Ursolic Acid Ameliorates Alcoholic Liver Injury through Attenuating Oxidative Stress-Mediated Ferroptosis and Modulating Gut Microbiota.

Ursolic acid (UA), a triterpenoid found in plants, has many health benefits for liver function. However, understanding how UA intervenes in alcohol-induced ferroptosis remains unclear because of the lack of research. This study explored the protective effects of UA on alcohol-induced liver injury and further elucidated its mechanism of action. Using a mouse model, acute liver injury was induced via high-dose alcohol gavage, and UA's protective effects were assessed by analyzing serum and liver indicators. The results indicated that UA has a significant protective effect against alcohol-induced liver injury in mice. UA significantly decreased serum ALT, AST, TC, and TG levels. Histopathological examination revealed that UA significantly ameliorated liver damage. UA increased ADH, ALDH, and CYP2E1 enzyme expression levels and alleviated alcohol-induced oxidative damage by regulating alcohol metabolism. Moreover, UA increased SOD and GSH-Px levels and lowered the MDA levels in the liver. Furthermore, UA regulated ACC expression by activating the LKB1/AMPK pathway, thereby inhibiting lipid synthesis and peroxidation. UA also upregulated the expression of GPX4 and SLC7A11 in the liver and exerted hepatoprotective effects by inhibiting alcohol-induced ferroptosis. Additionally, 16S rRNA amplicon sequencing showed that excessive alcohol consumption significantly affected the composition of the mouse gut microbiota, with UA intervention proving to be beneficial for improving gut microbiota imbalance. We also validated the protective effects of UA on alcohol-treated HepG2 cells at the cellular level. In summary, these results revealed that UA can alleviate alcoholic liver injury by inhibiting oxidative stress-mediated ferroptosis and regulating gut microbiota. These findings suggest that UA may serve as a functional component in the prevention of alcoholic liver disease.

Bombyx mori nucleopolyhedrovirus LEF-2 disrupts the cell cycle in the G2/M phase by triggering a host cell DNA damage response.

It is a common strategy for viruses to block the host cell cycle to favour their DNA replication. Baculovirus, being a double-stranded DNA virus, can arrest the cell cycle in the G2/M phase to facilitate its replication. However, the key viral genes and mechanisms crucial for inducing cell cycle arrest remain poorly understood. Here, we initially examined the impacts of several Bombyx mori nucleopolyhedrovirus (BmNPV) DNA replication-associated genes: ie1, lef-1, lef-2, lef-3, lef-4, odv-ec27 and dbp. We assessed their effects on both the host cells' DNA replication and cell cycle. Our findings reveal that when the lef-2 gene was overexpressed, it led to a significant increase in the number of cells in the G2/M phase and a reduction in the number of cells in the S phase. Furthermore, we discovered that the LEF-2 protein is located in the virogenic stroma and confirmed its involvement in viral DNA replication. Additionally, by employing interference and overexpression experiments, we found that LEF-2 influences host cell DNA replication and blocks the cell cycle in the G2/M phase by regulating the expression of CyclinB and CDK1. Finally, we found that BmNPV lef-2 triggered a DNA damage response in the host cell, and inhibiting this response removed the cell cycle block caused by BmNPV LEF-2. Thus, our findings indicate that the BmNPV lef-2 gene plays a crucial role in viral DNA replication and can regulate host cell cycle processes. This study furthers our understanding of baculovirus-host cell interactions and provides new insight into the molecular mechanisms of antiviral research.

Bioactive peptides of marine organisms: Roles in the reduction and control of cardiovascular diseases.

Cardiovascular diseases (CVDs) affect the quality of life or are fatal in the worst cases, resulting in a significant economic and social burden. Therefore, there is an urgent need to invent functional products or drugs for improving patient health and alleviating and controlling these diseases. Marine bioactive peptides reduce and control CVDs. Many of the predisposing factors triggering CVDs can be alleviated by consuming functional foods containing marine biopeptides. Therefore, improving CVD incidence through the use of effective biopeptide foods from marine sources has attracted increasing interest and attention. This review reports information on bioactive peptides derived from various marine organisms, focusing on the process of the separation, purification, and identification of biological peptides, biological characteristics, and functional food for promoting cardiovascular health. Increasing evidence shows that the bioactivity and safety of marine peptides significantly impact their storage, purification, and processing. It is feasible to develop further strategies involving functional foods to treat CVDs through effective safety testing methods. Future work should focus on producing high-quality marine peptides and applying them in the food and drug industry.

Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

The efficacy of cognitive behavioral therapies for depression in China in comparison with the rest of the world: A systematic review and meta-analysis.

OBJECTIVE: There is consistent evidence that cognitive behavioral therapies (CBTs) are effective interventions for adult depression. While some evidence has compared these effects in different countries, no prior systematic review and meta-analysis has compared the efficacy of CBTs between Chinese and people from the rest of the world. The current meta-analysis addressed this gap by a systematic review of eligible studies from Chinese and worldwide databases. METHOD: Hedges' g was calculated using a random-effects model. Subgroup analyses and multilevel meta-analytic models were conducted to examine the relationship among effect sizes and the characteristics in Chinese studies. Metaregression analyses were conducted to explore the difference of the efficacy of CBTs between Chinese studies and non-Chinese studies after controlling for the moderators. RESULTS: A total of 34 (n = 3,710) studies in China and 307 (n = 30,333) studies from the rest of the world were included. The effect size of CBTs on depression for Chinese participants was 1.19 (95% CI [0.86, 1.52]), which was higher (Q = 4.63, p = .03) than the effect size of the rest of the world (0.82, 95% CI [0.74, 0.90]). After controlling for moderators, the effect size of Chinese studies was still higher than non-Chinese studies (ß = 0.351, p = .011). CONCLUSIONS: CBTs are effective interventions for adult depression and deserve more attention in China for depression management. Moderators related to study design, clinical features, and cultural factors need to be considered in the interpretation of the results. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

GDF15 is a major determinant of ketogenic diet-induced weight loss.

A ketogenic diet (KD) has been promoted as an obesity management diet, yet its underlying mechanism remains elusive. Here we show that KD reduces energy intake and body weight in humans, pigs, and mice, accompanied by elevated circulating growth differentiation factor 15 (GDF15). In GDF15- or its receptor GFRAL-deficient mice, these effects of KD disappeared, demonstrating an essential role of GDF15-GFRAL signaling in KD-mediated weight loss. Gdf15 mRNA level increases in hepatocytes upon KD feeding, and knockdown of Gdf15 by AAV8 abrogated the obesity management effect of KD in mice, corroborating a hepatic origin of GDF15 production. We show that KD activates hepatic PPARγ, which directly binds to the regulatory region of Gdf15, increasing its transcription and production. Hepatic Pparγ-knockout mice show low levels of plasma GDF15 and significantly diminished obesity management effects of KD, which could be restored by either hepatic Gdf15 overexpression or recombinant GDF15 administration. Collectively, our study reveals a previously unexplored GDF15-dependent mechanism underlying KD-mediated obesity management.

Three dimensional graphene promotes the proliferation of cholinergic neurons.

BACKGROUND: An early substantial loss of basal forebrain cholinergic neurons (BFCNs) is a common property of Alzheimer's disease and the degeneration of functional BFCNs is related to learning and memory deficits. As a biocompatible and conductive scaffold for growth of neural stem cells, three-dimensional graphene foam (3D-GF) supports applications in tissue engineering and regenerative medicine. Although its effects on differentiation have been demonstrated, the effect of 3D-GF scaffold on the generation of BFCNs still remains unknown. METHODS: In this study, we used 3D-GF as a culture substrate for neural progenitor cells (NPCs) and demonstrated that this scaffold material promotes the differentiation of BFCNs while maintaining excellent cell viability and proliferation. RESULTS: Immunofluorescence analysis, RT-PCR, western blotting and ELISA revealed that the proportion of BFCNs at 21 days of differentiation reached approximately 30.5% on 3D-GF compared with TCPS group that only presented 9.7%. Furthermore, a cell adhesion study suggested that 3D-GF scaffold enhances the expression of adhesion proteins including vinculin, integrin and N-cadherin. These findings indicate that 3D-GF scaffold materials are preferable candidates for the differentiation of BFCNs from NPCs. CONCLUSIONS: These results suggest new opportunities for the application of 3D-GF scaffold as a neural scaffold for cholinergic neurons therapies based on NPCs.

miR-145-3p Inhibits MuSCs Proliferation and Mitochondria Mass via Targeting MYBL1 in Jianzhou Big-Eared Goats.

Muscle growth and injury-induced regeneration are controlled by skeletal muscle satellite cells (MuSCs) through myogenesis in postnatal animals. Meanwhile, myogenesis is accompanied by mitochondrial function and enzyme activity. Nevertheless, the underlying molecular mechanisms involving non-coding RNAs including circular RNAs (circRNAs) and microRNAs (miRNAs) remain largely unsolved. Here, we explored the myogenic roles of miR-145-3p and MYBL1 on muscle development and mitochondrial mass. We noticed that overexpression of miR-145-3p inhibited MuSCs proliferation and reduced the number of viable cells. Meanwhile, deficiency of miR-145-3p caused by LNAantimiR-145-3p or an inhibitor retarded the differentiation of MuSCs. miR-145-3p altered the mitochondrial mass in MuSCs. Moreover, miR-145-3p targeted and negatively regulated the expression of CDR1as and MYBL1. The knockdown of the MYBL1 using ASO-2'MOE modification simulated the inhibitory function of miR-145-3p on cell proliferation. Additionally, MYBL1 mediated the regulation of miR-145-3p on Vexin, VCPIP1, COX1, COX2, and Pax7. These imply that CDR1as/miR-145-3p/MYBL1/COX1, COX2, VCPIP1/Vexin expression at least partly results in a reduction in mitochondrial mass and MuSCs proliferation. These novel findings confirm the importance of mitochondrial mass during myogenesis and the boosting of muscle/meat development in mammals.

The Profiles and Functions of RNA Editing Sites Associated with High-Altitude Adaptation in Goats.

High-altitude environments dramatically influenced the genetic evolution of vertebrates. However, little is known about the role of RNA editing on high-altitude adaptation in non-model species. Here, we profiled the RNA editing sites (RESs) of heart, lung, kidney, and longissimus dorsi muscle from Tibetan cashmere goats (TBG, 4500 m) and Inner Mongolia cashmere goats (IMG, 1200 m) to reveal RNA editing-related functions of high-altitude adaptation in goats. We identified 84,132 high-quality RESs that were unevenly distributed across the autosomes in TBG and IMG, and more than half of the 10,842 non-redundant editing sites were clustered. The majority (62.61%) were adenosine-to-inosine (A-to-I) sites, followed by cytidine-to-uridine (C-to-U) sites (19.26%), and 32.5% of them had a significant correlation with the expression of catalytic genes. Moreover, A-to-I and C-to-U RNA editing sites had different flanking sequences, amino acid mutations, and alternative splicing activity. TBG had higher editing levels of A-to-I and C-to-U than IMG in the kidney, whereas a lower level was found in the longissimus dorsi muscle. Furthermore, we identified 29 IMG and 41 TBG population-specific editing sites (pSESs) and 53 population-differential editing sites (pDESs) that were functionally involved in altering RNA splicing or recoding protein products. It is worth noting that 73.3% population-differential, 73.2% TBG-specific, and 80% IMG-specific A-to-I sites were nonsynonymous sites. Moreover, the pSESs and pDESs editing-related genes play critical functions in energy metabolisms such as ATP binding molecular function, translation, and adaptive immune response, which may be linked to goat high-altitude adaptation. Our results provide valuable information for understanding the adaptive evolution of goats and studying plateau-related diseases.

Electric-Field-Driven Printed 3D Highly Ordered Microstructure with Cell Feature Size Promotes the Maturation of Engineered Cardiac Tissues.

Engineered cardiac tissues (ECTs) derived from human induced pluripotent stem cells (hiPSCs) are viable alternatives for cardiac repair, patient-specific disease modeling, and drug discovery. However, the immature state of ECTs limits their clinical utility. The microenvironment fabricated using 3D scaffolds can affect cell fate, and is crucial for the maturation of ECTs. Herein, the authors demonstrate an electric-field-driven (EFD) printed 3D highly ordered microstructure with cell feature size to promote the maturation of ECTs. The simulation and experimental results demonstrate that the EFD jet microscale 3D printing overcomes the jet repulsion without any prior requirements for both conductive and insulating substrates. Furthermore, the 3D highly ordered microstructures with a fiber diameter of 10-20 µm and spacing of 60-80 µm have been fabricated by maintaining a vertical jet, achieving the largest ratio of fiber diameter/spacing of 0.29. The hiPSCs-derived cardiomyocytes formed ordered ECTs with their sarcomere growth along the fiber and developed synchronous functional ECTs inside the 3D-printed scaffold with matured calcium handling compared to the 2D coverslip. Therefore, the EFD jet 3D microscale printing process facilitates the fabrication of scaffolds providing a suitable microenvironment to promote the maturation of ECTs, thereby showing great potential for cardiac tissue engineering.

Metabolism-related lncRNAs signature to predict the prognosis of colon adenocarcinoma.

BACKGROUND: Cell metabolism and long noncoding RNA (lncRNA) played crucial roles in cancer development. However, their association in colon adenocarcinoma (COAD) remains unclear. METHODS: The COAD gene expression data and corresponding clinical data were retrieved from The Cancer Genome Atlas (TCGA) database. Differential expression of metabolic genes and lncRNA were identified by comparing tumor and normal colon tissues. Pearson correlation analysis was performed to identify metabolism-associated lncRNA. COAD patients were divided into training cohort and validation cohort by randomization. Then, a univariate Cox regression analysis was introduced to evaluate the correlations between metabolism-related lncRNAs and overall survival (OS) of the patients in the training cohort. The least absolute shrinkage and selection operator (LASSO) method was introduced to determine and establish a prognostic prediction model. Subsequently, survival analysis, receiver operating characteristic (ROC) curve analysis, and Cox regression analysis were generated to estimate the prognostic role of the LncRNA risk score in training, validation, and entire cohorts. RESULTS: We identified 152 differentially expressed metabolism-associated lncRNAs (MRLncRNAs). A prognostic prediction model involving four metabolism-related lncRNAs were established using LASSO. In each cohort, COAD patients in the high-risk group had worse OS compared to those in the low-risk group. The ROC analyses demonstrated that the lncRNA signature performed well in predicting OS. Uni- and multivariate analysis indicated that the lncRNA signature as an independent prognostic factor. Furthermore, a correlation analysis demonstrated that LINC01138 was the most closely lncRNA related to metabolic genes. In vitro assays demonstrated that LINC01138 affects tumor progression in COAD. CONCLUSIONS: In summary, we established a metabolism-associated lncRNAs model to predict the prognosis in COAD patients.

Baculovirus LEF-11 interacts with BmIMPI to induce cell cycle arrest in the G2/M phase for viral replication.

Viruses arrest the host cell cycle and using multiple functions of host cells is an important approach for their replication. Baculovirus arrests infected insect cells at both the late S and G2/M phase, but the strategy employed by baculovirus is not clearly understood. Our research suggests that the Bombyx mori nucleopolyhedrovirus (BmNPV) could arrest the cell cycle in the G2/M phase to promote virus replication, and also that the viral protein LEF-11 could inhibit host cell proliferation and arrest the cell cycle by inhibiting the cell cycle checkpoint proteins BmCyclinB and BmCDK1. Furthermore, we found that LEF-11 interacts with BmIMPI to regulate cell proliferation, but not by direct interaction with BmCyclinB or BmCDK1. In addition, our findings showed that BmIMPI was important and necessary for LEF-11 induced cell cycle arrest in the G2/M phase. Moreover, BmIMPI was found to interact with BmCyclinB and BmCDK1, and down-regulate the expression of BmCyclinB and BmCDK1 to compromise the cell cycle and cell proliferation. Taken together, the data presented demonstrated that baculovirus LEF-11 regulates BmIMPI to inhibit host cell proliferation and provide a new insight into the molecular mechanisms employed by viruses to induce cell cycle arrest.

[Clinical effects of two different hydroxyapatite bone graft materials during maxillary sinus lifting surgery with bone grafting and simultaneous implantation of implants].

PURPOSE: To compare the clinical effects of two different hydroxyapatite bone graft materials in maxillary sinus lifting surgery with bone grafting and implantation at the same time. METHODS: Seventy-two patients with implantation in the maxillary posterior dental area and insufficient bone mass admitted to the First Affiliated Hospital of Bengbu Medical College were collected from March 2018 to April 2019, and they were divided into experimental group(n=36) and control group(n=36) by random number table. Patients in the control group used hydroxyapatite composite material, while patients in the experimental group used nano-hydroxyapatite composite material. The clinical effects, bone increment and bone density changes of the two groups of implants were compared, and postoperative implant stability and complications of the two groups were compared. Statistical analysis was performed with SPSS 18.0 software package. RESULTS: The survival rate of implants in the experimental group was significantly higher than that in the control group at 24 months (P＜0.05). Alveolar bone resorption in the experimental group was significantly lower than the control group 6 months after surgery(P＜0.05). The bone mineral density of implants in the experimental group was significantly higher than the control group 6 months and 12 months after operation(P＜0.05). The implant stability coefficient value of the experimental group was significantly higher than the control group 12 months after operation(P＜0.05). There was no significant difference in the total complication rate between the two groups(P＞0.05). CONCLUSIONS: In maxillary sinus lift, the survival rate of nano-hydroxyapatite composite material implanted in the same period is high, which can improve postoperative bone metabolism and increase implant stability with good safety.

Prone position reduces the risk of patients with mild or moderate COVID-19 progressing to severe or even critical cases: a retrospective study.

BACKGROUND: To investigate whether prone position can reduce the risk of patients with mild or moderate COVID-19 who progress to severe or critical illness. METHODS: The prone position group was treated in prone position on the day of admission in addition to conventional treatment. Indicators such as saturation of pulse oximetry (SpO2), heart rate, blood pressure, respiratory rate, and prone position-related adverse events were recorded before prone ventilation, 5 min after prone position and 30 min after prone position. Meanwhile, the cases of severe and critical patients, the percentage of transformation and the final clinical outcome of this group were analyzed. Conversion rates and mortality were calculated for patients with mild or moderate COVID-19 retrieved from the database who received only conventional care without combined prone positioning as control group. RESULTS: (1) A total of 34 patients were included in prone position group. There were significant differences in SpO2 between the first 4 days after admission and the day of discharge (F = 3.17, P < 0.001). (2) The main complications were back and neck muscle soreness (55.9%), followed by abdominal distension (8.9%). (3) In control group, a total of 4873 cases of mild and moderate patients were included from 19 literatures, with an average deterioration rate of 22.7% and mortality rate of 1.7%. (4) In prone position group, there were no severe or critical transformation cases and also no death cases. The prone position group had a significantly lower deterioration rate when compared with the control group (χ2 = 9.962, P < 0.01). CONCLUSION: Prone position improves SpO2 in patients with mild or moderate COVID-19. It can also reduce the percentage of mild or moderate patients progressing to severe or critical patients. The application of prone position is a simple, feasible, safe and effective treatment method in such patients.

Associations of prenatal exposure to perfluoroalkyl substances with preterm birth: A family-based birth cohort study.

Studies have investigated associations between maternal exposure to PFAS and preterm birth, but the impact of paternal and overall family exposure to PFAS mixtures on preterm birth remains unknown. To address this knowledge gap, a total of 355 preterm births and 481 controls were selected for a family-based birth cohort study in a coastal area of China, between 2016 and 2018. Seven PFAS, including perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were quantified in maternal, paternal and neonatal sera. Preterm birth was defined as live delivery at <37 completed gestational weeks. Bayesian kernel machine regression (BKMR) model was used to inspect the combined effect of family PFAS mixtures. Latent class analysis was used to identify family-level PFAS exposure profiles. Multiple linear regression analysis showed higher odds of preterm birth in association with higher maternal PFBA (OR = 1.16, 95%CI:1.09, 1.25), PFOA (OR = 1.51, 95%CI:1.27, 1.80), PFOS (OR = 2.07, 95%CI:1.70, 2.52) and PFNA (OR = 1.36, 95%CI: 1.01, 1.83), and neonatal PFBA (OR = 1.16, 95%CI:1.05,1.29), PFHxA (OR = 1.46, 95%CI:1.32, 1.62), PFHxS (OR = 1.15, 95%CI:1.05, 1.26) and PFNA (OR = 1.30, 95%CI:1.09,1.56). The associations were reversed between individual paternal PFAS exposures and preterm birth. At the family level, higher PFAS mixture concentration was associated with higher odds of preterm birth. In particular, higher PFNA and PFDA exposure was associated with greater preterm birth risk (OR = 2.55, 95%CI:1.45, 4.50). The PFAS-preterm association was modified by family-level seafood consumption. Our results suggest that higher family-level PFNA and PFDA exposure was associated with greater preterm birth risk, although the results for individual paternal, maternal and neonatal PFAS exposures were contradictory. If replicated in other coastal areas, these findings highlight a need to focus on the family triad and to consider seafood consumption when assessing the reproductive toxicity of PFAS exposure.

2D MXene interfaces preserve the basal electrophysiology of targeted neural circuits.

Neural interfaces enable the monitoring of the state of the brain and its composite cell networks, as well as stimulate them to treat nervous disorders. In addition to their highly efficient charge transduction and stability during operation, the neural electrodes should avoid altering the physiological properties of targeted neuronal tissues. Two-dimensional (2D) MXene materials integrate the advantages of metallic conductivity, high specific-surface area and surface functionality in aqueous dispersions, showing promising potential in neural interface applications. Here, we apply uncoated Ti3C2Tx MXene to interface neuronal development. The impacts of the uncoated Ti3C2Tx MXene interface on neuronal development and neuronal microcircuit activity were tested for the first time. Compared to the standard neuronal culture with a poly-L-ornithine coated coverslip, uncoated Ti3C2Tx MXene surfaces did not affect the cell morphology, density, neuron ratios, maturation or the compositions of the neuronal network. Moreover, calcium imaging, spontaneous postsynaptic currents (sPSCs) and also miniature postsynaptic currents (mPSCs) were recorded to demonstrate that Ti3C2Tx MXene interfaces preserved the basal physiology of neuronal activity. The ability to interface neuronal circuit development without altering neuronal signaling properties enables the construction of MXene-based neural prosthetic devices for neuroscience research, diagnosis, and therapies.

Temperature effect on vibrational properties of crystalline Dibenz[a,h]anthracene.

Vibrational properties associated with the intra- and intermolecular bonding of the crystalline Dibenz[a,h]anthracene at low temperatures are investigated by Raman scattering. A complete characterization of phonon spectra is given for this material. In the 120-150 K temperature region, several lattice modes show abrupt changes of splitting and the discontinuities in the temperature shift, but no emergence of new modes. Moreover, the intensity ratio of I68/38 is greater than 1 below 130 K. Meanwhile, the aromatic C-C stretching modes exhibit anomalous behaviors in frequencies, widths, and intensities at about 130 K. These spectroscopic results demonstrate a disorder-order transition occurred at about 130 K. However, the modes, corresponding to C-H out-of-plane bending, C-H in-plane bending, and/or C-H rocking, have no significant change in the whole temperature range. It indicates that the transition mainly results from the change of the tilt angle between the molecules. Our work is of great significance to understand the internal vibrational properties of Dibenz[a,h]anthracene, and it also provides considerable supports for the further study of this material.

Per- and perfluoroalkyl substances alternatives, mixtures and liver function in adults: A community-based population study in China.

Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: -0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.

CRISPR/Cpf1 multiplex genome editing system increases silkworm tolerance to BmNPV.

The CRISPR/Cas9 genome editing technology is now widely used in insect studies, but the use of CRISPR can be further increased to improve insect genome engineering. We established a direct mutation at multiple loci in several genes simultaneously used by CRISPR/Cpf1 multiplex genome editing technology to target the BmNPV genome. We constructed a transgenic line that can target the BmNPV ie-1, gp64, and DNApoly genes simultaneously, and hybridized this line with an FnCpf1 transgenic line to obtain an FnCpf1 × gNPVM binary hybrid expression system and to activate the FnCpf1 gene editing system. We showed that the multiple gene editing system introduced deletions, mutations, and insertions at three target sites, and that it did not affect the economic traits of transgenic silkworm lines. The antiviral response of multiplexed genome editing lines increased significantly, and viral gene transcription and replication were significantly affected in the transgenic silkworm lines. This study provides innovative resistance materials for silkworm breeding and also provides a simplified platform for efficient insect multi genome engineering and genetic operation.