Transcription factor GmAlfin09 regulates endoplasmic reticulum stress in soybean via peroxidase GmPRDX6.

Soybean (Glycine max [L.] Merr.) is a valuable oil crop but is also highly susceptible to environmental stress. Thus, developing approaches to enhance soybean stress resistance is vital to soybean yield improvement. In previous studies, transcription factor Alfin has been shown to serve as an epigenetic regulator of plant growth and development. However, no studies on Alfin have yet been reported in soybean. In this study, the endoplasmic reticulum (ER) stress- and reactive oxygen species (ROS)-related GmAlfin09 was identified. Screening of genes co-expressed with GmAlfin09 unexpectedly led to the identification of soybean peroxidase 6 (GmPRDX6). Further analyses revealed that both GmAlfin09 and GmPRDX6 were responsive to ER stress, with GmPRDX6 localizing to the ER under stress. Promoter binding experiments confirmed the ability of GmAlfin09 to bind to the GmPRDX6 promoter directly. When GmAlfin09 and GmPRDX6 were overexpressed in soybean, enhanced ER stress resistance and decreased ROS levels were observed. Together, these findings suggest that GmAlfin09 promotes the upregulation of GmPRDX6, and GmPRDX6 subsequently localizes to the ER, reduces ROS levels, promotes ER homeostasis, and ensures the normal growth of soybean even under ER stress. This study highlights a vital target gene for future molecular breeding of stress-resistant soybean lines.

Diffusion-based deep learning method for augmenting ultrastructural imaging and volume electron microscopy.

Electron microscopy (EM) revolutionized the way to visualize cellular ultrastructure. Volume EM (vEM) has further broadened its three-dimensional nanoscale imaging capacity. However, intrinsic trade-offs between imaging speed and quality of EM restrict the attainable imaging area and volume. Isotropic imaging with vEM for large biological volumes remains unachievable. Here, we developed EMDiffuse, a suite of algorithms designed to enhance EM and vEM capabilities, leveraging the cutting-edge image generation diffusion model. EMDiffuse generates realistic predictions with high resolution ultrastructural details and exhibits robust transferability by taking only one pair of images of 3 megapixels to fine-tune in denoising and super-resolution tasks. EMDiffuse also demonstrated proficiency in the isotropic vEM reconstruction task, generating isotropic volume even in the absence of isotropic training data. We demonstrated the robustness of EMDiffuse by generating isotropic volumes from seven public datasets obtained from different vEM techniques and instruments. The generated isotropic volume enables accurate three-dimensional nanoscale ultrastructure analysis. EMDiffuse also features self-assessment functionalities on predictions' reliability. We envision EMDiffuse to pave the way for investigations of the intricate subcellular nanoscale ultrastructure within large volumes of biological systems.

Engineering natural microbiomes toward enhanced bioremediation by microbiome modeling.

Engineering natural microbiomes for biotechnological applications remains challenging, as metabolic interactions within microbiomes are largely unknown, and practical principles and tools for microbiome engineering are still lacking. Here, we present a combinatory top-down and bottom-up framework to engineer natural microbiomes for the construction of function-enhanced synthetic microbiomes. We show that application of herbicide and herbicide-degrader inoculation drives a convergent succession of different natural microbiomes toward functional microbiomes (e.g., enhanced bioremediation of herbicide-contaminated soils). We develop a metabolic modeling pipeline, SuperCC, that can be used to document metabolic interactions within microbiomes and to simulate the performances of different microbiomes. Using SuperCC, we construct bioremediation-enhanced synthetic microbiomes based on 18 keystone species identified from natural microbiomes. Our results highlight the importance of metabolic interactions in shaping microbiome functions and provide practical guidance for engineering natural microbiomes.

Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

GASZ is indispensable for gametogenesis in the silkworm, Bombyx mori.

The prominent role of the P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway in animals is to silence transposable elements and maintain genome stability, ensuring proper gametogenesis in gonads. GASZ (Germ cell protein with Ankyrin repeats, Sterile alpha motif, and leucine Zipper) is an evolutionarily conserved protein located on the outer mitochondrial membrane of germ cells and plays vital roles in the piRNA pathway and spermatogenesis in mammals. In the model insect Drosophila melanogaster, GASZ is essential for piRNA biogenesis and oogenesis, whereas its biological functions in non-drosophilid insects are still unknown. Here, we describe a comprehensive investigation of GASZ functions in the silkworm, Bombyx mori, a lepidopteran model insect, by using a binary transgenic CRISPR/Cas9 system. The BmGASZ mutation did not affect growth and development, but led to sterility in both males and females. Eupyrene sperm bundles of mutant males exhibited developmental defects, while the apyrene sperm bundles were normal, which were further confirmed through double copulation experiments with sex-lethal mutants, which males possess functional eupyrene sperm and abnormal apyrene sperm. In female mutant moths, ovarioles were severely degenerated and the eggs in ovarioles were deformed compared with that of wild type (WT). Further RNA-seq and RT-qPCR analysis revealed that amounts of piRNAs and transposon expression were dysregulated in gonads of mutants. In summary, this study has demonstrated vital roles of BmGASZ in gametogenesis through regulating the piRNA pathway in B. mori.

Decitabine as epigenetic priming with CLAG induce improved outcome of relapsed or refractory acute myeloid leukemia in children.

BACKGROUND: Decitabine (DAC), a DNA methyltransferase inhibitor, has shown efficacy combined with chemotherapy for relapsed or refractory (R/R) acute myeloid leukemia (AML) in adults, but less is known about its efficacy in children. Accordingly, we conducted a study which involved a priming regimen consisting of DAC with cladribine, cytarabine, and granulocyte-stimulating factor (DAC-CLAG) and compared the efficacy and safety of this regimen with CLAG alone. METHODS: A total of 39 R/R AML children who received the CLAG or DAC-CLAG regimen in Shanghai Children's Hospital were retrospectively enrolled in this non-randomized study. These regimens were studied sequentially over time. Twenty-two patients received CLAG from 2015, while 17 patients were administered epigenetic priming with DAC before CLAG from 2020. Patients were subsequently bridged to stem cell transplantation (SCT) or consolidation chemotherapy. Complete remission (CR) and adverse effects were analyzed by Fisher's exact test, and survival was analyzed by the Kaplan-Meier method. RESULTS: DAC-CLAG conferred a numerically higher CR compared to CLAG (70.59% vs 63.64%; P = 0.740). High CR rates occurred in patients with good cytogenetics (P = 0.029) and prior induction without cladribine (P = 0.099). The 1-year event-free survival (EFS) was 64.71% ± 11.59% and 63.31% ± 10.35% in the DAC-CLAG and CLAG group (P = 0.595), and 1-year overall survival (OS) was 81.45% ± 9.72% and 77.01% ± 9.04%, respectively (P = 0.265). The 1-year OS and EFS after SCT were higher in the DAC-CLAG than in the CLAG cohort (100% vs 92.31% ± 7.39%, P = 0.072; 92.31% ± 7.39% vs 85.71% ± 9.35%, P = 0.158). Univariate analysis revealed that a good prognosis included good cytogenetics (P = 0.002), non-complex karyotype (P = 0.056), CR on reinduction (P < 0.0001), and bridging to SCT (P = 0.0007). Use of a hypomethylating agent (P = 0.049) and bridging to SCT (P = 0.011) were independent prognostic factors. Grade 3/4 hematologic toxicity and infection were the main adverse events. CONCLUSIONS: DAC prior to the CLAG regimen improved remission in pediatric R/R AML, and was feasible and well tolerated. CLAG ± DAC as a salvage therapy prior to SCT induced improved survival.

Corrigendum: Tpr deficiency disrupts erythroid maturation with impaired chromatin condensation in zebrafish embryogenesis.

[This corrects the article DOI: 10.3389/fcell.2021.709923.].

Recent Progress of Low-Dimensional Metal-Organic Frameworks for Aqueous Zinc-Based Batteries.

Aqueous zinc-based batteries (AZBs) are promising energy storage solutions with remarkable safety, abundant Zn reserve, cost-effectiveness, and relatively high energy density. However, AZBs still face challenges such as anode dendrite formation that reduces cycling stability and limited cathode capacity. Recently, low-dimensional metal-organic frameworks (LD MOFs) and their derivatives have emerged as promising candidates for improving the electrochemical performance of AZBs owing to their unique morphologies, high structure tunability, high surface areas, and high porosity. However, clear guidelines for developing LD MOF-based materials for high-performance AZBs are scarce. In this review, the recent progress of LD MOF-based materials for AZBs is critically examined. The typical synthesis methods and structural design strategies for improving the electrochemical performance of LD MOF-based materials for AZBs are first introduced. The recent noteworthy research achievements are systematically discussed and categorized based on their applications in different AZB components, including cathodes, anodes, separators, and electrolytes. Finally, the limitations are addressed and the future perspectives are outlined for LD MOFs and their derivatives in AZB applications. This review provides clear guidance for designing high-performance LD MOF-based materials for advanced AZBs.

Energy-Efficiency Co-Production of Benzoquinone and H2 by Resourcing Waste Phenol in a Hybrid Alkali/Acid Flow Cell.

In both the manufacturing and chemical industries, benzoquinone is a crucial chemical product. A perfect and economical method for making benzoquinone is the electrochemical oxidation of phenol, thanks to the traditional thermal catalytic oxidation of phenol process requires high cost, serious pollution and harsh reaction conditions. Here, a unique heterostructure electrocatalyst on nickel foam (NF) consisting of nickel sulfide and nickel oxide (Ni9S8-Ni15O16/NF) was produced, and this catalyst exhibited a low overpotential (1.35 V vs. RHE) and prominent selectivity (99%) for electrochemical phenol oxidation reaction (EOP). Ni9S8-Ni15O16/NF is beneficial for lowering the reaction energy barrier and boosting reactivity in the EOP process according to density functional theory (DFT) calculations. Additionally, an alkali/acid hybrid flow cell was successfully established by connecting Ni9S8-Ni15O16/NF and commercial RuIr/Ti in series to catalyze phenol oxidation in an alkaline medium and hydrogen evolution in an acid medium, respectively. A cell voltage of only 0.60 V was applied to produce a current density of 10 mA cm-2. Meanwhile, the system continued to operate at 0.90 V for 12 days, showing remarkable long-term stability. The unique configuration of the acid-base hybrid flow cell electrolyzer provides valuable guidance for the efficient and environmentally friendly electrooxidation of phenol to benzoquinone.

Concentration-QTc Modeling of the DPP-4 Inhibitor HSK7653 in a First-in-Human Study of Chinese Healthy Volunteers.

Cofrogliptin (HSK7653) is a long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus with a twice-monthly dosing regimen. This study included 62 participants (48 without food effect, 14 with food effect) receiving single doses of HSK7653 (5, 10, 25, 50, 100, and 150 mg) or placebo. Pharmacokinetic samples were collected over 24 hours postdosing and sampling times are aligned with 12-lead electrocardiograms (ECGs) which were derived from continuous ECG recordings. For the concentration-QT interval corrected for heart rate (C-QTc) analysis, we used linear mixed-effects modeling to characterize the correlation between plasma concentrations of HSK7653 and the change from baseline in the QT interval which was corrected by Fridericia's formula (ΔQTcF). The result showed that a placebo-corrected Fridericia corrected QT interval (ΔΔQTcF) prolongation higher than 10 milliseconds is unlikely at the mean maximum observed concentration (Cmax) (411 ng/mL) associated with the recommended therapeutic doses (25 mg twice-monthly), even at the highest supratherapeutic concentration (2425 ng/mL). Thus, HSK7653 does not significantly affect QT prolongation at either recommended doses or the highest supratherapeutic concentration.

Diabetes mellitus and intervertebral disc degeneration: a meta-analysis.

BACKGROUND: Diabetes mellitus (DM) has been related to a higher risk of intervertebral disc degeneration (IVDD). However, the previous studies showed inconsistent results. We performed a systematic review and meta-analysis to comprehensively investigate the association between DM and IVDD in adult population. METHODS: Observational studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. RESULTS: Eleven observational studies involving 2881170 adults were included. Among them, 1211880 had DM. Compared to those with normoglycemia, patients with DM were associated with a higher odds ratio (OR) of IVDD (OR: 1.68, 95% confidence interval [CI]: 1.24 to 2.29, p < 0.001; I2= 98%). Further sensitivity analysis excluding database studies with IVDD diagnosed via International Classification of Disease codes showed consistent results (OR: 1.47, 95% CI: 1.06 to 2.02, p = 0.02) with no statistical heterogeneity (I2 = 0%). Subgroup analyses showed a stronger association between DM and IVDD in cohort studies than that in cross-sectional studies, in studies evaluating overall IVDD than that evaluating lumbar disc degeneration, and in studies that adjusted age and body mass index (BMI) than that did not (p for subgroup differences all < 0.05). Subgroup analyses according to study country and quality score did not significantly affect the association. CONCLUSIONS: DM may be associated with IVDD in adult population, which seems to be independent of age and BMI.

Antimicrobial resistance and population genomics of emerging multidrug-resistant Salmonella 4,[5],12:i:- in Guangdong, China.

Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.

Longitudinal Extension of Double π-Helix Enables Near-Infrared Amplified Dissymmetry and Chiroptical Response.

Near-infrared (NIR) circularly polarized light absorbing or emitting holds great promise for highly sensitive and precise bioimaging, biosensing, and photodetectors. Aiming at designing NIR chiral molecular systems with amplified dissymmetry and robust chiroptical response, herein, we present a series of double π-helical dimers with longitudinally extended π-entwined substructures via Ullmann or Yamamoto homocoupling reactions. Circular dichroism (CD) spectra revealed an approximate linear bathochromic shift with the rising number of naphthalene subunits, indicating a red to NIR chiroptical response. Particularly, the terrylene diimide-entwined dimers exhibited the strongest CD intensities, with the maximal |Δε| reaching up to 393 M-1 cm-1 at 666 nm for th-TDI[2]; and a record-high chiroptical response (|ΔΔε|) between the neutral and dianionic species of 520 M-1 cm-1 at 833 nm for th-TDI[2]Cl was achieved upon further reduction to its dianionic state. Time-dependent density functional theory (TDDFT) calculations suggested that the pronounced intensification of the CD spectra originated from a simultaneous enhancement of both electric (µ) and magnetic (m) transition dipole moments, ultimately leading to an overall increase in the rotatory strength (R). Notably, the circularly polarized luminescence (CPL) brightness (BCPL) reached 77 M-1 cm-1 for th-TDI[2]Cl, among the highest values reported for NIR-CPL emitters. Furthermore, all chiral dianions exhibited excellent air stability under ambient conditions with half-life times of up to 10 days in N-methylpyrrolidone (NMP), which is significant for future biological applications and chiroptic switches.

Earth-abundant Zn-dipyrrin chromophores for efficient CO2 photoreduction.

The development of strong sensitizing and Earth-abundant antenna molecules is highly desirable for CO2 reduction through artificial photosynthesis. Herein, a library of Zn-dipyrrin complexes (Z-1-Z-6) are rationally designed via precisely controlling their molecular configuration to optimize strong sensitizing Earth-abundant photosensitizers. Upon visible-light excitation, their special geometry enables intramolecular charge transfer to induce a charge-transfer state, which was first demonstrated to accept electrons from electron donors. The resulting long-lived reduced photosensitizer was confirmed to trigger consecutive intermolecular electron transfers for boosting CO2-to-CO conversion. Remarkably, the Earth-abundant catalytic system with Z-6 and Fe-catalyst exhibits outstanding performance with a turnover number of >20 000 and 29.7% quantum yield, representing excellent catalytic performance among the molecular catalytic systems and highly superior to that of noble-metal photosensitizer Ir(ppy)2(bpy)+ under similar conditions. Experimental and theoretical investigations comprehensively unveil the structure-activity relationship, opening up a new horizon for the development of Earth-abundant strong sensitizing chromophores for boosting artificial photosynthesis.

A novel microfluidic chip integrated with Pt micro-thermometer for temperature measurement at the single-cell level.

Noninvasive and sensitive thermometry of a single cell during the normal physiological process is crucial for analyzing fundamental cellular metabolism and applications to cancer treatment. However, current thermometers generally sense the average temperature variation for many cells, thereby failing to obtain real-time and continuous data of an individual cell. In this study, we employed platinum (Pt) electrodes to construct an integrated microfluidic chip as a single-cell thermometer. The single-cell isolation unit in the microchip consisted of a main channel, which was connected to the inlet and outlet of a single-cell capture funnel. A single cell can be trapped in the funnel and the remaining cells can bypass and flow along the main channel to the outlet. The best capture ratio of a single MCF7 cell at a single-cell isolation unit was 90 % under optimal condition. The thermometer in the micro-chip had a temperature resolution of 0.007 °C and showed a good linear relationship in the range of 20-40 °C (R2 = 0.9999). Slight temperature increment of different single tumor cell (MCF7 cell, H1975 cell, and HepG2 cell) cultured on the chip was continuously recorded under normal physiological condition. In addition, the temperature variation of single MCF7 cell in-situ after exposure to a stimulus (4 % paraformaldehyde treatment) was also monitored, showing an amplitude of temperature fluctuations gradually decreased over time. Taken together, this integrated microchip is a practical tool for detecting the change in the temperature of a single cell in real-time, thereby offering valuable information for the drug screening, diagnosis, and treatment of cancer.

CD20highCD138low tumor-infiltrating lymphocytes predominantly related to cytokine‒cytokine receptor interactions are associated with favorable outcomes in neuroblastoma patients.

Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P < 0.001; EFS: P < 0.001) in the training dataset, whereas CD138 high expression was associated with poor OS and EFS (OS: P < 0.001; EFS: P < 0.001) in both the training and validation datasets. Accordingly, a combined pattern of CD20 and CD138 expression was developed, whereby neuroblastoma patients with CD20highCD138low expression had a consistently favorable OS and EFS compared with those with CD20lowCD138high expression in both the training and validation cohorts (P < 0.0001 and P < 0.01, respectively). Examination of potential molecular functions revealed that signaling pathways, including cytokine‒cytokine receptor interactions, chemokine, and the NF-kappa B signaling pathways, were involved. Differentially expressed genes, such as BMP7, IL7R, BIRC3, CCR7, CXCR5, CCL21, and CCL19, predominantly play important roles in predicting the survival of neuroblastoma patients. Our study proposes that a new combination of CD20 and CD138 signatures is associated with neuroblastoma patient survival. The related signaling pathways reflect the close associations among the number of TILs, cytokine abundance and patient outcomes and provide therapeutic insights into neuroblastoma.

Management of Triplet States in Modified Mononuclear Ruthenium(II) Complexes for Enhanced Photocatalysis.

Controlling the interplay between relaxation and charge/energy transfer processes in the excited states of photocatalysts is crucial for the performance of artificial photosynthesis. Metal-to-ligand charge-transfer triplet states (3MLCT*) of ruthenium(II) complexes are broadly implemented for photocatalysis, but an effective means of managing the triplets for enhanced photocatalysis has been lacking. Herein, We proposed a strategy to considerably prolong the triplet excited-state lifetime by decorating a ruthenium(II) phosphine complex (RuP-1) with pendent polyaromatic hydrocarbons (PAHs). Systematic studies demonstrate that in RuP-4 decorated with anthracene, sub-picosecond electron transfer from anthracene to 3MLCT* leads to a charge-separated state that can mediate the formation of the intra-ligand triplet state (3IL) of anthracene, resulting in an exceptionally long excited-state up to several milliseconds. This triplet management strategy enables impressive photocatalytic reduction of CO2 to CO with a turnover number (TON) of 404, an optimized quantum yield of 43% and 100% selectivity, which is the highest reported performance for mononuclear photocatalysts without additional photosensitizers. RuP-4 also catalyzes photochemical hydrogen generation under argon. This work opens up an avenue for regulating the excited-state charge/energy flow for the development of long-lived 3IL multi-functional mononuclear photocatalysts to boost artificial photosynthesis.

Artificial intelligence enables precision diagnosis of cervical cytology grades and cervical cancer.

Cervical cancer is a significant global health issue, its prevalence and prognosis highlighting the importance of early screening for effective prevention. This research aimed to create and validate an artificial intelligence cervical cancer screening (AICCS) system for grading cervical cytology. The AICCS system was trained and validated using various datasets, including retrospective, prospective, and randomized observational trial data, involving a total of 16,056 participants. It utilized two artificial intelligence (AI) models: one for detecting cells at the patch-level and another for classifying whole-slide image (WSIs). The AICCS consistently showed high accuracy in predicting cytology grades across different datasets. In the prospective assessment, it achieved an area under curve (AUC) of 0.947, a sensitivity of 0.946, a specificity of 0.890, and an accuracy of 0.892. Remarkably, the randomized observational trial revealed that the AICCS-assisted cytopathologists had a significantly higher AUC, specificity, and accuracy than cytopathologists alone, with a notable 13.3% enhancement in sensitivity. Thus, AICCS holds promise as an additional tool for accurate and efficient cervical cancer screening.

Pd/NHC catalyzed reduction and coupling of nitroaromatics for the synthesis of diarylamines.

Herein, we report a one-pot approach to diarylamines through the reductive homocoupling of nitroaromatics, employing triethylsilane as the reducing agent and Pd/NHC as the catalyst. This method enables nitroaromatics to serve both as electrophilic reagents and as precursors of nucleophilic reagents, allowing for the direct preparation of diarylamines without the need to isolate aromatic primary amines.

Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis.

BACKGROUND: Colon cancer is acknowledged as one of the most common malignancies worldwide, ranking third in United States regarding incidence and mortality. Notably, approximately 40% of colon cancer cases harbor oncogenic KRAS mutations, resulting in the continuous activation of epidermal growth factor receptor signaling. AIM: To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance. METHODS: Weighted gene co-expression network analysis, in combination with additional bioinformatics analysis, were conducted to screen the key factors driving the progression of KRAS mutant colon cancer. Meanwhile, various in vitro experiments were also conducted to explore the biological function of transglutaminase 2 (TGM2). RESULTS: Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival. Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer. Additionally, biological roles of the key gene TGM2 was also assessed, suggesting that the downregulation of TGM2 attenuated the proliferation, invasion, and migration of the KRAS mutant colon cancer cell line. CONCLUSION: This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer. This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.