BACKGROUND: Spatial transcriptomics (ST) is advancing our understanding of complex tissues and organisms. However, building a robust clustering algorithm to define spatially coherent regions in a single tissue slice and aligning or integrating multiple tissue slices originating from diverse sources for essential downstream analyses remains challenging. Numerous clustering, alignment, and integration methods have been specifically designed for ST data by leveraging its spatial information. The absence of comprehensive benchmark studies complicates the selection of methods and future method development.
RESULTS: In this study, we systematically benchmark a variety of state-of-the-art algorithms with a wide range of real and simulated datasets of varying sizes, technologies, species, and complexity. We analyze the strengths and weaknesses of each method using diverse quantitative and qualitative metrics and analyses, including eight metrics for spatial clustering accuracy and contiguity, uniform manifold approximation and projection visualization, layer-wise and spot-to-spot alignment accuracy, and 3D reconstruction, which are designed to assess method performance as well as data quality. The code used for evaluation is available on our GitHub. Additionally, we provide online notebook tutorials and documentation to facilitate the reproduction of all benchmarking results and to support the study of new methods and new datasets.
CONCLUSIONS: Our analyses lead to comprehensive recommendations that cover multiple aspects, helping users to select optimal tools for their specific needs and guide future method development.

UNASSIGNED: Brucellosis of the central nervous system (CNS) is rare and frequently fatal, often being overlooked or misdiagnosed.
UNASSIGNED: In April 2023, the Jinan CDC identified a case of CNS brucellosis in a 54-year-old woman through cerebrospinal fluid (CSF) culture. Upon confirming the diagnosis of brucellosis, the Jinan CDC immediately informed Qilu Hospital of Shandong University, to which the patient had been transferred, and she was subsequently tracked and successfully treated.
UNASSIGNED: The successful outcome can be attributed to the effective integration of a system that facilitated coordinated and collaborative actions between public health services and clinical institutions.

Graphene has tremendous potential in future electronics due to its superior force, electrical, and thermal properties. However, the development of graphene devices is limited by its complex, high-cost, and low-efficiency preparation process. This study proposes a novel laser bidirectional graphene printing (LBGP) process for the large-scale preparation of patterned graphene films. In LBGP, a sandwich sample composed of a thermoplastic elastomer (TPE) substrate, carbon precursor powder, and a glass cover is irradiated by a nanosecond pulsed laser. The laser photothermal effect converts the carbon precursor into graphene, with partial graphene sheets deposited directly on the TPE substrate and the remaining transferred to the glass cover via a laser-induced plasma plume. This method simultaneously prepares two face-to-face graphene films in a single laser irradiation, integrating synthesis, transfer, and patterning. The resulting graphene patterns demonstrate good performance in flexible pressure sensing and Joule heating, showcasing high sensitivity (7.7 kPa-1), fast response (37 ms), and good cycling stability (2000 cycles) for sensors, and high heating rate (1 °C s-1) and long-term stability (3000 s) for heaters. It is believed that the simple, low-cost, and efficient LBGP process can promote the development of graphene electronics and laser manufacturing processes.

Retroviral integration is mediated by intasome nucleoprotein complexes wherein a pair of viral DNA ends are bridged together by a multimer of integrase (IN). Atomic-resolution structures of HIV-1 intasomes provide detailed insights into the mechanism of integration and inhibition by clinical IN inhibitors. However, previously described HIV-1 intasomes are highly heterogeneous and have the tendency to form stacks, which is a limiting factor in determining high-resolution cryo-EM maps. We have assembled HIV-1 intasomes in the presence of excess IN C-terminal domain protein, which was readily incorporated into the intasomes. The purified intasomes were largely homogeneous and exhibited minimal stacking tendencies. The cryo-EM map resolution was further improved to 2.01 Å, which will greatly facilitate structural studies of IN inhibitor action and drug resistance mechanisms. The C-terminal 18 residues of HIV-1 IN, which are critical for virus replication and integration in vitro, have not been well resolved in previous intasome structures, and its function remains unclear. We show that the C-terminal tail participates in intasome assembly, resides within the intasome core, and forms a small alpha helix (residues 271-276). Mutations that disrupt alpha helix integrity impede IN activity in vitro and disrupt HIV-1 infection at the step of viral DNA integration.

Conventionally, the electromechanical system requires the installation of auxiliary displacement sensors and only the amount on the drive part and motion end, which increases volume, cost, and measurement error in the system. This paper presents an integrated measurement method with a sensing head, which takes the equal division characteristics of mechanical structures as part of the sensor, thus, the so-called self-sensing system. Moreover, the displacement is measured by counting the time pulses. The sensing head is integrated with the entire electromechanical system, including the driving, transmitting, and moving parts. Thus, the integration of the sensing part is greatly improved. Taking the rotary table as a special example, and the sensing head embedded into each part of the system, displacement information is obtained by the common processing system and fused by the adaptive weighted average method. The results of the experiment show that the fusion precision of each component is higher than only the motor position information as the feedback. The proposed method is a practical self-sensing technology with significant volume reduction and intelligent control benefits in the industry, especially suitable for extremely small and narrow spaces.

This article describes constructing an embedded system for a painting art and style presentation platform, achieving the automatic integration of digital painting art with traditional art design. The frontend components are designed using the Bootstrap framework, with Django as the web development framework and TensorFlow architecture integrated into the code. Furthermore, the Inception module and residual connections are introduced to optimize the visual geometry group (VGG) network for recognizing and analyzing image texture features. Compared to other models, experimental results indicate that the proposed model demonstrates a 2.6% increase in image style classification accuracy, reaching 87.34% and 95.33% in architectural and landscape image classification, respectively. The system\'s operational outcomes reveal that the proposed platform alleviates the burden on the logical function modules of the system, enhances scalability, and promotes the automated fusion of digital painting art with traditional art design expression.

The 329-type bismuth (Bi)-based metal halide (MH) polycrystalline films have potential to be applied in the new generation of X-ray imaging technology owing to high X-ray absorption coefficients and excellent detection properties. However, the mutually independent [Bi2X9]3- units and numerous grain boundaries in the material lead to low carrier transport and collection capabilities, severe ion migration, large dark currents, and poor response uniformity. Here, a new multi-phenyl ring methyltriphenylphosphonium (MTP) is designed to optimize the energy band structure. For the first time, the coupling between the A-site cation and [Bi2X9]3- is realized, making it the main contributor to the conduction band minimum (CBM), getting rid of dilemma that carrier transport is confined to [Bi2X9]3-. Further, the preparation of MTP3Bi2I9 amorphous large-area wafer is achieved by melt-quenching; the steric hindrance effect improves stability, increases ion migration energy, and promotes response uniformity (14%). Moreover, the amorphous structure takes advantage of A-site cation participation in the conductivity, achieving a record sensitivity (7601 µC Gy-1 cm-2) and low dark current (≈0.11 nA) in the field of amorphous X-ray detection, and features low-temperature large-area preparation. Ultimately, designing amorphous array imaging devices that exhibit excellent response uniformity and potential imaging capabilities is succeeded here.

Integration of the human papillomavirus (HPV) genome into the cellular genome is a key event that leads to constitutive expression of viral oncoprotein E6/E7 and drives the progression of cervical cancer. However, HPV integration patterns differ on a case-by-case basis among related malignancies. Next-generation sequencing technologies still face challenges for interrogating HPV integration sites. In this study, utilizing Nanopore long-read sequencing, we identified 452 and 108 potential integration sites from the cervical cancer cell lines (CaSki and HeLa) and five tissue samples, respectively. Based on long Nanopore chimeric reads, we were able to analyze the methylation status of the HPV long control region (LCR), which controls oncogene E6/E7 expression, and to identify transcriptionally-active integrants among the numerous integrants. As a proof of concept, we identified an active HPV integrant in between RUNX2 and CLIC5 on chromosome 6 in the CaSki cell line, which was supported by ATAC-seq, H3K27Ac ChIP-seq, and RNA-seq analysis. Knockout of the active HPV integrant, by the CRISPR/Cas9 system, dramatically crippled cell proliferation and induced cell senescence. In conclusion, identifying transcriptionally-active HPV integrants with Nanopore sequencing can provide viable targets for gene therapy against HPV-associated cancers.

UNASSIGNED: Periodontitis, a common chronic inflammatory disease, significantly impacted oral health. To provide novel biological indicators for the diagnosis and treatment of periodontitis, we analyzed public microarray datasets to identify biomarkers associated with periodontitis.
UNASSIGNED: The Gene Expression Omnibus (GEO) datasets GSE16134 and GSE106090 were downloaded. We performed differential analysis and robust rank aggregation (RRA) to obtain a list of differential genes. To obtain the core modules and core genes related to periodontitis, we evaluated differential genes through enrichment analysis, correlation analysis, protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network analysis. Potential biomarkers for periodontitis were identified through comparative analysis of dual networks (PPI network and ceRNA network). PPI network analysis was performed in STRING. The ceRNA network consisted of RRA differentially expressed messenger RNAs (RRA_DEmRNAs) and RRA differentially expressed long non-coding RNAs (RRA_DElncRNAs), which regulated each other\'s expression by sharing microRNA (miRNA) target sites.
UNASSIGNED: RRA_DEmRNAs were significantly enriched in inflammation-related biological processes, osteoblast differentiation, inflammatory response pathways and immunomodulatory pathways. Comparing the core ceRNA module and the core PPI module, C1QA, CENPK, CENPU and BST2 were found to be the common genes of the two core modules, and C1QA was highly correlated with inflammatory functionality. C1QA and BST2 were significantly enriched in immune-regulatory pathways. Meanwhile, LINC01133 played a significant role in regulating the expression of the core genes during the pathogenesis of periodontitis.
UNASSIGNED: The identified biomarkers C1QA, CENPK, CENPU, BST2 and LINC01133 provided valuable insight into periodontitis pathology.

UNASSIGNED: Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study aimed to investigate the HBV integration features in HBV-HCC patients who had undergone long-term antiviral therapy, evaluate their impact on clinical indicators, and analyze the potential mechanisms involved.
UNASSIGNED: We utilized genome-wide association study (GWAS) to analyze liver cancer tissues and detect the presence of HBV integration. Seventeen patients with HBV integration were included in the integration (Int) group, while the remaining five patients were included in the non-integration (N-int) group. Clinical indicators were regularly monitored and compared between the two groups. The characteristics of HBV integration patterns were analyzed, and differences between the groups were explored at the chromosome and genomic levels.
UNASSIGNED: After long-term antiviral therapy, although the frequency of HBV integration in HBV-HCC was reduced, residual HBV integration still accelerated the development of HCC. It affected the diagnosis, treatment, and prognosis of patients. HBV integration events led to changes in chromosome structure, which were closely related to HCC. Novel fusion genes were detected at a high frequency and had the potential to be specific detection sites for HBV-HCC.
UNASSIGNED: HBV integration events are synergistically involved in the human genome and HBV, which can lead to chromosome structural instability, gene rearrangement events closely related to HCC production, and the formation of new specific fusion genes.