Critical Residues Involved in the Coassembly of L1 and L2 Capsid Proteins of Human Papillomavirus 16.

Human papillomaviruses (HPV) are small DNA viruses associated with cervical cancer, warts, and other epithelial tumors. Structural studies have shown that the HPV capsid consists of 360 copies of the major capsid protein, L1, arranged as 72 pentamers in a T=7 icosahedral lattice, coassembling with substoichiometric amounts of the minor capsid protein, L2. However, the residues involved in the coassembly of L1 and L2 remain undefined due to the lack of structure information. Here, we investigated the solvent accessibility surfaces (SASs) of the central cavity residues of the HPV16 L1 pentamer in the crystal structure because those internal exposed residues might mediate the association with L2. Twenty residues in L1 protein were selected to be analyzed, with four residues in the lumen of the L1 pentamer identified as important: F256, R315, Q317, and T340. Mutations to these four residues reduced the PsV (pseudovirus) infection capacity in 293FT cells, and mutations to R315, Q317, and T340 substantially perturb L2 from coassembling into L1 capsid. Compared with wild-type (WT) PsVs, these mutant PsVs also have a reduced ability to become internalized into host cells. Finally, we identified a stretch of negatively charged residues on L2 (amino acids [aa] 337 to 340 [EEIE]), mutations to which completely abrogate L2 assembly into L1 capsid and subsequently impair the endocytosis and infectivity of HPV16 PsVs. These findings shed light on the elusive coassembly between HPV L1 and L2. IMPORTANCE Over 200 types of HPV have been isolated, with several high-risk types correlated with the occurrence of cervical cancer. The HPV major capsid protein, L1, assembles into a T=7 icosahedral viral shell, and associates with the minor capsid protein, L2, which plays a critical role in the HPV life cycle. Despite the important role of the L2 protein, its structure and coassembly with L1 remain elusive. In this study, we analyzed the amino acid residues at the proposed interface between L1 and L2. Certain mutations at these sites decreased the amount of L2 protein assembled into the capsid, which, in turn, led to a decrease in viral infectivity. Knowledge about these residues and the coassembly of L1 and L2 could help to expand our understanding of HPV biology and aid in the development of countermeasures against a wide range of HPV types by targeting the L2 protein.

Advances in the endoscopic management of gastric varices.

This review provides an overview of the treatment options available for gastric varices (GV) with a focus on endoscopic methods. Various minimally invasive techniques, including endoscopic band ligation, endoscopic cyanoacrylate injection, and transjugular intrahepatic portosystemic shunt, can be applied to the treatment of GV. Endoscopic cyanoacrylate injection is now recognized as a first-line treatment for GV. Endoscopic ultrasound-guided cyanoacrylate injection combined with coils has shown good security and effectiveness. Thrombin injection therapy is a promising treatment, with a similar hemostasis rate to cyanoacrylate injection but with fewer serious complications. With the deepening understanding of the hemodynamics of the GV system, various treatment methods and their combination are gradually evaluated to provide patients with safer and more effective treatment options.

An Improved YOLOv8 Network for Detecting Electric Pylons Based on Optical Satellite Image.

Electric pylons are crucial components of power infrastructure, requiring accurate detection and identification for effective monitoring of transmission lines. This paper proposes an innovative model, the EP-YOLOv8 network, which incorporates new modules: the DSLSK-SPPF and EMS-Head. The DSLSK-SPPF module is designed to capture the surrounding features of electric pylons more effectively, enhancing the model's adaptability to the complex shapes of these structures. The EMS-Head module enhances the model's ability to capture fine details of electric pylons while maintaining a lightweight design. The EP-YOLOv8 network optimizes traditional YOLOv8n parameters, demonstrating a significant improvement in electric pylon detection accuracy with an average mAP@0.5 value of 95.5%. The effective detection of electric pylons by the EP-YOLOv8 demonstrates its ability to overcome the inefficiencies inherent in existing optical satellite image-based models, particularly those related to the unique characteristics of electric pylons. This improvement will significantly aid in monitoring the operational status and layout of power infrastructure, providing crucial insights for infrastructure management and maintenance.

[Experimental study on improvement of cognitive impairment in Alzheimer's disease by different degrees of steaming and sunning of Polygoni Multiflori Radix based on fecal metabolomics].

The fecal metabolomics method was employed to investigate the cognitive improvement mechanism of Polygoni Multiflori Radix in Alzheimer's disease(AD) and examine the effects of different degrees of steaming and sunning on cognitive function in AD model mice. Additionally, the processing principle of Polygoni Multiflori Radix was discussed. Forty-eight 5-month-old APP/PS1 mice were randomly assigned to the following groups: model group, positive group, raw product group, three-steaming and three-sunning product group, six-steaming and six-sunning product group, and nine-steaming and nine-sunning product group. Seven negative control mice from the same litter were included as the blank group. After 150 days of intragastric administration, the learning and memory abilities of mice in each group were assessed by using the Barnes maze and dark avoidance tests. Fecal samples were collected for extensive targeted metabolomics testing. Principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and other multivariate statistical methods were utilized to analyze metabolites in mouse feces. Comparison of behavioral results between the model group and different product groups demonstrated that the six-steaming and six-sunning product group exhibited significantly reduced latency in the Barnes maze positioning and navigation test(P<0.05), as well as a notable decrease in the number of errors in the space exploration experiment(P<0.05). Moreover, the latency of mice entering the dark box for the first time in the dark avoidance experiment was significantly prolonged(P<0.05), indicating the best overall improvement in the learning and memory ability of AD model mice. Metabolomics results revealed that compared with the model group, the differential metabolites in other groups in descending order were as follows: six-steaming and six-sunning product group > nine-steaming and nine-sunning product group > raw product group > three-steaming and three-sunning product group, encompassing 146, 120, 95, and 81 potential biomarkers, respectively. Among them, 16 differential metabolites were related to AD disease. Further comparisons based on the degree of processing indicated that the six-steaming and six-sunning product group exhibited the most significant adjustments in total metabolic pathways, particularly regulating the interconversion of pentose and glucuronic acid, as well as amino acid anabolism and other pathways. In summary, the mechanism of Polygoni Multiflori Radix after processing in enhancing the learning and memory ability of APP/PS1 mice may be associated with improved amino acid metabolism and increased energy metabolism in the body. The six-steaming and six-sunning yielded the best outcomes.

Structural basis for the shared neutralization mechanism of three classes of human papillomavirus type 58 antibodies with disparate modes of binding.

Human papillomavirus type 58 (HPV58) is associated with cervical cancer and poses a significant health burden worldwide. Although the commercial 9-valent HPV vaccine covers HPV58, the structural and molecular-level neutralization sites of the HPV58 complete virion are not fully understood. Here, we report the high-resolution (∼3.5 Å) structure of the complete HPV58 pseudovirus (PsV58) using cryo-electron microscopy (cryo-EM). Three representative neutralizing monoclonal antibodies (nAbs 5G9, 2H3 and A4B4) were selected through clustering from a nAb panel against HPV58. Bypassing the steric hindrance and symmetry-mismatch in the HPV Fab-capsid immune-complex, we present three different neutralizing epitopes in the PsV58, and show that, despite differences in binding, these nAbs share a common neutralization mechanism. These results offer insight into HPV58 genotype specificity and broaden our understanding of HPV58 neutralization sites for antiviral research.IMPORTANCE Cervical cancer primarily results from persistent infection with high-risk types of human papillomavirus (HPV). HPV type 58 (HPV58) is an important causative agent, especially within Asia. Despite this, we still have limited data pertaining to the structural and neutralizing epitopes of HPV58, and this encumbers our in-depth understanding of the virus mode of infection. Here, we show that representative nAbs (5G9, 10B11, 2H3, 5H2 and A4B4) from three different groups share a common neutralization mechanism that appears to prohibit the virus from associating with the extracellular matrix and cell surface. Furthermore, we identify that the nAbs engage via three different binding patterns: top-center binding (5G9 and 10B11), top-fringe binding (2H3 and 5H2), and fringe binding (A4B4). Our work shows that, despite differences in the pattern in binding, nAbs against HPV58 share a common neutralization mechanism. These results provide new insight into the understanding of HPV58 infection.

Electronic structures of hydroxylated low index surfaces of rutile and anatase-type titanium dioxide.

Different surface planes of various types of titanium dioxide (TiO2) crystals have diverse catalysis effects on the splitting of H2O and H2 and the electronic structures of the formed hydroxylated TiO2 vary significantly. A series of sixteen types of hydroxylated TiO2 surfaces containing two types of hydroxyls (OH1 and OH2) on four kinds of low index surfaces [(001), (100), (101), and (110)] of two types of crystals [anatase (A) and rutile (R)] are studied using first-principles density functional theory calculations. The catalyzed splitting of H2O and H2 on the eight low index surfaces is compared using Gibbs free energy. The geometries and electronic structures including the total and partial density of states and the charge density distribution of the sixteen hydroxylated surfaces are systematically described. The electronic structures of R-101, R-001, A-110, A-100, and A-001 surfaces are more significantly influenced by hydroxylation than other surfaces and the effects of OH2 are larger than those of OH1. In particular, the band gap values decrease and a new electronic energy state appears in R-001-OH2 and A-100-OH2. A new electronic state appears in the middle of the bands of R-101 and A-110 surfaces upon hydroxylation. The electron spin balance at the edge of the conduction band minimum of A-001-OH2 is disturbed. This research can provide theoretical guidance for experimental researchers to design surface hydroxylated TiO2 materials with tunable electronic structures and high catalytic performance.

Peroxiredoxin 6 mediates the protective function of curcumin pretreatment in acute lung injury induced by serum from patients undergoing one-lung ventilation in vitro.

BACKGROUND: Curcumin has attracted much attention due to its wide range of therapeutic effects. In this study, we used serum collected from patients undergoing one-lung ventilation (OLV) to establish an in vitro acute lung injury (ALI) model to explore the potential protective mechanism of curcumin on ALI. Our study provides a new reference for the prevention and treatment of ALI induced by OLV. METHODS: A549 cells were treated with 20% serum from patients undergoing OLV to establish an in vitro ALI model. Curcumin, at a dose of 40 µg/ml, was administered two hours prior to this model. The levels of inflammation and oxidative stress markers were observed by Western blot, qRT-PCR, ELISA and reactive oxygen species assay. Additionally, the expression of peroxiredoxin 6 (Prdx6) and proteins involved in the NF-κB signaling pathway was evaluated. RESULTS: Twenty percent of serum collected from patients undergoing OLV downregulated the expression of Prdx6, leading to the activation of the NF-κB signaling pathway, which was associated with the subsequent overproduction of inflammatory cytokines and reactive oxygen species. Pretreatment with curcumin restored Prdx6 downregulation and inhibited NF-κB pathway activation by suppressing the nuclear translocation of P65, eventually reducing inflammation and oxidative stress damage in A549 cells. CONCLUSIONS: Prdx6 mediated the protective function of curcumin by inhibiting the activation of the NF-κB pathway in ALI in vitro.

Room temperature cupric halides mediated olefin alkoxylation of BODIPYs with methanol: mechanisms and scope.

We disclose an efficient methodology for olefin alkoxylation of fluorescent BODIPYs (boron-dipyrromethene) at the 3,5-styryl group with methanol by cupric halide (chloride or bromide) at room temperature. Mechanistic studies provide evidence for the alkoxylation reaction firstly initiated by a radical cation, that is, halide promotes the oxidizing ability of the Cu(ii) center to an extent that the single electron transfer (SET) from BODIPYs to the cupric ion and results in the production of a BODIPYs radical cation and Cu(i), then the BODIPYs radical cation subsequently reacts with methanol to afford the alkoxylated product. As the dialkoxylated product complexes with cuprous halide and further decreases its reducing ability, which is supported by DFT calculations, only strongly oxidative cupric bromide can mediate tetraalkoxylation and give rise to the tetraalkoxylated product. In addition, the expanded scope studies suggest that this method is also well suited for the alkoxylation of electron-rich conjugated olefins. The active benzyl bromide derivative may be another intermediate in the presence of cupric bromide. Therefore, the reaction is highly dependent on the anions of cupric salts; Cu(OAc)2, CuSO4 and Cu(NO3)2 containing weakly nucleophilic anions show no activity in alkoxylation.

Construction of a bacterial surface display system based on outer membrane protein F.

BACKGROUND: Bacterial surface display systems were developed to surface expose heterologous proteins or peptides for different applications, such as peptide libraries screening and live bacterial vaccine design. Various outer membrane proteins, such as outer membrane protein A (OmpA), OmpC and outer membrane pore protein E precursor (PhoE), have been used as carriers for surface display, fused to the proteins or peptides of interest in Gram-negative bacteria. Here, we investigated the utility of constitutively expressed OmpF for the display of foreign immune epitopes on the Escherichia coli cell surface and then compared it with plasmid-induced expression of OmpF and OmpC. RESULTS: Enhanced expression of OmpF was linked to a mutation in the OmpF promoter sequence. This mutation rendered OmpF an ideal carrier protein for the enriched display of a target of interest on the bacterial surface. To this end, we grafted two peptides, harboring important epitopes of the hepatitis B virus (HBV) S antigen and human papilloma virus (HPV) L2 protein, onto OmpF of E. coli by genome editing. The resultant fused OmpF proteins were constitutively expressed in the edited E. coli and purified by membrane component extraction. The epitope that displayed on the bacterial surface was verified by SDS-PAGE, western blotting, flow cytometry, and immunoelectron microscopy of the intact bacteria. We further compared this constitutive expression with plasmid-induced expression of OmpF and OmpC in bacterial cells using the same methods for verification. We found that plasmid-induced expression is much less efficient than constitutive expression of OmpF from the bacterial genome. CONCLUSIONS: Enhanced expression of OmpF in a plasmid-independent manner provides an amenable way to display epitopes on the bacterial surface and sheds light on ways to engineer bacteria for biotechnological applications.

The effects of atmospheric hydrogen sulfide on peripheral blood lymphocytes of chickens: Perspectives on inflammation, oxidative stress and energy metabolism.

Excessive hydrogen sulfide (H2S) affects poultry health. Exposure to air pollution induces inflammation, oxidative stress, energy metabolism dysfunction and adverse health effects. However, few detailed studies have been conducted on the molecular mechanisms of H2S-induced injury in poultry. To understand how H2S drives its adverse effects on chickens, twenty-four 14-day-old chickens were randomly divided into two groups. The chickens in the control group were raised in a separate chamber without H2S, and the chickens in the treatment group were exposed to 30 ppm H2S. After 14 days of exposure, peripheral blood samples were taken and the lymphocytes were extracted to detect inflammation, oxidative stress and energy metabolism in broilers. Overall, an increase in the inflammatory response was detected in the peripheral blood lymphocytes following H2S exposure compared to the control group, and the expression levels of the heat shock proteins (HSPs) and the transcription factors nuclear factor κB (NF-κB), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were up-regulated in the H2S group, which further suggested that H2S induced an inflammatory response via the NF-κB pathway. Because of the activation of NF-κB, which is a major regulator of oxidative stress, we also observed that reactive oxygen species (ROS) production was elevated under H2S exposure. In addition, we presumed that energy metabolism might be damaged due to the increased ROS production, and we found that H2S down-regulated the expression levels of energy metabolism-related genes, which indicated the occurrence of energy metabolism dysfunction. Altogether, this study suggests that exposure to excessive atmospheric H2S induces an inflammatory response, oxidative stress and energy metabolism dysfunction, providing a reference for comparative medicine.

Hydrogen sulfide inhalation-induced immune damage is involved in oxidative stress, inflammation, apoptosis and the Th1/Th2 imbalance in broiler bursa of Fabricius.

Hydrogen sulfide (H2S) is widely accepted to be a signaling molecule that exhibits some potentially beneficial therapeutic effects at physiological concentrations. At elevated levels, H2S is highly toxic and has a negative effect on human health and animal welfare. Studies have shown that H2S exposure induces an immune function in mice, but there are few studies of the effect of continuous H2S exposure on immune organs in poultry. In this study, one-day-old broilers were selected and exposed to 4 or 20 ppm of H2S gas for 14, 28 and 42 days of age. After exposure, the bursa of Fabricius (BF) was harvested. The results showed that continuous H2S exposure reduced the body weight, abdominal fat percentage, and antibody titer in broilers. H2S exposure also decreased mRNA expression of IgA, IgM and IgG in the broiler BF. A histological study revealed obvious nuclear debris, and a few vacuoles in the BF, and an ultrastructural study revealed mitochondrial and nuclear damage to BF cells after H2S exposure for 42 d. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay suggested H2S exposure remarkably increased the number of TUNEL positive nuclei and significantly increased apoptotic index. The expression of apoptotic genes also confirmed that H2S inhalation damaged the broiler BF. Increased cytokines and reduced antioxidant responses were detected in the BF after exposure to H2S. Cytokines promoted inflammation and caused a Th1/Th2 imbalance. We suggest that continuous H2S intoxication triggers oxidative stress, inflammation, apoptosis and a Th1/Th2 imbalance in the BF, leading to immune injury in broilers.

Alpinia oxyphylla Miq. fruit extract activates IGFR-PI3K/Akt signaling to induce Schwann cell proliferation and sciatic nerve regeneration.

BACKGROUND: It is known that the medicinal herb Alpinia oxyphylla Miq. is widely used as a remedy for diarrhea as well as the symptoms accompanying hypertension and cerebrovascular disorders. Moreover, it has also been reported that Alpinia oxyphylla Miq. has beneficial effects on anti-senescence and neuro-protection. This study focuses on the molecular mechanisms by which the Alpinia oxyphylla Miq. fruits promote neuron regeneration. METHODS: A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with various doses of Alpinia oxyphylla Miq. fruits to assess their regenerative effect on damaged nerves. Further, we investigated the role of Alpinia oxyphylla Miq. fruits in RSC96 Schwann cell proliferation. RESULTS: Our current results showed that treatment with the extract of Alpinia oxyphylla Miq. fruits triggers the phosphorylated insulin-like growth factor-1 receptor- phosphatidylinositol 3-kinase/serine-threonine kinase pathway, and up-regulated the proliferating cell nuclear antigen in a dose-dependent manner. Cell cycle analysis on RSC96 Schwann cells showed that, after exposure to Alpinia oxyphylla Miq. fruit extract, the transition from the first gap phase to the synthesis phase occurs in 12-18 h. The expression of the cell cycle regulatory proteins cyclin D1, cyclin E and cyclin A increased in a dose-dependent manner. Transfection with a small interfering RNA blocked the expression of phosphatidylinositol 3-kinase and induced down-regulation both on the mRNA and protein levels, which resulted in a reduction of the expression of the survival factor B-cell lymphoma 2. CONCLUSION: We provide positive results that demonstrate that Alpinia oxyphylla Miq. fruits facilitate the survival and proliferation of RSC96 cells via insulin-like growth factor-1 signaling.

XRCC1 and XPD genetic polymorphisms and susceptibility to age-related cataract: a meta-analysis.

OBJECTIVE: This meta-analysis aimed to determine the relationships between XRCC1 Arg399Gln (rs25487 G>A) and XPD Lys751Gln (rs1052559 A>C) polymorphisms and susceptibility to age-related cataract. METHODS: Medline (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013) were searched without language restrictions. Various combinations of the keywords and MeSH terms were used to screen for potentially relevant studies, specifically "genetic polymorphisms" or "SNPs" or "variation" or "single nucleotide polymorphism" or "polymorphism" or "mutation" or "variant"; "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "XPD" or "Xeroderma Pigmentosum Complementation Group D Protein" or "ERCC2" or "XRCC1" or "XRCC1 DNA repair protein"; and "Cataract" or " Membranous Cataract" or " Pseudoaphakia." Meta-analyses were conducted using Stata 12.0 software. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (95% CI) were calculated. RESULTS: Six independent case-control studies were included in the meta-analysis. Our results indicated that the association between the genetic polymorphisms of XRCC1 Arg399Gln G>A and XPD Lys751Gln A>C and increased susceptibility to age-related cataracts was statistically significant (XRCC1 Arg399Gln: OR=1.30, 95% CI=1.17-1.44, p<0.001; XPD Lys751Gln: OR=1.25, 95% CI=1.12-1.40, p<0.001, respectively). Ethnicity-stratified analysis indicated that the XRCC1 Arg399Gln G>A polymorphism was correlated with the development and progression of age-related cataract in China, India, and Turkey in the allele model and the dominant model. For the XPD Lys751Gln A>C variant, the association with the pathogenesis of age-related cataract in China and Turkey in the allele model and the dominant model was investigated. CONCLUSIONS: The association of XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms with age-related cataract susceptibility observed in our meta-analyses supports the view that XRCC1 and XPD may play important roles in susceptibility to age-related cataract.

A Cross-Sectional and Longitudinal Integrated Study on Brain Functional Changes in a Neuropathic Pain Rat Model.

Human and animal imaging studies demonstrated that chronic pain profoundly alters the structure and the functionality of several brain regions and even causes mental dysfunctions such as depression and anxiety disorders. In this article, we conducted a multimodal study cross-sectionally and longitudinally, to evaluate how neuropathic pain affects the brain. Using the spared nerve injury (SNI) model which promotes long-lasting mechanical allodynia, results showed that neuropathic pain deeply modified the intrinsic organization of the brain functional network 2 weeks after injury. There are significant changes in the activity of the left thalamus (Th_L) and left olfactory bulb (OB_L) brain regions after SNI, as evidenced by both the blood oxygen level-dependent (BOLD) signal and c-Fos expression. Importantly, these changes were closely related to mechanical pain behavior of rats. However, it is worth noting that after morphine administration for analgesia, only the increased activity in the TH region is reversed, while the decreased activity in the OB region becomes more prominent. Functional connectivity (FC) and c-Fos correlation analysis further showed these two regions of interest (ROIs) exhibit different FC patterns with other brain regions. Our study comprehensively revealed the adaptive changes of brain neural networks induced by nerve injury in both cross-sectional and longitudinal dimensions and emphasized the abnormal activity and FC of Th_L and OB_L in the pathological condition. It provides reliable assistance in exploring the intricate mechanisms of diseases.

Rational design of a cross-type HPV vaccine through immunodominance shift guided by a cross-neutralizing antibody.

In vaccine development, broadly or cross-type neutralizing antibodies (bnAbs or cnAbs) are frequently targeted to enhance protection. Utilizing immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization strategies. However, the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly elucidated. In this study, we discovered a cross-type neutralizing monoclonal antibody, 13H5, against human papillomavirus 6 (HPV6) and HPV11. This nAb exhibited a marked preference for HPV6, demonstrating superior binding activity to virus-like particles (VLPs) and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum (90% vs. 31%). Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex, we delineated the epitope as spanning four segments of amino acids (Phe42-Ala47, Gly172-Asp173, Glu255-Val275, and Val337-Tyr351) on the L1 surface loops. Further interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and L1. Substituting Ser341 with alanine, which is the residue type present in HPV11 L1, almost completely abolished binding activity to 13H5. By swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1 (Ser341, Thr338, and Thr339), we engineered chimeric HPV11-6HI VLPs. Remarkably, the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human primates. This approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

Visual analysis of social events and stock market volatility in China and the USA during the pandemic.

The COVID-19 pandemic is one of the most severe infectious diseases in recent decades, and has had a significant impact on the global economy, and the stock market. Most existing studies on stock market volatility during the pandemic have been conducted from a data science perspective, with statistical analysis and mathematical models often revealing the superficial relationship between Covid and the stock market at the data level. In contrast, few studies have explored the relationship between more specialised aspects of the pandemic. Specifically, the relationship found between major social events and the stock market. In this work, a multi-source, data-based relationship analysis method is proposed, that collects historical data on significant social events and related stock data in China and the USA, to further explore the potential correlation between stock market index fluctuations and the impact of social events by analysing cross-timeline data. The results suggest and offer more evidence that social events do indeed impact equity markets, and that the indices in both China and the USA were also affected more by the epidemic in 2020 than in 2021, and these indices became less affected by the epidemic as it became the world adapted. Moreover, these relationships may also be influenced by a variety of other factors not covered in this study. This research, so far, is in its initial stage, and the methodology is not rigorous and cannot be applied as an individual tool for decision; however, it could potentially serve as a supplementary tool and provide a multi-dimensional basis for stock investors and policymakers to make decisions.

Intestinal microbiome-targeted therapies improve liver function in alcohol-related liver disease by restoring bifidobacteria: a systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy of intestinal microbiome-targeted therapies (MTTs) in alcohol-related liver disease (ALD). Methods: With pre-specified keywords and strategies, we searched databases including Cochrane Library, PubMed, EMBASE, CNKI, Wanfang Data, and Weipu for RCTs on intestinal MTTs in ALD patients from January 2000 to May 2021. Two researchers independently conducted literature screening, data extraction, and quality evaluation according to the eligible criteria. Outcomes of interest included the effects of intestinal MTTs on ALT, AST, GGT, TBIL, TNF-α, IL-6, intestinal Escherichia coli, and Bifidobacteria when compared to the control group. Pooled data were compiled and analyzed with Revman 5.4 software. Results: Among 5 RCTs included with 456 ALD patients who received probiotics, the therapeutic pooled effects in the experimental group were the followings: ALT (MD = -7.16.95% CI: 10.71∼-3.60; p < 0.0001)、AST (MD = -25.11.95% CI: 30.57∼-19.47; p < 0.00001)、GGT (MD = -6.72.95% CI: 11.91∼-1.53; p = 0.01)、IL-6(SMD = -0.82.95% CI: 1.10∼-0.54; p < 0.00001), which were significantly better than those in the placebo or standard treatment group respectively, while the difference of TBIL (SMD = -0.06, 95%CI: 0.29-0.16; p = 0.59), TNF-α(SMD = -0.53.95% CI: 1.57-0.50; p = 0.31)in the two groups was not significant. After intestinal MTT treatment, the number of intestinal Bifidobacteria increased significantly (MD = 0.79.95% CI: 0.00-1.58; p = 0.05)in the experimental group. However, there were no significant changes in the number of E. coli in both groups (SMD = -0.29.95% CI: 0.92-0.34; p = 0.36). Conclusion: Intestinal MTTs can significantly improve liver function, associated with the increase of intestinal Bifidobacteria, which may be beneficial to ALD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246067, Identifier CRD42021246067.

Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis: A Randomized Double-Blind Controlled Trial.

OBJECTIVE: To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis. METHODS: This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed. RESULTS: Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment. CONCLUSION: BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).

Role of RUNX3 in Restriction Point Regulation.

A cell cycle is a series of events that takes place in a cell as it grows and divides. At the G1 phase of cell cycle, cells monitor their cumulative exposure to specific signals and make the critical decision to pass through the restriction (R)-point. The R-point decision-making machinery is fundamental to normal differentiation, apoptosis, and G1-S transition. Deregulation of this machinery is markedly associated with tumorigenesis. Therefore, identification of the molecular mechanisms that govern the R-point decision is one of the fundamental issues in tumor biology. RUNX3 is one of the genes frequently inactivated in tumors by epigenetic alterations. In particular, RUNX3 is downregulated in most K-RAS-activated human and mouse lung adenocarcinomas (ADCs). Targeted inactivation of Runx3 in the mouse lung induces adenomas (ADs), and markedly shortens the latency of ADC formation induced by oncogenic K-Ras. RUNX3 participates in the transient formation of R-point-associated activator (RPA-RX3-AC) complexes, which measure the duration of RAS signals and thereby protect cells against oncogenic RAS. This review focuses on the molecular mechanism by which the R-point participates in oncogenic surveillance.

Factors influencing axial elongation in myopic children using overnight orthokeratology.

Several factors influence axial length in children with myopia treated using overnight orthokeratology. To identify these factors, this retrospective study collected axial length and corneal aberration data on 78 eyes before and 1-year after orthokeratology. Patients were divided according to axial elongation (cut-off, 0.25 mm/year). Baseline characteristics included age, sex, spherical equivalent refraction, pupil diameter, axial length, and orthokeratology lens type. Corneal shape effects were compared through tangential difference maps. Group differences in higher-order aberrations of a 4 mm zone were compared at baseline and 1-year following therapy. Binary logistic regression analysis was conducted to identify the variables determined for axial elongation. Significant differences between both groups included the initial age of wearing orthokeratology lenses, type of orthokeratology lens, size of central flattening area, corneal total surface C12 (1-year), corneal total surface C8 (1-year), corneal total surface spherical aberration (SA) (1-year root mean square [RMS] values), change in total corneal surface C12, and change in front and total corneal surface SA (RMS values). The age when wearing an orthokeratology lens was the most important factor influencing axial length in children with orthokeratology-treated myopia, followed by lens type and change in the C12 of the total corneal surface.