Solid-State Electrocatalysis in Heteroatom-Doped Alloy Anode Enables Ultrafast Charge Lithium-Ion Batteries.

Electrocatalysis is generally confined to dynamic liquid-solid and gas-solid interfaces and is rarely applicable in solid-state reactions. Here, we report a paradigm shift strategy to exploit electrocatalysis to accelerate solid-state reactions in the context of lithium-ion batteries (LIBs). We employ heteroatom doping, specifically boron for silicon and sulfur for phosphorus, to catalyze electrochemical Li-alloying reactions in solid-state electrode materials. The preferential cleavage of polar dopant-host chemical bonds upon lithiation triggers chemical bond breaking of the host material. This solid-state catalysis, distinct from liquid and gas phases, requires a critical doping concentration for optimal performance. Beyond a critical concentration of ∼1 atom %, boron and sulfur doping drastically reduces activation energies and accelerates redox kinetics during lithiation/delithiation processes, leading to markedly enhanced rate performance in boron-doped silicon and sulfur-doped black/red phosphorus anode. Notably, a sulfur-doped black phosphorus anode coupled with a lithium cobalt oxide cathode achieves an ultrafast-charging battery, recharging 80% energy of a battery in 302 Wh kg-1 in 9 min, surpassing the thus far reported LIBs.

A Broad-specificity Neutralizing Nanobody against Hepatitis E Virus Capsid Protein.

Hepatitis E virus (HEV) is a worldwide zoonotic and public health concern. The study of HEV biology is helpful for designing viral vaccines and drugs. Nanobodies have recently been considered appealing materials for viral biological research. In this study, a Bactrian camel was immunized with capsid proteins from different genotypes (1, 3, 4, and avian) of HEV. Then, a phage library (6.3 × 108 individual clones) was constructed using peripheral blood lymphocytes from the immunized camel, and 12 nanobodies against the truncated capsid protein of genotype 3 HEV (g3-p239) were screened. g3-p239-Nb55 can cross-react with different genotypes of HEV and block Kernow-C1/P6 HEV from infecting HepG2/C3A cells. To our knowledge, the epitope recognized by g3-p239-Nb55 was determined to be a novel conformational epitope located on the surface of viral particles and highly conserved among different mammalian HEV isolates. Next, to increase the affinity and half-life of the nanobody, it was displayed on the surface of ferritin, which can self-assemble into a 24-subunit nanocage, namely, fenobody-55. The affinities of fenobody-55 to g3-p239 were ∼20 times greater than those of g3-p239-Nb55. In addition, the half-life of fenobody-55 was nine times greater than that of g3-p239-Nb55. G3-p239-Nb55 and fenobody-55 can block p239 attachment and Kernow-C1/P6 infection of HepG2/C3A cells. Fenobody-55 can completely neutralize HEV infection in rabbits when it is preincubated with nonenveloped HEV particles. Our study reported a case in which a nanobody neutralized HEV infection by preincubation, identified a (to our knowledge) novel and conserved conformational epitope of HEV, and provided new material for researching HEV biology.

Pathogenicity of two different genotypes avian hepatitis E strains in laying hens and silkie fowl.

To determine the pathogenicity of two different genotypes of avian hepatitis E strains in two species of birds, a total of thirty healthy 12-week-old birds were used. After inoculation, fecal virus shedding, viremia, seroconversion, serum alanine aminotransferase (ALT) increases and liver lesions were evaluated. The results revealed that CHN-GS-aHEV and CaHEV could both infect Hy-Line hens and silkie fowls, respectively. Compared to the original avian HEV strain, the cross-infected virus exhibited a delay of 2 weeks and 1 week in emerged seroconversion, viremia, fecal virus shedding, and increased ALT level, and also showed mild liver lesions. These findings suggested that CHN-GS-aHEV may have circulated in chickens. Overall, these two different genotypes of avian HEV showed some variant pathogenicity in different bird species. This study provides valuable data for further analysis of the epidemic conditions of two avian HEVs in Hy-Line hens and silkie fowls.

Modeling and biological evaluation of pegmolesatide, a novel and potent erythropoiesis-stimulating agent.

Pegmolesatide, a synthetic, polyethylene-glycolylated, peptide-based erythropoiesis-stimulating agent (ESA), has been recently approved in China. Pegmolesatide is derived from the structure of endogenous erythropoietin (EPO), a natural product in mammals. This study compared the in vitro effects and selectivity of pegmolesatide to those of recombinant EPO and carbamylated EPO (CEPO) through computer-aided analyses and biological tests. The findings indicate that pegmolesatide exhibited the same stimulating effect on erythropoiesis as EPO with fewer side effects than EPO and CEPO.

Incidence and risk factors of systemic lupus erythematosus in patients with primary immune thrombocytopenia: a systematic review and meta-analysis.

Background: Immune disorders and autoantibodies has been noted in both primary immune thrombocytopenia (ITP) and systemic lupus erythematosus (SLE). Whether the two disorders are correlated is unclear. The lack of evidence on the incidence of and risk factors for SLE in primary ITP patients poses a challenge for prediction in clinical practice. Therefore, we conducted this study. Methods: The protocol was registered with PROSPERO (CRD42023403665). Web of Science, Cochrane, PubMed, and EMBASE were searched for articles published from inception to 30 September 2023 on patients who were first diagnosed with primary ITP and subsequently developed into SLE. Furthermore, the risk factors were analyzed. Study quality was estimated using the Newcastle-Ottawa Scale. The statistical process was implemented using the R language. Results: This systematic review included eight articles. The incidence of SLE during the follow-up after ITP diagnosis was 2.7% (95% CI [1.3-4.4%]), with an incidence of 4.6% (95% CI [1.6-8.6%]) in females and 0 (95% CI [0.00-0.4%]) in males. Older age (OR = 6.31; 95% CI [1.11-34.91]), positive antinuclear antibody (ANA) (OR = 6.64; 95% CI [1.40-31.50]), hypocomplementemia (OR = 8.33; 95% CI [1.62-42.91]), chronic ITP (OR = 24.67; 95% CI [3.14-100.00]), organ bleeding (OR = 13.67; 95% CI [2.44-76.69]), and female (OR = 20.50; 95% CI [4.94-84.90]) were risk factors for subsequent SLE in ITP patients. Conclusion: Patients with primary ITP are at higher risk of SLE. Specific follow-up and prevention strategies should be tailored especially for older females with positive ANA, hypocomplementemia, or chronic ITP. In subsequent studies, we need to further investigate the risk factors and try to construct corresponding risk prediction models to develop specific prediction strategies for SLE.

Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide, responsible for approximately 20 million infections annually. Among the three open reading frames (ORFs) of the HEV genome, the ORF3 protein is involved in virus release. However, the host proteins involved in HEV release need to be clarified. In this study, a host protein, thioredoxin domain-containing protein 5 (TXNDC5), interacted with the non-palmitoylated ORF3 protein by co-immunoprecipitation analysis. We determined that the overexpression or knockdown of TXNDC5 positively regulated HEV release from the host cells. The 17FCL19 mutation of the ORF3 protein lost the ability to interact with TXNDC5. The releasing amounts of HEV with the ORF3 mutation (FCL17-19SSP) were decreased compared with wild-type HEV. The overexpression of TXNDC5 can stabilize and increase ORF3 protein amounts, but not the TXNDC5 mutant with amino acids 1-88 deletion. Meanwhile, we determined that the function of TXNDC5 on the stabilization of ORF3 protein is independent of the Trx-like domains. Knockdown of TXNDC5 could lead to the degradation of ORF3 protein by the endoplasmic reticulum (ER)-associated protein degradation-proteasome system. However, the ORF3 protein cannot be degraded in the knockout-TXNDC5 stable cells, suggesting that it may hijack other proteins for its stabilization. Subsequently, we found that the other members of protein disulfide isomerase (PDI), including PDIA1, PDIA3, PDIA4, and PDIA6, can increase ORF3 protein amounts, and PDIA3 and PDIA6 interact with ORF3 protein. Collectively, our study suggested that HEV ORF3 protein can utilize TXNDC5 for its stability in ER to facilitate viral release. IMPORTANCE: Hepatitis E virus (HEV) infection is the leading cause of acute viral hepatitis worldwide. After the synthesis and modification in the cells, the mature ORF3 protein is essential for HEV release. However, the host protein involved in this process has yet to be determined. Here, we reported a novel host protein, thioredoxin domain-containing protein 5 (TXNDC5), as a chaperone, contributing to HEV release by facilitating ORF3 protein stability in the endoplasmic reticulum through interacting with non-palmitoylated ORF3 protein. However, we also found that in the knockout-TXNDC5 stable cell lines, the HEV ORF3 protein may hijack other proteins for its stabilization. For the first time, our study demonstrated the involvement of TXNDC5 in viral particle release. These findings provide some new insights into the process of the HEV life cycle, the interaction between HEV and host factors, and a new direction for antiviral design.

Hepatitis E virus causes apoptosis of ovarian cells in hens and resulting in a decrease in egg production.

Previous studies have shown that avian hepatitis E virus (HEV) decreases egg production by 10-40% in laying hens, but have not fully elucidated the mechanism of there. In this study, we evaluated the replication of avian HEV in the ovaries of laying hens and the mechanism underlying the decrease in egg production. Forty 150-days-old commercial laying hens were randomly divided into 2 groups of 20 hens each. A total of 1 mL (104GE) of avian HEV stock was inoculated intravenously into each chicken in the experimental group, with 20 chickens in the other group serving as negative controls. Five chickens from each group were necropsied weekly for histopathological examination. The pathogenicity of avian HEV has been characterized by seroconversion, viremia, fecal virus shedding, ovarian lesions, and decreased egg production. Both positive and negative-strand avian HEV RNA, and ORF2 antigens can be detected in the ovaries, suggesting that avian HEV can replicate in the ovaries and serve as an important extrahepatic replication site. The ovaries of laying hens underwent apoptosis after avian HEV infection. These results indicate that avian HEV infection and replication in ovarian tissues cause structural damage to the cells, leading to decreased egg production.

Breaking Low-Strain and Deep-Potassiation Trade-Off in Alloy Anodes via Bonding Modulation for High-Performance K-Ion Batteries.

Alloy anode materials have garnered unprecedented attention for potassium storage due to their high theoretical capacity. However, the substantial structural strain associated with deep potassiation results in serious electrode fragmentation and inadequate K-alloying reactions. Effectively reconciling the trade-off between low-strain and deep-potassiation in alloy anodes poses a considerable challenge due to the larger size of K-ions compared to Li/Na-ions. In this study, we propose a chemical bonding modulation strategy through single-atom modification to address the volume expansion of alloy anodes during potassiation. Using black phosphorus (BP) as a representative and generalizing to other alloy anodes, we established a robust P-S covalent bonding network via sulfur doping. This network exhibits sustained stability across discharge-charge cycles, elevating the modulus of K-P compounds by 74%, effectively withstanding the high strain induced by the potassiation process. Additionally, the bonding modulation reduces the formation energies of potassium phosphides, facilitating a deeper potassiation of the BP anode. As a result, the modified BP anode exhibits a high reversible capacity and extended operational lifespan, coupled with a high areal capacity. This work introduces a new perspective on overcoming the trade-off between low-strain and deep-potassiation in alloy anodes for the development of high-energy and stable potassium-ion batteries.

Dissecting the genome sequence of a clinical isolated Cunninghamella bertholletiae Z2 strain with rich cytochrome P450 enzymes (Article).

Mucormycosis is receiving much more attention because of its high morbidity and extremely high mortality rate in immunosuppressed populations. In this study, we isolated a Cunnignhamella bertholletiae Z2 strain from a skin lesion of a 14 year, 9 months old girl with acute lymphoblastic leukemia who die of infection from the Z2 strain. Genome sequencing was performed after isolation and amplification of the Z2 strain to reveal potential virulence factors and pathogenic mechanisms. The results showed that the genome size of the Z2 strain is 30.9 Mb with 9213 genes. Mucoral specific virulence factor genes found are ARF, CalN, and CoTH, while no gliotoxin biosynthesis gene cluster was found, which is a known virulence factor in Aspergillus fumigatus adapted to the environment. The Z2 strain was found to have 69 cytochrome P450 enzymes, which are potential drug resistant targets. Sensitivity testing of Z2 showed it was only inhibited by amphotericin B and posaconazole. Detailed genomic information of the C. bertholletiae Z2 strain may provide useful data for treatment.

Molecular mechanism of Xuebijing in treating pyogenic liver abscess complicated with sepsis.

BACKGROUND: Xuebijing (XBJ) can alleviate the inflammatory response, improve organ function, and shorten the intensive care unit (ICU) stay in patients with pyogenic liver abscess (PLA) complicated with sepsis, but the molecular mechanisms have not been elucidated. This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach. METHODS: The active ingredients and targets of XBJ were retrieved from the ETCM database. Potential targets related to PLA and sepsis were retrieved from the GeneCards, PharmGKB, DisGeNet, Online Mendelian Inheritance in Man (OMIM), Therapeutic Targets Database (TTD), and DrugBank databases. The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets. Protein-protein interaction networks were analyzed using the STRING database. Potential treatment targets were imported into the Metascape platform for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was performed to validate the interactions between active ingredients and core targets. RESULTS: XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis. Interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor (TNF) were identified as core targets. KEGG enrichment analysis revealed important pathways, including the interleukin-17 (IL-17) signaling pathway, the TNF signaling pathway, the nuclear factor-kappa B (NF-κB) signaling pathway, and the Toll-like receptor (TLR) signaling pathway. Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets. CONCLUSION: XBJ may exert therapeutic effects on PLA complicated with sepsis by modulating signaling pathways, such as the IL-17, TNF, NF-κB, and TLR pathways, and targeting IL-1ß, IL-6, and TNF.

[Finite element analysis of the stability of Mason type â ¢ radial head fracture fixed with three cross-bridge headless compression screw and locking plate].

OBJECTIVE: To compare the biomechanical stability of three cross-bridge headless compression screws and locking plates in the fixation of Mason type Ⅲ radial head fractures by finite element method. METHODS: Using reverse modeling technology, the radial CT data and internal fixation data of a healthy 25-year-old male were imported into the relevant software. Three-dimensional finite element model of 3 cross-bridge headless compression screws and locking plates for MasonⅢ radial head fractures were established, and the radial head was loaded with 100 N axial loading. The maximum displacement, maximum Von Mises stress and stress distribution of the two groups were compared. RESULTS: The maximum displacements of the three cross-bridge screws group and locking plate group were 0.069 mm and 0.087 mm respectively, and the Von Mises stress peaks were 18.59 MPa and 31.85 MPa respectively. The stress distribution of the three screws group was more uniform. CONCLUSION: Both internal fixation methods can provide good fixation effect. CoMPared with the locking plate fixation method, the 3 cross-bridge headless compression screws fixation is more stable and the stress distribution is more uniform.

A novel strategy for an anti-idiotype vaccine: nanobody mimicking neutralization epitope of porcine circovirus type 2.

Vaccination is the most effective method to protect humans and animals from diseases. Anti-idiotype vaccines are safer due to their absence of pathogens. However, the commercial production of traditional anti-idiotype vaccines using monoclonal and polyclonal antibodies (mAb and pAb) is complex and has a high failure rate. The present study designed a novel, simple, low-cost strategy for developing anti-idiotype vaccines with nanobody technology. We used porcine circovirus type 2 (PCV2) as a viral model, which can result in serious economic loss in the pig industry. The neutralizing mAb-1E7 (Ab1) against PCV2 capsid protein (PCV2-Cap) was immunized in the camel. And 12 nanobodies against mAb-1E7 were screened. Among them, Nb61 (Ab2) targeted the idiotype epitope of mAb-1E7 and blocked mAb-1E7's binding to PCV2-Cap. Additionally, a high-dose Nb61 vaccination can also protect mice and pigs from PCV2 infection. Epitope mapping showed that mAb-1E7 recognized the 75NINDFL80 of PCV2-Cap and 101NYNDFLG107 of Nb61. Subsequently, the mAb-3G4 (Ab3) against Nb61 was produced and can neutralize PCV2 infection in the PK-15 cells. Structure analysis showed that the amino acids of mAb-1E7 and mAb-3G4 respective binding to PCV2-Cap and Nb61 were also similar on the amino acids sequences and spatial conformation. Collectively, our study first provided a strategy for producing nanobody-based anti-idiotype vaccines and identified that anti-idiotype nanobodies could mimic the antigen on amino acids and structures. Importantly, as more and more neutralization mAbs against different pathogens are prepared, anti-idiotype nanobody vaccines can be easily produced against the disease with our strategy, especially for dangerous pathogens.IMPORTANCEAnti-idiotype vaccines utilize idiotype-anti-idiotype network theory, eliminating the need for external antigens as vaccine candidates. Especially for dangerous pathogens, they were safer because they did not contact the live pathogenic microorganisms. However, developing anti-idiotype vaccines with traditional monoclonal and polyclonal antibodies is complex and has a high failure rate. We present a novel, universal, simple, low-cost strategy for producing anti-idiotype vaccines with nanobody technology. Using a neutralization antibody against PCV2-Cap, a nanobody (Ab2) was successfully produced and could mimic the neutralizing epitope of PCV2-Cap. The nanobody can induce protective immune responses against PCV2 infection in mice and pigs. It highlighted that the anti-idiotype vaccine using nanobody has a very good application in the future, especially for dangerous pathogens.

Bifunctional Interphase Promotes Li+ De-Solvation and Transportation Enabling Fast-Charging Graphite Anode at Low Temperature.

The most successful lithium-ion batteries (LIBs) based on ethylene carbonate electrolytes and graphite anodes still suffer from severe energy and power loss at temperatures below -20 °C, which is because of high viscosity or even solidification of electrolytes, sluggish de-solvation of Li+ at the electrode surface, and slow Li+ transportation in solid electrolyte interphase (SEI). Here, a coherent lithium phosphide (Li3P) coating firmly bonding to the graphite surface to effectively address these challenges is engineered. The dense, continuous, and robust Li3P interphase with high ionic conductivity enhances Li+ transportation across the SEI. Plus, it promotes Li+ de-solvation through an electron transfer mechanism, which simultaneously accelerates the charge transport kinetics and stands against the co-intercalation of low-melting-point solvent molecules, such as propylene carbonate (PC), 1,3-dioxolane, and 1,2-dimethoxyethane. Consequently, an unprecedented combination of high-capacity retention and fast-charging ability for LIBs at low temperatures is achieved. In full-cells encompassing the Li3P-coated graphite anode and PC electrolytes, an impressive 70% of their room-temperature capacity is attained at -20 °C with a 4 C charging rate and a 65% capacity retention is achieved at -40 °C with a 0.05 C charging rate. This research pioneers a transformative trajectory in fortifying LIB performance in cryogenic environments.

Who are the receivers and transmitters of volatility spillovers: oil, clean energy, and green and non-green cryptocurrency markets.

In the context of clean energy and green cryptocurrency development, the relationship between energy and cryptocurrency markets deserves further exploration. This study employs a quantile time-frequency connectedness approach to measure the dynamic connectedness and volatility propagation mechanisms between oil, clean energy, green cryptocurrency (GC), and non-green cryptocurrency (NGC) markets. Our findings suggest that, at median and low volatility levels, the oil and clean energy markets act as net receivers, taking on volatility spillovers from cryptocurrency markets. However, at high volatility levels, oil and clean energy markets transform into net transmitters. Most NGCs are volatility transmitters, while most GCs are volatility receivers in the median and extremely high volatility cases. We also observe that the total connectedness index (TCI) is heterogeneous over time and dependent on economic events. At median and low volatility levels, the short-run TCI makes the primary contribution. On the other hand, for high volatility levels, where short-term TCI does not have an absolute advantage, long-term TCI plays a greater role in many periods. Additionally, there is asymmetry in the TCI (including long-term and short-term TCI) at the quantile level. In the median and extreme scenarios, the COVID-19 has caused different levels of shock on oil, clean energy, GC, and NGC markets connectedness.

Adjuvant chemotherapy combined with immunotherapy in patients with cholangiocarcinoma after radical resection.

BACKGROUND: The malignancy of cholangiocarcinoma is highly pronounced, and it exhibits a propensity for recurrence and metastasis even in the presence of standard chemotherapy. The efficacy of adjuvant chemotherapy combined with immunotherapy in patients with resected cholangiocarcinoma needs to be substantiated. METHODS: Data from 101 patients with cholangiocarcinoma treated at the Sun Yat-sen University Cancer Center between 2015 and 2020 were studied. RESULTS: After propensity score matching, there were no significant differences in baseline characteristics between patients in the combined adjuvant chemotherapy and immunotherapy group (AC + IM group) and the adjuvant chemotherapy alone group (AC group) (all p > 0.05). The AC + IM group demonstrated a statistically significant improvement in relapse-free survival (RFS) compared to the AC group (p = 0.032). Likewise, the AC + IM group exhibited a significantly superior overall survival (OS) outcome when compared to the AC group (p = 0.044). Multivariate Cox analysis unveiled perineural invasion (p = 0.041), lymph node metastasis (p = 0.006), and postoperative immunotherapy (p = 0.008) as independent prognostic factors exerting a significant impact on the OS of patients. In the cohort of patients with perineural invasion, the AC + IM group exhibited significantly improved OS compared to the AC group (p = 0.0077). Similarly, within the subset of patients with lymph node metastasis, the AC + IM group exhibited a significantly superior OS outcome when compared to the AC group (p = 0.023). CONCLUSION: Combining postoperative adjuvant chemotherapy with immunotherapy extends the RFS and OS of patients with cholangiocarcinoma following radical resection.

Adjuvant chemotherapy in pancreatic cancer at different AJCC stages: a propensity score matching analysis.

OBJECTIVE: In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages. MATERIALS AND METHODS: Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis. RESULTS: 168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively). CONCLUSIONS: The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.

Cx43 Facilitates Mesenchymal Transition of Endothelial Cells Induced by Shear Stress.

OBJECTIVES: This study aimed to determine the function of Cx43 in the endothelial-to-mesenchymal transition (EndMT) process of endothelial cells (ECs) and to explore the potential signaling pathways underlying these functions. METHODS: ECs were extracted from rat aorta. ECs were transfected with Cx43 cDNA and Cx43 siRNA and then exposed to 5 or 12 dyne/cm2. Immunofluorescence staining was used to detect the expression of SM22α, Cx43, and acetylated α-tubulin in ECs. Western blotting was used to detect the protein expression of α-SMA, CD31, Cx43, H1-calponin, Ift88, and p-smad3 in ECs. RESULTS: The expression of αSMA, SM22α, and Cx43 was significantly increased, and CD31 was markedly decreased in ECs treated with laminar shear stress at 5 dyn/cm2. The Cx43 cDNA transfection could induce the expression of SM22α or H1-calponin and attenuate CD31 expression in ECs. Also, Cx43 overexpression harms cilia formation in ECs exposed to 5 dyn/cm2, accompanied with the regulated Ift88 and smad signaling. CONCLUSIONS: This study found that laminar shear stress at 5 dyn/cm2 would increase the expression of Cx43 to facilitate the EndMT process of ECs, associated with morphological changes in primary cilia and the decreased expression of Ift88 in ECs.

FOXD2 regulations IQGAP3 mediated Ca2+ signaling pathway to facilitate gastric adenocarcinoma cell promotion.

As a transcriptional factor, the Forkhead box (FOX) gene family is closely connected with apoptosis, proliferation, and other cellular processes. FOXD2, as one descendant of the FOX gene family, has been mentioned in many articles to show a high expression in several cancers. However, whether FOXD2 has a connection with gastric adenocarcinoma remains an unanswered question. Expression of FOXD2 and IQGAP3 in gastric adenocarcinoma was evaluated by bioinformatics analysis, which was further detected by real-time quantitative PCR (qRT-PCR) and western blot. The downstream target genes of FOXD2 were also mined by bioinformatics analysis. Pathway enrichment analysis was then performed on the target genes. Chromatin immunoprecipitation assay (ChIP) and dual-luciferase reporter assay were conducted to validate the regulatory relationship between FOXD2 and its downstream target gene IQGAP3. Methyl thiazolyl tetrazolium assay (MTT), combined with cell colony formation assay, was employed to assess the effect of FOXD2 and IQGAP3 on the proliferation of gastric adenocarcinoma cells. Intracytoplasmic Ca2+ concentration was measured by Fluo-3 fluorescence staining. FOXD2 showed a high expression in gastric adenocarcinoma tissues and cells, and FOXD2 silencing considerably attenuated gastric adenocarcinoma cell proliferation. IQGAP3, a downstream target gene of FOXD2, had a positive connection with the expression of FOXD2. The binding relationship between FOXD2 and the promoter region of IQGAP3 was further verified by ChIP and dual-luciferase reporter assays. The results of cell function experiments indicated that FOXD2 could promote gastric adenocarcinoma cell proliferation by transcriptionally activating IQGAP3 to induce an increase in intracellular Ca2+ level. This study confirmed that FOXD2 increased intracellular Ca2+ level through transcriptional activation of IQGAP3, which in turn propelled the proliferation of gastric adenocarcinoma cells, revealing the considerable significance of FOXD2 in the development of gastric adenocarcinoma.

Resource partitioning and amino acid assimilation in a terrestrial geothermal spring.

High-temperature geothermal springs host simplified microbial communities; however, the activities of individual microorganisms and their roles in the carbon cycle in nature are not well understood. Here, quantitative stable isotope probing (qSIP) was used to track the assimilation of 13C-acetate and 13C-aspartate into DNA in 74 °C sediments in Gongxiaoshe Hot Spring, Tengchong, China. This revealed a community-wide preference for aspartate and a tight coupling between aspartate incorporation into DNA and the proliferation of aspartate utilizers during labeling. Both 13C incorporation into DNA and changes in the abundance of taxa during incubations indicated strong resource partitioning and a significant phylogenetic signal for aspartate incorporation. Of the active amplicon sequence variants (ASVs) identified by qSIP, most could be matched with genomes from Gongxiaoshe Hot Spring or nearby springs with an average nucleotide similarity of 99.4%. Genomes corresponding to aspartate primary utilizers were smaller, near-universally encoded polar amino acid ABC transporters, and had codon preferences indicative of faster growth rates. The most active ASVs assimilating both substrates were not abundant, suggesting an important role for the rare biosphere in the community response to organic carbon addition. The broad incorporation of aspartate into DNA over acetate by the hot spring community may reflect dynamic cycling of cell lysis products in situ or substrates delivered during monsoon rains and may reflect N limitation.