Exploration of glutaredoxin-1 oxidative modification in carbon nanomaterial-induced hepatotoxicity.

Herein, we present toxicological assessments of carbon nanomaterials in HL-7702 cells, and it was found that reactive oxygen species (ROS) levels were elevated. Mass spectrometry results indicated that cysteine sulfhydryl of glutaredoxin-1 (GLRX1) was oxidized to sulfenic acids and sulfonic acids by excessive ROS, which broke the binding of GLRX1 to apoptosis signal-regulating kinase 1, causing the activation of the JNK/p38 signaling pathway and ultimately hepatocyte apoptosis. However, a lower level of ROS upregulated GLRX1 instead of sulfonation modification of its active sites. Highly expressed GLRX1 in turn enabled the removal of intracellular ROS, thereby exerting inconspicuous toxic effects on cells. Taken together, these findings emphasized that CNM-induced hepatotoxicity is attributable to oxidative modifications of GLRX1 arising from redox imbalance.

Prevalence and factors associated with trajectories of antenatal depression: a prospective multi-center cohort study in Chengdu, China.

BACKGROUND: Antenatal depression (AD) is a major depressive disorder during pregnancy, which may lead to devastating sequelae for the expectant mothers and infants. This study aimed to investigate the prevalence, to analyze trajectory model based on EPDS score, and to explore the influence factors of AD among pregnant women in Chengdu, China. METHODS: Participants from four maternity hospitals in Chengdu, China were recruited when they had their first pregnancy medical check-up during March 2019 to May 2020. All participants were required to fill in Edinburgh Postnatal Depression Scale Chinese version (EPDS) once during three trimesters and provided information about their health status, social-demographic etc. The trajectory model, chi-square test and multivariate binary logistic regression were used to analyze all collected data. RESULTS: A total of 4560 pregnant women were recruited, while 1051 women completed the study. The prevalence of depression symptoms during the first, second and third trimesters were 32.92% (346/1051), 19.79% (208/1051) and 20.46% (215/1051) respectively. According to the results of the latent growth mixture modeling, the trajectory model of three categories based on EPDS score were identified in this study: low-risk group (38.2%, 401/1051), medium-risk group (54.8%, 576/1051) and high-risk group (7%, 74/1051). Good marital relationship (P = 0.007, OR = 0.33, 95% CI 0.147 ~ 0.74), good relationship with parents-in-law (P = 0.011, OR = 0.561, 95% CI 0.36 ~ 0.874), planned pregnancy (P = 0.018, OR = 0.681, 95% CI 0.496 ~ 0.936) were the protective factors while lower education level (P = 0.036, OR = 1.355, 95% CI 1.02 ~ 1.799), fear about dystocia (P = 0.0, OR = 1.729, 95% CI 1.31 ~ 2.283), recent major negative life events (P = 0.033, OR = 2.147, 95% CI 1.065 ~ 4.329) were the risk factors of medium-risk group. Good marital relationship (P = 0.005, OR = 0.2, 95% CI 0.065 ~ 0.615), good relationship with parents-in-law (P = 0.003, OR = 0.319, 95% CI 0.15 ~ 0.679) were also protective factors of high-risk group, but the risk factors for high-risk group were medical history (P = 0.046, OR = 1.836, 95% CI 1.011 ~ 3.334), pregnancy complications (P = 0.022, OR = 2.015, 95% CI 1.109 ~ 3.662), worry about dystocia (P = 0.003, OR = 2.365, 95% CI 1.347 ~ 4.153), recent major negative life events (P = 0.011, OR = 3.661, 95% CI 1.341 ~ 9.993). No protective or risk factors were identified for low-risk group. CONCLUSION: Even the incidence and levels of depression in the first trimester of pregnancy were the highest, the probability of pregnancy women get depression during gestation period were higher than other population. Therefore, it's important to monitor the psychological status of pregnant women during the whole pregnancy, especially in the first trimester. The study suggested a good partner relationship and good relations with parents-in-law both protected pregnant women from depression and promoted the well-being of mothers and children.

Living Cell Nanoporation and Exosomal RNA Analysis Platform for Real-Time Assessment of Cellular Therapies.

Efficient transfection of therapeutic agents and timely potency testing are two key factors hindering the development of cellular therapy. Here we present a cellular-nanoporation and exosome assessment device, a quantitative platform for nanochannel-based cell electroporation and exosome-based in situ RNA expression analysis. In its application to transfection of anti-miRNAs and/or chemotherapeutics into cells, we have systematically described the differences in RNA expression in secreted exosomes and assessed cellular therapies in real time.

Functional Characterization of the GlcNAc Catabolic Pathway in Cryptococcus deneoformans.

The amino sugar N-acetyl-d-glucosamine (GlcNAc) is the key constituent of cell wall components and plays an important role in pathogenesis in a wide range of fungi. However, catabolism of GlcNAc has not been studied in basidiomycete fungi. In this study, we identified and characterized a gene cluster essential for GlcNAc utilization in Cryptococcus deneoformans, an environmental human fungal pathogen. The C. deneoformans genome contains a GlcNAc transporter (Ngt1), a GlcNAc kinase (Hxk3), a GlcNAc-6-phosphate deacetylase (Dac1), and a glucosamine-6-phosphate deaminase (Nag1). Their expression levels were highly induced in cultures containing GlcNAc as the sole carbon source, and the corresponding mutants showed severe growth defects in the presence of GlcNAc. Functional and biochemical analyses revealed that HXK3 encodes a novel GlcNAc kinase. Site-directed mutations of conserved residues of Hxk3 indicated that ATP binding and GlcNAc binding are essential for GlcNAc kinase activities. Taken together, the results from this study provide crucial insights into basidiomycete GlcNAc catabolism. IMPORTANCEN-Acetylglucosamine (GlcNAc) is recognized as not only the building block of chitin but also an important signaling molecule in fungi. The catabolic pathway of GlcNAc also plays an important role in vital biological processes in fungi. However, the utilization pathway of GlcNAc in the phylum Basidiomycota, which contains more than 41,000 species, remains unknown. Cryptococcus deneoformans is a representative basidiomycetous pathogen that causes life-threatening meningitis. In this study, we characterized a gene cluster essential for GlcNAc utilization in C. deneoformans and identified a novel GlcNAc kinase. The results of this study provide important insights into basidiomycete GlcNAc catabolism and offer a starting point for revealing its role in pathogenesis.

Quantify individual variation of real-time PM2.5 exposure in urban Chinese homes based on a novel method.

Fine particulate matter (PM2.5 ) concentrations show high variations in different microenvironments indoors, which has considerable impact on risk management. However, the real-time variations of PM2.5 exposure associated with per activity/microenvironment and intra-variation among family members remain undefined. In this study, real-time monitors were used to collect real-time PM2.5 data in different microenvironments in 32 households in urban community of China. Peak concentrations of PM2.5 were found in kitchen. The parallel levels of PM2.5 household indoor and outdoor indicated the benefit of clean energies use. To validly assess the health risk of individuals, we proposed a novel method to estimate the real-time exposure of all residents and firstly investigate the intra-variation of PM2.5 exposure among family members. The member who is responsible for cooking in the family had the maximum PM2.5 exposure. The ratios among intraindividual variations demonstrated children usually had lower exposure compared to the adults as they stayed more time in lower polluted microenvironments such as living room and bedroom. The exposure intensity in living room was above 1.0 for most residents, indicating it is warranted to alleviate the air pollution in living room. This study firstly focused on the intra differences of PM2.5 exposure among family members and provided a new insight for indoor air pollution management. The results suggested when adopting measures to reduce exposure, the microenvironments pattern of each member should be taken into consideration. Future work is welcomed to move another big step on this issue to protect the human health.

Functional Characterization of Flavanone 3-Hydroxylase (F3H) and Its Role in Anthocyanin and Flavonoid Biosynthesis in Mulberry.

Mulberry (Morus spp., Moraceae) is an important economic crop plant and is rich in flavonoids and anthocyanidins in ripe fruits. Anthocyanins are glycosides of anthocyanidins. Flavanone 3-hydroxylase (F3H) catalyzes the conversion of naringenin into dihydroflavonols and is responsible for the biosynthesis of flavonols and anthocyanidins. In this study, MazsF3H was cloned and characterized from Morus atropurpurea var. Zhongshen 1. Conserved motif analysis based on alignment and phylogenetic analysis indicated that MazsF3H belonged to 2-oxoglutarate-dependent dioxygenase and MazsF3H clustered with F3Hs from other plants. MazsF3H was located in both nucleus and cytosol. MazsF3H was expressed in stems, leaves, stigmas and ovaries, except buds. F3H expression levels showed a positive and close relationship with anthocyanin content during the anthocyanin-rich fruit ripening process, while it showed a negative correlation with anthocyanin content in LvShenZi, whose fruits are white and would not experience anthocyanin accumulation during fruit ripening. Significantly different F3H expression levels were also found in different mulberry varieties that have quite different anthocyanin contents in ripe fruits. Overexpression MazsF3H in tobacco showed unexpected results, including decreased anthocyanin content. Down-regulation of F3H expression levels resulted in co-expression of the genes involved in anthocyanin biosynthesis and a significant decrease in anthocyanin content, but the change in total flavonoid content was subtle. Our results indicated that F3H may play quite different roles in different varieties that have quite different fruit colors. In addition, possible complex regulation of flavonoid biosynthesis should be further explored in some of the featured plant species.

Knockdown of Trop2 inhibits proliferation and migration and induces apoptosis of endometrial cancer cells via AKT/ß-catenin pathway.

Endometrial cancer (EC) is the most common gynaecologic malignancy in western countries and has been reported to account for about 7% of female malignant tumours and 20% to 30% of female genital system malignant tumours. Accumulating evidence showed the expression of human trophoblast cell surface antigen 2 (Trop2) was abnormal in many cancers; however, the expression and role of Trop2 in EC are not clear. The Trop-2 protein expression was detected by western blot in EC cells. Cell proliferation, apoptosis, and migration were measured by CCK-8, flow cytometry, and Transwell assay, respectively. The epithelial mesenchymal transition (EMT) and AKT/ß-catenin signalling pathway-related proteins in EC cell lines were detected by western blot assay following Trop2 gene silencing. The present study revealed that the Trop2 protein was highly expressed in EC cell lines compared with human endometrial epithelial cells. The Trop2 mRNA and protein were obviously decreased following transfection with Trop2-siRNA sequence in KLE and Ishikawa cells. Meanwhile, Trop2 gene silencing in KLE and Ishikawa cells strongly inhibited cell proliferation and migration and increased cell apoptosis. Investigation into the molecular mechanism indicated that the Trop2 gene silencing suppressed EMT and AKT/ß-catenin signalling pathway activation. SIGNIFICANCE OF THE STUDY: These findings suggested that Trop2 silencing inhibited EC cell proliferation and migration and promoted cell apoptosis. The mechanism might be related to the inhibition of the AKT/ß-catenin signalling pathway in EC cells. Therefore, Trop2 may be a potential therapeutic target for the treatment of EC.

Association between social and family support and antenatal depression: a hospital-based study in Chengdu, China.

BACKGROUND: Antenatal depression (AD) is considered as one of the major health burdens and has adverse effects on the outcome of expectant mothers and newborns. The present study aims to investigate the prevalence of antenatal depression (AD), and to explore the potential risk factors of AD among pregnant women in Chengdu, including personal background, related social factors, family factors and cognitive factors. METHODS: The prospective nested case-control study included pregnant women who were in their second pregnancy and attended prenatal care at three tertiary hospitals and one regional hospital in Chengdu, China, between March 2015 and May 2016. Self-designed questionnaires were given to participants in their second and third trimesters to collect information on clinical and demographic characteristics, and a modified edition of Edinburgh Postnatal Depression Scale (EPDS) were used to measure AD. The logistic regression was applicated in analyses. RESULTS: A total of 996 pregnant women were included in analysis. Ninety-three women suffered from AD symptoms only in their second trimester, 96 only in their third trimester, and 107 displayed persistent depression in both trimesters. In the univariate analyses, age and marital relationships were linked with AD occurrence in both second and third trimester. In addition, increasing age, full-time job, higher education level, and no gender preference of spouse were associated with reduced persistent depression. Multivariate analysis showed that gender preference and marital relationship were the potential risk factors of persistent depression. CONCLUSIONS: Age, marital relationship relationships, with parents-in-law, the negative recognition of this pregnancy and husband's gender preference were found as risk factors of AD occurrence in some specific trimester. Gender preference of husbands and marital relationships were independently associated with persistent depression. These findings suggest that stronger family support can help improve mental health of pregnant women.

A Rice PECTATE LYASE-LIKE Gene Is Required for Plant Growth and Leaf Senescence.

To better understand the molecular mechanisms behind plant growth and leaf senescence in monocot plants, we identified a mutant exhibiting dwarfism and an early-senescence leaf phenotype, termed dwarf and early-senescence leaf1 (del1). Histological analysis showed that the abnormal growth was caused by a reduction in cell number. Further investigation revealed that the decline in cell number in del1 was affected by the cell cycle. Physiological analysis, transmission electron microscopy, and TUNEL assays showed that leaf senescence was triggered by the accumulation of reactive oxygen species. The DEL1 gene was cloned using a map-based approach. It was shown to encode a pectate lyase (PEL) precursor that contains a PelC domain. DEL1 contains all the conserved residues of PEL and has strong similarity with plant PelC. DEL1 is expressed in all tissues but predominantly in elongating tissues. Functional analysis revealed that mutation of DEL1 decreased the total PEL enzymatic activity, increased the degree of methylesterified homogalacturonan, and altered the cell wall composition and structure. In addition, transcriptome assay revealed that a set of cell wall function- and senescence-related gene expression was altered in del1 plants. Our research indicates that DEL1 is involved in both the maintenance of normal cell division and the induction of leaf senescence. These findings reveal a new molecular mechanism for plant growth and leaf senescence mediated by PECTATE LYASE-LIKE genes.

Hericium caput-medusae (Bull.:Fr.) Pers. polysaccharide enhance innate immune response, immune-related genes expression and disease resistance against Aeromonas hydrophila in grass carp (Ctenopharyngodon idella).

The objective was to add 0, 400, 800 or 1200 mg/kg of Hericium caput-medusae polysaccharide (HCMP) to the basal diet of grass carp (Ctenopharyngodon idella) and determine effects on humoral innate immunity, expression of immune-related genes and disease resistance. Adding HCMP enhanced (P < 0.05) bactericidal activity at 1, 2 and 3 weeks and also lysozyme activity, complement C3, and SOD activity at 2 and 3 weeks. Supplementing 800 or 1200 mg/kg of HCMP for 2 or 3 weeks increased (P < 0.05) serum concentrations of total protein, albumin and globulin. Two immune-related genes (IL-1ß and TNF-α) were up-regulated (P < 0.05) in HCMP supplemented groups given 800 or 1200 mg/kg HCMP after 2 and 3 weeks of feeding. Expression of anti-inflammatory cytokine IL-10 was down-regulated (P < 0.05) after receiving 800 or 1200 mg/kg HCMP for 2 or 3 weeks. Fish fed 800 mg/kg HCMP had maximal disease resistance against Aeromonas hydrophila (65.4%). In conclusion, HCMP enhanced immune response and expression of immune-related genes and increased disease resistance against Aeromonas hydrophila in grass carp, with greatest effects in fish given 800 mg/kg HCMP for 3 weeks.

PGL, encoding chlorophyllide a oxygenase 1, impacts leaf senescence and indirectly affects grain yield and quality in rice.

Chlorophyll (Chl) b is a ubiquitous accessory pigment in land plants, green algae, and prochlorophytes. This pigment is synthesized from Chl a by chlorophyllide a oxygenase and plays a key role in adaptation to various environments. This study characterizes a rice mutant, pale green leaf (pgl), and isolates the gene PGL by using a map-based cloning approach. PGL, encoding chlorophyllide a oxygenase 1, is mainly expressed in the chlorenchyma and activated in the light-dependent Chl synthesis process. Compared with wild-type plants, pgl exhibits a lower Chl content with a reduced and disorderly thylakoid ultrastructure, which decreases the photosynthesis rate and results in reduced grain yield and quality. In addition, pgl exhibits premature senescence in both natural and dark-induced conditions and more severe Chl degradation and reactive oxygen species accumulation than does the wild-type. Moreover, pgl is sensitive to heat stress.

Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation.

Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer.

Different perceptions of stress, coping styles, and general well-being among pregnant Chinese women: a structural equation modeling approach.

Few studies have examined different perceptions of stress or explored the positive aspects of well-being among pregnant Chinese women, so there is a need to explore these phenomena in order to fill the research gap. The aim of this study was to examine the relationships among the different perceptions of stress, coping styles, and general well-being using a structural equation modeling approach. We examined a hypothetical model among 755 pregnant Chinese women based on the integration of theoretical models. The Perceived Stress Scale (PSS), the Trait Coping Styles Questionnaire (TCSQ), and the General Well-Being Schedule (GWB) were used to measure perceived stress, coping styles, and general well-being, respectively. A structural equation model showed that positive and negative perceptions of stress significantly influenced positive and negative coping styles, respectively. Different perceptions of stress were significantly associated with general well-being, but different coping styles had no significant effects on general well-being. The model had a good fit to the data (IFI = 0.910, TLI = 0.904, CFI = 0.910, and RMSEA = 0.038). Different perception of stress was able to predict significant differences in coping styles and general well-being.

The roles of social support in helping chinese women with antenatal depressive and anxiety symptoms cope with perceived stress.

A community-based sample of 755 pregnant Chinese women were recruited to test the direct and moderating effects of social support in mitigating perceived stress associated with antenatal depressive or anxiety symptoms. The Social Support Rating Scale, the Perceived Stress Scale, the Edinburgh Depressive Postnatal Scale and the Zung Self-Rating Anxiety Scale were used. Social support was found to have direct effects and moderating effects on the women's perceived stress on antenatal depressive and anxiety symptoms in multiple linear regression models. This knowledge of the separate effects of social support on behavioral health is important to psychiatric nurse in planning preventive interventions.

Effect of Lentinus sajor-caju on the chemical composition and antioxidant activity of highland barley straw under solid-state fermentation.

Introduction: The efficient utilization of straw resources as animal feed has gained considerable attention. The objective of this study was to evaluate whether Lentinus sajor-caju treatment alters the chemical composition and antioxidant activity of highland barley straw and enhances its functional value as a ruminant feed. Methods: The chemical composition, antioxidant capacity, and metabolomic profile of highland barley straw were determined after 21 days of solid-state fermentation with L. sajor-caju at 25°C. The differential metabolites between fermented and unfermented highland barley straw were identified by LC-MS and the relationship between the identified metabolites and antioxidant capacity was elucidated. Results: The results showed that, compared with untreated highland barley straw, the crude protein and ether extract contents were higher (51.55 and 76.43%, respectively) in highland barley straw after 21 days of incubation with L. sajor-caju, whereas the hemicellulose, cellulose, and acid detergent lignin contents were lower (2.48, 25.08, and 45%, respectively). The total antioxidant capacity was significantly higher in L. sajor-caju-treated than in untreated highland barley straw. In total, 600 differential metabolites (301 upregulated and 299 downregulated) were identified between L. sajor-caju-fermented and unfermented highland barley straw. Correlation analysis results showed that Fe2+ scavenging and total phenolic content were strongly correlated with total antioxidant capacity. Meanwhile, the differential flavonoid metabolites between fermented and unfermented highland barley straw were primarily associated with antioxidant activity, with kaempferol 3-xylosylglucoside, isoginkgetin, and rhoifolin being the most representative. Conclusion: Thus, this study demonstrates that L. sajor-caju could enhance the functional value of highland barley straw, showing the potential of L. sajor-caju for improving the utilization of agricultural straws in ruminants.

Renal Replacement Therapy as a New Indicator of Voriconazole Clearance in a Population Pharmacokinetic Analysis of Critically Ill Patients.

AIMS: The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of using extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and those of various biological covariates on the voriconazole PK profile. METHODS: Modeling analyses of the PK parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) with a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different stratifications of quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges. RESULTS: A total of 408 critically ill patients with 746 voriconazole concentration-time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CLCR), platelets (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM. CONCLUSIONS: We found that qCRP, CRRT, CLCR, PLT, and PT affected the voriconazole clearance. The most commonly used clinical regimen of 200 mg q12h was sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L), regardless of whether CRRT was performed and the level of qCRP. When the MIC was 0.5 mg/L, 200 mg q12h was insufficient only when the qCRP was <40 mg/L and CRRT was performed. When the MIC was ≥2 mg/L, a dose of 300 mg q12h could not achieve ≥ 90% PTA, necessitating the evaluation of a higher dose.

The Functional Characterization of MaGS2 and Its Role as a Negative Regulator of Ciboria shiraiana.

Glutamine synthetase (GS) is a key enzyme involved in nitrogen metabolism. GS can be divided into cytosolic and plastidic subtypes and has been reported to respond to various biotic and abiotic stresses. However, little research has been reported on the function of GS in mulberry. In this study, the full length of MaGS2 was cloned, resulting in 1302 bp encoding 433 amino acid residues. MaGS2 carried the typical GS2 motifs and clustered with plastidic-subtype GSs in the phylogenetic analysis. MaGS2 localized in chloroplasts, demonstrating that MaGS2 is a plastidic GS. The expression profile showed that MaGS2 is highly expressed in sclerotiniose pathogen-infected fruit and sclerotiniose-resistant fruit, demonstrating that MaGS2 is associated with the response to sclerotiniose in mulberry. Furthermore, the overexpression of MaGS2 in tobacco decreased the resistance against Ciboria shiraiana, and the knockdown of MaGS2 in mulberry by VIGS increased the resistance against C. shiraiana, demonstrating the role of MaGS2 as a negative regulator of mulberry resistance to C. shiraiana infection.

Functional characterization of MaEXPA11 and its roles in response to biotic and abiotic stresses in mulberry.

Mulberry is a traditional economic tree with various values in sericulture, ecology, food industry and medicine. Expansins (EXPs) are known as cell wall expansion related proteins and have been characterized to involve in plant development and responses to diverse stresses. In present study, twenty EXP and expansin-like (EXL) genes were identified in mulberry. RNA-seq results indicated that three EXP and EXL genes showed up-regulated expression level under sclerotiniose pathogen infection in three independent RNA-seq datasets. The most significant upregulated EXPA11 was selected as key EXP involving in response to sclerotiniose pathogen infection in mulberry. Furthermore, a comprehensive functional analysis was performed to reveal subcellular location, tissue expression profile of MaEXPA11 in mulberry. Down-regulation of MaEXPA11 using virus induced gene silence (VIGS) was performed to explore the function of MaEXPA11 in Morus alba. Results showed that MaEXPA11 can positively regulate mulberry resistance to Ciboria shiraiana infection and negatively regulate mulberry resistance to cold or drought stress.

Lnc-PLCB1 is stabilized by METTL14 induced m6A modification and inhibits Helicobacter pylori mediated gastric cancer by destabilizing DDX21.

Helicobacter pylori (H. pylori) infection is considered to be an important factor in gastric cancer (GC). Long noncoding RNA (lncRNA) and m6A modification are involved in the occurrence and development of GC, but the role of lncRNA m6A modification in the development of GC mediated by H. pylori is still unclear. Here, we found that H. pylori infection downregulated the expression of lnc-PLCB1 through METTL14-mediated m6A modification and IRF2-mediated transcriptional regulation. Overexpression of lnc-PLCB1 inhibited the proliferation and migration of GC cells, while downregulation of lnc-PLCB1 promoted the proliferation and migration ability of GC cells. In addition, clinical analysis showed that lnc-PLCB1 is lower in GC tissues than in normal tissues. Further study found that lnc-PLCB1 reduced the protein stability of its binding protein DEAD-box helicase 21 (DDX21) and then downregulated the expression of CCND1 and Slug, thereby playing tumour suppressing role in the occurrence and development of GC. In conclusion, the METTL14/lnc-PLCB1/DDX21 axis plays an important role in H. pylori-mediated GC, and lnc-PLCB1 can be used as a new target for GC treatment.

Tracking and navigation of a microswarm under laser speckle contrast imaging for targeted delivery.

Micro/nanorobotic swarms consisting of numerous tiny building blocks show great potential in biomedical applications because of their collective active delivery ability, enhanced imaging contrast, and environment-adaptive capability. However, in vivo real-time imaging and tracking of micro/nanorobotic swarms remain a challenge, considering the limited imaging size and spatial-temporal resolution of current imaging modalities. Here, we propose a strategy that enables real-time tracking and navigation of a microswarm in stagnant and flowing blood environments by using laser speckle contrast imaging (LSCI), featuring full-field imaging, high temporal-spatial resolution, and noninvasiveness. The change in dynamic convection induced by the microswarm can be quantitatively investigated by analyzing the perfusion unit (PU) distribution, offering an alternative approach to investigate the swarm behavior and its interaction with various blood environments. Both the microswarm and surrounding environment were monitored and imaged by LSCI in real time, and the images were further analyzed for simultaneous swarm tracking and navigation in the complex vascular system. Moreover, our strategy realized real-time tracking and delivery of a microswarm in vivo, showing promising potential for LSCI-guided active delivery of microswarm in the vascular system.