) ranges remains a prominent challenge in the development and manufacturing of protein drugs. Due to the limitation of the sensitivity, resolution, or quantification level of various measurement systems, some instruments may not provide count information, while others can only count particles in a limited size range. Moreover, the reported concentrations of protein particles commonly have significant discrepancies owing to different methodological dynamic ranges and the detection efficiency of these analytical tools. Therefore, it is extremely difficult to accurately and comparably quantify protein particles within the desired size range at one time. To develop an efficient protein aggregation measurement method that can span the entire range of interest, we established, in this study, a single particle-sizing/counting method based on our highly sensitive lab-built flow cytometry (FCM) system. The performance of this method was assessed, and its capability of identifying and counting microspheres between 0.2 and 25 µm was demonstrated. It was also used to characterize and quantify both subvisible and submicron particles in three kinds of top-selling immuno-oncology antibody drugs and their lab-produced counterparts. These assessment and measurement results suggest that there may be a role for an enhanced FCM system as an efficient investigative tool for characterizing and learning the molecular aggregation behavior, stability, or safety risk of protein products.

Nucleic Acid Amplification by Template-Dominated Click Chemistry for Ultrasensitive DNA/RNA Detection on an Electrochemical Readout Platform.

As an enzyme-free exponential nucleic acid amplification method, the click chemistry-mediated ligation chain reaction (ccLCR) has shown great prospects in the molecular diagnosis. However, the current optics-based ccLCR is challenged by remarkable nonspecific amplification, severely hindering its future application. This study demonstrated that the severe nonspecific amplification was generated probably due to high random collision in the high DNA probe concentration (µM level). To solve this hurdle, a nucleic acid template-dominated ccLCR was constructed using nM-level DNA probes and read on an electrochemical platform (cc-eLCR). Under the optimal conditions, the proposed cc-eLCR detected a low-level nucleic acid target (1 fM) with a single-base resolution. Furthermore, this assay was applied to detect the target of interest in cell extracts with a satisfactory result. The proposed cc-eLCR offers huge possibility for click chemistry-mediated enzyme-free exponential nucleic acid amplification in the application of medical diagnosis and biomedical research.

Inserting Single-Atom Zn by Tannic Acid Confinement To Regulate the Selectivity of Pd Nanocatalysts for Hydrogenation Reactions.

Precisely controlling the selectivity of nanocatalysts has always been a hot topic in heterogeneous catalysis but remains difficult owing to their complex and inhomogeneous catalytic sites. Herein, an effective strategy to regulate the chemoselectivity of Pd nanocatalysts for selective hydrogenation reactions by inserting single-atom Zn into Pd nanoparticles is reported. Taking advantage of the tannic acid coating-confinement strategy, small-sized Pd nanoparticles with inserted single-atom Zn are obtained on the O-doped carbon-coated alumina. Compared with the pure Pd nanocatalyst, the Pd nanocatalyst with single-atom Zn insertion exhibits prominent selectivity for the hydrogenation of p-iodonitrobenzene to afford the hydrodeiodination product instead of nitro hydrogenation ones. Further computational studies reveal that the single-atom Zn on Pd nanoparticles strengthens the adsorption of the nitro group to avoid its reduction and increases the d-band center of Pd atoms to facilitate the reduction of the iodo group, which leads to enhanced selectivity. This work provides new guidelines to tune the selectivity of nanocatalysts with guest single-atom sites.