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Integration of aluminum (Al) and titanium (Ti) alloys offers an effective approach to sustainable and high-quality development of the automotive and aviation industries. However, challenges arise when welding Al alloys to Ti alloys due to the formation of detrimental intermetallic compounds at the interface. With the implementation of ultrasonic vibrations, the temperature and strain rate were both increased during Al/Ti friction stir welding (FSW), leading to the formation of an amorphous interlayer, instead of intermetallic compound (IMC), at the interface. The interfacial microcracks were eliminated in the ultrasonic vibrations assisted friction stir welding (UVFSW). There were Ti particles separated from the Ti substrate and dispersed in the Al alloy, thereby resulting in a more gradual and moderate evolution of the interfacial microstructure. Due to the improved interfacial microstructure with ultrasonic vibrations, the lap shear strength was almost twice that of the conventional FSW welds within same welding conditions. Meanwhile, ultrasonic vibrations also improved the fabrication efficiency with a higher optimal traversing speed. The failure mode shifted from interface separation of FSW welds to a shear dimple fracture of the UVFSW welds, demonstrating the better plasticity and reliability of the UVFSW Al/Ti dissimilar joints.

The interactions between human serum albumin (HSA) and the hemostatic components of the Chinese medicine Sanguisorbae Radix (SR), specifically phenolic acid compounds such as caffeic acid (CA), ferulic acid (FA) and their 1:1 mixture (1:1) were studied to investigate the molecular mechanism underlying the hemostatic effect of SR. Network pharmacology combined with the experimental and computational data revealed that HSA is one of the hemostatic targets to SR phenolic acids. SDS-PAGE and multi-spectroscopy demonstrated that the phenolic acids bind to the Sudlow site I on HSA, altering its structure and influencing its migration velocity. There is an observed synergistic effect upon the mixture of CA and FA. Quantum chemistry, molecular docking, and molecular dynamics simulations indicate that the binding of phenolic acids to HSA is stable, and variations in binding efficiency are associated with the hydrophobicity of the substituent at the C3 position of the side chain, and also, the key amino acids and functional groups for hemostasis of SR were identified, along with the active sites that contribute to the synergistic enhancement by phenolic acids.

High glycogen in oysters contributes to their flavor, quality, and hardiness, making it a crucial target trait for breeding purposes. Until now, the upstream regulatory mechanism for glycogen synthesis has remained unclear. Protein phosphatase-1 regulatory subunit 3 (PPP1R3) is a member of a family that directs the protein phosphatase-1 (PP1) to glycogen, resulting in the activation of glycogen synthase (GS) and the inactivation of glycogen phosphorylase (GP). However, their functions in molluscan species have remained unclear until now. In our study, we verified the function of the PP1α/PPP1R3D pathways in the glycogen metabolism process in Crassostrea gigas. Initially, we conducted a phylogenetic analysis and identified two PP1 and PPP1R3 members in molluscan species, emphasizing copy number variations in eukaryotic animals. Additionally, we identified distinct substitutions of conserved motifs specific to bivalves, Cephalopoda, or Gastropods, revealing functional diversity in PP1 and PPP1R3. Our primary focus was on PP1α/PPP1R3D in the oyster C.gigas, detected in the muscle glycogen fraction of bivalve species, with mRNA expression showing a positive correlation with glycogen content. By manipulating CgPPP1R3D expression in oysters through adenovirus-mediated overexpression or siRNA-mediated downregulation, we established a direct positive correlation between CgPPP1R3D expression levels and glycogen content. Colocation analysis confirmed protein interactions between CgPP1α and CgPPP1R3D. Furthermore, to elucidate the correlation between gene expression and glycogen accumulation, we conducted an association analysis and identified a cluster of significant SNP loci upstream of CgPPP1R3D significantly related to glycogen content. The high polymorphism observed may be linked to differential expressions of CgPPP1R3D in oyster individuals with high and low glycogen levels. These findings serve as a crucial reference for enhancing glycogen traits in molluscan species.

Background: The tumor microenvironment (TME) affected the prognosis of tumors. However, its effect on the outcomes of obese endometrial cancer (EC) patients had not been reported. Methods: This research performed a retrospective analysis of the transcriptome profiles and medical data of 503 EC patients. Immune scores were assessed by estimation algorithms. Cox and LASSO regression analyses were utilized to pinpoint key genes linked to prognosis, and the RPS was created to forecast the outcomes of obese EC patients. The relationship among genetic mutations and RPS was examined using CNV and somatic mutation information. ssGSEA and GSVA were employed to detect immune infiltration and immune pathway enrichment associated with key genes. The TIDE algorithm and GDSC database were utilized to forecast patients’ responses of patients to immunotherapy and chemotherapy, respectively. Finally, we employed the 'rms' R software package to construct the nomogram. Results: The prognosis of obese EC patients was associated with immune scores. Three key genes (EYA4, MBOAT2 and SCGB2A1) were identified. The risk prognosis score (RPS) for obese EC patients was established by risk stratification and prognostic prediction using prognostic genes. The higher the RPS, the worse the prognosis, and the more malignant the genomic alterations. The high RPS group had a significantly reduced proportion of most immune cells in comparison to the low RPS group. The high RPS group was linked to G2M, MYC and E2F related pathways such as cell proliferation, cell cycle and cell death. Cisplatin, tamoxifen and topotecan had a greater effect on the low RPS group. Notably, the nomogram had a good predictive ability. Conclusion: Our study designed a reliable RPS for obese EC patients to forecast their prognosis, immune aggressiveness, and responses to immunotherapy and drug treatments.

Purpose: Pure mucinous breast cancer (PMC) is a rare histological type with a favourable prognosis. However, cases with recurrence have been reported and diagnosed in clinical practice. The mechanisms underlying PMC recurrence remain unknown. In this study, we aimed to identify the prognostic factors associated with PMC. Materials and methods: A total of 166 patients diagnosed with PMC were included. We compared the clinicopathological characteristics between patients with and without recurrence. The 21-gene assay was performed in 10 patients with recurrence and 20 TNM stage-matched patients without recurrence. Whole-exon sequencing was performed in 12 PMC primary tumours and four positive lymph nodes (LNs). Results: Tumour size, lymph node status and TNM staging differed significantly between recurrent group and non-recurrent group. And the 21-gene recurrence scores did not differ significantly between recurrent group and its TNM stage-matched non-recurrent group. The most frequently mutated genes in the primary tumours of regional LN-positive PMCs were ADCY10 (3/6) and SHANK3 (3/6), and they more recurrently harboured gains of 15q23, 17q23.2 and 20p11.21, and loss of 21p11.2. And these alterations were not detected in primary tumours of regional LN-negative PMCs. Conclusion: TNM stage is an important prognostic factor in PMC. Although we revealed that regional LN-positive PMCs show increased occurrence of duplication variants at 15q23, 17q23.2 and 20p11.21, and deletion variants at 21p11.2. Further investigation, including multi-omics studies, are needed and may provide additional insights into the nature of PMC.

Background: To explore whether specific clinicopathological covariates are predictive for a benefit from capecitabine maintenance in early-stage triple-negative breast cancer (TNBC) in the SYSUCC-001 phase III clinical trial. Methods: Candidate covariates included age, menstrual status, type of surgery, postoperative chemotherapy regimen, Ki-67 percentage, histologic grade, primary tumor size, lymphovascular invasion, node status, and capecitabine medication. Their nonlinear effects were modeled by restricted cubic spline. The primary endpoint was disease-free survival (DFS). A survival prediction model was constructed using Cox proportional hazards regression analysis. Results: All 434 participants (306 in development cohort and 128 in validation cohort) were analyzed. The estimated 5-year DFS in development and validation cohorts were 77.8 % (95 % CI, 72.9%–82.7 %) and 78.2 % (95 % CI, 70.9%–85.5 %), respectively. Age and node status had significant nonlinear effects on DFS. The prediction model constructed using four covariates (node status, lymphovascular invasion, capecitabine maintenance, and age) demonstrated satisfactory calibration and fair discrimination ability, with C-index of 0.722 (95 % CI, 0.662–0.781) and 0.764 (95 % CI, 0.668–0.859) in development and validation cohorts, respectively. Moreover, patient classification was conducted according to their risk scores calculated using our model, in which, notable survival benefits were reported in low-risk subpopulations. An easy-to-use online calculator for predicting benefit of capecitabine maintenance was also designed. Conclusions: The evidence-based prediction model can be readily assessed at baseline, which might help decision making in clinical practice and optimize patient stratification, especially for those with low-risk, capecitabine maintenance might be a potential strategy in the early-disease setting.

Underground hydrogen storage (UHS) and compressed air energy storage (CAES) are two viable large-scale energy storage technologies for mitigating the intermittency of wind and solar power. Therefore, it is meaningful to compare the properties of hydrogen and air with typical thermodynamic storage processes. This study employs a multi-physical coupling model to compare the operations of CAES and UHS, integrating gas thermodynamics within caverns, thermal conduction, and mechanical deformation around rock caverns. Gas thermodynamic responses are validated using additional simulations and the field test data. Temperature and pressure variations of air and hydrogen within rock caverns exhibit similarities under both adiabatic and diabatic simulation modes. Hydrogen reaches higher temperature and pressure following gas charging stage compared to air, and the ideal gas assumption may lead to overestimation of gas temperature and pressure. Unlike steel lining of CAES, the sealing layer (fibre-reinforced plastic FRP) in UHS is prone to deformation but can effectively mitigates stress in the sealing layer. In CAES, the first principal stress on the surface of the sealing layer and concrete lining is tensile stress, whereas UHS exhibits compressive stress in the same areas. Our present research can provide references for the selection of energy storage methods.

Using CO2-derived dimethyl carbonate (DMC) instead of diphenyl carbonate (DPC) as a carbonyl source for synthesizing bio-based polycarbonates is a green and cost-effective route. However, the synthesis of high-performance polycarbonates via the DMC route remains challenging due to the poor reactivity and selectivity of DMC compared to DPC. Herein, we designed a series of highly active protic ionic liquid (PIL) catalysts for the synthesis of poly(isosorbide carbonate) (PIC) from DMC with ISB. The influences of the structures of anion and cation on the catalytic activity of PILs were systematically studied. Compared with the reported aprotic IL catalysts, the unique reactive hydrogen of the cation in PILs could form a strong hydrogen bond interaction with the carbonyl group of DMC, resulting in higher reactivity of the carbonyl carbon of DMC. Moreover, the nucleophilicity of the anion could be easily tuned by adjusting the pKa value, which effectively realized the balance of the reactivity difference between exo-OH and endo-OH in ISB. Among them, [DBUH][Im] showed the highest catalytic activity, and the weight-average molecular weight (Mw) and glass transition temperature of PIC reached 55,700 g/mol and 160 °C, respectively. Combined with NMR analyses and DFT calculations, the mechanism that exhibited the synergetic catalytic effect of anion-cation for the polymerization of DMC and ISB was presented.

Aims: To examine the concurrent validity of the Chinese version of Physical Activity Neighborhood Environment Scale (PANES-CHN) among urban adults in regional China. Methods: With multistage sampling approaches, 801 eligible urban adults aged 35–74 years were recruited from Nanjing municipality of China between July and September of 2019. The neighbourhood built environment features were measured subjectively with PANES-CHN and objectively with geographic information system. The concurrent validity of PANES was assessed using Spearman’s correlations (rs). Results: Among the total 801 participants, the mean age was 54.4 (standard deviation = 11.5), while 48.7 % were men. Overall, of all the five objectively-measurable built environment characteristics, the Spearman correlations were examined significant between subjective and objective measurements for commercial facilities (item 2) (rs = 0.19, 95CI%=0.12, 0.25), recreational facilities (item 6) (rs = 0.10, 95CI%=0.02, 0.16), traffic junctions (item 12) (rs = 0.15, 95CI%=0.07, 0.22), medical/education facilities (item 17) (rs = 0.22, 95CI%=0.15, 0.29), but not for public transport stops. Similar scenarios were observed for participants aged 35–60 years, with sufficient physical activity, men or women. The rs value for medical/education facilities (item 17) was significantly higher in participants aged 35–59 years (0.28 vs. 0.13; p = 0.04) than those aged 60 + years. Conclusions: PANES-CHN generally has an acceptable validity for assessing built environment characteristics among urban adults in China, which implies that PANES-CHN can be used to measure built environment attributes in health-related population studies.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder characterized by hepatic steatosis, inflammation and fibrosis. Ganfule (GFL), a traditional Chinese medicine, has demonstrated therapeutic potential in the treatment of NAFLD but the mechanisms involved are not fully understood.To evaluate the biochemical mechanisms of GFL in treating NAFLD by examining its effects on biological networks, key therapeutic targets, histopathological changes and clinical implications. Methods: Chemical component screening, key target prediction, biological functional enrichment analysis, lipid profile localization analysis and complex network analysis were performed on GFL using multi-database mining, network analysis and molecular docking. An NAFLD rat model was then established and treated with different doses of GFL. Histopathological evaluation and western blotting were used to verify the expression levels of key target proteins in GFL-treated NAFLD rats. Results: Network analysis analysis identified 12 core targets, 12 core active ingredients and 7 core Chinese medicinal herbs in GFL potentially involved in the treatment of NAFLD. Biological functional enrichment analysis revealed the involvement of lipid metabolism, apoptosis and intracellular signaling pathways. Molecular docking confirmed a strong affinity between GFL's core compounds and certain target proteins. Histopathological examination of an NAFLD rat model showed reduced hepatocellular steatosis after GFL treatment. Western blotting revealed significant downregulation of PPARA and PPARD protein expression and upregulation of PIK3CG and PRKACA protein expression in NAFLD rats treated with lower doses of GFL. Conclusions: Our results suggest that GFL modulates key proteins involved in lipid metabolism and apoptosis pathways. GFL improved the histopathological features of NAFLD rats by regulating lipid metabolism as well as reducing hepatocyte apoptosis and hepatocellular steatosis. These findings offer insights into the biochemical mechanism of action of GFL and support its use in the treatment for NAFLD.

Summary: Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the structure-function relationship governing ligand recognition between these substances and their receptors in the brain. Recent studies indicate the significant involvement of trace amine-associated receptor 1 (TAAR1) in the signaling regulation of the hallucinogen lysergic acid diethylamide (LSD) and other antipsychotic drugs. This study presents structures of the TAAR1-Gs protein complex recognizing LSD, which exhibits a polypharmacological profile, and the partial agonist RO5263397, which is a drug candidate for schizophrenia and addiction. Moreover, we elucidate the cross-species recognition and partial activation mechanism for TAAR1, which holds promising implications from a drug discovery perspective. Through mutagenesis, functional studies, and molecular dynamics (MD) simulations, we provide a comprehensive understanding of a versatile TAAR1 pocket in recognizing various ligands as well as in the ligand-free state, underpinning the structural basis of its high adaptability. These findings offer valuable insights for the design of antipsychotic drugs.

Microbubble-mediated therapeutic gene or drug delivery is a promising strategy for various cardiovascular diseases (CVDs), but the efficiency and precision need to be improved. Here, we propose a cavitation bubble-driven drug delivery strategy that can be applied to CVDs. A bubble-pulse-driving theory was proposed, and the formula of time-averaged thrust driven by bubble pulses was derived. The continuous motion of particles propelled by cavitation bubbles in the ultrasonic field is investigated experimentally by high-speed photography. The cavitation bubbles grow and collapse continuously, and generate periodic pulse thrust to drive the particles to move in the liquid. Particles attached to bubbles will move in various ways, such as ejection, collision, translation, rotation, attitude variation, and circular motion. The cavity attached to the particle is a relatively large cavitation bubble, which does not collapse to the particle surface, but to the axis of the bubble perpendicular to the particle surface. The cavitation bubble expands spherically and collapses asymmetrically, which makes the push on the particle generated by the bubble expansion greater than the pull on the particle generated by the bubble collapse. The time-averaged force of the cavitation bubble during its growth and collapse is the cavitation-bubble-driven force that propels the particle. Both the cavitation-bubble-driven force and the primary Bjerknes force act in the same position on the particle surface, but in different directions. In addition to the above two forces, particles are also affected by the mass force acting on the center of mass and the motion resistance acting on the surface, so the complex motion of particles can be explained.

Exposure to ambient PM2.5 is associated with neurodegenerative disorders, in which microglia activation plays a critical role. Thus far, the underlying mechanisms for PM2.5-induced microglia activation have not been well elucidated. In this study, a human microglial cell line (HMC3) was used as the in vitro model to examine the inflammatory effect (hall marker of microglia activation) of PM2.5 and regulatory pathways. The expression of inflammatory mediators including interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) as well as the brain derived neurotrophic factor (BDNF) were determined by ELISA and/or real-time PCR, respectively. Flow cytometry was used to measure the production of intracellular reactive oxygen species (ROS). Western blot was used to measure protein levels of Toll-like receptor 4 (TLR4), NF-κB inhibitor α (IκBα) and COX-2. It was shown that PM2.5 stimulation increased IL-6 and COX-2 expression but decreased BDNF expression in a dose-dependent manner. Further studies showed that PM2.5 triggered the formation of ROS and pre-treatment with the ROS scavenger acetylcysteine (NAC) significantly suppressed PM2.5-induced IL-6 and COX-2 expression. Moreover, the nuclear factor kappa B (NF-κB) inhibitor BAY11–7085 or the TLR4 neutralizing antibody markedly blocked PM2.5-induced IL-6 and COX-2 expression. However, NAC or BAY11–7085 exhibited minimal effect on PM2.5-induced BDNF down-regulation. In addition, pre-treatment with BAY11–7085 or TLR4 neutralizing antibody reduced ROS production induced by PM2.5, and NAC pre-treatment inhibited TLR4 expression and NF-κB activation induced by PM2.5. Collectively, PM2.5 treatment induced IL-6 and COX-2 but suppressed BDNF expression. PM2.5-induced IL-6 and COX-2 expression was mediated by interactive oxidative stress and TLR4/NF-κB pathway.

ABSTRACT: Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.

As one of the most common malignant tumors in the world, lung cancer has limited benefits for patients despite its diverse treatment methods due to factors such as personalized medicine targeting histological type, immune checkpoint expression, and driver gene mutations. The high mortality rate of lung cancer is partly due to the immune-suppressive which limits the effectiveness of anti-cancer drugs and induces tumor cell resistance. The currently widely recognized TAM phenotypes include the anti-tumor M1 and pro-tumor M2 phenotypes. M2 macrophages promote the formation of an immune-suppressive microenvironment and hinder immune cell infiltration, thereby inhibiting activation of the anti-tumor immune system and aiding tumor cells in resisting treatment. Analyzing the relationship between different treatment methods and macrophages in the TME can help us better understand the impact of TAMs on lung cancer and confirm the feasibility of targeted TAM therapy. Targeting TAMs to reduce the M2/M1 ratio and reverse the immune-suppressive microenvironment can improve the clinical efficacy of conventional treatment methods and potentially open up more efficient combination treatment strategies, maximizing the benefit for lung cancer patients.

Copper plays a crucial role in the heterogenous dissociation of chlorothiophenols (CTPs) to form chlorothiophenoxy radicals (CTPRs), which is the initial and critical step in the formation of polychlorinated thianthrenes/dibenzothiophenes (PCTA/DTs). Here, first-principles calculations were performed to investigate the activity of Cu(111) surface towards the formation of adsorbed 2-CTPR from 2-CTP. The interaction between 2-CTP and Cu(111) surface was explored to find stable adsorption configurations. Besides, the decomposition routes of 2-CTP on the Cu(111) surface were further explored. Moreover, the effects of water on the formation of absorbed 2-CTPR on the Cu(111) surface were examined. Our results demonstrate that the flat adsorption of 2-CTP on the surface with adsorption energy in the range of −33.21 kcal/mol to −28.37 kcal/mol is more stable than the vertical adsorption with adsorption energy ranging from −23.53 kcal/mol to −13.38 kcal/mol. The Cu(111) surface catalyzes the conversion of 2-CTP into the adsorbed 2-CTPR with a modest energy barrier of 9.46 kcal/mol. Furthermore, water molecules exhibit stronger catalytic activity in this process with a decreased energy barrier of 5.87 kcal/mol through “water bridge” and hydrogen bonding. Specifically, the water accepts the hydrogen atom from 2-CTP and donates another hydrogen to the surface via “water bridge”. This research provides a molecular-level understanding of the heterogeneous formation of PCTA/DTs by fly ash, suggesting novel approaches for control strategy and legislation of dioxin analogues.

Noni (Morinda citrifolia L.) is a tropical fruit rich in bioactive compounds. Little is known about its polyphenol composition at different ripeness levels and digestive characteristics. Here, we studied changes in polyphenols and antioxidant activity as noni ripened. Rutin and kaempferol-3-O-rutinoside were found in high amounts in noni, with antioxidant capacity increasing as it ripened. Under simulated digestion, polyphenols were gradually released from the oral to gastrointestinal phases, partially decomposing in the small intestine due to their instability. Conversely, fiber-bound phenols were released during colonic fermentation, leading to high bioaccessible antioxidant activity. Additionally, noni consumption affected the intestinal microbiome by reducing the Firmicutes/Bacteroidetes ratio and increasing bacteria with prebiotic properties like Prevotella and Ruminococcus. These findings demonstrate that polyphenols significantly contribute to the health benefits of noni fruit by providing absorbable antioxidants and improving the structure of the intestinal microbiome.

Background: The Ze-Qi decoction (ZQD) is a traditional Chinese herbal formula commonly applied to treat lung cancer in China. This study aimed to assess the effective ingredients and molecular mechanisms of ZQD in treating non-small cell lung cancer (NSCLC) based on network pharmacology combined with experimental validation. Methods: Network pharmacology, bioinformatics, and molecular docking analyses were conducted to explore the mechanism of ZQD for treating NSCLC, which was further confirmed by animal experiments. Results: In total, 117 bioactive ingredients and 499 target proteins of ZQD were identified. Network pharmacology revealed 7 core active ingredients and 74 core target proteins. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the PI3K/Akt and p53 signaling pathways may be crucial in NSCLC treatment. Molecular docking analysis revealed that the seven crucial bioactive ingredients complexed with PI3K, Akt, and p53. The animal experiment results validated that ZQD treatment promoted cell apoptosis and cell cycle arrest, thereby inhibiting NSCLC growth and metastasis. Furthermore, ZQD treatment caused a significant increase in p53 and Bax, while leading to a distinct reduction in p-PI3K (Tyr317), p-Akt (Ser473), VEGFA, CD31, MMP2, MMP9, Bcl2, and CDK2. Conclusions: ZQD inhibited the growth and metastasis of NSCLC subcutaneous tumors in C57BL/6J mice via the PI3K/Akt/p53 signaling pathway.

The degradation of high molecular weight organic matter (HMWOM) is a core process of oceanic carbon cycle, which is determined by the activity of microbial communities harboring hundreds of different species. Illustrating the active microbes and their interactions during HMWOM processing can provide key information for revealing the relationship between community composition and its ecological functions. In this study, the genomic and transcriptional responses of microbial communities to the availability of alginate, an abundant HMWOM in coastal ecosystem, were elucidated. The main degraders transcribing alginate lyase (Aly) genes came from genera Alteromonas, Psychrosphaera and Colwellia. Meanwhile, some strains, mainly from the Rhodobacteraceae family, did not transcribe Aly gene but could utilize monosaccharides to grow. The co-culture experiment showed that the activity of Aly-producing strain could promote the growth of Aly-non-producing strain when alginate was the sole carbon source. Interestingly, this interaction did not reduce the alginate degradation rate, possibly due to the easily degradable nature of alginate. This study can improve our understanding of the relationship between microbial community activity and alginate metabolism function as well as further manipulation of microbial community structure for alginate processing.

The feed conversion rate (FCR) is a crucial economic trait in aquaculture fish, as feed costs account for the vast majority of aquaculture costs. Given the importance of this trait, there have little efforts to unravel the genomic architecture of FCR and identify key genes or genomic regions useful as selection makers. This situation may stem from the inherent swimming behavior of fish, which presents challenges in obtaining individual FCRs. In this work, we developed a specialized small cage culture system. Through this system, the Feed Conversion Ratio (FCR) of 300 individuals was successfully determined, marking the first successful determination of individual FCRs for turbot. The results revealed a range of FCR values from 35.3% to 192.6%, with an average of 126.5% ± 23.5%. On this basis, a genome-wide association study (GWAS) was conducted to identify single nucleotide polymorphisms (SNP) associated with FCR. A total of 2613,115 SNPs on 22 chromosomes were selected for GWAS analysis by Efficient Mixed-Model Association eXpedited (EMMAX) software. A linear mixed model was employed to test the association between each SNP and FCR, considering population structure and genetic relatedness among individuals. Two significant SNPs on Chr6 were identified to be correlated with FCR. According to their localization in genome, four candidate genes were identified on Chr6, including uncharacterized protein KIAA1755, Kinesin Family Member 21B (KIF21B), Discs large homolog-associated protein 4B (DLGAP4B), and Copine 5B (CPNE5B), all of which are closely located in the genome and exhibit significant functional similarities. Our results will facilitate the implementation of marker-assisted selection in breeding programs and serve as a foundation for future research in this area.

The extent of gut inflammation depends largely on the gut barrier’s integrity and enteric neuroimmune interactions. However, the factors and molecular mechanisms that regulate inflammation-related changes in the enteric nervous system (ENS) remain largely unexplored. Eph/ephrin signaling is critical for inflammatory response, neuronal activation, and synaptic plasticity in the brain, but its presence and function in the ENS have been largely unknown to date. This review discusses the critical role of Eph/ephrin in regulating gut homeostasis, inflammation, neuroimmune interactions, and pain pathways. Targeting the Eph/ephrin system offers innovative treatments for gut inflammation disorders, offering hope for enhanced patient prognosis, pain management, and overall quality of life.

Background: Ginsenoside compound K (CK) stimulated activation of the PI3K-Akt signaling is one of the major mechanisms in promoting cell survival after stroke. However, the underlying mediators remain poorly understood. This study aimed to explore the docking protein of ginsenoside CK mediating the neuroprotective effects. Materials and methods: Molecular docking, surface plasmon resonance, and cellular thermal shift assay were performed to explore ginsenoside CK interacting proteins. Neuroscreen-1 cells and middle cerebral artery occlusion (MCAO) model in rats were utilized as in-vitro and in-vivo models. Results: Ginsenoside CK interacted with recombinant human PTP1B protein and impaired its tyrosine phosphatase activity. Pathway and process enrichment analysis confirmed the involvement of PTP1B and its interacting proteins in PI3K-Akt signaling pathway. PTP1B overexpression reduced the tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) after oxygen-glucose deprivation/reoxygenation (OGD/R) in neuroscreen-1 cells. These regulations were confirmed in the ipsilateral ischemic hemisphere of the rat brains after MCAO/R. Ginsenoside CK treatment reversed these alterations and attenuated neuronal apoptosis. Conclusion: Ginsenoside CK binds to PTP1B with a high affinity and inhibits PTP1B-mediated IRS1 tyrosine dephosphorylation. This novel mechanism helps explain the role of ginsenoside CK in activating the neuronal protective PI3K-Akt signaling pathway after ischemia-reperfusion injury.

Lung cancer (LC) is one of the leading causes of cancer-related deaths worldwide, with a significant morbidity and mortality rate, endangering human life and health. The introduction of immunotherapies has significantly altered existing cancer treatment strategies and is expected to improve immune responses, objective response rates, and survival rates. However, a better understanding of the complex immunological networks of LC is required to improve immunotherapy efficacy further. Tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) are significantly expressed by LC cells, which activate dendritic cells, initiate antigen presentation, and activate lymphocytes to exert antitumor activity. However, as tumor cells combat the immune system, an immunosuppressive microenvironment forms, enabling the enactment of a series of immunological escape mechanisms, including the recruitment of immunosuppressive cells and induction of T cell exhaustion to decrease the antitumor immune response. In addition to the direct effect of LC cells on immune cell function, the secreting various cytokines, chemokines, and exosomes, changes in the intratumoral microbiome and the function of cancer-associated fibroblasts and endothelial cells contribute to LC cell immune escape. Accordingly, combining various immunotherapies with other therapies can elicit synergistic effects based on the complex immune network, improving immunotherapy efficacy through multi-target action on the tumor microenvironment (TME). Hence, this review provides guidance for understanding the complex immune network in the TME and designing novel and effective immunotherapy strategies for LC.

Developing denoising algorithms for hyperspectral remote sensing images (HSIs) can alleviate noise problem, improve data utilization as well as the accuracy of subsequent applications. However, existing denoising techniques are usually unstable due to the variations of landscapes, resulting in local distortion of HSIs, especially in heterogeneous areas. To tackle this issue, we propose a spatial–spectral interactive restoration (SSIR) framework by exploiting the complementarity of model-based and data-driven methods. Specifically, a deep learning-based denoising module that incorporates both convolutional neural networks (CNN) and Swin Transformer (TF) blocks is designed. This denoiser can achieve local–global dependencies modeling and content-based interactions to better capture global heterogeneity differences in HSIs. Moreover, we introduce an unsupervised unmixing module that utilizes spectral autocorrelation as prior information to effectively capture the differences in reflectance characteristics among different land cover components. This parameter-free module further improves the generalization ability of SSIR and enables stable denoising performance across different scenarios. Both modules are iteratively updated and fuel each other in SSIR. The proposed SSIR is shown to outperform others in preserving spatial details, maintaining spectral fidelity, and adapting to different landscapes based on simulated and real experiments conducted on various HSIs under diverse noise conditions.

Summary: Bone stress injuries are common overuse injuries, especially in soldiers, athletes, and performers. In contrast to various post-injury treatments, early protection against bone stress injuries can provide greater benefit. This study explored the early protection strategies against bone stress injuries by mobilization of endogenous targeted bone remodeling. The effects of various pharmaceutical/biophysical approaches, individual or combinational, were investigated by giving intervention before fatigue loading. We optimized the dosage and administration parameters and found that early intervention with pulsed electromagnetic field and parathyroid hormone (i.e., PEMF+PTH) resulted in the most pronounced protective effects among all the approaches against the bone stress injuries. In addition, the mechanisms by which the strategy mobilizes targeted bone remodeling and enhances the self-repair capacity of bone were systematically investigated. This study proposes strategies to reduce the incidence of bone stress injuries in high-risk populations (e.g., soldiers and athletes), particularly for those before sudden increased physical training.

Summary: Large biosynthetic gene cluster (BGC) cloning is important for discovering natural product-based drugs and remains challenging in high GC content microorganisms (e.g., Actinobacteria). Here, we present an in vitro CRISPR-Cas12a-mediated protocol for direct cloning of large DNA fragments. We describe steps for crRNA design and preparation, genomic DNA isolation, and CRISPR-Cas12a cleavage and capture plasmid construction and linearization. We then detail target BGC and plasmid DNA ligation and transformation and screening for positive clones.For complete details on the use and execution of this protocol, please refer to Liang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Objectives: Cardiopulmonary bypass (CPB) is a major part of cardiac surgery that provokes systemic inflammatory reactions, myocardial ischemia, and ischemia and reperfusion damage. The aim of this study is to summarize the available evidence and evaluate whether exogenous nitric oxide administered via CPB circuits can improve recovery after cardiac surgery in children. Method: A comprehensive search of the PubMed Medline, Ovid, Cochrane Library and Embase databases was conducted in September 2022. Only randomized controlled trials that compared nitro oxide with placebo or standard care were included. Results: This pooled analysis included 5 RCTs containing 1642 patients. There were significant differences in the duration of postoperative mechanical ventilation between the nitric oxide group and the control group (mean difference −5.645 h; 95% CL = −9.978, −1.313; P = 0.01). Meta-analysis of the length of ICU stay and hospital stay showed no significant differences. Conclusion: Delivering nitric oxide via CPB in pediatric cardiac surgery has an effect on reducing the duration of mechanical ventilation. Considering the small effect size, we should be cautious and think comprehensively in clinical practice.

The unfrozen water content of rock during freezing and thawing has an important influence on its physical and mechanical properties. This study presented a model for calculating the unfrozen water content of rock during freezing and thawing process, considering the influence of unfrozen water film and rock pore structure, which can reflect the hysteresis and super-cooling effects. The pore size distribution curves of red sandstone and its unfrozen water content under different temperatures during the freezing and thawing process were measured using nuclear magnetic resonance (NMR) to validate the proposed model. Comparison between the experimental and calculated results indicated that the theoretical model accurately reflected the water content change law of red sandstone during the freezing and thawing process. Furthermore, the influences of Hamaker constant and surface relaxation parameter on the model results were examined. The results showed that the appropriate magnitude order of Hamaker constant for the red sandstone was 10−19 J to 10−18 J; and when the relaxation parameter of the rock surface was within 25–30 μm/ms, the calculated unfrozen water content using the proposed model was consistent with the experimental value.

Background: Ginsenoside Rd is a natural compound with promising neuroprotective effects. However, the underlying mechanisms are still not well-understood. In this study, we explored whether ginsenoside Rd exerts protective effects on cerebral endothelial cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and its potential docking proteins related to the underlying regulations. Method: Commercially available primary human brain microvessel endothelial cells (HBMECs) were used for in vitro OGD/R studies. Cell viability, pyroptosis-associated protein expression and tight junction protein degradation were evaluated. Molecular docking proteins were predicted. Subsequent surface plasmon resonance (SPR) technology was utilized for validation. Flow cytometry was performed to quantify caspase-1 positive and PI positive (caspase-1+/PI+) pyroptotic cells. Results: Ginsenoside Rd treatment attenuated OGD/R-induced damage of blood-brain barrier (BBB) integrity in vitro. It suppressed NLRP3 inflammasome activation (increased expression of NLRP3, cleaved caspase-1, IL-1β and GSDMD-N terminal (NT)) and subsequent cellular pyroptosis (caspase-1+/PI + cells). Ginsenoside Rd interacted with SLC5A1 with a high affinity and reduced OGD/R-induced sodium influx and potassium efflux in HBMECs. Inhibiting SLC5A1 using phlorizin suppressed OGD/R-activated NLRP3 inflammasome and pyroptosis in HBMECs. Conclusion: Ginsenoside Rd protects HBMECs from OGD/R-induced injury partially via binding to SLC5A1, reducing OGD/R-induced sodium influx and potassium efflux, thereby alleviating NLRP3 inflammasome activation and pyroptosis.

Objective: To report three families with chromosome 15q11q13 duplications. Case report: We report the prenatal diagnosis and genetic counseling of three 15q11q13 duplications. Conclusion: Chromosomal microdeletions and microduplications are difficult to be detected by conventional cytogenetics. With molecular genetic techniques including array-based methods, the number of reported cases has rapidly increased. An integration of prenatal ultrasound, NIPT, karyotype analysis, CMA and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.

Recent research highlights the function of regulatory T cells (Tregs) in white matter integrity in CNS diseases. Approaches that expand the number of Tregs have been utilized to improve stroke recovery. However, it remains unclear if Treg augmentation preserves white matter integrity early after stroke or promotes white matter repair. This study evaluates the effect of Treg augmentation on white matter injury and repair after stroke. Adult male C57/BL6 mice randomly received Treg or splenocyte (2 million, iv) transfer 2 h after transient (60 min) middle cerebral artery occlusion (tMCAO). Immunostaining showed improved white matter recovery after tMCAO in Treg-treated mice compared to mice received splenocytes. In another group of mice, IL-2/IL-2 antibody complexes (IL-2/IL-2Ab) or isotype IgG were administered (i.p) for 3 consecutive days starting 6 h after tMCAO, and repeated on day 10, 20 and 30. The IL-2/IL-2Ab treatment boosted the number of Tregs in blood and spleen and increased Treg infiltration into the ischemic brain. Longitudinal in vivo and ex vivo diffusion tensor imaging analysis revealed an increase in fractional anisotropy 28d and 35d, but not 14d, after stroke in IL-2/IL-2Ab-treated mice compared to isotype-treated mice, suggesting a delayed improvement in white matter integrity. IL-2/IL-2Ab also improved sensorimotor functions (rotarod test and adhesive removal test) 35d after stroke. There were correlations between white matter integrity and behavior performance. Immunostaining confirmed the beneficial effects of IL-2/IL-2Ab on white matter structures 35d after tMCAO. IL-2/IL-2Ab treatment starting as late as 5d after stroke still improved white matter integrity 21d after tMCAO, suggesting long-term salutary effects of Tregs on the late-stage tissue repair. We also found that IL-2/IL-2Ab treatment reduced the number of dead/dying OPCs and oligodendrocytes in the brain 3d after tMCAO. To confirm the direct effect of Tregs on remyelination, Tregs were cocultured with lysophosphatidyl choline (LPC)-treated organotypic cerebella. LPC exposure for 17 h induced demyelination in organotypic cultures, followed by gradual spontaneous remyelination upon removal of LPC. Co-culture with Tregs accelerated remyelination in organotypic cultures 7d after LPC. In conclusion, Boosting the number of Tregs protects oligodendrocyte lineage cells early after stroke and promotes long-term white matter repair and functional recovery. IL-2/IL-2Ab represents a feasible approach of Treg expansion for stroke treatment.

Li-rich manganese-based (LRM) cathode materials are known as one of the most promising cathode materials for new-generation lithium-ion batteries. At present, exploring the complex voltage decay mechanism of LRM is the main task to promote its commercialization. Herein, the structural evolution and transition metal valence state change of LRM during different reaction stages under different temperatures are discussed, and the mechanism of voltage decay is finally determined based on the electrochemical properties. The results show the evolution of irreversible thermodynamic structure is the fundamental cause leading to voltage decay of LRM cathode, and it worsens with increasing temperature. The early activation of inert Mn, multiple phase transitions, migration of transition metals to the surface, anisotropy of internal valence states caused by partial valence failure and severe interfacial reactions are all strong proofs of the above views. In summary, the reason for voltage decay is revealed by investigating the sensitivity of the LRM cathode materials to temperature. This work not only provides strong evidence for the mechanism of the voltage decay, but also points out the direction to modification design for achieving future commercialization of LRM cathode materials.

Human epidermal growth factor receptor 2 (HER2) amplification or activating mutations are found in 1.6%–4% of non-small cell lung cancer (NSCLC). Pyrotinib has been reported to have better potency in NSCLC patients with HER2 exon 20 insertion (ex20ins) mutations; however, more clinical evidence is urgently needed to guide pyrotinib-based therapy in NSCLC with HER2 amplification or heterogeneous mutations. We retrospectively analyzed advanced NSCLC patients with HER2 amplification or mutations who were treated with pyrotinib-based therapy between September 25, 2018 and October 30, 2020 in our hospital. Molecular dynamics simulation was used to explore the bioactive conformation and binding mechanisms of pan-ErbB tyrosine kinase inhibitors (TKIs) including pyrotinib for different HER2 ex20ins variants. In this study, 79 eligible patients were included with 70 ex20ins variants, 6 missense mutations and 3 primary HER2 amplifications identified. A775_G776insYVMA insertion was the most common observed subtype. The median progression-free survival (mPFS) was 5.8 (95% CI: 4.1–7.4) months. Use of pyrotinib-based therapy in first-/second-line settings showed a significantly better prognosis than that observed in third-line settings or above (mPFS: 9.1 vs. 4.4 months; P = 0.0003). Compared with HER2 amplification and exon 20 non-YVMA insertion variants, patients with HER2 missense mutations had a visible mPFS benefit (12.2 vs. 6.8 vs. 5.2 months). Computational docking simulations revealed that pyrotinib failed to interact with the specific insertion variant P780_Y781insGSP. These results indicated that pyrotinib-based therapy exhibited good anti-tumor activity and acceptable safety profile in HER2-altered advanced NSCLC.

Domestic refrigerator is a widely used appliance to keep food fresh and retard food spoilage in household. However, our understanding of microbial health risk associated with food under such circumstance still remains very poor. Here, typical types of food (vegetable, fish, and pork) were kept in a domestic refrigerator at 4 °C for 3–30 days. Temporal dynamics of antibiotic resistome, pathogens, bacterial and fungal communities during this period were investigated via high-throughput quantification and Illumina sequencing technologies. Results showed that a large number (21–134) of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) were detected across the three food types, including 10.06 % of high-risk ARGs classified by their risk ranks. Moreover, four bacterial pathogens (i.e., Bacillus cereus, Cronobacter spp., Klebsiella pneumoniae and Staphylococcus aureus) targeted by marker genes including the pathogen-specific genes or virulence factor genes, and some potential fungal pathogens (e.g., Fusarium, Candida, and Aspergillus) were detected, indicating the occurrence of microbial risk even at the normally regarded safe storage temperature. Among all food types, the total bacterial density and ARG abundances in fish rapidly increased after only 3 days, much faster than vegetable and pork after 10 days. In addition, fish samples contained the highest ARG and pathogen abundances, indicating its potentially higher health risk than other food types. Finally, the shifts of ARG pattern were mainly contributed by bacterial communities and MGEs. This study highlights that food preserved in refrigerator at 4 °C could still be an unneglected microbial risk, and raises awareness of improving food safety in domestic environment.

With the increasingly widespread use of sub-pixel mapping techniques in land cover/use mapping, more accurate area information is often required for a specific land cover type in a particular study region. However, the bias of area counted from sub-pixel maps (called area bias below), and the inadequate understanding of the area bias's origin and influential factors pose a challenge to using this information accurately. Traditional model-assisted estimators combining the map and the reference sample showed unreliable performances in the case of small sample sizes collected in target regions. This work presented a theoretical analysis of the origin of area bias. It then proposed a novel bias-adjusted estimator which can effectively deal with the small sample sizes. The theoretical analysis illustrated that area bias mainly originates from two terms, i.e., the abundance-dependent error and the probability distribution of abundances. We next developed a stratified bias-adjusted area estimator named the two-term method (TTM) by incorporating the sub-pixel map and a reference sample obtained from both target and external regions. We validated the effects of different sub-pixel mapping methods, different spatial resolutions, the varying spatial structures of statistical units on area bias, and the performance of TTM in correcting the biased areas in multiple cases. The results showed that area bias varied from zero to approximately 20% with the variation of three influential factors. TTM effectively corrected the biased area values to nearly the true values, showing approximate equivalence with the traditional stratified regression estimator (STRE) when adequate reference samples are collected sorely inside target regions. However, in cases of small samples from target regions, TTM showed significant superiority over STRE in reducing the variance and MSE due to the incorporation of external reference samples. We conclude that the theoretical analysis resulted in a better understanding of area bias counted from sub-pixel maps and an improved area estimator for dealing with the cases of small sample sizes inside target regions.

Due to the fast pace of urbanization worldwide, industrial sand mining activities have imposed great pressure on the environment, and consequently, these activities have led to serious environmental problems in aquatic ecosystems. However, the current understanding of the effect of sand mining on heavy metal remobilization in river sediments remains incomplete. The present study employed sediment quality guidelines (SQGs) and the sequential extraction (SE) and diffusive gradients in thin films (DGT) techniques to comprehensively investigate the effect of sand mining on the remobilization process of heavy metals in the aquatic system of the Jialing River. The SQGs results indicated that stations (S1 to S4) with sand mining disturbance exhibited Pb and Cd accumulation in surface sediments. Both Ctotal-Pb (61.78–122.04 mg·kg−1) and Ctotal-Cd (0.85–3.96 mg·kg−1) were higher than CSQGI (60 mg·kg−1 for Pb and 0.5 mg·kg−1 for Cd) and TEC (35.8 mg·kg−1 for Pb and 0.99 mg·kg−1 for Cd) limitation in most of sand mining stations. Pb and Cd were mainly bounded in the acid-soluble/exchangeable fraction (F1) and oxidizable fraction (F3) of the surface sediments. At the four stations with sand mining disturbance, about 5–10 folds of DGT-labile Pb and Cd were released in deep sediments (−9 to −12 cm), and Pb and Cd exhibited a transport trend from the sediments into the overlying water, while the above phenomenon was not observed at the two stations without sand mining activities. Correlation analysis revealed that DGT-labile Pb and Cd were suitably correlated with the F1 and F3 fractions, indicating that the acid-soluble/exchangeable and oxidizable fractions were the main sources leading to Pb and Cd remobilization in the sediments. A potential mechanism explanation may be that (1) intense sediment stirring could result in remobilization of the weakly bound fraction, which is related to the contribution of the F1 fraction, and (2) Cd/Pb experienced a corelease process with sulfur due to O2 introduction (elevation of the dissolved oxygen level) attributed to sediment evacuation, which is related to the contribution of the F3 fraction. The above results suggested that sand mining in the Jialing River should be paid high attention to prevent heavy metal pollution in aquatic ecosystem.

A polysaccharide from jackfruit pulp (JFP-Ps) has been found to exhibit various types of bioactivities. This study aimed to investigate the effects and potential mechanisms of JFP-Ps on non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet in rats. The pathological changes in the liver and liver function were determined using hematoxylin-eosin staining and biochemical analysis. RT-qPCR and Western blots were employed to study the expression of proteins associated with lipid metabolism and proinflammatory cytokines. Results showed that JFP-Ps reduced liver weight and liver index, and influenced liver function in high-fat diet rats. Furthermore, JFP-Ps up-regulated the lipolytic genes (PPARα, LPL, CPT1, HSL) expression, downregulated the expression of lipogenic genes (SREBP-1c, ACC, FAS) and proinflammatory cytokines (TNF-α, IL-6) genes. JFP-Ps increased the protein expression of p-AMPK, and decreased the protein expression of SREBP-1c and AMPK. These results revealed that JFP-Ps might improve liver function and alleviate NAFLD through activating PPAR and AMPK signaling pathways.

Niobium addition in candidate accident tolerant fuel (ATF) cladding FeCrAl alloy has received much attention, but its effect on high temperature water corrosion behavior has not been revealed. Four alloys with different Nb content (0 wt%, 0.5 wt%, 1.0 wt% and 1.5 wt%) based on Fe-13Cr-4.5Al-2Mo model alloy were designed, and the corrosion behavior was investigated by in-situ electrochemistry and microscopy. The in-situ electrochemistry analyses, including open circuit potential (OCP), polarization and electrochemical impedance spectrum, were carried out in 360 °C/19.0 MPa lithiated and borated water connected with a loop system to monitor the water chemistry. The oxide films formed after immersion for 85 days were deeply investigated by focused ion bombarding and transmission electron microscopy. Results have shown that OCP decreased with elevated temperature and corrosion potential increased with time. FeCrAl alloys have satisfactory corrosion resistance because of small corrosion currents and thin oxide films. Only monolayer multicrystal spinel oxide forms on FeCrAl alloys. Slight Nb addition (0.5 wt% and 1.0 wt%) benefits the corrosion resistance due to relatively large impedance of oxide and delayed oxidation of Fe2Nb particles. Porosities with Fe depletion were spotted in oxide and especially severe in 1.5 wt%-Nb alloy. Cathodic Tafel kinetics and corrosion mechanisms of FeCrAl were further discussed.

An increasing number of studies have clarified the functional roles of RNA-binding proteins (RBPs) in driving post-transcriptional mechanisms of cancer progression. In this study, we integrated data from the RBP database and Gene Expression Omnibus (GEO) data with RNA sequencing (RNA-seq) data from 10 ovarian cancer tissues and 8 normal ovarian tissues and identified an RBP, CUGBP- and ETR-3-like family 2 (CELF2). We found that CELF2 expression was downregulated in ovarian cancer and positively correlated with the overall survival (OS) and progression-free survival (PFS) of patients with ovarian cancer. Altered CELF2 expression led to changes in the proliferation, migration, and invasion of ovarian cancer cells in vitro and in vivo. CELF2 expression increased the stability of its target, FAM198B, by binding to AU/U-rich elements (AREs) in the 3′ untranslated region (3′ UTR). FAM198B knockdown restored the CELF2-mediated suppression of proliferation and migration. We also found that CELF2/FAM198B may repress ovarian cancer progression by inhibiting the mitogen-activated protein kinase/extracellular-regulated protein kinase (MAPK/ERK) signaling pathway. Finally, a curcumin-induced increase in CELF2 expression resulted in increased ovarian cancer cell sensitivity to cisplatin. Our study elucidated a novel mechanism by which the CELF2/FAM198B axis regulates proliferation and metastasis in ovarian cancer, providing novel, potential therapeutic targets for ovarian cancer.

Objective: To study the correlation between vaginal micro-ecological composition and the outcome of human papillomavirus (HPV) infection by High-Throughput Metagene Sequencing Information Technology on the Illumina Platform, and to improve the efficiency of clinical infection detection. Methods: With the aid of Illumina high-throughput sequencing platform and sequence research method, the composition and diversity of vaginal microorganisms in high-risk HPV (HR-HPV) infected women and healthy women were analyzed. The differences in vaginal flora of HR-HPV infected women and healthy women were compared to explore the correlation between HR-HPV infection and vaginal flora. Results: The structure of vaginal flora in healthy women was relatively single, with Lactobacillus as the dominant genus, accounting for more than 80%. The structure of vaginal flora in women infected with HR-HPV was significantly different from that in non-infected women. The former had a significantly increased species diversity, which was mainly manifested by a decrease in Lactobacillus and an increase in Gardnerella vaginalis. Mycoplasma and Ureaplasma urealyticum might play a synergistic role in the initial stage of cervical lesions caused by HR-HPV infection. Conclusion: The prevention and treatment of mycoplasma and Ureaplasma urealyticum should be valued clinically to prevent the occurrence of HR-HPV infection and cervical lesions.

The world has witnessed an unprecedented growth of WF installation, driven by national and international energy policies. Considering the negative impacts of fossil fuel and associated climate changes, wind is an important form of renewable energy. Nevertheless, the conventional WFs also have some environmental effects. Besides, the conventional WTs lack in performance due to technical limitations. Upon comprehensively reviewing the impacts and the technicalities, this literature focused on the recent developments in the research community to predict the potential research pathways for technical optimization and modification of the relevant policies.

Background: Panax ginseng has been used for a variety of medical purposes in eastern countries for more than two thousand years. From the extensive experiences accumulated in its long medication use history and the substantial strong evidence in modern research studies, we know that ginseng has various pharmacological activities, such as antitumor, antidiabetic, antioxidant, and cardiovascular system–protective effects. The active chemical constituents of ginseng, ginsenosides, are rich in structural diversity and exhibit a wide range of biological activities. Methods: Ginsenoside constituents from P. ginseng flower buds were isolated and purified by various chromatographic methods, and their structures were identified by spectroscopic analysis and comparison with the reported data. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H- tetrazolium bromide method was used to test their cytotoxic effects on three human cancer cell lines. Results: Six ginsenosides, namely 6'–malonyl formyl ginsenoside F1 (1), 3β–acetoxyl ginsenoside F1 (2), ginsenoside Rh24 (6), ginsenoside Rh25 (7), 7β–hydroxyl ginsenoside Rd (8) and ginsenoside Rh26 (10) were isolated and elucidated as new compounds, together with four known compounds (3–5 and 9). In addition, the cytotoxicity of these isolated compounds was shown as half inhibitory concentration values, a tentative structure–activity relationship was also discussed based on the results of our bioassay. Conclusion: The study of chemical constituents was useful for the quality control of P. ginseng flower buds. The study on antitumor activities showed that new Compound 1 exhibited moderate cytotoxic activities against HL-60, MGC80-3 and Hep-G2 with half inhibitory concentration values of 16.74, 29.51 and 20.48 μM, respectively. Keywords: 7β–hydroxyl ginsenoside Rd, Acylated ginsenosides, Cytotoxicity, Dammarane–type triterpene saponin, Panax ginseng flower buds

Water conservation is one of the most critical ecosystem service functions of river basins and is an important indicator of regional eco-environmental conditions. Beijiang River Basin (BRB) is an important water source and ecological barrier for the Guangdong-Hong Kong-Macau Greater Bay Area (GBA), and its water conservation function is of widespread concern. In this study, based on the hydrological model WEP-L (Water and Energy transfer Processes in Large River basin), and the water balance principle, we analysed the multiple time-scale characteristics of water conservation in the BRB during 1960–2018 and revealed the response of water conservation to climate change based on scenario setting and hydrological simulation. The results showed that annual water conservation exhibited an insignificant reducing trend of −4.69 mm/10a. Water conservation reduced insignificantly in spring, summer, and autumn, while it showed a nonsignificant increasing trend of 4.69 mm/10a in winter. The spatial distribution of water conservation in the BRB was low in the south and high in the north, mainly due to the spatial distribution of land use. Precipitation was the main factor affecting water conservation. The results can provide a reference for water resource planning and management, and provide a theoretical foundation for ecosystem restoration and reconstruction.

Summary: To explore the relative contributions of higher-order and primary visual cortex (V1) to visual perception, we compared cats' behavioral and V1 neuronal contrast sensitivity functions (CSF) and threshold versus external noise contrast (TvC) functions before and after top-down influence of area 7 (A7) was modulated with transcranial direct current stimulation (tDCS). We found that suppressing top-down influence of A7 with cathode-tDCS, but not sham-tDCS, reduced behavioral and neuronal contrast sensitivity in the same range of spatial frequencies and increased behavioral and neuronal contrast thresholds in the same range of external noise levels. The neuronal CSF and TvC functions were highly correlated with their behavioral counterparts both before and after the top-down suppression. Analysis of TvC functions using the Perceptual Template Model (PTM) indicated that top-down influence of A7 increased both behavioral and V1 neuronal contrast sensitivity by reducing internal additive noise and the impact of external noise.

Growing tumor cells possess a distinct metabolic phenomenon that allows them to preferentially utilize glucose through aerobic glycolysis, which is referred to as the “Warburg effect.” Accumulating evidence suggests that microRNAs (miRNAs) could regulate such metabolic reprogramming. Our microarray analysis and quantitative real-time PCR validation revealed that miR-885-5p was strongly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. To investigate miR-885-5p’s biological functions in HCC progression, malignant phenotypes were analyzed in different types of hypoxic model and indicated that overexpression of miR-885-5p significantly inhibited HCC cell proliferation and migration and induced apoptosis in vitro and tumor growth in vivo. Subsequent investigations of whether miR-885-5p regulated the glycometabolic activity of cancer cells demonstrated that forced expression of miR-885-5p in SMMC-7721 cells significantly reduced glucose uptake and lactate production by repressing several key enzymes related to glycolysis. Particularly, miR-885-5p directly targets the 3′ UTR of hexokinase 2 (HK2), which is a key enzyme that catalyzes the irreversible first step of glycolysis and associates with poor patient outcomes. The miR-885-5p/HK2 axis strongly links aerobic glycolysis to carcinogenesis and may become a promising therapeutic target and prognostic predictor for HCC patients. Keywords: Warburg effect, HCC, miRNAs, HK2, hypoxia, prognosis