Accurate estimation of biological age and its application in disease prediction using a multimodal image Transformer system.

Aging in an individual refers to the temporal change, mostly decline, in the body's ability to meet physiological demands. Biological age (BA) is a biomarker of chronological aging and can be used to stratify populations to predict certain age-related chronic diseases. BA can be predicted from biomedical features such as brain MRI, retinal, or facial images, but the inherent heterogeneity in the aging process limits the usefulness of BA predicted from individual body systems. In this paper, we developed a multimodal Transformer-based architecture with cross-attention which was able to combine facial, tongue, and retinal images to estimate BA. We trained our model using facial, tongue, and retinal images from 11,223 healthy subjects and demonstrated that using a fusion of the three image modalities achieved the most accurate BA predictions. We validated our approach on a test population of 2,840 individuals with six chronic diseases and obtained significant difference between chronological age and BA (AgeDiff) than that of healthy subjects. We showed that AgeDiff has the potential to be utilized as a standalone biomarker or conjunctively alongside other known factors for risk stratification and progression prediction of chronic diseases. Our results therefore highlight the feasibility of using multimodal images to estimate and interrogate the aging process.

Reinforced medication adherence improves Helicobacter pylori eradication rate in developing countries: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The eradication rate of Helicobacter pylori (H. pylori) remains variable for the same eradication regime even in the identical region, especially in developing countries. Herein, we conducted a systematic review to assess the effect of reinforced medication adherence on H. pylori eradication rate in developing countries. MATERIALS AND METHODS: A systematic review was conducted in literature databases to identify relevant randomized controlled trials (RCTs) from inception to March 2023. The core indicator was the changes in eradication rate after enhanced adherence. A meta-analysis was performed to estimate the pooled relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: Nineteen RCTs that included a total of 3286 patients were assessed. The measures to enhance compliance were mainly through face-to-face communication, phone calls, text messages, and social software. Compared with the control group, patients received reinforced measures showed a better medication adherence (89.6% vs. 71.4%, RR = 1.26 95% CI: 1.16-1.37), higher H. pylori eradication rate (intention-to-treat analysis: 80.2% vs. 65.9%, RR = 1.25, 95% CI: 1.12-1.31; per-protocol analysis: 86.8% vs. 74.8%, RR = 1.16, 95% CI: 1.09-1.23), higher symptom relief rates (81.8% vs. 65.1%, RR = 1.23, 95% CI: 1.09-1.38), higher degree of satisfaction (90.4% vs. 65.1%, RR = 1.26, 95% CI: 1.19-1.35), higher disease knowledge rates (SMD = 1.82, 95% CI: 0.77-2.86, p = 0.0007), and lower incidence of total adverse events (27.3% vs. 34.7%, RR = 0.72, 95% CI: 0.52-0.99). CONCLUSION: Based on available evidence, reinforced medication adherence as a nonnegligible measure improves H. pylori eradication rate in developing countries.

Effects of different preservation methods of human iliac veins.

With the progress of vascular anastomosis technology, the radical resection surgery of cancer combining with vascular resection and reconstruction has been focused by surgeon. As a natural substitute material for blood vessel, vascular allografts have good vascular compliance and histocompatibility. Generally, the donated veins could not be used immediately, and need to be well preserved. So, it is greatly significant to do research in the preservation effects of different preservation methods on veins. In this study, the effects of different preservative methods of human iliac veins were compared and analyzed in terms of cell viability, vascular wall structure and tension resistance. The donated human iliac veins were randomly divided into three groups: Cold Storage Group (4 °C) (CSG), Frozen Storage Group (-186 °C) (FSG)and Fresh Control Group (FCG). Six detection time-points of preservation for 1, 3, 5, 7, 14, 28 days were set respectively. There are ten samples in each group and each time-point separately. Survival and apoptosis of vascular cell were evaluated by MTT assay and Tunel fluorescence staining. Tensile test was used to evaluate mechanical properties of vessels. The changes of vascular endothelial cells, smooth muscle cells, collagen fibers and elastic fibers were evaluated by HE staining, Masson staining and EVG staining. Furthermore, the changes of organelles were observed by transmission electron microscope. With the extension of preservation period, the vascular cell viability and tension resistance of two groups decreased, and the apoptotic cells increased gradually. The apoptosis index of CSG was higher than FSG at each time point (P < 0.05). In terms of cell viability, CSG was higher within 3 days (P < 0.05), both groups were same between 3 and 14 days, and then CSG lower than FSG after 14 days (P < 0.05). In terms of tension resistance, CSG was stronger than FSG (P < 0.05) in first 7 days, both groups were same in 2nd week, and then CSG was weaker in 4th week (P < 0.05). In terms of vascular wall structure, in CSG, vascular endothelial cells were damaged and shed, smooth muscle cells were edema after 14 days, but the cell membrane and intercellular connection were still intact. In 4th week, endothelial cells were completely damaged and shed, the boundary of smooth muscle cell membrane was unclear, intercellular connection was damaged. Moreover, organelles were destroyed and disappeared, perinuclear condensation of chromatin was observed, and some cells had incomplete nuclear membrane or nuclear fragmentation; However, there were no obvious changes in the FSG within 28 days. Finally, local exfoliation and destruction of endothelial cells and edema-like changes of organelles were observed; the collagen fibers and elastic fibers of blood vessels in the two groups had no obvious damage and change within 28 days. For excised human iliac vein, cold and frozen storage can effectively preserve the cell viability, wall structure and tension resistance of blood vessels. With the extension of preservation time, the related performance of vessels declined in varying degrees. Within first week, the effect of cold storage is better than frozen storage, but frozen storage is significantly better than cold storage after 2 weeks.

No significant relationship exists between tumor size and prognosis in distant metastatic hepatocellular carcinoma: a propensity score matching analysis based on SEER database.

BACKGROUND: Previous studies have shown that tumor size has an impact on the prognosis of hepatocellular carcinoma (HCC). Whether tumor size is related to the prognosis of distant metastatic HCC is unclear. The purpose of this study was to investigate the effect of tumor size on the prognosis of distant metastatic HCC. METHODS: Data on patients with HCC were collected from the (SEER) database of surveillance, epidemiology and final results. Propensity score matching (PSM) was used to reduce confounding factors and comprehensively evaluate the clinicopathological features and prognosis of distant metastatic HCC. RESULTS: There were 189 patients with distant metastatic HCC whose tumor size was ≤ 50 mm and 615 patients with a tumor size > 50 mm. The tumor sizes of distant metastatic HCC patients were associated with race, grade, surgical treatment, N and AFP. The Kaplan-Meier analysis showed that the mortality rate of patients with a tumor size > 50 mm was higher than that of patients with a tumor size ≤ 50 mm (p = 0.00062). However, there were no significant differences in mortality rates after adjusting for confounding variables by using propensity score matching (p = 0.23). CONCLUSION: This propensity score matching study provides the best data in support of the following assertions: tumor size is not an independent prognostic factor for distant metastatic HCC.

Atg5 knockdown induces age-dependent cardiomyopathy which can be rescued by repeated remote ischemic conditioning.

Altered autophagy is implicated in several human cardiovascular diseases. Remote ischemic conditioning (RIC) is cardioprotective in multiple cardiovascular injury models and modifies autophagy signaling, but its effect in cardiomyopathy induced by gene manipulation has not been reported. To investigate the cardiac effects of chronically reduced autophagy as a result of Atg5 knockdown and assess whether RIC can rescue the phenotype. Atg5 knockdown was induced with tamoxifen for 14 days in cardiac-specific conditional Atg5 flox mice. Autophagy proteins and cardiac function were evaluated by Western blot and echocardiography, respectively. RIC was induced by cyclical hindlimb ischemia and reperfusion using a tourniquet. RIC or sham procedure was performed daily during tamoxifen induction and, in separate experiments, chronically 3 times per week for 8 weeks. Cardiac responses were assessed by end of the study. Cardiac-specific knockdown of Atg5 reduced protein levels by 70% and was associated with a significant increase in mTOR, a reduction of LC3-II and increased upstream autophagy proteins including LC3-I, P62, and Beclin. The changes in biochemical markers were associated with development of an age-related cardiomyopathy during the 17-month follow-up indicated by increased heart weight body weight ratio, progressive decline in cardiac function, and premature death. RIC increased cardiac ATG5 and rescued some of the Atg5 knockdown-induced cardiomyopathy phenotype and associated morphological remodeling. We conclude that cardiac-specific Atg5 knockdown leads to the development of age-related cardiomyopathy. RIC reverses the molecular and structural phenotype when administered both acutely and chronically.

Long-term survival in patients with distal cholangiocarcinoma after pancreaticoduodenectomy combined with portal vein system resection and reconstruction.

PURPOSE: Pancreaticoduodenectomy combined with portal vein resection for distal cholangiocarcinoma is rarely reported because it is a rare disease. We developed a program to evaluate the vascular invasion type, operation procedure, and long-term survival of distal cholangiocarcinoma patients with portal vein invasion. METHODS: We retrospectively reviewed data for 123 distal cholangiocarcinoma patients after pancreaticoduodenectomy between January 2013 and December 2019. Portal vein system invasion was confirmed pathologically in 17 patients. RESULTS: Multivariable Cox regression identified tumor differentiation degree, portal vein system invasion, and lymph node metastasis as independent risk factors affecting long-term survival. The 1- and 2-year overall survival rates for patients without and with portal vein system invasion were 79.7% and 58.9%, and 48.6% and 10.8%, respectively. Median overall survival in patients without and with portal vein system invasion was 33 months and 12 months, respectively. CONCLUSION: Portal vein system invasion is an important independent risk factor affecting long-term survival in patients with distal cholangiocarcinoma. Pancreaticoduodenectomy combined with portal vein system resection and reconstruction did not increase the incidence of perioperative complications or mortality.

Outer inflammatory protein of Helicobacter pylori impacts IL-8 expression, adherence, cell apoptosis and cell cycle of gastric cells independent of its copy number.

Outer inflammatory protein (OipA) is an important virulence factor of Helicobacter pylori (H. pylori), but the correlation between oipA copy number and its virulence remains unknown. The study was designed to investigate whether the duplicate oipA gene loci showed more virulent than one oipA gene in vitro. H. pylori strain CCS9803 (China Chongqing Strain 9803) that carries duplicate oipA loci was used to construct one or two oipA knockout mutant strain, which was further verified by qPCR and western blot. Gastric epithelial cells AGS and GES-1 were infected with wild-type (WT) or oipA mutants for 6 or 24 h. The expression levels of IL-8, bacterial adhesion, cell apoptosis and cell cycle were performed to analyze the function of oipA. The WT and oipA mutant strains induce significantly higher mRNA and protein levels of IL-8 than the uninfected group (P < 0.05), but only oipA2 mutants induced significantly decreased expression levels than the WT-infected group (P < 0.05). Adherence to gastric cells was significantly decreased by inactivated two oipA loci (P < 0.05). The WT strain caused a significant rising proportion of early apoptosis cell, which had dropped after duplicate oipA genes were both knockout (P < 0.05). WT and oipA1 mutants failed to affect cell cycle; however, the oipA2 mutants increased M phase and reduced S phase when compared to the uninfected group. In conclusion, our study demonstrated that oipA impacts IL-8 expression, adherence, cell apoptosis and cell cycle of gastric cells independent of its gene copy number.

Synthesis and application of benzoxazole derivative-based fluorescent probes for naked eye recognition.

A fluorescent probe to detect biothiols (GSH/Hcy/Cys) was synthesized with benzothiazole as the fluorophore and nitromethane as the recognition group. The recognition mechanism of the fluorescent probe was deduced. It was found that a nitroalkene in the molecule was used as the recognition site for this probe and reacted with the mercapto group of the biothiols by electrophilic addition, significantly enhancing the fluorescent signal. Experimental results showed that the fluorescent probe had a low detection limit, good selectivity, strong anti-interference ability, and good naked eye recognition. The probe could detect biothiols (GSH/Hcy/Cys) in 20% organic solvent, with detection limits of 0.33 µM, 0.70 µM, and 0.87 µM, respectively. The probe will be applied further in biosensors and other fields.

Acute and chronic remote ischemic conditioning attenuate septic cardiomyopathy, improve cardiac output, protect systemic organs, and improve mortality in a lipopolysaccharide-induced sepsis model.

Remote ischemic conditioning (RIC) is acutely cardioprotective in ischemia-reperfusion injury. We aimed to evaluate the effect of RIC on septic cardiomyopathy and associated multi-organ failure in a lipopolysaccharide (LPS)-induced sepsis mouse model. Balb/c mice were divided into sham, LPS, and LPS + RIC groups. LPS 10 mg/kg or saline control was injected intraperitoneally. RIC was performed by four cycles of 5 min ischemia and 5 min reperfusion of the left lower limb just before the LPS injection. Cardiac function on echocardiography, circulating mediators, blood biochemistry, and MAPK signalling was assessed. Survival 7 days after LPS injection was evaluated in sham-treated, RIC, and daily repeated RIC groups. An LPS-induced decrease in cardiac output was ameliorated by RIC with preserved left ventricular systolic function. LPS-induced increases in TNF-α, IL-1ß, IL-6, and high-mobility group box 1 protein (HMGB1) were significantly suppressed by RIC. RIC also suppressed increases in plasma cardiac troponin I, aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine with suppressed ERK and JNK phosphorylation in heart, liver, and kidney tissue. RIC significantly improved survival rate (p = 0.0037). Survival rate in the daily repeated RIC group was 100%, and it was higher than that in the RIC group (p = 0.0088). In summary, RIC reduced circulating and myocardial inflammatory mediators associated with septic cardiomyopathy, and led to improved ventricular function, cardiac output, and survival. Our data also revealed that chronic RIC has additional benefit in terms of mortality in sepsis. While further studies are required, RIC may be a clinically useful tool to ameliorate sepsis-induced cardiomyopathy.

Intravenous miR-144 reduces left ventricular remodeling after myocardial infarction.

MicroRNA-144 is a cytoprotective miRNA. Our previous study showed that miR-144 provides potent acute cardioprotection in an ischemia/reperfusion injury model. This study was performed to further assess whether miR-144 improves post-MI remodeling in a non-reperfused myocardial infarction (MI) model. C57BL/6 mice were subjected to MI by permanent left anterior descending artery (LAD) ligation. miR-144 was delivered by intravenous injections of 8 mg/kg, 16 mg/kg, or 32 mg/kg at day 0, day 1, day 3, and then a similar dose given once every 3 days, until day 28 after MI. Cardiac function was evaluated using echocardiography. At the end of the study, heart function was also evaluated using a pressure volume catheter. The percentage of the length of the infarct scar on the left ventricle (LV) circumferential length was calculated for heart each section. The miR-144 KO mice showed a worse heart failure phenotype with ventricular dilation and impaired contractility after LAD ligation. Ischemia decreased miR-144 levels, and the miR-144 level was restored to baseline by administration of intravenous miR-144. Cy3-labeled miR-144 was localized to the infarct and border zone, and was taken up by cardiomyocytes and macrophages. In miR-144-treated groups, at 28 days MI size was significantly reduced, and cardiac function was improved [LV fractional shortening, end-systolic volume (µL), end-diastolic volume (µL), ejection fraction (%), dP/dt max (mmHg/s), dP/dt min (mmHg/s), Tau (ms)], compared with controls (p < 0.01). This beneficial effect was associated with reduced border zone fibrosis, inflammation and apoptosis, these effects were associated with significant changes in autophagy signaling. Intravenous miR-144 has potent effects on post-MI remodeling. These findings suggest that miR-144 has potential as a therapeutic agent after MI.

Temperature-dependent development of Asian citrus psyllid on various hosts, and mortality by two strains of Isaria.

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is a devastating pest of Citrus spp. The aim of present study was to investigate the development and mortality of ACP on citrus (Citrus sinensis) (healthy and Huánglóngbìng- (HLB) diseased) and jasmine (Murraya paniculata) plants at various temperatures. Two new Isaria strains were collected from citrus orchards of Fuzhou (China), and HLB-diseased plants were verified by running PCR for 16S gene of Candidatus Liberibacter asiaticus (CLas). Development observations were recorded for egg, nymph and adult stages on all plants and three different temperatures (20, 25 and 30 °C) whereas mortality observations were recorded for the nymph (fifth instar) and adults on all plants at 25 °C. Field collected Isaria strains were belonged to previously reported Chinese strains under Maximum Parsimony (MP) and Maximum Likelihood methods, as well as, CLas isolates were belonged to previously reported Chinese isolates under MP and Neighbor-Joining methods. The fastest development and mortality was observed on HLB-diseased plants whereas longest time was taken by development and mortality completion on jasmine plants at all temperatures. The fastest developmental times of egg, nymph (first to fourth and fifth instar) and adult stages were ranged from 3.02 to 3.72 d, to 7.63-9.3 d, 5.35-5.65 d and 24.46-28.47 d on HLB-diseased plants at 30-20 °C, respectively. On the other hand, I. javanica caused the fastest mortality of nymphs and adults (32.21 ± 4.47% and 19.33 ± 4.51%) on HLB-diseased plants with the concentration of 1 × 108 conidia.mL-1 after 3 d and 7 d, respectively. It is concluded that there is a need for extensive molecular work to understand the extra-development and mortality of ACP on diseased plants, because, CLas bacterium can be supportive to uptake more sap from plant phloem.

The Long Journey of Pollen Tube in the Pistil.

In non-cleistogamous plants, the male gametophyte, the pollen grain is immotile and exploits various agents, such as pollinators, wind, and even water, to arrive to a receptive stigma. The complex process of pollination involves a tubular structure, i.e., the pollen tube, which delivers the two sperm cells to the female gametophyte to enable double fertilization. The pollen tube has to penetrate the stigma, grow in the style tissues, pass through the septum, grow along the funiculus, and navigate to the micropyle of the ovule. It is a long journey for the pollen tube and its two sperm cells before they meet the female gametophyte, and it requires very accurate regulation to perform successful fertilization. In this review, we update the knowledge of molecular dialogues of pollen-pistil interaction, especially the progress of pollen tube activation and guidance, and give perspectives for future research.

Intravenous miR-144 inhibits tumor growth in diethylnitrosamine-induced hepatocellular carcinoma in mice.

Previous in vitro studies have demonstrated that miR-144 inhibits hepatocellular carcinoma cell proliferation, invasion, and migration. We have shown that miR-144, injected intravenously, is taken up by the liver and induces endogenous hepatic synthesis of miR-144. We hypothesized that administered miR-144 has tumor-suppressive effects on liver tumor development in vivo. The effects of miR-144 on tumorigenesis and tumor growth were tested in a diethylnitrosamine-induced hepatocellular carcinoma mouse model. MiR-144 injection had no effect on body weight but significantly reduced diethylnitrosamine-induced liver enlargement compared with scrambled microRNA. MiR-144 had no effect on diethylnitrosamine-induced liver tumor number but reduced the tumor size above 50%, as evaluated by magnetic resonance imaging (scrambled microRNA 23.07 ± 5.67 vs miR-144 10.38 ± 2.62, p < 0.05) and histological analysis (scrambled microRNA 30.75 ± 5.41 vs miR-144 15.20 ± 3.41, p < 0.05). The levels of miR-144 was suppressed in tumor tissue compared with non-tumor tissue in all treatment groups (diethylnitrosamine-phosphate-buffered saline non-tumor 1.05 ± 0.09 vs tumor 0.54 ± 0.08, p < 0.01; diethylnitrosamine-scrambled microRNA non-tumor 1.23 ± 0.33 vs tumor 0.44 ± 0.10, p < 0.05; diethylnitrosamine-miR-144 non-tumor 54.72 ± 11.80 vs tumor 11.66 ± 2.75, p < 0.01), but injection of miR-144 greatly increased miR-144 levels both in tumor and non-tumor tissues. Mechanistic studies showed that miR-144 targets epidermal growth factor receptor and inhibits the downstream Src/AKT signaling pathway which has previously been implicated in hepatocellular carcinoma tumorigenesis. Exogenously delivered miR-144 may be a therapeutic strategy to suppress tumor growth in hepatocellular carcinoma.

Macrophage Tim-3 maintains intestinal homeostasis in DSS-induced colitis by suppressing neutrophil necroptosis.

T-cell immunoglobulin domain and mucin domain-3 (Tim-3) is a versatile immunomodulator that protects against intestinal inflammation. Necroptosis is a type of cell death that regulates intestinal homeostasis and inflammation. The mechanism(s) underlying the protective role of macrophage Tim-3 in intestinal inflammation is unclear; thus, we investigated whether specific Tim-3 knockdown in macrophages drives intestinal inflammation via necroptosis. Tim-3 protein and mRNA expression were assessed via double immunofluorescence staining and single-cell RNA sequencing (sc-RNA seq), respectively, in the colonic tissues of patients with inflammatory bowel disease (IBD) and healthy controls. Macrophage-specific Tim3-knockout (Tim-3M-KO) mice were generated to explore the function and mechanism of Tim-3 in dextran sodium sulfate (DSS)-induced colitis. Necroptosis was blocked by pharmacological inhibitors of receptor-interacting protein kinase (RIP)1, RIP3, and reactive oxygen species (ROS). Additionally, in vitro experiments were performed to assess the mechanisms of neutrophil necroptosis induced by Tim-3 knockdown macrophages. Although Tim-3 is relatively inactive in macrophages during colon homeostasis, it is highly active during colitis. Compared to those in controls, Tim-3M-KO mice showed increased susceptibility to colitis, higher colitis scores, and increased pro-inflammatory mediator expression. Following the administration of RIP1/RIP3 or ROS inhibitors, a significant reduction in intestinal inflammation symptoms was observed in DSS-treated Tim-3M-KO mice. Further analysis indicated the TLR4/NF-κB pathway in Tim-3 knockdown macrophages mediates the TNF-α-induced necroptosis pathway in neutrophils. Macrophage Tim-3 regulates neutrophil necroptosis via intracellular ROS signaling. Tim-3 knockdown macrophages can recruit neutrophils and induce neutrophil necroptosis, thereby damaging the intestinal mucosal barrier and triggering a vicious cycle in the development of colitis. Our results demonstrate a protective role of macrophage Tim-3 in maintaining gut homeostasis by inhibiting neutrophil necroptosis and provide novel insights into the pathogenesis of IBD.

A bibliometric analysis of inflammatory bowel disease and COVID-19 researches.

Background: Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and are hence susceptible to various opportunistic viral and bacterial infections. In this regard, many studies on IBD and COVID-19 have been conducted. However, no bibliometric analysis has been performed. This study provides a general overview of IBD and COVID-19. Methods: Publications about IBD and COVID-19 from 2020 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviewer, CiteSpace, and HistCite. Results: A total of 396 publications were retrieved and considered in this study. The maximum number of publications were from the United States, Italy, and England, and the contributions of these countries were significant. Kappelman ranked first in article citations. The Icahn School of Medicine at Mount Sinai and Inflammatory Bowel Diseases were the most prolific affiliation and journal, respectively. The most influential research topics were "management", "impact", "vaccination", and "receptor". The following keywords represented research frontiers: "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination". Conclusions: Over the past 3 years, most studies on IBD and COVID-19 have focused on clinical research. In particular, topics such as "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination" were noted to have received much attention recently. Future research should focus on our understanding of the immune response to COVID-19 vaccination in biologically treated patients, the psychological impact of COVID-19, IBD management guidelines, and the long-term impact of COVID-19 in IBD patients. This study will provide researchers with a better understanding of research trends on IBD during COVID-19.

Knowledge landscape of tumor-associated macrophage research: A bibliometric and visual analysis.

Background and aims: Tumor-associated macrophage (TAM) is a highly abundant immune population in tumor microenvironment, which plays an important role in tumor growth and progression. The aim of our study was to explore the development trends and research hotspots of TAM by bibliometric method. Methods: The publications related to TAM were obtained from the Web of Science Core Collection database. Bibliometric analysis and visualization were conducted using VOSviewer, CiteSpace and R software. Results: A total of 6,405 articles published between 2001 and 2021 were included. The United States and China received the most citations, whereas the University of Milan, the university of California San Francisco and Sun Yat-sen University were the main research institutions. Mantovani, Alberto from Humanitas University was the most productive authors with the most citations. Cancer Research published the most articles and received the most co-citations. Activation, angiogenesis, breast cancer, NF-κB and endothelial growth factor were important keywords in TAM research. Among them, PD-1/L1, nanoparticle, PI3Kγ, resistance and immune microenvironment have become the focus of attention in more recent research. Conclusions: The research on TAM is rapidly evolving with active cooperation worldwide. Anticancer therapy targeting TAM is emerging and promising area of future research, especially in translational application. This may provide guidance and new insights for further research in the field of TAM.

Spatial transcriptomics reveals the heterogeneity and FGG+CRP+ inflammatory cancer-associated fibroblasts replace islets in pancreatic ductal adenocarcinoma.

Background: Understanding the spatial heterogeneity of the tumor microenvironment (TME) in pancreatic cancer (PC) remains challenging. Methods: In this study, we performed spatial transcriptomics (ST) to investigate the gene expression features across one normal pancreatic tissue, PC tissue, adjacent tumor tissue, and tumor stroma. We divided 18,075 spatial spots into 22 clusters with t-distributed stochastic neighbor embedding based on gene expression profiles. The biological functions and signaling pathways involved in each cluster were analyzed with gene set enrichment analysis. Results: The results revealed that KRT13+FABP5+ malignant cell subpopulation had keratinization characteristics in the tumor tissue. Fibroblasts from adjacent tumor tissue exhibited a tumor-inhibiting role such as "B-cell activation" and "positive regulation of leukocyte activation." The FGG+CRP+ inflammatory cancer-associated fibroblasts replaced the islets in tumor stroma. During PC progression, the damage to pancreatic structure and function was heavier in the pancreatic exocrine (AMYA2+PRSS1+) than in the endocrine (INS+GCG+). Conclusion: Our results revealed the spatial heterogeneity of dynamic changes and highlighted the significance of impaired exocrine function in PC.

The Motivation of Media Users and China's National Media Digitization Construction in the Post-COVID-19 Era.

The sudden arrival of COVID-19 has had an enormous impact on the lives of people around the world, including significant psychological pressure and increased emotional needs. In China, research into user psychology and the motivations of commercial digital media has become more popular, but the national media should pay more attention to user psychology and perform more research on user motivations to improve the effectiveness of communication. We investigated people's internal psychology and motivation for using national media digital platforms in China during the pandemic. We collected data through online questionnaires and analyzed the use of apps of CCTV and The People's Daily by individual users during the pandemic and the psychological needs of national digital media users. In the first stage of our research, we selected national digital media app users through the WeChat platform. In the second stage, more active users were chosen by snowballing upon the original sample. We surveyed 210 participants and ultimately obtained 180 valid samples. We analyzed the data using used SPSS 23.0. The results showed that with the help of digital media platforms and diversified media technology, the Chinese national media not only met the needs of users for information acquisition, but also provided sufficient emotional mutual assistance and comfort to users through the network aggregation formed by digital scene communication.