Single-cell and spatial omics technologies are spearheading a profound paradigm shift in the life sciences,moving beyond'population averages'to'single-cell resolution'and reintegrating'cellu-lar constitution'with'tissue spatial architecture',thereby dramatically advancing our understanding of biological complexity.This review provides a brief comprehensive overview of recent advancements in the field.Technologically,the evolution has progressed from single-cell transcriptomics to integrated approa-ches capturing multiple molecular layers simultaneously,while the emergence of transcriptome-badsed spatial omics has successfully preserved the spatial positioning of cells or microscosystem within native tis-sues,and further enabling spatial epigenomics and spatial-multiomics.Computationally,artificial intelli-gence and machine learning have become central engines,powering tools for data integration,spatial de-convolution,cellular communication and other novel foundation models,which not only tackle the chal-lenges of massive datasets but also serve as instruments for novel biological discovery.These technological leaps have fostered significant theoretical innovations.In clinical translation,these technologies,particu-larly in precision oncology,demonstrate transformative potential by dissecting tumor heterogeneity,map-ping the spatial architecture of the tumor immune microenvironment,and enabling disease modeling through single-cell-guided deconvolution of bulk data,offering new avenues for diagnosis,prognosis,and personalized therapy.Despite ongoing challenges in technological throughput,computational scalability,and clinical integration,the continued convergence of single-cell and spatial omics with AI promises to propel basic research towards a more mechanistic and predictive era,ultimately reshaping the future of precision medicine.

Single-cell and spatial omics technologies are spearheading a profound paradigm shift in the life sciences,moving beyond'population averages'to'single-cell resolution'and reintegrating'cellu-lar constitution'with'tissue spatial architecture',thereby dramatically advancing our understanding of biological complexity.This review provides a brief comprehensive overview of recent advancements in the field.Technologically,the evolution has progressed from single-cell transcriptomics to integrated approa-ches capturing multiple molecular layers simultaneously,while the emergence of transcriptome-badsed spatial omics has successfully preserved the spatial positioning of cells or microscosystem within native tis-sues,and further enabling spatial epigenomics and spatial-multiomics.Computationally,artificial intelli-gence and machine learning have become central engines,powering tools for data integration,spatial de-convolution,cellular communication and other novel foundation models,which not only tackle the chal-lenges of massive datasets but also serve as instruments for novel biological discovery.These technological leaps have fostered significant theoretical innovations.In clinical translation,these technologies,particu-larly in precision oncology,demonstrate transformative potential by dissecting tumor heterogeneity,map-ping the spatial architecture of the tumor immune microenvironment,and enabling disease modeling through single-cell-guided deconvolution of bulk data,offering new avenues for diagnosis,prognosis,and personalized therapy.Despite ongoing challenges in technological throughput,computational scalability,and clinical integration,the continued convergence of single-cell and spatial omics with AI promises to propel basic research towards a more mechanistic and predictive era,ultimately reshaping the future of precision medicine.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.
Mice ; Animals ; Receptors, Somatostatin/metabolism* ; Hematopoietic Stem Cells/metabolism* ; Epithelial Cells

Humans ; Infant ; Infant, Newborn ; Infant, Extremely Low Birth Weight ; Mesenchymal Stem Cell Transplantation ; Umbilical Cord/cytology* ; Skin/injuries*

Objective: To examine the outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma (PCNSL). Methods: The clinical data of 18 patients with PCNSL who were treated according to Tiantan first-aid protocol at Department of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University from November 2019 to December 2021 were retrospectively analyzed. There were 9 males and 9 females, aged (56.9±11.1)years (range: 29 to 77 years). The median Karnofsky performance status(KPS) score at admission was 40 (range: 20 to 60). Three patients were mild coma, 3 were lethargy and 12 were conscious. The mean midline shift was 0.7 cm (range: 0 to 1.8 cm). After admission, all patients were treated according to the plan of rapid biopsy, rapid routine pathology and rapid salvage chemotherapy. The treatment procedures, clinical and radiographic outcomes, KPS score and adverse reactions of patients after chemotherapy were collected. Results: All of the 18 patients completed the first-aid treatment. The median duration from admission to the biopsy was 1 day (range: 0 to 5 days), from biopsy to routine pathological diagnosis was 1 day (range: 1 to 4 days) and from routine pathology to salvage chemotherapy was 1 day (range: 0 to 4 days). All the patients were pathologically confirmed with diffuse large B cell lymphoma, 1 patient was double-hit lymphoma. Seventeen patients underwent clinical remission and 1 died of cardiac dysfunction. The successful salvage rate was 17/18. Radiologically, complete remission was observed in 1 case, partial remission in 16 cases, and stable disease in 1 case. The median KPS score at discharge was 60 (range: 30 to 80). The mild gastrointestinal, hematological and hepatic adverse effects were observed after chemotherapy. Conclusion: Tiantan first-aid protocol is effective for critically ill patients with PCNSL, which has the merit to be popularly used and improved.
Central Nervous System ; Central Nervous System Neoplasms/therapy* ; Critical Illness ; Female ; Humans ; Lymphoma/therapy* ; Male ; Retrospective Studies

The quality difference of pharmaceutical excipients from different sources affects the molding properties of the powder, resulting in changes in the properties of the final product. In this study, the critical quality attributes of hydroxypropyl methylcellulose (HPMC) with different specifications from two manufacturers (manufacturer A and manufacturer B) were characterized including particle size, physical morphology, viscosity and powder physical quality attributes. Aminophylline, diclofenac sodium, and metformin hydrochloride were utilized as model drugs with different solubility to prepare sustained-release tablets, and the effect of HPMC from different sources on drug release of sustained-release tablets in vitro was investigated. The results showed that HPMC with the same viscosity specification from different sources had outstanding differences in the physicochemical properties (including particle size, physical morphology, viscosity, dimension, compressibility and powder flow), which could change the hardness and friability of the sustained-release tablets. The differences in the physicochemical properties of HPMC had different effects on the dissolution of different sustained-release tablets in vitro. It had no significant effect on the release of easily soluble aminophylline and metformin hydrochloride, but had a greater impact on the release of poorly soluble diclofenac sodium. Compared with manufacturer A, the sustained-release effect of matrix tablets prepared by HPMC from manufacturer B was more excellent. The results of this study will provide a theoretical reference on selecting the appropriate excipients for formulation design.

INTRODUCTION: Fragile X syndrome (FXS) is the most prevalent X-linked intellectual disability (ID) and a leading genetic cause of autism, characterised by cognitive and behavioural impairments. The hyperexpansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene leads to abnormal hypermethylation, resulting in the lack or absence of its protein. Tools for establishing the diagnosis of FXS have been extensively developed, including assays based on triplet-primed polymerase chain reaction (TP-PCR) for detection and quantification of the CGG trinucleotide repeat expansion, as well as determination of the methylation status of the alleles. This study aimed to utilise a simple, quick and affordable method for high sensitivity and specificity screening and diagnosis of FXS in institutionalised individuals with ID. METHODS: A total of 109 institutionalised individuals at the Center for Social Rehabilitation of Intellectual Disability Kartini, Temanggung, Central Java, Indonesia, were screened in a three-step process using FastFrax™ Identification, Sizing and Methylation Status Kits. RESULTS: Two samples that were classified as indeterminate with respect to the 41-repeat control at the identification step were subsequently determined to be non-expanded by both sizing and methylation status analyses. Two samples classified as expanded at the identification step were determined to carry full mutation expansions > 200 repeats that were fully methylated using sizing and methylation status analyses, respectively, yielding a disease prevalence of 1.83%. CONCLUSION Repeat expansion and methylation-specific TP-PCR is practical, effective and inexpensive for the diagnosis of FXS, especially in high-risk populations of individuals with ID of undetermined aetiology.

Objective To investigate the effect of lysophosphatidic acid (LPA) on migration of hepatocellular carcinoma MHCC97H cells and its involved mechanisms. Methods Transwell was utilized to investigate the impact of LPA on cell migration of MHCC97H cells. Furthermore, the role of ROCK in the migration of MHCC97H cells through Y-27632 (a specific inhibitor of ROCK). Then, the expression of F-actin was observed with immunofluorescence staining and Western blotting. Atomic force microscopy (AFM) was employed to investigate elastic modulus of MHCC97H cells. Results LPA significantly promoted the migration of MHCC97H cells, while Y-27632 significantly blocked the migration of MHCC97H induced by LPA. Moreover, LPA up-regulated the expression of F-actin and decreased the elastic modulus of MHCC97H cells. Conclusions LPA promotes MHCC97H cell migration through decreasing the cell stiffness via ROCK/F-actin.

Animals ; Macaca mulatta ; surgery ; Magnetic Resonance Imaging ; Neuronavigation ; standards ; Stereotaxic Techniques ; standards