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Abstract Background Studies have shown that Averrhoa carambola L. possesses therapeutic potential for diabetes and related complications. However, the specific beneficial effects and molecular mechanisms of 2-dodecyl-6-meth-oxycyclohexa-2,5-diene-1,4-dione (DMDD) isolated from Averrhoa carambola L. on diabetic nephropathy (DN) require further investigation. Methods 80 C57BL/6 J male mice were subjected to a 1-week adaptive feeding, followed by a high-fat diet and intraperitoneal injection of 100 mg/kg streptozotocin (STZ) to construct an in vivo DN model. Additionally, human renal proximal tubular epithelial cells (HK-2) induced by high glucose (HG) were used as an in vitro DN model. The expression levels of epithelial-mesenchymal transition (EMT), endoplasmic reticulum stress (ERS), and autophagy-related proteins in renal tubular cells were detected by Western Blot, flow cytometry, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) staining. Transcriptome analysis revealed was conducted to elucidate the specific mechanism of by which DMDD mitigates DN by inhibiting ERS and autophagy. HK-2 cells were transfected with IRE1α overexpression lentivirus to reveal the role of IRE1α overexpression in HG-induced HK-2. Results The experimental data showed that DMDD significantly reduced blood glucose levels and improved renal pathological alterations in DN mice. Additionally, DMDD inhibited the calcium (Ca2+) pathway, manifested by decreased autophagosome formation and downregulation of LC3II/I, Beclin-1, and ATG5 expression. Moreover, in HG-induced HK-2 cells, DMDD suppressed the overexpression of GRP78, CHOP, LC3II/I, Beclin1, and ATG5. Notably, IRE1α overexpression significantly increased autophagy incidence; however, DMDD treatment subsequently reduced the expression of LC3II/I, Beclin1, and ATG5. Conclusion DMDD effectively inhibits excessive ERS and autophagy, thereby reducing renal cell apoptosis through the IRE1α pathway and Ca 2+ pathway.

Background: Panax quinquefolius L, widely recognized for its valuable contributions to medicine, has aroused considerable attention globally. Different from the extensive research has been dedicated to the root of P. quinquefolius, its berry has received relatively scant focus. Given its promising medicinal properties, this study was focused on the structural characterizations and anti-inflammatory potential of acidic polysaccharides from the P. quinquefolius berry. Materials and methods: P. quinquefolius berry was extracted with hot water, precipitated by alcohol, separated by DEAE-52-cellulose column to give a series of fractions. One of these fractions was further purified via Sephadex G-200 column to give three fractions. Then, the main fraction named as AGBP-A3 was characterized by methylation analysis, NMR spectroscopy, etc. Its anti-inflammatory activity was assessed by RAW 264.7 cell model, zebrafish model and molecular docking. Results: The main chain comprised of α-L-Rhap, α-D-GalAp and β-D-Galp, while the branch consisted mainly of α-L-Araf, β-D-Glcp, α-D-GalAp, β-D-Galp. The RAW264.7 cell assay results showed that the inhibition rates against IL-6 and IL-1β secretion at the concentration of 625 ng/mL were 24.83 %, 11.84 %, while the inhibition rate against IL-10 secretion was 70.17 % at the concentration of 312 ng/mL. In the zebrafish assay, the migrating neutrophils were significantly reduced in number, and their migration to inflammatory tissues was inhibited. Molecular docking predictions correlated well with the results of the anti-inflammatory assay. Conclusion: The present study demonstrated the structure of acidic polysaccharides of P. quinquefolius berry and their effect on inflammation, providing a reference for screening anti-inflammatory drugs.

Calculating the parameters of the ground shock induced by an underground explosion is a complex energy coupling problem. It is difficult to establish a unified ground shock coupling law from limited test data. This paper summarizes the research results obtained at home and abroad and systematically analyzes the coupling mechanism of craters formed by an underground explosion and the ground shock. The differences between the concepts of “closed-explosion critical depth” and “equivalent closed-explosion critical depth” are clearly explained. The spreading of the ground shock energy is attributed to the explosive expansion of the air cavity, revealing a linear relationship between the volume of the cavity region (or the volume of the crack region) and the ground shock energy associated with the underground explosion. The proportionality factor is related to the mechanical properties of the medium and is independent of the magnitude of the explosion equivalent. Based on this, a theoretical calculation formula and conversion method for the ground shock coupling coefficient were established. Explosion tests were conducted in clay and Plexiglass under varying burial depths. The test results were consistent with the theoretically calculated results. Our study provides a theoretical basis for the design of explosion-resistant structures in underground engineering.

Apostichopus japonicus (A. japonicus) is known as one of the most popular varieties in aquaculture due to its rich nourishment and potential medicinal value. In recent years, with the abnormal change of marine environment and global climate, new challenges are arising continually in the culture process of A. japonicus. Intestinal flora plays an important role in host health and growth, and a lot of studies confirmed the close relationship between the composition change of intestinal flora and the growth of sea cucumbers. In this study, polypeptidin belonging to bacteriocins, was as an additive ingredient in sea cucumber feed. The growth of A. japonicus increased significantly after polypeptidin feeding, and the growth rate reached the highest with 1 % polypeptidin especially. Subsequently 16 S rRNA of gut microbiota from 1 % polypeptidin group was sequenced and analyzed for richness and diversity index, but the results showed that polypeptidin supplement did not markedly change the diversity and main composition of gut microbiota compared to the control. So the further analyze was performed by dependent t-test for paired samples, and found that the abundance of only a few of species at the class level changed significantly, including Alphaproteobacteria, Desulfotomaculia and Chlamydiae, but many species at the genus level changed significantly. Some important metabolic pathways were identified through function prediction, like TCA cycle, streptomycin biosynthesis and phenylalanine metabolism. At this basis, the analysis combined with the genuses and the metabolic pathways demonstrated that polypeptidin might regulate the richness of some bacteria, which could be involved in enzyme degradation, antibacterial substances secreting or underlying pathogenic tendency of gut microbiota ecosystem. These fine-tunings instead of main community structure change were probably more beneficial to the intestinal flora health, and finally contributed to the growth of A. japonicus. Thus, polypeptidin serves as a mild, non-stimulating feed supplement for A. japonicus, and has good prospects for application.

Background: Because adverse reactions or drug resistance are often found after current chemotherapies for metastatic colorectal cancer (mCRC), new treatments are still in demand. Shenqi Sanjie Granules (SSG), an antitumor compound preparation of traditional Chinese medicine, has been recognized for its ability in clinical practice of oncotherapy. Nevertheless, the precise effects of SSG in colorectal cancer (CRC) and underlying mechanisms through which SSG inhibits CRC remain uncertain. The current study aimed to evaluate the anti-CRC activity of the Chinese herbal compound preparation SSG and investigate the underlying mechanisms of action. Materials and methods: Initially, nine distinct cancer cell lines, including five CRC cell lines, one breast cancer cell line, two lung adenocarcinoma cell lines and one cervical cancer cell line, were used to evaluate the antitumor activity of SSG, and the mouse CRC cell line CT26 were used for further research. In vitro experiments utilizing diverse assays were conducted to assess the inhibitory effects of the SSG on CT26. Furthermore, subcutaneous syngeneic mouse model and AOM (azoxymethane)/DSS (dextran sodium sulfate) induced in-situ colitis-related mouse CRC model were used to evaluate the antitumor potential and biotoxicity of SSG in vivo. To elucidate the underlying molecular mechanisms, transcriptome sequencing and network pharmacology analysis were performed. Meanwhile, verification is carried out with quantitative real-time PCR (qRT-PCR) and flow cytometry (FCM) analysis. Results: Our in vitro inhibition study showed that SSG could effectively inhibit CRC cell line CT26 growth and metastasis, and induce cell death. Neither of apoptosis inhibitor, necroptosis inhibitor, ferroptosis inhibitor, but the combination of the three diminished SSG-induced cell death, suggesting that multiple cell death pathways were involved. Both the syngeneic CRC model and the in-situ CRC model indicated SSG inhibited CRC in vivo with few toxic side effects. Further mechanistic study suggested SSG treatment activated the ferroptosis pathway, particularly mediated by Hmox1, which was upregulated scores of times. Network pharmacology analysis indicated that the active ingredients of SSG, including Quercetin, Luteolin and Kaempferol were potential components directly upregulated Hmox1 expression. Conclusions: Collectively, our findings indicate that the administration of SSG has the potential to inhibit CRC both in vitro and in vivo. The mechanism by which this compound preparation exerts its action is, at least partly, the induction of ferroptosis through upregulating Hmox-1 by its three active ingredients Quercetin, Luteolin and Kaempferol.

The majority of previous studies have asserted that the high quality of local institutions can improve the productivity effects of trade policies; yet, only a few studies have acknowledged the heterogeneous impact of these institutions. Using data from Chinese manufacturing plants, we examine the moderating effects of regional-level regulations on the effectiveness of national services trade policy. The key findings are threefold: First, as the initial degree of service liberalization advances, the productivity effect of trade liberalization diminishes. Second, opening access to foreign enterprises can substitute for pro-competitive regulatory reform. Regardless of whether the regulatory institutions related to administrative processes, law enforcement, and commercial service have improved, services trade liberalization can have significant productivity effects. Third, in contrast, when regulations to protect for local incumbents impose prohibitive costs for new entrants, the impact of services trade liberalization is highly contingent on local regulatory improvement. The confirmation that trade liberalization can potentially serve as an alternative measure for local regulation reform in Chinese context distinguishes this study from others.

Abstract Background Ubiquitination plays an important role in proliferating and invasive characteristic of glioblastoma (GBM), similar to many other cancers. Tripartite motif 25 (TRIM25) is a member of the TRIM family of proteins, which are involved in tumorigenesis through substrate ubiquitination. Methods Difference in TRIM25 expression levels between nonneoplastic brain tissue samples and primary glioma samples was demonstrated using publicly available glioblastoma database, immunohistochemistry, and western blotting. TRIM25 knockdown GBM cell lines (LN229 and U251) and patient derived GBM stem-like cells (GSCs) GBM#021 were used to investigate the function of TRIM25 in vivo and in vitro. Co-immunoprecipitation (Co-IP) and mass spectrometry analysis were performed to identify NONO as a protein that interacts with TRIM25. The molecular mechanisms underlying the promotion of GBM development by TRIM25 through NONO were investigated by RNA-seq and validated by qRT-PCR and western blotting. Results We observed upregulation of TRIM25 in GBM, correlating with enhanced glioblastoma cell growth and invasion, both in vitro and in vivo. Subsequently, we screened a panel of proteins interacting with TRIM25; mass spectrometry and co-immunoprecipitation revealed that NONO was a potential substrate of TRIM25. TRIM25 knockdown reduced the K63-linked ubiquitination of NONO, thereby suppressing the splicing function of NONO. Dysfunctional NONO resulted in the retention of the second intron in the pre-mRNA of PRMT1, inhibiting the activation of the PRMT1/c-MYC pathway. Conclusions Our study demonstrates that TRIM25 promotes glioblastoma cell growth and invasion by regulating the PRMT1/c-MYC pathway through mediation of the splicing factor NONO. Targeting the E3 ligase activity of TRIM25 or the complex interactions between TRIM25 and NONO may prove beneficial in the treatment of GBM.

In the human body, non-centrosymmetric biological structures exhibit piezoelectric effect across from microscopic biomolecular building blocks to macroscopic tissues and organs. However, the fabrication of piezoelectric devices from discarded natural tissues and organs has rarely been exploited for energy harvesting applications. Herein, the extracted human teeth were recycled as an active layer in a piezoelectric nanogenerator for power generation. Due to the piezoelectric effect of enamel and dentin, a human teeth-based sandwiched piezoelectric nanogenerator was fabricated, producing high and stable power outputs with an open-circuit voltage of approximately 0.9 V under an external force at 60 N. Furthermore, the high mechanical durability of the piezoelectric nanogenerator was also verified after 1600 pressing-and-releasing cycles without noticeable output degradation. Notably, for the first time, a light-emitting diode (LED) was illuminated by the human teeth-based piezoelectric device. This work exemplifies a sustainable strategy to recycle the extracted human teeth by fabricating a piezoelectric nanogenerator for energy harvesting, providing inspiration for converting waste into wealth toward green energy in bionanotechnology.

In this work, a self-compacting potassium salt magnesium phosphate cement (PMPC) coating slurry was prepared by improving the water binder ratio and adding an appropriate amount of water glass (WG) and silica microfume (SMP). By performing long-term solution immersion tests, the following conclusions can be drawn: the remaining flexural and compressive strength values (Δff and Δfc) of the PMPC specimens (M2) containing 2 % WG and 10 % SMP immersed in water, 3.5 % NaCl solution, and 5 % Na2SO4 solution for 540 days were greater than 95 % and 90 %, respectively. In comparison to the reference PMPC specimen without WG and SMP (M0), the Δff and Δfc increased by more than 30 % and 25 %, respectively. After 540 days in 3.5 % NaCl solution and 5 % Na2SO4 solution, the salt corrosion coefficients (Kf and Kc) of the M2 specimen were all greater than 1. After excluding the factor of water corrosion, the salt crystals in the solution had a strengthening effect on the hardened PMPC paste. The M2 specimens experienced volume expansion after being immersed in a solution composed of water, 3.5 % NaCl solution, and 5 % Na2SO4 solution for 540 days (7.21× 10−4, 13.52 × 10−4, and 10.92 × 10−4); this expansion was significantly lower than that of the M0 specimen under the same conditions (13×10−4, 18.5×10−4, and 21.5×10−4) due to the relatively denser initial structure. The initial water absorption rate of M2 (0.64 %–0.66 %) was significantly lower than that of M0 (0.72 %–0.75 %). After soaking in water, 3.5 % NaCl solution, and 5 % Na2SO4 solution for 540 days, the water absorption of the M2 specimens increased by 64.6 %, 7.6 %, and 12.5 %, respectively, which is clearly lower than that of M0 specimens (95.9 %, 22.7 %, and 30.6 %). The increase in the water absorption of the specimen in the salt solution was also obviously smaller than that in the aqueous solution.

One of the major challenges in the aquaculture of marine organisms is the susceptibility to pathogens. Immune cells defend bacterial invasion by recognizing pathogen-associated molecular patterns (PAMPs) such as Lipopolysaccharides (LPS) in Gram-negative bacteria. The white body are key organs for immune response and hematopoiesis, and play an important role in understanding the antimicrobial biological response in gold-ringed octopus (Amphioctopus fangsiao). In the present research, transcriptome sequencing and bioinformatics analysis were conducted on A. fangsiao white body tissue after 6 h and 24 h of LPS stimulation. The results showed 2,029 and 73 differentially expressed genes (DEGs) at the 6- and 24-hour time points, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were beneficial in determining immune-related terms and signaling pathways. Subsequently, a protein-protein interaction (PPI) network was constructed and 20 hub genes, such as AKT3, MAPK14, and PIK3CA, were identified. These genes are involved in a variety of signaling pathways, including the Hippo signaling pathway, chemokine signaling pathway, and leukocyte trans endothelial migration. Using qRT-PCR, the accuracy of the 20 hub genes was verified. The present study provides a substantial theoretical foundation for the research on A. fangsiao white body immunity, enhancing the current understanding of cephalopods' innate immunity.

IntroductionAnkle fractures require temporary fixation to allow swelling to subside prior to surgery; this is typically achieved using calcaneal distraction or cast immobilization. We compared the results of these methods in the treatment of Danis–Weber type C ankle fractures.MethodsThis retrospective study analyzed the data of 86 patients with Danis–Weber type C ankle fractures, of whom 40 underwent calcaneal distraction and 46 underwent cast immobilization. Clinical measures including preoperative detumescence time, daily swelling value, skin condition, and pain, SF-36 Health Survey (SF-36) score and ankle scores were compared between the two groups.ResultsBaseline characteristics did not differ significantly between the groups. Calcaneal distraction resulted in a lower preoperative detumescence time (6.22 ± 0.64 vs. 8.94 ± 0.82 days) and lower daily swelling values compared with cast immobilization, leading to a lower skin necrosis rate. Resting pain scores were significantly lower in the calcaneal distraction group than in the cast immobilization group at various postoperative time points (P

ABSTRACT: Phage therapy is gaining momentum as an alternative to antibiotics in the treatment of salmonellosis caused by Salmonella. In this study, a novel Salmonella phage, vB_SalS_JNS02, was isolated successfully from poultry farms in Shandong, China. The biological characteristics of vB_SalS_JNS02 were analysed, which revealed a short latent period of approximately 10 min and a burst size of 110 PFU/cell. Moreover, vB_SalS_JNS02 exhibited remarkable stability across a wide pH range (pH 3–12) and temperatures ranging from 30 to 80°C. Genome sequencing analysis provided valuable insights into the genetic composition of vB_SalS_JNS02, which consists of a double-stranded DNA genome that spans 42,450 base pairs and has a G + C content of 49.4%. Of significant importance, the genomic sequence of vB_SalS_JNS02 did not contain any genes related to lysogenicity, virulence, or antibiotic resistance. The phage's efficacy was evaluated in a larval challenge study. Treatment with the phage resulted in increased survival of Galleria mellonella larvae (100, 70, and 85%) (MOI 0.1) in the prophylactic treatment, co-infection treatment, and remedial treatment experiments, respectively. Another in vivo experiment investigated the potential application of the phage in broiler chickens and revealed that a single oral dose of vB_SalS_JNS02 (108 PFU/mL, 100 µL/chick) administered 3 h after S. enteritidis oral administration provided effective protection. The introduction of bacteriophage not only enhances the production of secretory immunoglobulin A (sIgA), but also induces alterations in the composition of the gut microbial community. Phage therapy increases the relative abundance of beneficial bacteria, which helps to maintain intestinal barrier homeostasis. However, it is unable to fully restore the disrupted intestinal microbiome caused by S. enteritidis infection. Importantly, no significant adverse effects were observed in the animal subjects following oral administration of the phage, and our findings highlight vB_SalS_JNS02 is a hopeful candidate as a promising tool to target Salmonella infections in poultry.

Sepia esculenta is a tasty and nutritious cephalopod. But the trend toward global warming is accelerating with massive emissions of greenhouse gases. An increase in seawater temperature and a decrease in pH are a great challenge for artificial breeding and culture of S. esculenta. In this study, we investigated the contingency mechanism of S. esculenta larvae under both high temperature and low pH conditions by transcriptome analysis. A total of 1235 DEGs were identified. functional enrichment analysis results suggest that high temperature and low pH conditions led to malignant proliferation in exceptional cells of S. esculenta larvae. A comprehensive analysis of the KEGG signaling pathway and protein-protein interaction network (PPI) identified sixteen key genes under both high temperature and low pH conditions. The three genes with the highest quantities of interactions or involved in more KEGG signaling pathways were identified as hub genes affecting normal physiological processes in S. esculenta. In this study, the effects of global warming and ocean acidification on the metabolism and immunity of S. esculenta larvae were preliminarily investigated to provide necessary help for S. esculenta captive breeding in the face of global climate change.

Pathogenic infections significantly limit the culture of marine organisms, such as cephalopods. However, there is a lack of immune information regarding cephalopods to address pathogen problems. Polyriboinosinic polyribocytidylic acid (Poly I:C), a synthetic virus-like molecule, can be recognized by the immune cells as pathogen-associated molecular patterns (PAMPs), and this process is often used to simulate the invasion of viruses. The white body is an immune and hematopoietic organ, and its RNA-seq information obtained from Amphioctopus fangsiao stimulated by Poly I:C is essential for understanding the antiviral immune response in this species. In this research, we performed transcriptome sequencing and bioinformatics analysis of A. fangsiao white body tissue within 24 h stimulated by Poly I:C. A large number of differentially expressed genes (DEGs) were detected in this study, including 2,613 and 8 DEGs at 6 h and 24 h, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used for searching immune-related terms and genes. A protein–protein interaction (PPI) network was constructed to identify the relationship between immune genes. Finally, the 20 hub genes including RAC1, MAPK14, PIK3CA and other seventeen hub genes were identified based on the network and pathway analyses, and we validated the accuracy of 20 hub genes using qRT-PCR. These hub genes mainly participated in PI3K-Akt signaling pathway, Chemokine signaling pathway and other signaling pathways, in addition to the ubiquitin family. These research results provided a valuable theoretical basis for researching A. fangsiao white body immunity and significantly improved our cognition about innate immunity of cephalopods.

Abstract Objective Risk stratification plays a critical role in patients with asymptomatic carotid atherosclerotic stenosis. Heavy macrophage infiltration (HMC) is an important factor of plaque destabilization. However, in vivo imaging technologies and screening criteria for HMC remain limited. We aimed to (i) introduce algorithms for in vivo detection of macrophage infiltrations using optical coherence tomography (OCT) and (ii) to investigate the threshold of HMC and its association with plaque vulnerability. Methods Ex vivo OCT images were co‐registered with histopathology in 282 cross‐sectional pairs from 19 carotid endarterectomy specimens. Of these, 197 randomly selected pairs were employed to define the parameters, and the remaining 85 pairs were used to evaluate the accuracy of the OCT‐based algorithm in detecting macrophage infiltrations. Clinical analysis included 93 patients receiving carotid OCT evaluation. The prevalence and burden of macrophage infiltration were analyzed. Multivariable and subgroup analysis were performed to investigate the association between HMC and plaque rupture. Results The sensitivity and specificity of algorithm for detecting macrophage infiltration were 88.0% and 74.9%, respectively. Of 93 clinical patients, ruptured plaques exhibited higher prevalence of macrophage infiltration than nonruptured plaques (83.7% [36/43] vs 32.0% [16/50], p

Abstract Background and aim The health implications of BMI and MetS in lactating women are significant. This study aims to investigate the relationship between risk of Mets in lactation and BMI in four stages: pre-pregnancy, prenatal period, 42 days postpartum, and current lactation. Methods and results A total of 1870 Lactating Women within 2 years after delivery were included from "China Child and Lactating Mother Nutrition Health Surveillance (2016–2017)". Logistic regression model and Restricted cubic spline (RCS) were used to estimate the relationship between BMI and risk of MetS. ROC analysis was used to determine the threshold for the risk of MetS. Chain mediating effect analysis was used to verify the mediating effect. BMI of MetS group in all stages were higher than non-MetS group (P

Purpose – The purpose of this study is to examine the impact of managerial short-termism on green innovation of firms and the moderating role of digital transformation of enterprises in the association between managerial short-termism and green innovation. Design/methodology/approach – This study uses data from Chinese A-share listed companies from 2001 to 2021 and employ panel fixed model and moderating effect model to examine the impact of managerial short-termism on green innovation of firms and the moderating role of digital transformation of enterprises in the association between managerial short-termism and green innovation. Findings – The findings of this study reveal that managerial short-termism exerts negative influence on green innovation. Digital transformation enables firms to reduce the adverse effect of managerial short-termism on green innovation because digital transformation enhances information processing ability and then improves internal corporate governance and analyst coverage. Moreover, the moderating role of digital transformation is more prominent for firms with lower internal corporate governance, for firms with less analyst coverage and for non-state-owned enterprises. Originality/value – This paper intends to address the following two questions: what is the impact of managerial short-termism on green innovation and what is the role of digital transformation in the two variables’ association? By using data of Chinese A-share listed companies from 2001 to 2021 and developing two individual indexes to measure managerial short-termism and digital transformation, the authors empirically test these above two questions. The results of this study indicate that: First, drawn on time-oriented theory and upper echelon theory, managerial short-termism has an adverse effect on firms’ green innovation. Second, digital transformation enables firms to reduce the negative effect of managerial short-termism on green innovation. Furthermore, the moderating mechanism tests show that the corporate governance effects of digital transformation play a supervisory role that impels managers to reduce short-term investments and promote firms’ green R&D investments, which helps to reduce the negative effect of managerial short-termism on green innovation. Additionally, the heterogeneity checks show that the moderating role of digital transformation in the relation between managerial short-termism and green innovation is more prominent for firms with lower internal corporate governance, with less analyst coverage and for non-state-owned enterprises.

With the development of commercialized planting of genetically modified crops, their ecological security risks remain a key topic of public concern. Insect-resistant genetically modified maize, Ruifeng125, which expresses a fusion Bt protein (Cry1Ab-Cry2Aj), has obtained the application safety certificate issued by the Chinese government. To determine the effects of Ruifeng125 on the diversity and dynamics of bacterial communities, the accumulation and degradation pattern of the fusion Bt protein in the rhizosphere soil of transgenic maize were detected. Results showed that the contents of Bt protein varied significantly at different developmental stages, but after straw was returned to the field, over 97% of Bt proteins were degraded quickly at the early stages (≤10 d) and then they were degraded at a relatively slow rate. In addition, the variations in bacterial community diversity in the rhizosphere soil were detected by 16S ribosomal RNA (Rrna) high-throughput sequencing technology. A total of 44 phyla, 435 families, and 842 genera were obtained by 16S rRNA sequencing, among which Proteobacteria, Actinobacia, Acidobacter Acidobacterium, and Chloroflexi were the dominant taxa. At the same developmental stage, no significant differences in soil bacterial diversity were detected between Ruifeng125 and its non-transgenic control variety. Further analysis revealed that developmental stage, rather than the transgenic event, made the greatest contribution to the changes in soil microbial diversity. This research provides important information for evaluating the impacts of Bt crops on the soil microbiome and establishes a theoretical foundation for their environmental safety assessment.

Marine mollusks, including oysters, are highly tolerant to high levels of cadmium (Cd), but the molecular mechanisms underlying their molecular response to acute Cd exposure remain unclear. In this study, the Pacific oyster Crassostrea gigas was used as a biological model, exposed to acute Cd stress for 96 h. Transcriptomic analyses of their gills were performed, and metabolomic analyses further validated these results. In our study, a total of 111 differentially expressed metabolites (DEMs) and 2108 differentially expressed genes (DEGs) were identified under acute Cd exposure. Further analyses revealed alterations in key genes and metabolic pathways associated with heavy metal stress response. Cd exposure triggered physiological and metabolic responses in oysters, including enhanced oxidative stress and disturbances in energy metabolism, and these changes revealed the biological response of oysters to acute Cd stress. Moreover, oysters could effectively enhance the tolerance and detoxification ability to acute Cd exposure through activating ABC transporters, enhancing glutathione metabolism and sulfur relay system in gill cells, and regulating energy metabolism. This study reveals the molecular mechanism of acute Cd stress in oysters and explores the molecular mechanism of high tolerance to Cd in oysters by using combined metabolomics and transcriptome analysis.

Spermatogenesis is the production of spermatozoa by the testes, a process that is associated with reproduction in males. Amphioctopus fangsiao is an economically important species from the northern coast of China, and little research has been done on spermatogenesis in this species. In this study, we performed transcriptome analysis of testis and other somatic tissues. The maturing stage of testis development was selected, in which the emergence of spermatozoa was observed. A total of 15,773 differentially expressed genes were identified, including 8,922 upregulated genes and 6,851 downregulated genes. GO and KEGG enrichment analyses were performed to explore the functions of genes related to spermatogenesis, and the interactions between genes were examined by constructing protein interaction networks. Pathways and genes related to spermatogenesis were identified, including the oxytocin signaling pathway, the calcium signaling pathway, the FOXO signaling pathway, the DNAH family, and other key genes. The expression levels of 25 key genes were verified by qRT-PCR. The results for spermatogenesis-related genes will provide insights into the processes of spermatogenesis and testis development in A. fangsiao.

Abstract Accumulating evidence suggests that changes in the tumor microenvironment caused by radiotherapy are closely related to the recurrence of glioma. However, the mechanisms by which such radiation‐induced changes are involved in tumor regrowth have not yet been fully investigated. In the present study, how cranial irradiation‐induced senescence in non‐neoplastic brain cells contributes to glioma progression is explored. It is observed that senescent brain cells facilitated tumor regrowth by enhancing the peripheral recruitment of myeloid inflammatory cells in glioblastoma. Further, it is identified that astrocytes are one of the most susceptible senescent populations and that they promoted chemokine secretion in glioma cells via the senescence‐associated secretory phenotype. By using senolytic agents after radiotherapy to eliminate these senescent cells substantially prolonged survival time in preclinical models. The findings suggest the tumor‐promoting role of senescent astrocytes in the irradiated glioma microenvironment and emphasize the translational relevance of senolytic agents for enhancing the efficacy of radiotherapy in gliomas.

The emergence of triploid oysters has freed the oyster market from the problem of interruptions in the breeding season, allowing for year-round availability. However, according to recent statistics, the phenomenon of fertility in triploid oysters has been increasing yearly, perhaps eventually leading to the loss of the sterility characteristic. This has in turn affected the oyster farming industry. Therefore, we attempted to mine key genes through transcriptomics to find the causes of triploid fertility. During our surveys and sampling, we found that most of the fertile triploid Crassostrea gigas were females, with a much smaller percentage of males. Therefore, the main objective of this study was to analyze the differences between fertile and sterile triploid female C. gigas. We performed transcriptome analysis of fertile female triploid C. gigas and sterile female triploid C. gigas and identified 2361 up-regulated differentially expressed genes (DEGs) and 1541 down-regulated DEGs, respectively. Enrichment analysis of these DEGs revealed that most GO terms and KEGG pathways were associated with mitosis. We then created a protein–protein interaction (PPI) network using genes enriched in mitosis-associated KEGG pathways. Finally, we screened and validated 26 key genes by quantitative RT-PCR and all were found to be downregulated in expression in sterile female triploids. The main cause of sterility is the suppression of the expression of genes that control the process of germ cell proliferation, the failure of the mitotic cycle to proceed smoothly, and the inability to produce an oogonium. These results can be used to explore ways to reduce the fertility of triploid C. gigas and to promote the breeding of higher quality triploid oysters.

Abstract One of the main characteristics of optical imaging systems is spatial resolution, which is restricted by the diffraction limit to approximately half the wavelength of the incident light. Along with the recently developed classical super-resolution techniques, which aim at breaking the diffraction limit in classical systems, there is a class of quantum super-resolution techniques which leverage the non-classical nature of the optical signals radiated by quantum emitters, the so-called antibunching super-resolution microscopy. This approach can ensure a factor of $$\sqrt{n}$$ n improvement in the spatial resolution by measuring the n -th order autocorrelation function. The main bottleneck of the antibunching super-resolution microscopy is the time-consuming acquisition of multi-photon event histograms. We present a machine learning-assisted approach for the realization of rapid antibunching super-resolution imaging and demonstrate 12 times speed-up compared to conventional, fitting-based autocorrelation measurements. The developed framework paves the way to the practical realization of scalable quantum super-resolution imaging devices that can be compatible with various types of quantum emitters.

Near-infrared spectroscopy (NIR) has become an essential tool for non-destructive analysis in various fields, including aquaculture. This study presents a pioneering application of portable NIR spectrometers to analyze glycogen content in the gonadal tissues of the Pacific oyster (Crassostrea gigas), marking the first instance of developing quantitative models for glycogen in tetraploid C. gigas. The research also provides a comparative analysis with models for diploid and triploid oysters, underscoring the innovative use of portable NIR technology in aquaculture. Two portable NIR spectrometers were employed: the Micro NIR 1700 (908–1676 nm) and the Micro PHAZIR RX (1624–2460 nm). Near-infrared spectra were acquired from the gonadal tissues of diploid, triploid, and tetraploid C. gigas. Quantitative models for glycogen content were developed and validated using cross-validation methods. Additionally, qualitative models for different ploidies and genders were established. For the Micro NIR 1700, the cross-validation correlation coefficients (Rcv) and cross-validation relative predictive errors (RPDcv) for glycogen were 0.949 and 3.191 for diploids, 0.915 and 2.498 for triploids, and 0.902 and 2.310 for tetraploids. The Micro PHAZIR RX achieved Rcv and RPDcv values of 0.781 and 2.240 for diploids, 0.839 and 2.504 for triploids, and 0.717 and 1.851 for tetraploids. The Micro NIR 1700 demonstrated superior quantitative performance, with RPD values exceeding 2, indicating its effectiveness in predicting glycogen content across different ploidy levels. Qualitative models showed a performance index of 91.6 for diploid and 95 for tetraploid genders using the Micro NIR 1700, while the Micro PHAZIR RX achieved correct identification rates of 99.79% and 100% for diploid and tetraploid genders, respectively. However, differentiation of ploidies was less successful with both instruments. This study’s originality lies in establishing the first quantitative models for glycogen content in tetraploid C. gigas using portable NIR spectrometers, highlighting the significant advancements in non-destructive glycogen analysis. The applicability of these findings is substantial for oyster breeding programs focused on enhancing meat quality traits. These models provide a valuable phenotyping tool for selecting oysters with optimal glycogen content, demonstrating the practical utility of portable NIR technology in aquaculture.

Over the years, oysters have faced recurring mass mortality issues during the summer breeding season, with Vibrio infection emerging as a significant contributing factor. Tubules of gill filaments were confirmed to be in the hematopoietic position in Crassostrea gigas, which produce hemocytes with immune defense capabilities. Additionally, the epithelial cells of oyster gills produce immune effectors to defend against pathogens. In light of this, we performed a transcriptome analysis of gill tissues obtained from C. gigas infected with Vibrio alginolyticus for 12 h and 48 h. Through this analysis, we identified 1024 differentially expressed genes (DEGs) at 12 h post-injection and 1079 DEGs at 48 h post-injection. Enrichment analysis of these DEGs revealed a significant association with immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. To further investigate the immune response, we constructed a protein–protein interaction (PPI) network using the DEGs enriched in immune-associated KEGG pathways. This network provided insights into the interactions and relationships among these genes, shedding light on the underlying mechanisms of the innate immune defense mechanism in oyster gills. To ensure the accuracy of our findings, we validated 16 key genes using quantitative RT-PCR. Overall, this study represents the first exploration of the innate immune defense mechanism in oyster gills using a PPI network approach. The findings provide valuable insights for future research on oyster pathogen control and the development of oysters with enhanced antimicrobial resistance.

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have emerged as a new mode of intercellular crosstalk and are responsible for many of the therapeutic effects of MSCs. To promote the application of MSC-EVs, recent studies have focused on the manipulation of MSCs to improve the production of EVs and EV-mediated activities. The current paper details an optimization method using non-invasive low-intensity pulsed ultrasound (LIPUS) as the stimulation for improving oral MSC-EV production and effectiveness. Stem cells from apical papilla (SCAP), a type of oral mesenchymal stem cell, displayed intensity-dependent pro-osteogenic and anti-inflammatory responses to LIPUS without significant cytotoxicity or apoptosis. The stimuli increased the secretion of EVs by promoting the expression of neutral sphingomyelinases in SCAP. In addition, EVs from LIPUS-induced SCAP exhibited stronger efficacy in promoting the osteogenic differentiation and anti-inflammation of periodontal ligament cells in vitro and alleviating oral inflammatory bone loss in vivo. In addition, LIPUS stimulation affected the physical characteristics and miRNA cargo of SCAP-EVs. Further investigations indicated that miR-935 is an important mediator of the pro-osteogenic and anti-inflammatory capabilities of LIPUS-induced SCAP-EVs. Taken together, these findings demonstrate that LIPUS is a simple and effective physical method to optimize SCAP-EV production and efficacy.

Many societies around the world are rapidly aging and this has implications for social and economic development. We collect data on NEEQ-listed enterprises from 2010 to 2021 in China and empirically test the effect of population aging on the digital transformation of small and medium-sized enterprises (SMEs). The findings show that population aging has a significant positive impact on SME digital transformation, and private enterprises and enterprises in eastern regions of China tend to benefit more than other regions. The mechanism studies find that population aging positively impacts SME digital transformation by increasing labor costs, facilitating human capital accumulation, and raising savings rates. Furthermore, the threshold effect analyses find that the marginal promotion effect of population aging will weaken with greater aging and will strengthen with a higher level of marketization. Finally, we provide policy recommendations for promoting digital transformation in SMEs against the background of population aging.

BackgroundExposure to heavy metals (cadmium, mercury, and lead) has been linked with adverse health outcomes, especially their nephrotoxic effects at high levels of exposure. We conducted a replication study to examine the association of low-level heavy metal exposure and chronic kidney disease (CKD) using a larger NHANES data set compared to previous studies.MethodsThe large cross-sectional study comprised 5,175 CKD cases out of 55677 participants aged 20-85 years from the 1999-2020 National Health and Nutrition Examination Survey [NHANES]. Logistic regression analysis was applied to estimate the associations between CKD and heavy metals [Cd, Pb, Hg] measured as categorical variables after adjusting with age, race, gender, socioeconomic status, hypertension, diabetes mellitus and blood cotinine level as smoking status.ResultsCompared to the lowest quartile of blood Cd, exposures to the 2nd, 3rd and 4th quartiles of blood Cd were statistically significantly associated with higher odds of CKD after adjustment for blood Pb and Hg, with OR = 1.79, [95% CI; 1.55-2.07, pConclusionsOur findings showed that low blood levels of Cd and Pb were associated with higher odds of CKD while low blood levels of Hg were associated with lower odds of CKD in the US adult population. However, temporal association cannot be determined as it is a cross sectional study.

BackgroundSarcopenia can lead to significant personal, social, and economic burdens. The diagnosis of sarcopenia heavily relies on the identification of Low Skeletal Muscle Mass (LSMM), which is an independent predictor of frailty, disability, and increased risk of death among seniors. Women have physiologically lower levels of skeletal muscle mass than men, and female sarcopenia appears to be more influenced by menopause. They also tend to have higher body fat levels than man, which increases the risk of sarcopenia obesity. On another front, it’s also recognized that humans are largely prone to Helicobacter pylori (H. pylori) infection, with global prevalence rates often surpassing 50%. Nevertheless, the interconnection between H. pylori infection and LSMM remains relatively unexplored. Hence, our study specifically targeted women as the research population and sought to explore several risk factors for LSMM. Additionally, we delved into the potential correlation between LSMM and H. pylori infection in women, hoping to gain insights into potential preventative measures or treatment options that may enhance the quality of life for women affected by sarcopenia.MethodsWe conducted a cross-sectional study among women aged over 18 years undergoing physical examination. We performed 13C-urea breath test (UBT) for diagnosis of H. pylori infection and Bioelectrical impedance analysis (BIA) for the assessment of LSMM. Logistic regression models were used to analyze the associations of H. pylori infection with LSMM.ResultsThis study enrolled 1984 Chinese women who were undergoing health check-ups. A univariate logistic regression analysis did not reveal a direct correlation between H. pylori infection and LSMM among this female population (OR=1.149, 95% CI 0.904-1.459, p=0.257). Yet, upon dividing the participants into age-based subgroups, an evident link was observed between H. pylori infection and LSMM in women aged 40 or above (OR=1.381, 95%CI 1.032-1.848, p= 0.030). After adjusting for variables including Age, BMI, TP, ALK, Cre, this relationship remained statistically relevant (OR=1.514, 95%CI 1.085-2.113, p= 0.015).ConclusionsWomen who are over 40 years old and currently infected with H. pylori have an increased risk of developing LSMM. Therefore, timely treatment for H. pylori eradication is recommended for this group of women to reduce the occurrence of LSMM.

The bonding force of hardened magnesium phosphate cement (MPC) based materials comes from the ionic and covalent bonds with high bond energy and strength between cementitious phosphate hydrates, resulting in high brittleness under stress. Fiber reinforced MPC matrix composites can consume energy through the various effects of fibers, thereby improving the brittleness of the MPC matrix. This study uses glass fiber three-dimensional spacing fabric with good fiber directional reinforcement ability and interlayer shear resistance as the reinforcement material, and potassium magnesium phosphate cement (MPKC) mortar was used as the matrix to prepare glass fiber reinforced MKPC based composite materials. Design and optimize the surface treatment method of three-dimensional spacing fabrics through uniaxial tensile testing of fiber reinforcement and its pull-out test in MKPC matrix. The mechanical properties of MKPC based composite material specimens reinforced with fabric were studied through compressive and four point bending tests. The results are as follows: the axial tensile force of the glass fibre reinforcement treated with water glass impregnation containing an appropriate amount of magnesium oxide powder is 2.5 times that of the untreated fibre reinforcement (the reference sample), and its tensile force in the MKPC matrix can reach 2 times that of the reference sample. The three-dimensional spacing fabric can improve the compressive strength of MKPC-based material specimens, and the larger the spacing between the fabric sandwich layers, the better the reinforcement effect. The reinforcement effect of the three-dimensional fabric impregnated with water glass containing magnesium oxide powder is better, and its compressive strength can be increased by 14.3% in comparison to the reference specimens without fabric fibers. The MKPC thin plate containing three-dimensional spacing fabric can withstand larger loads after initial cracking, and multiple cracks develop simultaneously. The initial cracking strength and initial cracking displacement slightly increase, and the ultimate strength and ultimate displacement significantly increase. The toughening effect of spacing fabrics with low-core columns on MKPC-based thin plate specimens is better than that of spacing fabrics with high-core columns. Impregnating three-dimensional spacer fabrics with water glass containing magnesium oxide powder can significantly improve the initial crack strength, deformation, ultimate strength, and displacement of MKPC-based thin plate specimens. In comparison to the reference sample without fabric fibers, the surface treated fabric reinforced MKPC matrix composite material specimen M1–1 exhibited a significant increase in cracking load and strain (26.01% and 33.96%), and its ultimate load and displacement were significantly increased (113.26% and 1125.13%). The above research content provides a theoretical basis for further research and engineering applications of this type of composite material.

Background: Echocardiographic data investigating the association between left ventricular (LV) function and gout is still limited.Purpose: To analyze the association of echocardiographic parameters based on two-dimentional speckle tracking analysis with clinically related indicators in patients with gout, and to provide a clinical basis for the early diagnosis and treatment of cardiovascular disease in patients with gout.Methods: This study collected gout patients who visited the outpatient and inpatient departments of the first affiliated hospital of chengdu medical college from November 2019 to December 2020. Spearman correlation test was performed to analyze the correlation coefficients between the laboratorial indicators with echocardiographic parameters. And the logistic regression analysis was performed to evaluate the independent effects.Results: The results of multivariate logistic regression showed that fasting plasma glucose (FPG) was a risk factor for the decrease in absolute value of global longitudinal strain [GLS (OR = 2.34; 95% CI, 1.01–5.39; p = 0.04)], Urea was a risk factor for absolute reduction in GCS (OR = 1.40; 95% CI, 1.07–1.85; p = 0.02), age (OR = 1.09, 95% CI, 1.04–1.16; p = 0.001), and hypertension (OR = 8.35; 95% CI, 1.83–38.02; p = 0.006) were risk factors for increased E/Em. High urea levels were significantly related with high risks of LVH (OR = 1.59, 95% CI, 1.04–2.43; p = 0.03) and enlargement of LAVI (OR = 1.68, 95% CI, 1.01–2.80; p = 0.04).Conclusion: Our study found that elevated urea and FPG were risk factors for subclinical LV myocardial dysfunction in patients with gout, which might provide a theoretical basis for the early diagnosis and treatment of heart disease in clinical practice.

Abstract Liver hepatocellular carcinoma (LIHC) is one of the most common malignancies and places a heavy burden on patients worldwide. HAUS augmin-like complex subunit 5 (HAUS5) is involved in the occurrence and development of various cancers. However, the functional role and significance of HAUS5 in LIHC remain unclear. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO) databases were used to analyze the mRNA expression of HAUS5. The value of HAUS5 in predicting LIHC prognosis and the relationship between HAUS5 and clinicopathological features were assessed by the Kaplan–Meier plotter and UALCAN databases. Functional enrichment analyses and nomogram prediction model construction were performed with the R packages. The LinkedOmics database was searched to reveal co-expressed genes associated with HAUS5. The relationship between HAUS5 expression and immune infiltration was explored by searching the TISIDB database and single-sample gene set enrichment analysis (ssGSEA). The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (HPA) databases were used to evaluate HAUS5 protein expression. Finally, the effect of HAUS5 on the proliferation of hepatoma cells was verified by CCK-8, colony formation and EdU assays. HAUS5 is aberrantly expressed and associated with a poor prognosis in most tumors, including LIHC. The expression of HAUS5 is significantly correlated with clinicopathological indicators in patients with LIHC. Functional enrichment analysis showed that HAUS5 was closely related to DNA replication, cell cycle and p53 signaling pathway. HAUS5 may serve as an independent risk factor for LIHC prognosis. The nomogram based on HAUS5 had area under the curve (AUC) values of 0.74 and 0.77 for predicting the 3-year and 5-year overall survival (OS) of LIHC patients. Immune correlation analysis showed that HAUS5 was significantly associated with immune infiltration. Finally, the results of in vitro experiments showed that when HAUS5 was knocked down, the proliferation of hepatoma cells was significantly decreased. The pan-oncogene HAUS5 is a positive regulator of LIHC progression and is closely associated with a poor prognosis in LIHC. Moreover, HAUS5 is involved in immune infiltration in LIHC. HAUS5 may be a new prognostic marker and therapeutic target for LIHC patients.

This paper discusses a type of mixed-delay quaternion-valued neural networks (QVNNs) under impulsive and stochastic disturbances. The considered QVNNs model are treated as a whole, rather than as complex-valued neural networks (NNs) or four real-valued NNs. Using the vector Lyapunov function method, some criteria are provided for securing the mean-square exponential stability of the mixed-delay QVNNs under impulsive and stochastic disturbances. Furthermore, a type of chaotic QVNNs under stochastic and impulsive disturbances is considered using a previously established stability analysis method. After the completion of designing the linear feedback control law, some sufficient conditions are obtained using the vector Lyapunov function method for determining the mean-square exponential synchronization of drive–response systems. Finally, two examples are provided to demonstrate the correctness and feasibility of the main findings and one example is provided to validate the use of QVNNs for image associative memory.

Background: Studies suggest associations between long-term ambient air pollution exposure and outcomes related to Alzheimer’s disease (AD). Whether a link exists between pollutants and brain amyloid accumulation, a biomarker of AD, is unclear. We assessed whether long-term air pollutant exposures are associated with late-life brain amyloid deposition in Atherosclerosis Risk in Communities (ARIC) study participants. Methods: We used a chemical transport model with data fusion to estimate ambient concentrations of PM2.5 and its components, NO2, NOx, O3 (24-hour and 8-hour), CO, and airborne trace metals. We linked concentrations to geocoded participant addresses and calculated 10-year mean exposures (2002 to 2011). Brain amyloid deposition was measured using florbetapir amyloid positron emission tomography (PET) scans in 346 participants without dementia in 2012–2014, and we defined amyloid positivity as a global cortical standardized uptake value ratio ≥ the sample median of 1.2. We used logistic regression models to quantify the association between amyloid positivity and each air pollutant, adjusting for putative confounders. In sensitivity analyses, we considered whether use of alternate air pollution estimation approaches impacted findings for PM2.5, NO2, NOx, and 24-hour O3. Results: At PET imaging, eligible participants (N = 318) had a mean age of 78 years, 56% were female, 43% were Black, and 27% had mild cognitive impairment. We did not find evidence of associations between long-term exposure to any pollutant and brain amyloid positivity in adjusted models. Findings were materially unchanged in sensitivity analyses using alternate air pollution estimation approaches for PM2.5, NO2, NOx, and 24-hour O3. Conclusions: Air pollution may impact cognition and dementia independent of amyloid accumulation, though whether air pollution influences AD pathogenesis later in the disease course or at higher exposure levels deserves further consideration.

Lung injury and pulmonary fibrosis contribute to morbidity and mortality, and, in particular, are characterized as leading cause on confirmed COVID-19 death. To date, efficient therapeutic approach for such lung diseases is lacking. N-Acetylglucosamine (NAG), an acetylated derivative of glucosamine, has been proposed as a potential protector of lung function in several types of lung diseases. The mechanism by which NAG protects against lung injury, however, remains unclear. Here, we show that NAG treatment improves pulmonary function in bleomycin (BLM)-induced lung injury model measured by flexiVent system. At early phase of lung injury, NAG treatment results in silenced immune response by targeting ARG1+ macrophages activation, and, consequently, blocks KRT8+ transitional stem cell in the alveolar region to stimulate PDGF Rβ+ fibroblasts hyperproliferation, thereby attenuating the pulmonary fibrosis. This combinational depression of immune response and extracellular matrix deposition within the lung mitigates lung injury and pulmonary fibrosis induced by BLM. Our findings provide novel insight into the protective role of NAG in lung injury.

Autism spectrum disorder (ASD)—a congenital mental disorder accompanied by social dysfunction and stereotyped behaviors—has attracted a great deal of attention worldwide. A combination of genetic and environmental factors may determine the pathogenesis of ASD. Recent research of multiple ASD models indicates that microRNAs (miRNAs) play a central role at the onset and progression of ASD by repressing the translation of key mRNAs in neural development and functions. As such, miRNAs show great potential to serve as biomarkers for ASD diagnosis or prognosis and therapeutic targets for the treatment of ASD. In this review, we discuss the regulatory mechanisms by which miRNAs influence ASD phenotypes through various in vivo and in vitro models, including necropsy specimens, animal models, cellular models, and, in particular, induced pluripotent stem cells derived from patients with ASD. We then discuss the potential of miRNA-based therapeutic strategies for ASD currently being evaluated in preclinical studies.

Feathers are important economic products. Anser cygnoide (AC) is superior in reproduction, growth and feather quality, while Anser anser (AA) has an advantage in feather yield. Understanding the development of feather follicles facilitates deliberate crossbreeding. Here, we compared feather follicles morphogenesis between AC and AA. Feathers and dorsal skin were sampled at multiple embryonic days to investigate feather phenotypes, feather follicle morphology and the expression of hub molecules (FZD4, β-catenin, LEF1, TCF4 and c-Myc) in the Wnt signalling pathway. We found a marked difference in plumage colour between the two breeds. Feather colour in AA has undergone a ‘black dorsum’ stage and cavity formation in AC was earlier. Furthermore, different trends in molecular hub expression helped explain the phenotypical and morphological differences: the upregulated Wnt signals in AC at E12 and/or E15, as well as in AA at E18, were associated with early epidermal placode formation and cavity formation in AC, also, related to the development of the secondary feather follicles and ‘black dorsum’ in AA. Summarily, breed-specific expression patterns of Wnt signalling pathway between AC and AA might participate in the shaping of breed-specific feather follicles morphogenesis and feather phenotypes. This work provides references for feather follicles development in geese.

Sepia esculenta is a cephalopod widely distributed in the Western Pacific Ocean, and there has been growing research interest due to its high economic and nutritional value. The limited anti-stress capacity of larvae renders challenges for their adaptation to high ambient temperatures. Exposure to high temperatures produces intense stress responses, thereby affecting survival, metabolism, immunity, and other life activities. Notably, the molecular mechanisms by which larval cuttlefish cope with high temperatures are not well understood. As such, in the present study, transcriptome sequencing of S. esculenta larvae was performed and 1,927 differentially expressed genes (DEGs) were identified. DEGs were subjected to functional enrichment analyses using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The top 20 terms of biological processes in GO and 20 high-temperature stress-related pathways in KEGG functional enrichment analysis were identified. A protein-protein interaction network was constructed to investigate the interaction between temperature stress-related genes. A total of 30 key genes with a high degree of participation in KEGG signaling pathways or protein-protein interactions were identified and subsequently validated using quantitative RT-PCR. Through a comprehensive analysis of the protein-protein interaction network and KEGG signaling pathway, the functions of three hub genes (HSP90AA1, PSMD6, and PSMA5), which belong to the heat shock protein family and proteasome, were explored. The present results can facilitate further understanding of the mechanism of high temperature resistance in invertebrates and provide a reference for the S. esculenta industry in the context of global warming.

The primary influencer of aquaculture quality in Amphioctopus fangsiao is pathogen infection. Both lipopolysaccharides (LPS) and polyinosinic:polycytidylic acid (Poly I:C) are recognized by the pattern recognition receptor (PRR) within immune cells, a system that frequently serves to emulate pathogen invasion. Hemolymph, which functions as a transport mechanism for immune cells, offers vital transcriptome information when A. fangsiao is exposed to pathogens, thereby contributing to our comprehension of the species’ immune biological mechanisms. In this study, we conducted analyses of transcript profiles under the influence of LPS and Poly I:C within a 24 h period. Concurrently, we developed a Weighted Gene Co-expression Network Analysis (WGCNA) to identify key modules and genes. Further, we carried out Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to investigate the primary modular functions. Co-expression network analyses unveiled a series of immune response processes following pathogen stress, identifying several key modules and hub genes, including PKMYT1 and NAMPT. The invaluable genetic resources provided by our results aid our understanding of the immune response in A. fangsiao hemolymph and will further our exploration of the molecular mechanisms of pathogen infection in mollusks.

Background: The occurrence of compound hot extreme (CHE) events in China is increasingly frequent. This study aimed to investigate the association between CHEs and all-cause mortality in Shandong Province and to estimate the attributable excess deaths. Methods: We collected daily data on weather, air pollution, and all-cause mortality at the subdistrict level in Shandong Province from 2013 to 2018. A CHE was defined as both daily maximum and minimum temperatures being higher than their historical 90th percentiles during 2013–2018 hot seasons. A case time-series analysis with a distributed lagged non-linear model was applied to analyze the subdistrict-specific association between different hot extremes and mortality risk, which were then pooled at the province level using meta-analysis. Results: Hot nights (RR = 1.44, 95%CI: 1.35–1.53) and CHEs (RR = 1.77, 95%CI: 1.64–1.90) were significantly associated with an increased mortality risk. CHEs had a greater effect for females (RR = 1.99, 95%CI: 1.81–2.19) and the elderly (>74 years) (RR = 2.14, 95%CI: 1.93–2.38) than their counterparts, respectively. Cardiovascular and respiratory deaths were more susceptible to CHEs than other deaths. Each year, 4888 (95%CI: 4133–5811) excess deaths in Shandong Province were attributable to CHEs, accounting for 2.60% (95%CI: 2.20–3.10%) of all-cause deaths and equating to 50 (95%CI: 42–58) deaths per 1,000,000 residents. The CHE-related mortality burden varied across subdistricts, with the highest occurring in the southeastern area and the lowest occurring in the northeastern and southwestern regions. Conclusion: CHEs and hot nights were substantially associated with excess deaths in Shandong Province, especially for females, the elderly, and residents living in the southeastern area. Our findings may facilitate the development of a heat alert warning system and preventive measures for vulnerable populations.

The impacts of hydraulic fracturing (HF) on birth defects have been suggested by previous studies but remain largely inconclusive. In this study, we assessed whether pregnant women who lived in areas with high HF activities had increased risks of giving birth to offspring with overall or specific birth defects, including atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA), microcephaly (MIC), and hydrocephaly without spina bifida (HSB). All live births between 1999 and 2014 among the residents in the four core counties of Denton, Johnson, Tarrant, and Wise in the Barnett Shale region, Texas, were analyzed. Standardized Morbidity Ratio (SMR) and Poisson regressions were applied for statistical analysis. Compared to the statewide risk, the risks of ASD, VSD, and PDA in four selected counties with high HF activities were significantly higher. The Annual Natural Gas Production from HF was significantly correlated with risks of ASD, PDA, MIC, and total birth defect after adjusting for counties and years. No significant associations of HF activities were found with VSD and HSB. This ecological study suggested that hydraulic fracturing might be associated with the increased risk of some birth defects in the Barnett Shale Region, TX, which warrants further investigations due to the limitation of an ecological study design.

Sea cucumber Apostichopus japonicus, an important marine benthic animal, is particularly sensitive to environmental temperature stress, which affected the growth, metabolism, and reproduction even survival. In this study, we used whole genome bisulfite sequencing (WGBS) to perform a comprehensive comparative analysis of the DNA methylation profiles of A. japonicus at three temperatures: normal (20 °C), aestivation (26 °C), and lethal (32 °C). The results showed that the total methylation level was highest in group T26 and lowest in group T32. Most of the DNA methylation occurred on the C bases of the CG type, and the degree of DNA methylation on the CG-type C bases was 13.32–14.99%, reflecting a moderate level of DNA methylation. Comparison of differentially methylated regions (DMRs) in the CG sequence context, we identified 17,174 DMRs in group T26_vs_T20 and 16,216 DMRs in group T32_vs_T26. There were more hypermethylated regions than hypomethylated regions, and this difference was more obvious in group T32_vs_T26. DMRs analysis of the promoter regions and the gene body regions identified more DMR-related genes in the gene body region than in the promoter region in both comparison groups (T26_vs_T20 and T32_vs_T26). GO and KEGG analysis showed that pathways such as protein processing in the endoplasmic reticulum, ubiquitin mediated proteolysis, and endocytosis, etc., were highly enriched in the DMR-related genes in the comparison groups. Some of these pathways that were significantly enriched in the hypermethylated genes in group T26_vs_T20 but were enriched in the hypomethylated genes in group T32_vs_T26. Enrichment analysis of genes both differentially methylated and differentially expressed showed that downregulated genes in group T32_vs_T26 that were also hypomethylated in the gene body region were significantly enriched in the metabolic and the antioxidant-related glutathione metabolism pathway. Our results suggested that DNA methylation develop a lot of variation in the regulation of the response of A. japonicus to two levels of heat stress: at aestivation temperature and at lethal temperature, and there are many differences between the two. The results of this study provide important insights into the epigenetic mechanisms underlying the response of A. japonicus to the pressure of environmental temperature.

Sperm storage is an important reproductive strategy in Amphioctopus fangsiao. Sperm can be stored in the oviducal glands up to eight months before fertilization. However, studies on the underlying storage mechanisms remain limited. In this study, the morphological structures of the oviductal glands and the changes adapted for sperm storage and fertilization were investigated by Hematoxylin eosin (HE) staining, transmission electron microscopy (TEM), and Alcian blue periodic acid Schiff (AB-PAS) staining. Results revealed that the nucleo-cytoplasmic ratio of the peripheral gland cells decreased and the eosinophilic secretory granules (glycoproteins) appeared in the cytoplasm and lumen during sperm storage. The cytoplasm of the central gland appeared vacuolated and AB pH 2.5 (+) secretions (acid mucins) were dispersed in the cells. These secretions may pass through the central cavity into the oviducts and be involved in zygote packaging. The spermathecae are composed of columnar epithelial ciliated cells with secretory functions. PAS (+) glycoproteins were found in the lumen, providing a microenvironment conducive to sperm survival. Cilia in the oviducts, central cavity, and spermathecae may help with sperm delivery, storage, and release, and egg transport. This study enhances our understanding of the biological reproduction process in A. fangsiao.

Using data on Chinese A-share listed firms from 2008 to 2017, we explore how corporate social responsibility (CSR) performance is affected by managerial short-termism and what factors influence the association between the two. First, by employing text analysis in conjunction with machine learning, we construct a new managerial short-termism indicator. Using panel fixed models, we find that managerial short-termism has an adverse impact on CSR performance, and the results are consistent in a series of robustness checks. The heterogeneous test results show that the negative effect is significant only for firms with lower internal corporate governance, for firms in less competitive industries, for firms with less analyst attention, and for state-owned enterprises (SOEs). Additionally, a better institutional environment weakens the negative impact of managerial short-termism on CSR performance. The findings shed light on policy implications for emerging countries.

The virtual inertia technology of DGs (Distributed Generations) can provide inertia and damping support for the power system by imitating the traditional synchronous machine. However, the inherent delay problems around the communication and process links of the virtual inertia control will make an impact on the fast support effect. In this paper, the virtual inertia based hierarchical control scheme considering communication delay for distributed generations integration systems is proposed. The hierarchical control architecture including the PQ primary control and the virtual inertia based secondary control method which can realize the optimal power utilization and certain frequency support under the situation of communication signal delay at the same time. Firstly, the basic hierarchical control scheme for distributed generations and corresponding small signal modeling considering communication delay are presented. Then to enhance the inertia support ability of the distributed generation integration system, an improved hierarchical control strategy considering communication delay is designed based on the robust passivity method to compensate the equivalent delay disturbance. Finally, the effectiveness verification of the proposed control is carried out with the simulation cases in PSCAD platform.

As many schools remain closed during the COVID-19 pandemic, various courses have to be migrated online. Previous studies have showed that students’ satisfaction of the courses could reflect the quality of online learning, which is determined by students’ perception of online courses. Although the community of inquiry (CoI) framework provided an effective tool for measuring students’ perception in online learning, the mechanisms between the CoI and satisfaction, especially the role of academic emotion and self-regulation, still need to be investigated in the online context. The present study aimed to (1) explore the relationships among three elements of the CoI framework; and (2) explore the relationships between the CoI and satisfaction, as well as the mediating role of academic emotion and self-regulation. The data was collected from 461 university students who were taking online courses in China. The results of Structural Equation Modeling showed that teaching presence significantly and positively predicted social presence and cognitive presence; both positive and negative academic emotions played the mediating roles between teaching presence, social presence and satisfaction; self-regulation played the mediating role between teaching presence, cognitive presence and satisfaction. The present study provided empirical evidence for the dynamics among the CoI framework as well as mechanisms between CoI and satisfaction in the online education environment.