Exposure to PM2.5 and its constituents is associated with metabolic dysfunction-associated fatty liver disease: a cohort study in Northwest of China.

Accumulating animal studies have demonstrated associations between ambient air pollution (AP) and metabolic dysfunction-associated fatty liver disease (MAFLD), but relevant epidemiological evidence is limited. We evaluated the association of long-term exposure to AP with the risk of incident MAFLD in Northwest China. The average AP concentration between baseline and follow-up was used to assess individual exposure levels. Cox proportional hazard models and restricted cubic spline functions (RCS) were used to estimate the association of PM2.5 and its constituents with the risk of MAFLD and the dose-response relationship. Quantile g-computation was used to assess the joint effects of mixed exposure to air pollutants on MAFLD and the weights of the various pollutants. We observed 1516 cases of new-onset MAFLD, with an incidence of 10.89%. Increased exposure to pollutants was significantly associated with increased odds of MAFLD, with hazard ratios (HRs) of 2.93 (95% CI: 1.22, 7.00), 2.86 (1.44, 5.66), 7.55 (3.39, 16.84), 4.83 (1.89, 12.38), 3.35 (1.35, 8.34), 1.89 (1.02, 1.62) for each interquartile range increase in PM2.5, SO42-, NO3-, NH4+, OM, and BC, respectively. Stratified analyses suggested that females, frequent exercisers and never-drinkers were more susceptible to MAFLD associated with ambient PM2.5 and its constituents. Mixed exposure to SO42-, NO3-, NH4+, OM and BC was associated with an increased risk of MAFLD, and the weight of BC had the strongest effect on MAFLD. Exposure to ambient PM2.5 and its constituents increased the risk of MAFLD.

Association between urinary polycyclic aromatic hydrocarbons and risk of metabolic associated fatty liver disease.

OBJECTIVE: To investigate the effect of urinary PAHs on MAFLD. METHODS: The study included 3,136 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2016. Among them, 1,056 participants were diagnosed with MAFLD and were designated as the case group. The analysis of the relationship between monohydroxy metabolites of seven PAHs in urine and MAFLD was carried out using logistic regression and Bayesian kernel regression (BKMR) models. RESULTS: In single-pollutant models, the concentration of 2-hydroxynaphthalene (2-OHNAP) was positively correlated with MAFLD (OR = 1.47, 95% CI 1.18, 1.84), whereas 3-hydroxyfluorene (3-OHFLU) and 1-hydroxypyrene (1-OHPYR) demonstrated a negative correlation with MAFLD (OR = 0.59, 95% CI 0.48 0.73; OR = 0.70, 95% CI 0.55, 0.89). Conversely, in multi-pollutant models, 2-OHNAP, 2-hydroxyfluorene (2-OHFLU), 2-hydroxyphenanthrene, and 3-hydroxyphenanthrene (2&3-OHPHE) displayed positive correlations with MAFLD (OR = 6.17, 95% CI 3.15, 12.07; OR = 2.59, 95% CI 1.37, 4.89). However, 3-OHFLU and 1-OHPYR continued to exhibit negative correlations with MAFLD (OR = 0.09, 95% CI 0.05, 0.15; OR = 0.62, 95% CI 0.43, 0.88). Notably, the BKMR analysis mixtures approach did not indicate a significant joint effect of multiple PAHs on MAFLD, but identified interactions between 3-OHFLU and 2-OHFLU, 1-OHPYR and 2-OHFLU, and 1-OHPYR and 3-OHFLU. CONCLUSION: No significant association was found between mixed PAHs exposure and the risk of MAFLD. However, interactions were observed between 3-OHFLU and 2-OHFLU. Both 2-OHFLU and 2&3-OHPHE exposure are significant risk factors for MAFLD, whereas 3-OHFLU is a key protective factor for the disease.

Preparation and Application of Degradable Lignin/Poly (Vinyl Alcohol) Polymers as Urea Slow-Release Coating Materials.

The massive amount of water-soluble urea used leads to nutrient loss and environmental pollution in both water and soil. The aim of this study was to develop a novel lignin-based slow-release envelope material that has essential nitrogen and sulfur elements for plants. After the amination reaction with a hydrolysate of yak hair keratin, the coating formulation was obtained by adding different loadings (2, 5, 8, 14 wt%) of aminated lignin (AL) to 5% polyvinyl alcohol (PVA) solution. These formulations were cast into films and characterized for their structure, thermal stability, and mechanical and physicochemical properties. The results showed that the PVA-AL (8%) formulation had good physical and chemical properties in terms of water absorption and mechanical properties, and it showed good degradation in soil with 51% weight loss after 45 days. It is suitable for use as a coating material for fertilizers. Through high-pressure spraying technology, enveloped urea particles with a PVA-AL (8%) solution were obtained, which showed good morphology and slow-release performance. Compared with urea, the highest urea release was only 96.4% after 30 days, conforming to Higuchi model, Ritger-Peppas model, and second-order dynamic model. The continuous nitrogen supply of PVA-AL coated urea to Brassica napus was verified by potting experiments. Therefore, the lignin-based composite can be used as a coating material to produce a new slow-release nitrogen fertilizer for sustainable crop production.

Exploration of Holistic Nursing Strategy for Diabetic Patients with Pulmonary Tuberculosis.

Objective: To explore the application effect of comprehensive nursing based on medical-care integration in diabetic patients with pulmonary tuberculosis. Methods: 80 diabetic patients with pulmonary tuberculosis who were treated at Affiliated Hospital of Hebei University from March 2022 to March 2023 were randomly divided into the routine nursing group and the comprehensive nursing group. The routine nursing group received conventional nursing care, while the comprehensive nursing group received comprehensive nursing based on medical-care integration and routine care. The blood glucose levels, tuberculosis cure rate, negative emotions, quality of life, and satisfaction with nursing care were compared before and after nursing in both groups. Results: After receiving comprehensive nursing care, participants had lower fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin levels than those who received routine nursing care. Compared to patients receiving standard care, patients under comprehensive care demonstrated increased rates of tuberculosis lesion resolution and tuberculosis bacilli conversion. The assessments of patients' negative emotions using SAS and SDS scores showed lower levels, while their scores for physiological, psychological, and social functions were higher. Additionally, they reported heightened levels of satisfaction with nursing care. Conclusion: The provision of comprehensive nursing based on medical-care integration for patients suffering from diabetes complicated by pulmonary tuberculosis by medical and nursing personnel is advantageous for fostering amelioration in the clinical manifestations of individuals afflicted with this condition. Additionally, it facilitates patients' recuperation while significantly enhancing their emotional well-being, quality of life, and nursing satisfaction.

Developing a prognosis and chemotherapy evaluating model for colon adenocarcinoma based on mitotic catastrophe-related genes.

Mitotic catastrophe (MC) is a novel form of cell death that plays an important role in the treatment and drug resistance of colon adenocarcinoma (COAD). However, MC related genes in COAD treatment and prognosis evaluation are rarely studied. In this study, the transcriptome data, somatic mutation and copy number variation data were obtained from The Cancer Genome Atlas (TCGA) database. The mitotic catastrophe related genes (MCRGs) were obtained from GENCARDS website. Differential gene analysis was conducted with LIMMA package. Univariate Cox regression analysis was used to identify prognostic related genes. Mutation analysis was performed and displayed by maftools package. RCircos package was used for localizing the position of genes on chromosomes. "Glmnet" R package was applied for constructing a risk model via the LASSO regression method. Consensus clustering analyses was implemented for clustering different subtypes. Functional enrichment analysis through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods, immune infiltration analysis via single sample gene set enrichment analysis (ssGSEA), tumor mutation burden and drug sensitivity analysis by pRRophetic R package were also carried out for risk model or molecular subtype's assessment. Additionally, the connections between the expression of hub genes and overall survival (OS) were obtained from online Human Protein Atlas (HPA) website. Real-Time Quantitative Polymerase Chain Reaction (RT­qPCR) further validated the expression of hub genes. A total of 207 differentially expressed MCRGs were selected in the TCGA cohort, 23 of which were significantly associated with OS in COAD patients. Subsequently, we constructed risk score prognostic models with 5 hub MCRGs, including SYCE2, SERPINE1, TRIP6, LIMK1, and EEPD1. The high-risk patients suffered from poorer prognosis. Furthermore, we developed a nomogram that gathered age, sex, staging, and risk score to accurately forecast the clinical survival outcomes in 1, 3, and 5 years. The results of functional enrichment suggested a significant correlation between MCRGs characteristics and cancer progression, with important implications for the immune microenvironment. Moreover, patients who displayed high TMB and high risk score showed worse prognosis, and risk characteristics were associated with different chemotherapeutic agents. Finally, RT­qPCR verified the increased expression of the five MCRGs in clinical samples. The five MCRGs in the prognostic signature were associated with prognosis, and could be treated as reliable prognostic biomarkers and therapeutic targets for COAD patients with distinct clinicopathological characteristics, thereby providing a foundation for the precise application of pertinent drugs in COAD patients.

Sesquiterpene coumarins from Ferula sinkiangensis and their anti-pancreatic cancer effects.

Eight previously unreported sesquiterpene coumarins, namely (+)- and (-)-ferulasinkian A (1), (-)-fukanefuromarin M (2), (±)-ferulasinkian C (3), (±)-ferulasinkian D (4), ferulasinkian E (5), ferulasinkian F (7), and ferulasinkian G (8), together with two known compounds, (+)-fukanefuromarin M (2) and 7-hydroxyferprenin (6), have been isolated from the roots of Ferula sinkiangensis (Umbelliferae). The structures of all compounds were elucidated by spectroscopic analysis, along with ECD calculations and optical rotation calculations. Compounds 1-6 are dimers consisting of a chain sesquiterpene and a coumarin with an oxygen-containing six-membered ring connected from coumarin C-3 and C-4. Currently, there are only seven such structures reported in the genus Ferula, and their absolute configurations have not yet been determined. Compounds 7-8 are sesquiterpene coumarin derivatives with a chain sesquiterpene connected with coumarin C-4. In the present study, the chiral separation of compounds (±)-1 and (±)-2 was successfully carried out, and the absolute configurations of compounds (±)-1, (±)-2, 5, 7 and 8 were determined. The isolates were evaluated for their cytotoxic activity against human pancreatic cancer cell lines including CFPAC-1, PANC-1, CAPAN-2 and SW 1990. Compounds (+)-1, (-)-1 and 7 exhibited potent cytotoxicity against pancreatic cancer cells with IC50 values ranging from 4.57 ± 0.94 to 14.01 ± 1.03 µM. Furthermore, the primary mechanistic study of (-)-1 demonstrated that it could induce apoptosis in CFPAC-1 cells.

The characteristics of the urogenital fascia in the retrorectal space based on male cadaveric dissection and its clinical application.

BACKGROUND: The architecture of retrorectal fasciae is complex, as determined by different anatomical concepts. The aim of this study was to examine the anatomical characteristics of the inferomedial extension of the urogenital fascia (UGF) involving the pelvis to explore its relationship with the adjacent fasciae. Furthermore, we have expounded on the clinical application of UGF. METHOD: For our study, we examined 20 adult male pelvic specimens fixed in formalin, including 2 entire pelvic specimens and 18 semipelvic specimens. Our department has performed 466 laparoscopic rectal cancer procedures since January 2020. We reviewed the surgical videos involving UGF preservation and analyzed the anatomy of the UGF. RESULTS: The bilateral hypogastric nerves ran between the visceral and parietal layers of the UGF. The visceral fascia migrated ventrally at the fourth sacral vertebra, which formed the rectosacral fascia together with the fascia propria of the rectum; the parietal layer continually extended to the pelvic diaphragm, terminating at the levator ani muscle. At the third to fourth sacral vertebra level, the two layers constituted the lateral ligaments. CONCLUSION: The double layers of the UGF are vital structures for comprehending the posterior fascia relationship of the rectum. The upper segment between the fascia propria of the rectum and the visceral layer has no evident nerves or blood vessels and is regarded as the " holy plane" for the operation.

The "Y"-shaped Denonvilliers' fascia and its adjacent relationship with the urogenital fascia based on a male cadaveric anatomical study.

BACKGROUND: Controversies regarding the anatomical structure of Denonvilliers' fascia and its relationship with surrounding fasciae have sparked a heated discussion, especially concerning whether Denonvilliers' fascia is multilayered. This study aimed to expound on the anatomical structure of Denonvilliers' fascia and its correlation with the peritoneum from the sagittal view and clarify the complex fascial relationship. METHODS: Our study was performed on 20 adult male pelvic specimens fixed in formalin, including 2 entire pelvic specimens and 18 semipelvic specimens. The local adjacent organs and fasciae were dissected, and Denonvilliers' fascia was observed and removed for histological examination. RESULTS: Denonvilliers' fascia was typically single-layered and tough. On the sagittal plane, the peritoneum constituting the peritoneal reflection and Denonvilliers' fascia formed a "Y" shape. Denonvilliers' fascia originated from the peritoneal reflection, extended along the ventral side of the seminal vesicles and prostate, continuing caudally; its bilateral sides closely connected to the urogenital fascia (UGF) of the pelvic wall. In addition, histology preliminarily indicated that the basal cell layers of the peritoneum and Denonvilliers' fascia were continuous and formed a "Y" shape. Furthermore, the basal cells of the two peritonea extended to Denonvilliers' fascia, creating a fused double-layered structure. Some tiny blood vessels or a network of such vessels extended from the peritoneum to Denonvilliers' fascia. CONCLUSION: Denonvilliers' fascia, the extension of the peritoneum in the pelvic floor, appears as a single-layered "Y"-shape on the sagittal plane. Our study provides new support for the peritoneal fusion theory. Understanding the anatomical characteristics of Denonvilliers' fascia and its relationship with the UGF is of guiding significance for inexperienced colorectal surgeons to conduct rectal cancer surgery.

Antirheumatoid Arthritic Effects of Sabia parviflora Wall. Leaf Extracts via the NF-κB Pathway and Transient Receptor Potential Protein Family.

As an important traditional medicine of Buyi and Miao ethnic groups in Guizhou, Sabia parviflora Wall. provides antiviral properties against hepatitis, eliminates wind and dampness, and exhibits anti-inflammatory and pain relief properties. It has also been shown to treat rheumatoid arthritis (RA) and other diseases. However, the pharmacodynamic mechanism of S. parviflora Wall. for RA has not been reported. In this study, we identified the effective compounds of S. parviflora Wall. leaves against RA and discussed the mechanism against complete Freund's adjuvant-induced arthritis (AIA) based on inflammatory proteins and transient receptor potential (TRP) proteins. S. parviflora Wall. leaf extracts (0.64 g/kg, 0.32 g/kg, and 0.16 g/kg, once daily) were given orally for 21 days. On the 15th day of complete Freund's adjuvant-induced RA, the effects of this medicine on RA rats were investigated. S. parviflora Wall. extracts increased body weight, decreased foot swelling, and reduced thymus and spleen indices in model rats. Most of pannus in the synovial tissue of RA rats disappeared upon treatment, and the local inflammatory cells were greatly reduced when given the fraction of n-butanol (0.64 g/kg/d, 0.32 g/kg/d, and 0.16 g/kg/d) of 70% alcohol-soluble fraction of S. parviflora Wall. leaves. In addition, the release of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-15 (IL-15), and vascular endothelial growth factor (VEGF) in the RA rat serum was inhibited. The active compounds inhibited the expression of TNF-α, IL-1ß, IL-6, IL-10, IL-15 and nuclear factor kappa-Bp65 (NF-κBp65) inflammatory protein and TRP protein transient receptor potential melastatin-5 (TRPM-5) and transient receptor potential channel-6 (TRPC-6), to reduce the expression of VEGF in synovial tissue of RA rats and relieve redness and edema. High-performance liquid chromatography identified six flavonoids and three triterpenoid saponins as active compounds. These findings suggest S. parviflora Wall. leaves may play a role in RA treatment by inhibiting the release of inflammatory factors as well as participating in the inflammatory protein expression in the NF-κB pathway and TRP protein family.

Comparison Between Hemodialysis and Peritoneal Dialysis in the Risks for Disease Activity in LN-ESRD Patients: A Systematic Review and Meta-analysis.

Context: End-stage renal disease (ESRD) is the advanced stage of a progressive loss of kidney function. About 10% of all patients with lupus nephritis (LN) eventually progress to ESRD, which may necessitate renal replacement therapy (RRT), such as hemodialysis (HD), peritoneal dialysis (PD), and/or kidney transplant. Research hasn't confirmed which dialysis options, prior to kidney transplantation, are beneficial to patients' prognoses. Objective: The study intended to compare the risks-related to disease activity, exercise, all-cause infection, all-cause cardiovascular events, and mortality-of the use of HD and PD for LN-ESRD adults, as the initial alternative treatment before renal transplantation. Design: The research team performed a narrative review and analyzed the data obtained about clinical outcomes for HD and peritoneal dialysis. For the review, the research team searched the PubMed, EMBASE, and SCOPUS databases. The search used the keywords: end-stage renal disease, renal replacement therapy, hemodialysis and peritoneal dialysis. Setting: The study made in Affiliated Hospital of Hebei University, China. Participants: The studies included 15 636 patients who had been diagnosed with LN-ESRD prior to renal transplantation. Outcome Measures: For the data analysis, the research team divided the data into two groups, one of which included the data on the clinical outcomes for HD patientsand one of which included the data on the clinical outcomes for PD patients. The study evaluated four types of risks: lupus-flare risks, all-cause infection risks, all-cause cardiovascular events risk, and risk of mortality. Results: The 16 studies found in the review reported one or more outcomes of interest for the two dialysis modalities, HD and PD. The analysis of the data from the 16 studies showed that HD was associated with a higher risk than PD: (1) of lupus flares, with RR = 1.23 (confidence interval: 0.82, 1.85), but the difference didn't reach statistical significance (P = .31); (2) of all-cause infection risk, with RR = 1.02 (confidence interval: 0.66, 1.59), but the difference didn't reach statistical significance (P = .92); (3) of all-cause cardiovascular events, with RR = 1.44 (confidence interval: 1.02, 2.04), and the difference reached statistical significance (P = .04); and (4) of mortality risk, with RR = 1.29 (confidence interval: 0.95, 1.75), but the difference didn't reach statistical significance (P = .10). Conclusions: The current study may have reference significance for clinical treatment of ESRD. Except for all-cause cardiovascular events in which PD was superior to HD, offering better outcomes, both treatment modalities provide more or less similar clinical outcomes as effective initial choices for RRT in LN-ESRD patients prior to renal transplant. The current research team, however, encourages further research on the question, addressing better the possible sources of biases encountered in the current study.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes.

OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes

SUMMARY OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Urogenital fascia anatomy study in the inguinal region of 10 formalin-fixed cadavers: new understanding for laparoscopic inguinal hernia repair.

PURPOSE: To investigate the urogenital fascia (UGF) anatomy in the inguinal region, to provide anatomical guidance for laparoscopic inguinal hernia repair (LIHR). METHODS: The anatomy was performed on 10 formalin-fixed cadavers. The peritoneum and its deeper fascial tissues were carefully dissected. RESULTS: The UGF's bilateral superficial layer extended and ended in front of the abdominal aorta. At the posterior axillary line, the superficial layer medially reversed, with extension represented the UGF's deep layer. The UGF's bilateral deep layer medially extended beside the vertebral body and then continued with the transversalis fascia. The ureters, genital vessels, and superior hypogastric plexus moved between both layers. The vas deferens and spermatic vessels, ensheathed by both layers, moved through the deep inguinal ring. From the deep inguinal ring to the midline, the superficial layer extended to the urinary bladder's posterior wall, whereas the deep layer extended to its anterior wall. Both layers ensheathed the urinary bladder and extended along the medial umbilical ligament to the umbilicus and in the sacral promontory, extended along the sacrum, forming the presacral fascia. The superficial layer formed the rectosacral fascia at S4 sacral vertebra, and the deep layer extended to the pelvic diaphragm, terminating at the levator ani muscle. CONCLUSION: The UGF ensheaths the kidneys, ureters, vas deferens, genital vessels, superior hypogastric plexus, seminal vesicles, prostate, and urinary bladder. This knowledge of the UGF's anatomy in the inguinal region will help find correct LIHR targets and reduce bleeding and other complications.

mTORC1 and mTORC2 Converge on the Arp2/3 Complex to Promote KrasG12D-Induced Acinar-to-Ductal Metaplasia and Early Pancreatic Carcinogenesis.

BACKGROUND & AIMS: Oncogenic KrasG12D induces neoplastic transformation of pancreatic acinar cells through acinar-to-ductal metaplasia (ADM), an actin-based morphogenetic process, and drives pancreatic ductal adenocarcinoma (PDAC). mTOR (mechanistic target of rapamycin kinase) complex 1 (mTORC1) and 2 (mTORC2) contain Rptor and Rictor, respectively, and are activated downstream of KrasG12D, thereby contributing to PDAC. Yet, whether and how mTORC1 and mTORC2 impact on ADM and the identity of the actin nucleator(s) mediating such actin rearrangements remain unknown. METHODS: A mouse model of inflammation-accelerated KrasG12D-driven early pancreatic carcinogenesis was used. Rptor, Rictor, and Arpc4 (actin-related protein 2/3 complex subunit 4) were conditionally ablated in acinar cells to deactivate the function of mTORC1, mTORC2 and the actin-related protein (Arp) 2/3 complex, respectively. RESULTS: We found that mTORC1 and mTORC2 are markedly activated in human and mouse ADM lesions, and cooperate to promote KrasG12D-driven ADM in mice and in vitro. They use the Arp2/3 complex as a common downstream effector to induce the remodeling the actin cytoskeleton leading to ADM. In particular, mTORC1 regulates the translation of Rac1 (Rac family small GTPase 1) and the Arp2/3-complex subunit Arp3, whereas mTORC2 activates the Arp2/3 complex by promoting Akt/Rac1 signaling. Consistently, genetic ablation of the Arp2/3 complex prevents KrasG12D-driven ADM in vivo. In acinar cells, the Arp2/3 complex and its actin-nucleation activity mediated the formation of a basolateral actin cortex, which is indispensable for ADM and pre-neoplastic transformation. CONCLUSIONS: Here, we show that mTORC1 and mTORC2 attain a dual, yet nonredundant regulatory role in ADM and early pancreatic carcinogenesis by promoting Arp2/3 complex function. The role of Arp2/3 complex as a common effector of mTORC1 and mTORC2 fills the gap between oncogenic signals and actin dynamics underlying PDAC initiation.

Further sesquiterpenoids from the rhizomes of Homalomena occulta and their anti-inflammatory activity.

The rhizomes of Homalomena occulta are called Qian-nian-jian in Traditional Chinese Medicine (TCM), which is widely consumed in China owing to its health benefits for the treatment of rheumatoid arthritis and for strengthening tendons and bones. A phytochemical investigation on this famous TCM yielded 19 sesquiterpenoids (1-19) with various carbocyclic skeletons including isodaucane (2, 8, and 9), guaiane (3), eudesmane (4 and 10-15), oppositane (5, 16, and 17), and aromadendrane (18 and 19) types. The structures of new compounds, Homalomenins A-E (1-5), were determined by diverse spectroscopic data. Compound 1 possessed a rare sesquiterpenoid skeleton and compound 5 represented the first example of 1,4-oxa-oppositane sesquiterpenoid. These isolates were evaluated for their inhibitory effects on COX-2 mRNA, COX-2 protein expression, and prostaglandin E2 (PGE2) production in Raw264.7 cells, which demonstrated that compounds 5, 18, 19 showed potent anti-inflammatory activity by suppressing LPS-induced COX-2 expression and PGE2 production in a dose-dependent manner.

The Accumulated Response of Deciduous Liquidambar formosana Hance and Evergreen Cyclobalanopsis glauca Thunb. Seedlings to Simulated Nitrogen Additions.

Nitrogen depositions in the Yangtze River Delta have is thought to shift the coexistence of mixed evergreen and deciduous species. In this study, the seedlings of the dominant evergreen species Cyclobalanopsis glauca Thunb. and the deciduous species Liquidambar formosana Hance from the Yangtze River Delta were chosen to test their responses to simulated N additions using an ecophysiological approach. N was added to the tree canopy at rates of 0 (CK), 25 kg N ha-1 year-1 (N25), and 50 kg N ha-1 year-1 (N50). The leaf N content per mass (N m, by 44.03 and 49.46%) and total leaf chlorophyll content (Chl, by 72.15 and 63.63%) were enhanced for both species, and C. glauca but not L. formosana tended to allocate more N to Chl per leaf area (with a higher slope). The enhanced N availability and Chl promoted the apparent quantum yield (AQY) significantly by 15.38 and 43.90% for L. formosana and C. glauca, respectively. Hydraulically, the increase in sapwood density (ρ) for L. formosana was almost double that of C. glauca. Synchronous improved sapwood specific hydraulic conductivity (K S, by 37.5%) for C. glauca induced a significant reduction in stomatal conductance (g s) (p < 0.05) in the N50 treatments, which is in contrast to the weak varied g s accompanied by a 59.49% increase in K S for L. formosana. As a result, the elevated maximum photosynthesis (A max) of 12.19% for L. formosana in combination with the increase in the total leaf area (indicated by a 37.82% increase in the leaf area ratio-leaf area divided by total aboveground biomass) ultimately yielded a 34.34% enhancement of total biomass. In contrast, the A max and total biomass were weakly promoted for C. glauca. The reason for these distinct responses may be attributed to the lower water potential at 50% of conductivity lost (P 50) for C. glauca, which enables higher hydraulic safety at the cost of a weak increase in Amax due to the stomatal limitation in response to elevated N availability. Altogether, our results indicate that the deciduous L. formosana would be more susceptible to elevated N availability even if both species received similar N allocation.

Ductal obstruction promotes formation of preneoplastic lesions from the pancreatic ductal compartment.

Pancreatitis is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). Previous studies in mice have demonstrated that pancreatitis contributes to oncogenic Kras-driven carcinogenesis, probably initiated in acinar cells; however, oncogenic Kras alone or in combination with caerulein-induced pancreatitis is not sufficient in initiating PDAC from the ductal compartment. We thus introduced ductal obstruction - which induces a more severe form of pancreatitis - by pancreatic ductal ligation in mice harbouring oncogenic Kras. This induced a particular phenotype with highly proliferative nonmucinous cells with nuclear atypia. Around these lesions, there was a significant proliferation of activated fibroblasts and infiltration of immune cells, corroborating the pathological features of preneoplastic lesions. Lineage-tracing experiments revealed that these preneoplastic cells derived from two distinctive cellular sources: acinar and ductal cells. Phenotypic characterisation revealed that the duct-derived preneoplastic lesions show a high proliferative potential with persistent activation of tumour-promoting inflammatory pathways while the acinar-derived ones were less proliferative with persistent p53 activation. Furthermore, the duct-derived preneoplastic cells have a particularly high nuclear-to-cytoplasmic ratio. These data demonstrate that ductal obstruction promotes preneoplastic lesion formation from the pancreatic ductal compartment.

Mesoporous phenylalanine ammonia lyase microspheres with improved stability through calcium carbonate templating.

Cross-linked enzyme aggregates (CLEAs) have recently emerged as a promising method for enzyme immobilization due to its simplicity and low cost. However, a lack of good size and morphological control over the as-prepared CLEAs has limited their practical applications in some cases. Here, monodisperse spherical CLEAs of phenylalanine ammonia lyase (PAL microspheres) were prepared based on CaCO3 microtemplates. The preparation procedure involves filling porous CaCO3 microtemplates with the protein by salt precipitation, glutaraldehyde crosslinking, and dissolution of the microtemplates. The formulation of CaCO3 templates with controlled size was studied in detail. Characterization of the prepared PAL microspheres was investigated. The results showed that the PAL microspheres with high immobilization efficiency (79%) exhibited excellent stability, including increased tolerance to proteolysis, low pH, and denaturants, and excellent mechanical properties. For example, free PAL almost lost all activity after they were incubated in the presence of trypsin for 2min, whereas PAL microspheres still retained 95% of their initial activity. Moreover, scanning electron microscope, transmission electron microscope, and N2 adsorption-desorption isotherms revealed that the resultant PAL microspheres possessed good monodispersity and mesoporous structure instead of the amorphous clusters of conventional CLEAs with few pores. Compared with conventional CLEAs, the monodisperse PAL microspheres with mesoporous make them more potentially useful for biomedical and biotechnological applications.

Encapsulation of Spherical Cross-Linked Phenylalanine Ammonia Lyase Aggregates in Mesoporous Biosilica.

Cross-linked enzyme aggregates (CLEAs) have recently emerged as a promising tool for enzyme immobilization because of their simplicity and low cost. However, a lack of good size and morphological control over the as-prepared CLEAs has limited their practical applications. For example, the prepared CLEAs exhibit amorphous large clusters that would cause significant mass-transfer limitations, which lead to a low catalytic efficiency. Here, inspired by biomineralized core-shell structures in nature, we develop a novel mesoporous spherical CLEA with a biosilica shell by using phenylalanine ammonia lyase based on CaCO3 microtemplates and biomimetic mineralization. The resultant CLEAs exhibited a spherical structure with good monodispersity instead of the amorphous clusters of conventional CLEAs and showed activity higher than that of conventional CLEAs. Moreover, the thermostability, tolerance against denaturants, and mechanical stability of the spherical CLEAs with a biosilica shell were enhanced significantly compared with those of conventional CLEAs. In particular, the spherical CLEAs with a biosilica shell retained 70% of their original activity after 13 cycles, whereas the conventional CLEAs retained only 35% of their original activity. This approach could be an efficient strategy for improving the catalytic properties of CLEAs.