Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.

Objective To understand the viral spectrum of inpatients with acute respiratory infection in Pudong New Area, and to explore the composition of pathogens in hospitalized children and adults. Methods Samples of acute respiratory infection cases from 10 medical institutions were collected from 2011 to 2020 and tested for human influenza virus, human adenovirus, rhinovirus, human parainfluenza virus, respiratory syncytial virus, human coronavirus, human metapneumovirus and human boca virus. Results A total of 3 145 inpatients were monitored, with a median age of 61 years. The positive rate of any virus was 32.43% (1 020/3 145), and the single virus infection accounted for 85.98% (877/1 020). In single virus infection, the positive rate of human influenza virus was the highest (9.67%, 304/3 145), with influenza A (80.26%, 244/304) as the main virus. The second was rhinovirus (3.97%, 125/3 145). The positive rate of any virus in different age groups was statistically significant (χ²=103.38，P<0.001). The positive rate of respiratory syncytial virus was the highest in the ~5-year-old group, adenovirus was the highest in the 6-14-year-old group, and influenza virus was the highest in the 15-64-year-old group and the 65year-old group. There was a significant difference in the positive rate of any virus in each month (χ²=123.06，P<0.001). The human influenza virus was the dominant virus in winter (December to February) and summer (July to September), and rhinoviruses distributed sporadically in each month. The positive rate of any virus in different departments was significantly different (χ²=90.37，P<0.001). Conclusion The positive rate of virus in hospitalized patients with acute respiratory infection is relatively high in Pudong New Area, Shanghai, with human influenza virus being the main virus. The virus spectrum of hospitalized children and adults is inconsistent. In the future, in-depth research should be strengthened, focusing on the distribution of pathogens in different populations and seasonal prevention and treatment.

Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.

Objective We aimed to compared matrix metalloproteinase-13 (MMP-13) and transforming growth factor-β1 (TGF-β1) in synovial fluid,the phosphorylation level of Smad3 in articular cartilage (P-Smad3),and their correlation with traditional Chinese medicine (TCM) patterns in patients with knee osteoarthritis (KOA) of liver-kidney deficiency pattern and pattern of intermingled phlegm and blood stasis.Methods Using a cross-sectional field investigation method,KOA patients hospitalized in the Orthopedics Department of Dongzhimen Hospital,Beijing University of Chinese Medicine from September 2019 to February 2023 were collected. A total of 112 KOA patients were included,among which 63 cases were diagnosed with liver-kidney deficiency pattern,and 49 cases were diagnosed with pattern of intermingled phlegm and blood stasis. The intensity of knee pain,function,and X-ray imaging result were quantified using the Visual Analogue Scale (VAS),Lysholm Knee Scoring Scale,and Kellgren-Lawrence (K-L) Grading Scale,respectively. The TCM pattern was identified and quantified using a TCM Pattern Scoring Scale. Immunohistochemistry was used to determine the phosphorylation characteristics of Smad3 in articular cartilage,and ELISA was used to measure the contents of MMP-13 and TGF-β1 in synovial fluid. The level characteristics and their correlation with the degree of syndrome were analyzed.Results (i) There was no statistically significant difference in VAS scores,Lysholm scores,and K-L grades between KOA patients with different TCM patterns. (ii) Compared with KOA patients with pattern of intermingled phlegm and blood stasis,patients with pattern of liver-kidney deficiency had higher levels of MMP-13 in synovial fluid and lower levels of TGF-β1 in synovial fluid (P<0.05). (iii) In KOA patients with liver-kidney deficiency pattern,there was a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.292,P=0.020),while there was a negative correlation between the level of TGF-β1 in synovial fluid and the score of TCM pattern (r=-0.781,P<0.001). In KOA patients with pattern of intermingled phlegm and blood stasis,there was also a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.936,P<0.001). (iv) The mean optical density value of P-Smad3 in articular cartilage was lower in KOA patients with liver-kidney deficiency pattern than in pattern of intermingled phlegm and blood stasis (P<0.05).Conclusion KOA patients with liver-kidney deficiency pattern or pattern of intermingled phlegm and blood stasis have different levels of TGF-β1 and MMP-13 in synovial fluid,as well as varying degrees of Smad3 phosphorylation in articular cartilage,which is consistent with the analysis of etiology and pathogenesis under different patterns. The levels of TGF-β1 and MMP-13 in synovial fluid of patients with liver-kidney deficiency pattern can reflect the severity of the pattern to a certain extent,and the mechanism may be related to the inhibition of the activation level of the TGF-β/Smad signaling pathway. This study enriches the research content of the material basis of TCM patterns.

Objective:To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above.Methods:Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis.Results:The M( Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions:The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.