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Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. GC is determined by multiple (epi)genetic and environmental factors; can occur at distinct anatomic positions of the stomach; and displays high heterogeneity, with different cellular origins and diverse histological and molecular features. This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics. In the past decade, great progress has been made in the study of GC, particularly in molecular subtyping, investigation of the immune microenvironment, and defining the evolutionary path and dynamics. Preclinical mouse models, particularly immunocompetent models that mimic the cellular and molecular features of human GC, in combination with organoid culture and clinical studies, have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion, and the development of novel therapeutic strategies. Herein, we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models, emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.

Abstract Cultural capital is vital for equitable educational development. This paper studies the effect of family cultural capital on the performance of middle school students with regard to gender, using a multiple linear regression model. Participants from four representative middle schools, totalling 1036 students, were selected during the online learning period. The study found that institutionalised and objectified cultural capital had a pronounced positive effect on students’ school outcomes, but cultural capital that was embodied had both positive and negative effects. Significant differences in the effects of cultural capital on school success were found between male and female students. The educational level of a mother has a significant impact on the school attainment of female students in Chinese, English, math and overall achievement, whereas a father’s education level has a significant effect on male students’ English achievement and overall achievement. The results of the study showed that cultural capital contributed to the academic success of middle school students in different ways. The results presented above contribute to a better comprehension of the mechanisms of the influence of cultural capital on the school performance of middle school students, which has important implications for students’ educational equity. This study recommends improving the mechanism of collaborative education among schools, families and society, by paying attention to vulnerable groups that lack cultural capital, improving the methods of educational evaluation and providing tailor-made education for all types of students.

Objective To provide a neuroimaging basis for exploring the role of the prefrontal cortex in human urinary control function. Methods Hemodynamic data from the prefrontal cortex of the brain during the task of pelvic floor muscle contraction from 20 healthy female volunteers were collected using functional near-infrared spectroscopy （fNIRS） under two different states of bladder filling and emptying， and these data were processed accordingly to compare the differences in the activation state among different brain compartments of the prefrontal cortex by analyzing the Beta values corresponding to the relative amount of changes in the concentration of oxyhemoglobin extracted from each individual channel. Results A total of 30 channels were activated during bladder filling， whereas 8 channels were activated during bladder emptying （all P < 0.05）， including 7 co-activated channels. The prefrontal cortex activation was more significant during bladder filling than bladder emptying， and the activation was predominantly in the right prefrontal cortex， with the differences mainly in the right dorsolateral prefrontal cortex and frontopolar cortex （all P < 0.05）. Conclusions The prefrontal cortex can be activated by pelvic floor muscle contraction. Under the state of bladder filling， the prefrontal cortex may perceive the pressure change of the bladder through neural reflex activity and thus participate in the regulation of the voluntary pelvic floor muscle contraction， plays a role in human urinary control function. The right dorsolateral prefrontal cortex region possibly plays a more significant role in this process.

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

Abstract Alteration of the size and stiffness of the nucleus triggered by environmental cues are thought to be important for eukaryotic cell fate and function. However, it remains unclear how context-dependent nuclear remodeling occurs and reprograms gene expression. Here we identify the nuclear envelope proteins SUN1/2 as mechano-regulators of the nucleus during M1 polarization of the macrophage. Specifically, we show that LPS treatment decreases the protein levels of SUN1/2 in a CK2-βTrCP-dependent manner to shrink and soften the nucleus, therefore altering the chromatin accessibility for M1-associated gene expression. Notably, the transmembrane helix of SUN1/2 is solely required and sufficient for the nuclear mechano-remodeling. Consistently, SUN1/2 depletion in macrophages facilitates their phagocytosis, tissue infiltration, and proinflammatory cytokine production, thereby boosting the antitumor immunity in mice. Thus, our study demonstrates that, in response to inflammatory cues, SUN1/2 proteins act as mechano-regulators to remodel the nucleus and chromatin for M1 polarization of the macrophage.

BackgroundFew studies on molecular epidemiology have studied people with newly diagnosed HIV infection and ART Failure Patients at the same time in rural China. With more serious HIV epidemic than in other provinces in China, Sichuan is an area suitable for this study.ObjectiveTo analyze the characteristics of HIV-1 molecular networks and factors related to network entry among newly diagnosed HIV infection and ART Failure Patients in three county-level cities (A, B, C) in Sichuan Province, to provide scientific basis for accurate prevention and control.MethodsNested PCR amplification method was used to amplify HIV-1 pol gene region of 530 blood samples, Sequencer 4.9 was used to edit, clean and splice the gene sequence, Bioedit correction, Fastree 2.1.8 and Figtree 1.4.2 to construct evolutionary tree and determine genotype. HyPhy2.2.4 and Cytoscape 3.6.1 software were used to construct molecular network. Logistic regression analysis was applied.Results523(98.68%) pol sequences were obtained, and a total of 518 valid sequences with basic information came into the final analyses. A total of 6 genotypes were detected, namely CRF01_AE (320,61.78%), CRF07_BC (149,28.76%), B (30,5.79%), CRF08_BC (11, 2.12%), CRF55_01B (6, 1.16%) and C (2, 0.39%). 186 of 518(35.91%) sequences entered the network at a genetic distance of 0.8%, forming 42 propagation clusters. "High-risk transmitters"(connected with two and more) accounted for 21.62%. Logistic regression showed that≥50 years old (OR = 2.474) were more risky than 18-49 years old, CRF07_BC sub-type (OR = 0.174) were less risky than CRF01_AE sub-type, B sub-type (OR = 6.698) is higher risky than CRF01_AE sub-type, and District B (OR = 0.077) less risky than that of A city.ConclusionThe sources of HIV infection in rural Sichuan are diversified and complicated. The prevention and control of HIV infection in Sichuan Province should focus on strengthening the long-term dynamic detection of elderly population, B strain sub-type, and in City A.

Abstract Preeclampsia (PE) is a multisystemic and placental inflammatory disease that causes maternal and infant health issues. As one of the active components in peony root extract, paeonol (Pae) exerts anti‐apoptosis and anti‐inflammatory effects. Nonetheless, the protective role of Pae in PE has not yet been characterized. A mouse model of PE was constructed through tail vein injection of 1 mg/d phosphatidylserine/dioleoyl‐phosphatidycholine suspension. The levels of inflammatory cytokines in the placenta were examined via enzyme‐linked immunosorbent assay (ELISA). The mRNA levels of inflammatory cytokines (TNF‐α, IL‐6, IFN‐γ, and IL‐4) and apoptosis markers (Bax, Bcl‐2, and caspase‐3) were tested using quantitative reverse transcription‐polymerase chain reaction (qRT–PCR). Western blot analysis was performed to detect the protein levels of apoptosis markers and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway‐related molecules. Here, Pae repressed the inflammatory response in the placenta of PE‐like mouse models, as demonstrated by the decreased concentrations and mRNA levels of TNF‐α, IL‐6, and IFN‐γ and the increased concentrations and mRNA levels of IL‐4. Apoptosis in the placentas of PE‐like mouse models was attenuated by Pae, as manifested by the downregulated mRNA and protein levels of Bax and cleaved‐caspase‐3 and the upregulated Bcl‐2. Administration of Pae inhibited the phosphorylation of JAK2 and STAT3 in the placental tissues of PE mice. The JAK2/STAT3 pathway agonist (SC‐39100) reversed Pae treatment‐mediated suppression of placental inflammation and apoptosis in PE mice. Overall, Pae inhibits the JAK2/STAT3 signaling pathway to attenuate placental inflammation and apoptosis in PE mice.