Circ_0002395 promotes aerobic glycolysis and proliferation in pancreatic adenocarcinoma cells via miR-548c-3p/PDK1 axis.

Circular RNAs (circRNAs) showing unusual expressions have been discovered in pancreatic adenocarcinoma (PAAD). However, the functions and underlying mechanisms of these circRNAs still remain largely unclear. Our current study discovered a notable increase in the expression of circRNA hsa_circ_0002395 (circ_0002395) in both PAAD tissues and cell lines. This up-regulation of circ_0002395 was found to be associated with larger tumor sizes and lymph node metastasis. Furthermore, our findings showed that circ_0002395 facilitated aerobic glycolysis and cell proliferation in PAAD cells by regulating the miR-548c-3p/PDK1 axis. Mechanistically, we identified circ_0002395 as a competing endogenous RNA (ceRNA) that sponged miR-548c-3p, thereby promoting PDK1 expression and aerobic glycolysis, and ultimately resulting in the enhancement of cell proliferation. Our findings found that circ_0002395 promoted proliferation of PAAD cells by enhancing PDK1 expression and aerobic glycolysis by sponging miR-548c-3p.

Apoptosis-related long non-coding RNA LINC5438 of Bombyx mori promotes the proliferation of BmNPV.

Apoptosis, as an important part of the immune response, is one of the core events in the host-virus interaction. Studies have shown that long non-coding RNAs (lncRNAs) play important roles in the process of cell apoptosis and pathophysiology. To investigate the apoptosis-related lncRNAs involved in Bombyx mori nucleopolyhedrovirus (BmNPV) infecting silkworms, transcriptome sequencing was conducted based on silkworm cells infected with BmNPV before and after B. mori inhibitor of apoptosis (Bmiap) gene knockout. A total of 23 differentially expressed lncRNAs were identified as being associated with the mitochondrial apoptosis pathway. Moreover, we demonstrated that B. mori LINC5438 has the function of inhibiting apoptosis in silkworm cells. Overexpression of LINC5438 promoted the proliferation of BmNPV, while interference with LINC5438 inhibited its proliferation, indicating that LINC5438 plays an important role in BmNPV infection. Our results also showed that LINC5438 can regulate the expression of Bmiap, BmDronc, BmICE, and its predicted target gene BmAIF, suggesting that LINC5438 may function through the mitochondrial pathway. These findings provide important insights into the mechanisms of virus-host interaction and the applications of baculoviruses as biological insecticides.

miR-6769b-5p targets CCND-1 to regulate proliferation in cadmium-treated placental trophoblasts: Association with the impairment of fetal growth.

Environmental cadmium (Cd) is positively associated with placental impairment and fetal growth retardation. Nevertheless, its potential mechanisms remain unclear. microRNAs (miRNAs) are known to influence placental development and fetal growth. This work was aimed to determine which miRNAs are involved in Cd-impaired placental and fetal development based on the mRNA and miRNA expression profiles analysis. As a result, gestational Cd exposure deceased fetal and placental weight, and reduced the protein level of PCNA in human and mouse placentae. Furthermore, the results of mRNA microarray showed that Cd-downregulated mRNAs were predictively correlated with several biological processes, including cell proliferation, differentiation and motility. In addition, the results of miRNA microarray and qPCR assay demonstrated that Cd significantly increased the level of miR-6769b-5p, miR-146b-5p and miR-452-5p. Integrated analysis of Cd-upregulated miRNAs predicted target genes and Cd-downregulated mRNAs found that overlapping mRNAs, such as CCND1, CDK13, RINT1 and CDC26 were also significantly associated with cell proliferation. Further experiments showed that miR-6769b-5p inhibitor, but not miR-146b-5p and miR-452-5p, markedly reversed Cd-downregulated the expression of proliferation-related mRNAs, and thereby restored Cd-decreased the proteins level of CCND1 and PCNA in human placental trophoblasts. Dual luciferase reporter assay further revealed that miR-6769b-5p directly targets CCND1. Finally, the case-control study demonstrated that increased miR-6769b-5p level and impaired cell proliferation were observed in small-for-gestational-age human placentae. In conclusion, miR-6769b-5p targets CCND-1 to regulate proliferation in Cd-treated placental trophoblasts, which is associated with the impairment of fetal growth. Our findings imply that placental miR-6769b-5p may be used as an epigenetic marker for environmental pollutants-caused fetal growth restriction and its late-onset chronic diseases.

LncRNA KCNQ1OT1 is a key factor in the reversal effect of curcumin on cisplatin resistance in the colorectal cancer cells.

The development of cisplatin resistance is a common cause of cancer recurrence in colorectal cancer (CRC). Though many studies have reported the oncogenic function of long non-coding RNA (LncRNA) KCNQ1OT1 in multiple cancers, few studies explored its role in cisplatin resistance of CRC. Curcumin is a natural phenolic compound extracted from turmeric, which can effectively suppress cisplatin resistance in CRC. This study aims to expound the role of KCNQ1OT1 in cisplatin resistance in CRC cells and whether KCNQ1OT1 participates in the reversal effect of curcumin on cisplatin resistance in CRC. The interplay between KCNQ1OT1 and miR-497 was determined using RNA pull-down assay and dual-luciferase reporter gene assay. The combination of B-cell lymphoma 2 (Bcl-2) and miR-497 was confirmed using dual-luciferase reporter gene assay. Compared with CRC cell line HCT8, the cisplatin-resistant CRC cell line HCT8/DDP exhibited a higher expression level of KCNQ1OT1. Functionally, the silence of KCNQ1OT1 suppressed proliferation and boosted apoptosis in HCT8/DDP cells. Subsequently, we found that KCNQ1OT1 could act as a sponge of miR-497 and remove the suppressive effect of miR-497 on Bcl-2 expression. Curcumin treatment restrained proliferation and facilitated apoptosis in HCT8/DDP cells. While KCNQ1OT1 overexpression removed the effect of curcumin on HCT8/DDP cells via miR-497/ Bcl-2 axis. Finally, the in vivo experiments showed that the inhibitory effect of curcumin on the growth of cisplatin-resistant CRC cells was reserved by the ectopic expression of KCNQ1OT1. In conclusion, KCNQ1OT1 aggravated cisplatin resistance in CRC cells via the miR-497/Bcl-2 axis. Administration of curcumin could effectively downregulate KCNQ1OT1 expression, thus reversing cisplatin resistance in CRC cells.

Maternal cadmium exposure during late pregnancy causes fetal growth restriction via inhibiting placental progesterone synthesis.

Cadmium (Cd) is a major environmental pollutant. Maternal Cd exposure throughout pregnancy caused fetal growth restriction (FGR). However, the pivotal time window of Cd-evoked FGR and its mechanism are unknown. Here, we will establish a murine model to explore the effects of maternal Cd exposure at different stages of gestation on fetal growth and placental progesterone biosynthesis. Pregnant mice were randomly divided into four groups. For Cd groups, mice were given with CdCl2 (150 mg/L) through drinking water at early (GD0-GD6), middle (GD7-GD12) and late (GD13-GD17) gestation, respectively. The controls received reverses osmosis (RO) water. Results showed that maternal cadmium exposure only in late gestation lowered fetal weight and length. Correspondingly, placental Cd level in late gestational Cd exposure is the highest among three different gestational stages. Although gestational Cd exposure had few adverse effects in the weight and diameter of mouse placenta, placental vascular development, as determined by H&E staining and cluster of differentiation-34 (CD-34) immunostaining, was impaired in mice exposed to Cd during late pregnancy. Additionally, late gestational exposure to cadmium markedly reduced progesterone level in maternal serum and placenta. In line, the expression of key progesterone synthetases, including steroidogenic acute regulatory protein (StAR) and 3ß-hydroxyl steroid dehydrogenase (3ß-HSD), was obviously downregulated in placenta from mice was exposed Cd during late pregnancy. These data suggest that maternal Cd exposure during late pregnancy, but not early and middle pregnancy, induces fetal growth restriction partially via inhibiting placental progesterone synthesis.

Folic Acid Functionalized Zirconium-Based Metal-Organic Frameworks as Drug Carriers for Active Tumor-Targeted Drug Delivery.

Nanoscale metal-organic frameworks (NMOFs) have proven to be a class of promising drug carriers as a result of their high porosity, crystalline nature with definite structure information, and potential for further functionality. However, MOF-based drug carriers with active tumor-targeting function have not been extensively researched until now. Here we show a strategy for constructing active tumor-targeted NMOF drug carriers by anchoring functional folic acid (FA) molecules onto the metal clusters of NMOFs. Two zirconium-based MOFs, MOF-808 and NH2 -UiO-66, were chosen as models to reduce to the nanoscale for application as drug carriers, and then the terminal carboxylates of FA molecules were coordinated to Zr6 clusters on the surfaces of the nanoparticles by substitution of the original formate or terminal -OH ligands. The successful modification with FA was confirmed by solid-state 13 C MAS NMR and UV/Vis spectroscopy and other characterization methods. Drug loading and controlled release behavior at different pH were determined by utilizing the anticancer drug 5-fluorouracil (5-FU) as the model drug. Confocal laser scanning microscopy measurements further demonstrated that 5-FU-loaded FA-NMOFs have excellent targeting ability through the efficient cellular uptake of FA-NMOFs. This work opens up a new avenue to the construction of active tumor-targeted NMOF-based drug carriers with potential for cancer therapies.

Subchronic cadmium exposure upregulates the mRNA level of genes associated to hepatic lipid metabolism in adult female CD1 mice.

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in humans and shows adverse effects on health. Accumulating evidence reveals that environmental Cd exposure is associated with hepatic lipid accumulation and metabolic alterations in adult male mice. However, whether Cd exposure induces hepatic lipid accumulation and metabolic alterations in female mice remains poorly understood. In the present study, we aimed to investigate the effects of Cd exposure on insulin resistance, hepatic lipid accumulation and associated metabolic pathways. Female CD1 mice were administrated with CdCl2 (10 and 100 mg l-1 ) by drinking water. We found that Cd exposure did not induce obesity, insulin resistance and hepatic lipid accumulation. By contrary, mice in the Cd-100 mg l-1 group presented a significant reduction of the glucose area under the curve during the glucose tolerance test. However, there was a significant elevation in the mRNA level of Fasn and Scd-1, which were critical genes during hepatic fatty acid synthesis. Moreover, hepatic Fabp1 and Fabp4, two genes for hepatic fatty acid uptake were upregulated in Cd-treated mice. Of interest, Lpl, a key gene for hepatic lipoprotein lysis, was also upregulated in Cd-treated mice. Collectively, our results suggest that Cd exposure upregulated mRNA level of genes related to hepatic lipid metabolism although there was no insulin resistance and hepatic lipid accumulation shown in the present study.

Effects of drying pretreatment and particle size adjustment on the composting process of discarded flue-cured tobacco leaves.

The main characteristic of discarded flue-cured tobacco leaves is their high nicotine content. Aerobic composting is an effective method to decrease the nicotine level in tobacco leaves and stabilize tobacco wastes. However, high levels of nicotine in discarded flue-cured tobacco leaves complicate tobacco waste composting. This work proposes a drying pretreatment process to reduce the nicotine content in discarded flue-cured tobacco leaves and thus enhance its carbon-to-nitrogen ratio to a suitable level for composting. The effect of another pretreatment method, particle size adjustment, on composting efficiency was also tested in this work. The results indicated that the air-dried (nicotine content: 1.35%) and relatively long discarded flue-cured tobacco leaves (25 mm) had a higher composting efficiency than damp (nicotine content: 1.57%) and short discarded flue-cured tobacco leaves (15 mm). When dry/25 mm discarded flue-cured tobacco leaves mixed with tobacco stems in an 8:2 ratio was composted at a temperature above 55 °C for 9 days, the nicotine content dropped from 1.29% to 0.28%. Since the discarded flue-cured tobacco leaves was successfully composted to a fertile and harmless material, the germination index values increased to 85.2%. The drying pretreatment and particle size adjustment offered ideal physical and chemical conditions to support microbial growth and bioactivity during the composting process, resulting in efficient conversion of discarded flue-cured tobacco leaves into a high quality and mature compost.

Synthesis of BiOClx Br1-x Nanoplate Solid Solutions as a Robust Photocatalyst with Tunable Band Structure.

The use of bismuth oxyhalides as photocatalysts has received extensive interest because of their high photocatalytic activity and stability. However, available methods for the synthesis of bismuth oxyhalides with tailored morphologies, well-defined facets, and tunable band gaps are still lacking. In this work, two-dimensional BiOClx Br1-x solid solution with exposed {001} facets and tunable band gaps were synthesized by using solvothermal methods. The BiOClx Br1-x solid solution nanoplates crystallized in a homogeneous crystal structure but possessed continuously tuned band gaps from 3.39 to 2.78 eV by decreasing the ratio of Cl/Br. Among the synthesized nanoplates, the BiOCl0.5 Br0.5 sample exhibited the highest photocatalytic activity for degrading Rhodamine B (RhB), a typical organic pollutant, under visible light. The highest photoactivity of the BiOCl0.5 Br0.5 sample was attributed to a synergetic effect of higher surface area, facets exposed, and optimized band structure. The results are of profound significance for the design of novel photocatalyst materials.

A machine learning radiomics based on enhanced computed tomography to predict neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma.

Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.

Coexistence of Gaussian and non-Gaussian statistics in vector integrable turbulence.

Integrable turbulence studies the complex dynamics of random waves for the nonlinear integrable systems, and it has become an important element in exploring the sophisticated turbulent phenomena. In the present work, based on the coupled nonlinear Schrödinger models, we have shown the coexistence of Gaussian and non-Gaussian single-point statistics in multiple wave components, which might be viewed as an exclusive feature for the vector integrable turbulence. This coexistent statistic can relate to different distributions of the vector solitonic excitations depending on the time-invariant nonlinear spectra. Our results are expected to shed light on a deeper understanding of the turbulent behaviors of vector waves and may motivate relevant experiments in the coupled optical or atomic systems.

Cholangioscopy-assisted extraction through novel papillary support for small-calibre and sediment-like common bile duct stones.

BACKGROUND: To date, endoscopic retrograde cholangiopancreatography has become a well-established treatment for common bile duct (CBD) stones. However, it is not suitable for some special patients, such as pregnant women, children or those who cannot stop taking anti-coagulation/anti-platelet agents because of radiation injury and the risk of postoperative bleeding resulting from endoscopic sphincterotomy. To overcome these two problems, this study introduced cholangioscopy-assisted extraction through a novel papillary support for small-calibre and sediment-like CBD stones. AIM: To assess the feasibility and safety of cholangioscopy-assisted extraction through a novel papillary support (CEPTS) for small-calibre and sediment-like common bile duct (CBD) stones. METHODS: This Retrospective study was approved by the Ethics Committee of the Chinese PLA General Hospital. We designed a covered single dumbbell-style papillary support between 2021 and 2022. Between July 2022 and September 2022, 7 consecutive patients with small-calibre (cross diameter ≤ 1.0 cm) or sediment-like CBD stones underwent CETPS procedures in our center. The clinical characteristics and treatment outcomes of these 7 patients were extracted from a prospectively collected database. And the related data were analyzed. Informed consent was obtained from all participating patients. RESULTS: A total of 2 patients had yellow sediment-like CBD stones, and aspiration extraction was performed after the insertion of papillary support. Of the 5 patients with clumpy CBD stones (0.4-1.0 cm), 2 underwent basket extraction under direct vision for a single stone (0.5-1.0 cm, black and black grey), 1 underwent balloon plus aspiration extraction under direct vision for 5 stones (0.4-0.6 cm, brown), and 2 underwent aspiration extraction only for a single stone (0.5-0.6 cm, yellow, none). Technical success, namely, no residual stones in the CBD or left and right hepatic ducts, was achieved in all 7 cases (100%). The median operating time was 45.0 minutes (range 13.0-87.0 minutes). Postoperative pancreatitis (PEP) occurred in one case (14.3%). Hyperamylasaemia without abdominal pain was noted in 2 of 7 patients. No residual stones or cholangitis were found during the follow-up. CONCLUSION: CETPS appeared to be feasible to treat patients with small-calibre or sediment-like CBD stones. Patients, especially pregnant women and those who cannot stop anticoagulation/anti-platelet agents, could benefit from this technique.

Muscarinic acetylcholine receptor M3 in proliferation and perineural invasion of cholangiocarcinoma cells.

BACKGROUND: Cholangiocarcinoma, a type of malignant tumor, originates from epithelial cells of the bile duct. Perineural invasion is common path for cholangiocarcinoma metastasis, and it is highly correlated with postoperative recurrence and poor prognosis. It has been reported that muscarinic acetylcholine receptor M3 (mAChR M3) is widely expressed in digestive tract cancer, and may play an important role in the proliferation, differentiation, transformation and carcinogenesis of tumors. This study was to explore the effect of mAChR M3 on the growth of cholangiocarcinoma cells in vitro and provide a new approach to the pathogenesis and treatment of cholangiocarcinoma. METHODS: Streptavidin-biotin complex immunohistochemistry was carried out to assess the expression of mAChR M3 in surgical specimens of cholangiocarcinomas (40 cases) and normal bile duct tissues (9), as well as to investigate nerve infiltration. The cholangiocarcinoma cells were treated with different concentrations of selective M-receptor agonist pilocarpine and M-receptor blocker atropine sulfate to induce changes in cell proliferation. The experimental data were analyzed by the Chi-square test. RESULTS: The strongly-positive expression rate of mAChR M3 was much higher in poorly-differentiated (69%, 9/13) than in well- and moderately-differentiated cholangiocarcinomas (30%, 8/27) (X2=5.631, P<0.05). The strongly-positive mAChR M3 expression rate in hilar cholangiocarcinoma (50%, 14/28) was higher than that in cholangiocarcinomas from the middle and lower common bile duct (25%, 3/12) (X2=2.148, P<0.05). Cholangiocarcinomas with distant metastasis had a strongly-positive expression rate (75%, 9/12), which was much higher than those without distant metastasis (29%, 8/28) (X2=7.410, P<0.01). The absorbance value in the pilocarpine+atropine group was significantly higher than the corresponding value in the pilocarpine group. CONCLUSIONS: The expression of mAChR M3 is influenced by the extent of differentiation, distant metastasis and the site of cholangiocarcinoma. It also plays a key role in the proliferation and metastasis of cholangiocarcinoma.

Metastasis of liver cancer to the thyroid after surgery: A case report.

BACKGROUND: Secondary thyroid malignancies are rarely reported, especially thyroid metastasis after resection of hepatocellular carcinoma (HCC). We report a patient with thyroid metastasis after resection of HCC. CASE SUMMARY: A 42-year-old female underwent partial hepatectomy for HCC three years ago. She attended hospital because of neck discomfort. After various examinations, she was diagnosed with metastatic HCC. She survived after surgical resection of the affected side of the thyroid. CONCLUSION: Although secondary malignant tumor of the thyroid is classified as distant metastasis, surgical resection is still necessary according to the patient's condition.

[Mechanisms of Penicillin Wastewater Treatment by Coupled Electrocatalytic and Bioelectrochemical Systems].

Large amounts of wastewater containing residual antibiotics are produced in antibiotics production, but it is difficult for traditional biological wastewater treatment to efficiently treat this high concentration antibiotic wastewater. Coupled electrocatalytic and bioelectrochemical systems were proposed to treat typical ß-lactam antibiotics (penicillin) wastewater. The penicillin wastewater was oxidized by a boron-doped diamond (BDD) electrocatalytic electrode and then steadily treated by a bioelectrochemical system (BES). The penicillin removal rate of the electrocatalytic system was 89%, and 79% of the residual penicillin was further removed by the BES. The maximum power density of the BES with pretreated penicillin of (1124±28) mW·m-2 was increased by 473% compared with that of the BES with raw penicillin. The total penicillin removal rate was 98% in the electrocatalytic and bioelectrochemical system. The results of the BES anode biomass and biofacies showed that Acinetobacter was the dominant bacterial group on the anode before penicillin addition, and it was the main microorganism in the formation of the anode biofilm. Bacillus is an electricity-producing bacterium with a power generation function. Penicillin inhibited the biomass of the mixed anode bacteria and the biological activity of Proteus microorganisms, which were the main electricity-producing bacteria, and reduced the biomass of Acinetobacter and Bacillus. This was the main factor affecting the power generation performance and reactor treatment effect. The pretreatment of penicillin wastewater by electrocatalytic degradation can significantly decrease its concentration, efficiently alleviate the inhibition of the BES by penicillin, and improve the biodegradability of wastewater. The coupled electrocatalytic and bioelectrochemical system is a new technology for antibiotic wastewater treatment with a high efficiency and low energy consumption.

Experimental scheme and noise analysis of weak-light phase locked loop for large-scale intersatellite laser interferometer.

In the current space gravitational wave (GW) detection, satellites are separated by millions of kilometers. As a result, watts of laser from one satellite is attenuated to the picowatt level at the other end due to the Gaussian beam divergence and the finite aperture of the telescope. Establishing an effective interferometry with such weak-light is a major challenge. The key is to enhance the weak-light while preserving its phase information, which carries the actual GW signal. This can be accomplished by employing an optical phase-locked loop (PLL) to lock the phase of a local oscillator (LO) laser to the weak-light and then sending the power-amplified LO back to the interferometer on the other satellite. Although shot-noise-limited performance of the picowatt level weak-light PLL has been achieved for high frequencies, it remains elusive for frequencies below 0.1 Hz. Here, we propose a three-step experimental scheme to identify the main noise sources of the weak-light PLL, which turn out to be the low-frequency phase measurement noise, the weak-light shot noise, and the laser phase noise. In this paper, the first step experiment result shows that the out-loop phase noise can be suppressed to a level less than 6 × 10-6 rad/√Hz from 6 mHz to 1 Hz by first using the special pilot-tone technique in the PLL to directly reduce the sampling time jitter noise in the digital phasemeter. The out-loop phase noise is mainly limited by the signal amplitude variation and differential time jitter noise of the reference clock.

Maternal selenium deficiency during gestation is positively associated with the risks for LBW and SGA newborns in a Chinese population.

BACKGROUND: Maternal selenium (Se) deficiency is associated with some adverse pregnant outcomes. However, it remains controversial whether maternal Se deficiency during gestation enhances the risks for low-birth-weight (LBW) and small-for-gestational-age (SGA) newborns. METHODS: For our cohort study, total 3133 mother-and-infant pairs were selected. Maternal serum Se concentration was detected by graphite furnace atomic absorption spectrometry. According to international references for maternal serum Se concentration, subjects were divided into Se deficiency (<45.0 µg/L), Se insufficiency (45.0-94.9 µg/L) and Se sufficiency (≥95.0 µg/L). RESULTS: There was a positive relation of maternal serum Se concentration in gestation and neonatal birth weight. Further analysis showed that the risks for LBW and SGA in SD group were significantly higher than that in SI and SS group, the adjusted ORs for LBW and SGA newborns were 1.87 (95%CI: 1.02, 3.45; P = 0.04) and 1.47 (95%CI: 1.07, 2.02; P = 0.02) in SI group, and 3.92 (95%CI: 2.03, 7.57; P < 0.001) and 2.77 (95%CI: 1.92, 4.02; P < 0.001) in SD group compared to SS group. In different gender subgroup, positive relations were observed between maternal Se deficiency and the risk for LBW girls, as well as the risks for both SGA girls and boys. CONCLUSION: Maternal Se deficiency in gestation was positively associated with the risk for LBW girls, as well as the risks for both SGA girls and boys.

Comparative genome-wide DNA methylation analysis reveals epigenomic differences in response to heat-humidity stress in Bombyx mori.

DNA methylation is an important epigenetic modification and has been shown to be involved in the response to abiotic stress. However, there are few studies on DNA methylation in insect response to environmental signals. In this study, we conducted a comprehensive comparative analysis of DNA methylation profiles between two silkworm strains with significantly different resistance to heat and humidity by whole-genome bisulfite sequencing (WGBS). We identified, in total, 2934 differentially methylated regions (DMRs) between RT_48h (resistant strain with high-temperature/humidity treatment for 48 h) and ST_48h (sensitive strain with high-temperature/humidity treatment for 48 h) under cytosine context (CG), which corresponded to 1230 DMR-related genes (DMGs), and the DMRs were primarily located in the gene body (exon and intron) region. Gene ontology (GO) and KEGG analysis showed that these DMGs were most significantly enriched in binding, cellular metabolic process, and RNA transport pathways. Moreover, 10 DMGs have been revealed to be involved in the heat-humidity stress response in the silkworm. The results of this study indicated that DNA methylation plays crucial roles in silkworm response to environmental stressors and provides important clues to identify key resistance genes in silkworm under high-temperature/humidity stress response.

Perineural invasion of cancer: a complex crosstalk between cells and molecules in the perineural niche.

Perineural invasion (PNI) can be found in a variety of malignant tumors. It is a sign of tumor metastasis and invasion and portends the poor prognosis of patients. The pathological description and clinical significance of PNI are clearly understood, but exploration of the underlying molecular mechanism is ongoing. It was previously thought that the low-resistance channel in the anatomic region led to the occurrence of PNI. However, with rapid development of precision medicine and molecular biology, we have gradually realized that the occurrence of PNI is not the result of a single factor. The latest study suggests that PNI of cancer is a continuous and multistep process. A specific peripheral microenvironment, also called the perineural niche, is formed by neural cells, supporting cells, recruited inflammatory cells, altered extracellular matrix, blood vessels, and immune components in the background of carcinoma. Various soluble signaling molecules and their receptors comprise a complex signal network, which achieves the interaction between nerve and tumor. Nerve cells and tumor cells can interact directly or through the opening and closing of the signal transduction pathways and/or the recognition and response of the ligands and receptors. The information is transferred to the targets accurately and effectively, leading to the specific interactions between the nerve cells and the malignant tumor cells. PNI occurs through changes in nerve cells and supporting cells in the background of cancer; change and migration of the perineural matrix; enhancement of the viability, mobility, and invasiveness of the tumor cells; injury and regeneration of nerve cells; interaction, chemotactic movement, contact, and adherence of the nerve cells and the tumor cells; escape from autophagy, apoptosis, and immunological surveillance of tumor cells; and so on. Certainly, exploring the mechanism of PNI clearly has great significance for blocking tumor progression and improving patient survival. The current review aims to elucidate the cellular and molecular mechanisms of PNI, which may help us find a strategy for improving the prognosis of malignant tumors.

Activation of autophagy inhibits cadmium-triggered apoptosis in human placental trophoblasts and mouse placenta.

Cadmium (Cd), a ubiquitous environmental pollutant, is known to impair placental development. However, the underlying mechanisms remain unclear. The present study used in vivo and in vitro models to investigate the effects of Cd on apoptosis and autophagy in placental trophoblasts and its mechanism. Pregnant mice were exposed to CdCl2 (4.5 mg/kg) on gestational day (GD) 9. Human JEG-3 cells were exposed to CdCl2 (0-40 µM) for different time points. Gestational Cd exposure obviously lowered the weight and diameter of mouse placentas. Number of TUNEL-positive cells was markedly elevated in Cd-administered mouse placentas and JEG-3 cells. Correspondingly, Cd significantly up-regulated cleaved caspase-3 protein level, a key indicator of apoptosis, in murine placentas and JEG-3 cells. Simultaneously, Cd also triggered autophagy, as determined by an elevation of LC3B-II and p62 protein, and accumulation of LC3-positive puncta, in placental trophoblasts. Chloroquine an autophagy inhibitor, obviously aggravated Cd-induced apoptosis in JEG-3 cells. By contrast, rapamycin, a specific autophagy inducer, significantly alleviated Cd-triggered apoptosis in JEG-3 cells. Mechanistically, autophagy inhibited Cd-induced apoptosis mainly via degrading caspase-9. Co-localizations of p62, a classical autophagic receptor, and caspase-9 were observed in Cd-stimulated human JEG-3 cells. Moreover, p62 siRNAs pretreatment markedly blocked the degradation of caspase 9 proteins via Cd-activated autophagy in JEG-3 cells. Collectively, our data suggest that activation of autophagy inhibits Cd-induced apoptosis via p62-mediated caspase-9 degradation in placental trophoblasts. These findings provide a new mechanistic insight into Cd-induced impairments of placental and fetal development.