The adhesin RadD enhances Fusobacterium nucleatum tumour colonization and colorectal carcinogenesis.

Fusobacterium nucleatum can bind to host cells and potentiate intestinal tumorigenesis. Here we used a genome-wide screen to identify an adhesin, RadD, which facilitates the attachment of F. nucleatum to colorectal cancer (CRC) cells in vitro. RadD directly binds to CD147, a receptor overexpressed on CRC cell surfaces, which initiated a PI3K-AKT-NF-κB-MMP9 cascade, subsequently enhancing tumorigenesis in mice. Clinical specimen analysis showed that elevated radD gene levels in CRC tissues correlated positively with activated oncogenic signalling and poor patient outcomes. Finally, blockade of the interaction between RadD and CD147 in mice effectively impaired F. nucleatum attachment and attenuated F. nucleatum-induced oncogenic response. Together, our study provides insights into an oncogenic mechanism driven by F. nucleatum RadD and suggests that the RadD-CD147 interaction could be a potential therapeutic target for CRC.

Testosterone Mediates Reproductive Toxicity in Caenorhabditis elegans by Affecting Sex Determination in Germ Cells through nhr-69/mpk-1/fog-1/3.

Testosterone (T), an environmental androgen, significantly disrupts endocrine systems in wildlife and ecosystems. Despite growing concern over its high levels in aquatic environments, the reproductive toxicity of testosterone and its mechanisms are not well understood. In this study, we investigated the reproductive toxicity and mechanisms of testosterone using Caenorhabditis elegans (C. elegans) and assessed its ecological toxicity through the benchmark dose (BMD) method. Our results indicate that T concentrations exceeding 0.01 µg/L significantly reduce the brood size, decrease germ cell counts, and prolong the generation time in C. elegans as T concentrations increase. Furthermore, to elucidate the specific mechanisms, we analyzed the expression of nhr-69, mpk-1, and other genes involved in sex determination. These findings suggest that the nhr-69-mediated reproductive toxicity of T primarily affects sperm formation and the offspring number by influencing its downstream targets, mpk-1 and fog-1/3, which are critical in the germ cell sex-determining pathway. Additionally, this study determined that the 10% lower boundary of the baseline dose (BMDL10) is 1.160 ng/L, offering a more protective reference dose for the ecological risk assessment of T. The present study suggests that nhr-69 mediates the reproductive toxicity of T by influencing mpk-1 and fog-1/3, critical genes at the end of the germ cell sex-determining pathway, thereby providing a basis for establishing reproductive toxicity thresholds for T.

Associations of Urinary Heavy Metal Mixtures with High Remnant Cholesterol among US Adults: Evidence from the National Health and Nutrition Examination Survey (1998-2018).

The main objective of our study is to explore the associations between combined exposure to urinary heavy metals and high remnant cholesterol (HRC), a known cardiovascular risk factor. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we conducted a cross-sectional analysis of 5690 participants, assessing urinary concentrations of ten heavy metals. Ten heavy metals in urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Fasting residual cholesterol ≥0.8 mmol/L was defined as HRC (using blood samples). Statistical analyses included weighted multivariable logistic regression, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the associations of heavy metal exposure with HRC. Stratified analyses based on individual characteristics were also conducted. Multivariable logistic regression found that the four metals (OR Q4 vs. Q1: 1.33, 95% CI: 1.01-1.75 for barium (Ba); OR Q4 vs. Q1: 1.50, 95% CI: 1.16-1.94 for cadmium (Cd); OR Q4 vs. Q1: 1.52, 95% CI: 1.15-2.01 for mercury (Hg); OR Q4 vs. Q1: 1.35, 95% CI: 1.06-1.73 for lead (Pb)) were positively correlated with the elevated risk of HRC after adjusting for covariates. In addition, all three mixed models, including WQS (OR: 1.25; 95% CI: 1.07-1.46), qgcomp (OR: 1.17; 95% CI: 1.03-1.34), and BKMR, consistently showed a significant positive correlation between co-exposure to heavy metal mixtures and HRC, with Ba and Cd being the main contributors within the mixture. These associations were more pronounced in younger adults (20 to 59 years), males, and those with a higher body mass index status (≥25 kg/m2). Our findings reveal a significant relationship between exposure to the mixture of heavy metals and HRC among US adults, with Ba and Cd being the major contributors to the mixture's overall effect. Public health efforts aimed at reducing heavy metal exposure can help prevent HRC and, in turn, cardiovascular disease.

Plasmonic Near-Infrared-Response S-Scheme ZnO/CuInS2 Photocatalyst for H2O2 Production Coupled with Glycerin Oxidation.

Solar fuel synthesis is intriguing because solar energy is abundant and this method compensates for its intermittency. However, most photocatalysts can only absorb UV-to-visible light, while near-infrared (NIR) light remains unexploited. Surprisingly, the charge transfer between ZnO and CuInS2 quantum dots (QDs) can transform a NIR-inactive ZnO into a NIR-active composite. This strong response is attributed to the increased concentration of free charge carriers in the p-type semiconductor at the interface after the charge migration between ZnO and CuInS2, enhancing the localized surface plasmon resonance (LSPR) effect and the NIR response of CuInS2. As a paradigm, this ZnO/CuInS2 heterojunction is used for H2O2 production coupled with glycerin oxidation and demonstrates supreme performance, corroborating the importance of NIR response and efficient charge transfer. Mechanistic studies through contact potential difference (CPD), Hall effect test, and finite element method (FEM) calculation allow for the direct correlation between the NIR response and charge transfer. This approach bypasses the general light response issues, thereby stepping forward to the ambitious goal of harnessing the entire solar spectrum.

Three-dimensional Ni foam supported Pt/NiFe LDH catalyst with enhanced oxygen activation for room-temperature formaldehyde oxidation.

Room-temperature catalytic oxidation of formaldehyde (HCHO) has been extensively investigated due to its high efficiency, convenience, and environmental friendliness. Herein, nickel-iron layered double hydroxide (NiFe LDH) nanosheets were synthesized in-situ on a nickel foil (NF) using a facile one-step hydrothermal method, followed by the deposition of ultra-low content (0.069 wt%) of Pt nanoparticles through NaBH4 reduction. The resulting three-dimensional (3D) hierarchical Pt/NiFe-NF catalyst exhibited exceptional activity for the complete decomposition of formaldehyde to carbon dioxide (CO2) at room temperature (∼95 % conversion within 1 h), as well as remarkable cycling stability. The 3D porous structure of Pt/NiFe-NF provides fast transport channels for the diffusion of gas molecules, making the active catalyst surfaces more accessible. Moreover, abundant hydroxyl groups in NiFe LDH serve as adsorption centers for HCHO molecules to form dioxymethylene (DOM) and formate intermediates. Furthermore, electronic interactions between NiFe LDH and Pt enhance the adsorption and activation of O2 on Pt surfaces, leading to the complete decomposition of intermediates into non-toxic products. This work presents new insights into the design and preparation of Pt-based 3D hierarchical catalysts with surface-rich hydroxyl groups for the efficient removal of indoor HCHO.

Molecularly Tunable Heterostructured Co-Polymers Containing Electron-Deficient and -Rich Moieties for Visible-Light and Sacrificial-Agent-Free H2O2 Photosynthesis.

As an alternative to hydrogen peroxide (H2O2) production by complex anthraquinone oxidation process, photosynthesis of H2O2 from water and oxygen without sacrificial agents is highly demanded. Herein, a covalently connected molecular heterostructure is synthesized via sequential C-H arylation and Knoevenagel polymerization reactions for visible-light and sacrificial-agent-free H2O2 synthesis. The subsequent copolymerization of the electron-deficient benzodithiophene-4,8-dione (BTD) and the electron-rich biphenyl (B) and p-phenylenediacetonitrile (CN) not only expands the π-conjugated domain but also increases the molecular dipole moment, which largely promotes the separation and transfer of the photoinduced charge carriers. The optimal heterostructured BTDB-CN0.2 manifested an impressive photocatalytic H2O2 production rate of 1920 µmol g-1 h-1, which is 2.2 and 11.6 times that of BTDB and BTDCN. As revealed by the femtosecond transient absorption (fs-TA) and theoretical calculations, the linkage serves as a channel for the rapid transfer of photogenerated charge carriers, enhancing the photocatalytic efficiency. Further, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) uncovers that the oxygen reduction reaction occurs through the step one-electron pathway and the mutual conversion between C=O and C-OH with the anchoring of H+ during the catalysis favored the formation of H2O2. This work provides a novel perspective for the design of efficient organic photocatalysts.

Enhancing photocatalytic H2O2 production with Au co-catalysts through electronic structure modification.

Gold-based co-catalysts are a promising class of materials with potential applications in photocatalytic H2O2 production. However, current approaches with Au co-catalysts show limited H2O2 production due to intrinsically weak O2 adsorption at the Au site. We report an approach to strengthen O2 adsorption at Au sites, and to improve H2O2 production, through the formation of electron-deficient Auδ+ sites by modifying the electronic structure. In this case, we report the synthesis of TiO2/MoSx-Au, following selective deposition of Au onto a MoSx surface which is then further anchored onto TiO2. We further show that the catalyst achieves a significantly increased H2O2 production rate of 30.44 mmol g-1 h-1 in O2-saturated solution containing ethanol. Density functional theory calculations and X-ray photoelectron spectroscopy analysis reveal that the MoSx mediator induces the formation of electron-deficient Auδ+ sites thereby decreasing the antibonding-orbital occupancy of Au-Oads and subsequently enhancing O2 adsorption. This strategy may be useful for rationally designing the electronic structure of catalyst surfaces to facilitate artificial photosynthesis.

Associations of Combined Exposure to Metabolic and Inflammatory Indicators with Thyroid Nodules in Adults: A Nested Case-Control Study.

Objective: To explore associations of combined exposure to metabolic/inflammatory indicators with thyroid nodules. Methods: We reviewed personal data for health screenings from 2020 to 2021. A propensity score matching method was used to match 931 adults recently diagnosed with thyroid nodules in a 1 : 4 ratio based on age and gender. Conditional logistic regression and Bayesian kernel machine regression (BKMR) were used to explore the associations of single metabolic/inflammatory indicators and the mixture with thyroid nodules, respectively. Results: In the adjusted models, five indicators (ORQ4 vs. Q1: 1.30, 95% CI: 1.07-1.58 for fasting blood glucose; ORQ4 vs. Q1: 1.30, 95% CI: 1.08-1.57 for systolic blood pressure; ORQ4 vs. Q1: 1.26, 95% CI: 1.04-1.53 for diastolic blood pressure; ORQ4 vs. Q1: 1.23, 95% CI: 1.02-1.48 for white blood cell; ORQ4 vs. Q1: 1.28, 95% CI: 1.07-1.55 for neutrophil) were positively associated with the risk of thyroid nodules, while high-density lipoproteins (ORQ3 vs. Q1: 0.75, 95% CI: 0.61-0.91) were negatively associated with the risk of thyroid nodules. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the metabolic and inflammatory mixture exhibited a significant positive association with thyroid nodules in a dose-response pattern, with systolic blood pressure being the greatest contributor within the mixture (conditional posterior inclusion probability of 0.82). No interaction effects were found among the five indicators. These associations were more prominent in males, participants with higher age (≥40 years old), and individuals with abnormal body mass index status. Conclusions: Levels of the metabolic and inflammatory mixture have a linear dose-response relationship with the risk of developing thyroid nodules, with systolic blood pressure levels being the most important contributor.

Mixed-state ptychography for quantitative optical properties measurement of vector beam.

Recent advances in ptychography have extended to anisotropic specimens, but vectorial reconstruction of probes owing to polarization aliasing remains a challenge. A polarization-sensitive ptychography that enables full optical property measurement of vector light is proposed. An optimized reconstruction strategy, first calibrating the propagation direction and then performing faithful retrieval, is established. This method avoids multiple image acquisitions with various polarizer configurations and significantly improves the measurement accuracy by correlating the intensity and position of different polarization components. The capability of the proposed method to quantify anisotropic parameters of optical materials and polarization properties of vector probe is demonstrated by experiment.

Fusobacterium nucleatum induces chemoresistance in colorectal cancer by inhibiting pyroptosis via the Hippo pathway.

Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific environmental risk factor. In this study, enrichment of F. nucleatum was elucidated to be significantly associated with CRC recurrence after chemotherapy. Functional experiments showed that F. nucleatum could inhibit pyroptosis induced by chemotherapy drugs, thereby inducing chemoresistance. Furthermore, mechanistic investigation demonstrated that F. nucleatum could regulate the Hippo pathway and promote the expression of BCL2, thereby inhibiting the Caspase-3/GSDME pyroptosis-related pathway induced by chemotherapy drugs and mediating CRC cell chemoresistance. Taken together, these results validated the significant roles of F. nucleatum in CRC chemoresistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of CRC.

D-A Conjugated Polymer/CdS S-Scheme Heterojunction with Enhanced Interfacial Charge Transfer for Efficient Photocatalytic Hydrogen Generation.

Owing to the improved charge separation and maximized redox capability of the system, Step-scheme (S-scheme) heterojunctions have garnered significant research attention for efficient photocatalysis of H2 evolution. In this work, an innovative linear donor-acceptor (D-A) conjugated polymer fluorene-alt-(benzo-thiophene-dione) (PFBTD) is coupled with the CdS nanosheets, forming the organic-inorganic S-scheme heterojunction. The CdS/PFBTD (CP) composite exhibits an impressed hydrogen production rate of 7.62 mmol g-1 h-1 without any co-catalysts, which is ≈14 times higher than pristine CdS. It is revealed that the outstanding photocatalytic performance is attributed to the formation of rapid electron transfer channels through the interfacial Cd─O bonding as evidenced by the density functional theory (DFT) calculations and in situ X-ray photoelectron spectroscopy (XPS) analysis. The charge transfer mechanism involved in S-scheme heterojunctions is further investigated through the photo-irradiated Kelvin probe force microscopy (KPFM) analysis. This work provides a new point of view on the mechanism of interfacial charge transfer and points out the direction of designing superior organic-inorganic S-scheme heterojunction photocatalysts.

Age differences in the association of body mass index-defined obesity with abdominal aortic calcification.

Objectives: In cardiovascular disease, previous studies have suggested young age as one of the reasons to explain the obesity paradox. This study attempts to provide a different opinion on this claim through unexpected findings. Methods: We used a cross-sectional analysis of the US nationally representative data, total of 10,175 participants were recruited in 2013-2014 from NHANES. A total of 947 participants were selected to be included in this study through inclusion criteria and exclusion criteria for statistical analysis of the relationship between obesity and abdominal aortic calcification(AAC). Smooth curve fitting and multivariate regression analyses were conducted to examine the associations of obesity with AAC after adjusting for age, gender and associated variates. Results: Depending on the age of the population, the relationship between obesity and AAC showed the different outcome. Obesity was associated with the lower risk of AAC among individuals older than 52 years of age. According to the difference of adjusted covariates, the AAC scores in the obesity group decreased by 0.92, 0.87, and 1.11 for 52 years old or older individuals. In particular, the risk of AAC was lower for patients with obesity with the following characteristics: male, low LDL, low triglyceride, DM, non-cancer patient, smoking, drinking, vigorous work activity, low annual household income, education of 9 - 11th grades and non-Hispanic white. Conclusions: In US, adults aged 52 years or older, obesity was associated with decreased AAC risk. Older age may be one potential reason for the obesity paradox.

COF/In2S3 S-Scheme Photocatalyst with Enhanced Light Absorption and H2O2-Production Activity and fs-TA Investigation.

Photocatalytic hydrogen peroxide (H2O2) synthesis from water and O2 is an economical, eco-friendly, and sustainable route for H2O2 production. However, single-component photocatalysts are subjected to limited light-harvesting range, fast carrier recombination, and weak redox power. To promote photogenerated carrier separation and enhance redox abilities, an organic/inorganic S-scheme photocatalyst is fabricated by in situ growing In2S3 nanosheets on a covalent organic framwork (COF) substrate for efficient H2O2 production in pure water. Interestingly, compared to unitary COF and In2S3, the COF/In2S3 S-scheme photocatalysts exhibit significantly larger light-harvesting range and stronger visible-light absorption. Partial density of state calculation, X-ray photoelectron spectroscopy, and femtosecond transient absorption spectroscopy reveal that the coordination between In2S3 and COF induces the formation of mid-gap hybrid energy levels, leading to smaller energy gaps and broadened absorption. Combining electron spin resonance spectroscopy, radical-trapping experiments, and isotope labeling experiments, three pathways for H2O2 formation are identified. Benefited from expanded light-absorption range, enhanced carrier separation, strong redox power, and multichannel H2O2 formation, the optimal composite shows an impressive H2O2-production rate of 5713.2 µmol g-1 h-1 in pure water. This work exemplifies an effective strategy to ameliorate COF-based photocatalysts by building S-scheme heterojunctions and provides molecular-level insights into their impact on energy level modulation.

The effects of pks+ Escherichia coli and bile acid in colorectal tumorigenesis among people with cholelithiasis or cholecystectomy.

BACKGROUND AND AIM: Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances of getting colorectal adenoma (CRA) or cancer (CRC). We aimed to figure out the effects of gut microbiota and bile acid on colorectal neoplasm in CL and CE patients. METHODS: This was a retrospective observational study that recruited 514 volunteers, including 199 people with normal gallbladders (normal), 152 CL, and 163 CE patients. Discovery cohort was established to explore the difference in gut microbiota through 16S rRNA and metagenomics sequencing. Validation cohort aimed to verify the results through quantitative polymerase chain reaction (qPCR). RESULTS: Significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in the discovery cohort (16S rRNA sequencing, PNormal-CL = 0.013, PNormal-CE = 0.042; metagenomics sequencing, PNormal-CE = 0.026) and validation cohort (PNormal-CL < 0.0001, PNormal-CE < 0.0001). Pks+ E. coli was found enriched in CL and CE patients through qPCR (in discovery cohort: PNormal-CE = 0.018; in validation cohort: PNormal-CL < 0.0001, PNormal-CE < 0.0001). The differences in bile acid metabolism were found both through Tax4Fun analysis of 16S rRNA sequencing (Ko00120, primary bile acid biosynthesis, PNormal-CE = 0.014; Ko00121, secondary bile acid biosynthesis, PNormal-CE = 0.010) and through metagenomics sequencing (map 00121, PNormal-CE = 0.026). The elevation of serum total bile acid of CE patients was also found in validation cohort (PNormal-CE < 0.0001). The level of serum total bile acid was associated with the relative abundance of pks+ E. coli (r = 0.1895, P = 0.0012). CONCLUSIONS: E. coli, especially pks+ species, was enriched in CL and CE patients. Pks+ E. coli and bile acid metabolism were found associated with CRA and CRC in people after cholecystectomy.

Liproxstatin-1 alleviates cartilage degradation by inhibiting chondrocyte ferroptosis in the temporomandibular joint.

BGROUND INFORMATION: Ferroptosis contributes to temporomandibular joint osteoarthritis (TMJOA) lesion development and is still poorly understood. RESULTS: In this study, we used different TMJOA animal models to examine whether ferroptosis was related to disease onset in TMJOA induced by monosodium iodoacetate (MIA), IL-1ß, occlusion disorder (OD), and unilateral anterior crossbite (UAC). Immunohistochemical staining and Western blot analysis were used to detect ferroptosis- and cartilage degradation-related protein expression. Our results revealed reduced levels of the ferroptosis-related protein GPX4 in the cartilage layer, but the levels of ACSL4 and P53 were increased in the condyle. Injection of the ferroptosis inhibitor liproxstatin-1 (Lip-1) effectively decreased ACSL4, P53 and TRF expression. In vitro, IL-1ß reduced cartilage extracellular matrix expression in mandibular condylar chondrocytes (MCCs). Lip-1 maintained the morphology and function of mitochondria and ameliorated the exacerbation of lipid peroxidation and reactive oxygen species (ROS) production induced by IL-1ß. CONCLUSION: These results suggest that chondrocyte ferroptosis plays an important role in the development and progression of TMJOA. SIGNIFICANCE: Inhibiting condylar chondrocyte ferroptosis could be a promising therapeutic strategy for TMJOA.

Effect of a Nursing Health Education Model Based on the Rosenthal Effect on Posttraumatic Growth of Patients with a First Accidental Fracture.

Objective: To investigate the effect of a nursing health education model based on the Rosenthal effect on the posttraumatic growth of patients with a first accidental fracture. Methods: We recruited 212 patients with a first accidental fracture from February 2021 to February 2022; the patients were divided into a control group (n = 106) and an Rosenthal Group (n = 106). The control group received daily care during hospitalization, and the Rosenthal Group received treatment based on a Rosenthal effect health education model. We compared the 2 groups before and after treatment using the Chinese Posttraumatic Growth Inventory (C-PTGI), the Connor-Davidson Resilience Scale (CD-RISC), the Pittsburgh Sleep Quality Index (PSQI), a Visual Analog Scale (VAS) to assess pain, the 36-item Short Form Health Survey (SF-36) to assess quality of life, the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD). Results: The psychological resilience of both groups of patients improved after treatment, as assessed by C-PTGI and CD-RISC (all P < .05), and the Rosenthal Group improved more than the control group after treatment (all P < .05). The sleep quality and pain scores, as measured by PSQI and VAS, improved for both groups of patients after treatment, and the Rosenthal group improved more than the control group after treatment (all P < .05). The quality of life, as assessed by SF-36, of both groups of patients was similar before treatment (all P > .05) and improved significantly after treatment (all P < .05). The patients' depression and anxiety, as assessed by HAMA and HAMD, improved in both groups after treatment (all P < .05), and the Rosenthal group improved more than the control group after treatment (all P < .05). Conclusion: The Rosenthal effect nursing health education model promotes the posttraumatic psychological growth of patients with a first accidental fracture and enhances their psychological resilience, showing that the Rosenthal effect has important health benefits and can be promoted for clinical application to adjust a patient's psychological state.

Short-term effects of heatwaves on clinical and subclinical cardiovascular indicators in Chinese adults: A distributed lag analysis.

AIMS: Previous studies have related heat waves to morbidity and mortality of cardiovascular diseases; however, potential mechanisms remained limited. Our aims were to investigate the short-term effects of heat waves on a series of clinical/subclinical indicators associated with cardiovascular health. METHODS: Our study used 80,574 health examination records from the Health Management Center of Nanjing Zhongda Hospital during the warm seasons of 2019-2021, including 62,128 participants. A total of 11 recognized indicators of cardiovascular risk or injury were assessed. Air pollution and meteorological data were obtained from the Nanjing Ecological Environment Bureau and the China Meteorological Data Network, respectively. Heat waves were defined as a daily average temperature over the 95th percentile for three or more consecutive days from May to September. We used a combination of linear mixed effects models and distributed lag nonlinear models to assess the lagged effects of heat waves on clinical and subclinical cardiovascular indicators. Stratified analyses based on individuals' characteristics, including gender, age, body mass index (BMI), diabetes, and hypertension, were also performed. RESULTS: Heat waves were related to significant changes in most indicators, with the magnitude of effects generally peaking at a lag of 0 to 3 days. Moreover, the cumulative percentage changes over lag 0-7 days were -0.82 % to -2.55 % in blood pressure, 1.32 % in heart rate, 0.20 % to 2.66 % in systemic inflammation markers, 0.36 % in a blood viscosity parameter, 9.36 % in homocysteine, and 1.35 % to 3.25 % in injuring myocardial enzymes. Interestingly, females and males showed distinct susceptibilities in different indicators. Stronger effects were also found in participants aged 50 years or over, individuals with abnormal BMI status, and patients with diabetes. CONCLUSION: Short-term exposure to heat waves could significantly alter clinical/subclinical cardiovascular indicator profiles, including blood pressure changes, increased heart rate, acute systemic inflammation, elevated blood viscosity, and myocardial injury.

Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions.

OBJECTIVE: To study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection. METHODS: To investigate the outcome of high-risk (HR)-HPV infection in the female genital tract and analyze the associated risk factors affecting their outcome, a total of 196 women with positive HR-HPV test results and non-CIN or cervical cancer cervical pathology results were selected for follow-up at the Cervical Disease Clinic of the Obstetrics and Gynecology Hospital, Zhejiang University School of Medicine from January 2017 to March 2020. The follow-up interval was every 6 months, and both cervical cytology (TCT) and HR-HPV testing were performed at each follow-up visit. If the cervical cytology results were normal upon recheck and the HR-HPV test was negative, the woman was considered to be cleared of the HPV infection and was entered into the routine cervical screening population. When the repeat HR-HPV test remained positive after 6 months, the woman was defined as having a persistent HR-HPV infection. If HR-HPV persisted but the TCT results were normal, follow-up was continued. If HR-HPV persisted and the TCT results were abnormal, a colposcopy-guided biopsy was performed immediately. In this situation, if the histological results were still non-CIN or cervical cancer, the follow-up was continued. If the histological results confirmed the development of CIN or invasive cancer, then enter another study follow-up to further track its development and outcome, and the woman commenced the treatment process. The HPV infection clearance time was analyzed by the Kaplan-Meier method, and the comparison of the HPV clearance rate and infection clearance time between each of the different groups was performed using aχ2 test or Fisher's exact test, as appropriate. After the univariate analysis, several significant factors were included in the Cox model and independent risk factors were analyzed. RESULTS: A total of 163 women were enrolled in this study. The median age was 40.0 years (22-67 years) and the median follow-up time was 11.5 months (6-31 months). The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery (P < 0.05). CONCLUSIONS: In women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. Age and the initial viral load were independent associated factors affecting the spontaneous clearance of HR-HPV infection in the female genital tract. These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection. Thus, intensive screening should be recommended.

Dietary lysozyme improves growth performance and intestinal barrier function of weaned piglets.

Lysozyme (LZ) is a purely natural, nonpolluting and nonspecific immune factor, which has beneficial effects on the healthy development of animals. In this study, the influences of LZ on the growth performance and intestinal barrier of weaned piglets were studied. A total of 48 weaned piglets (Landrace × Yorkshire, 22 d old) were randomly divided into a control group (basal diet) and a LZ group (0.1% LZ diet) for 19 d. The results showed that LZ could significantly improve the average daily gain (ADG, P < 0.05) and average daily feed intake (ADFI, P < 0.05). LZ also improved the intestinal morphology and significantly increased the expression of occludin in the jejunum (P < 0.05). In addition, LZ down-regulated the expression of interleukin-1ß (IL-1ß, P < 0.05) and tumor necrosis factor-α (TNF-α, P < 0.05), and inhibited the expression of the genes in the nuclear factor-k-gene binding (NF-κB, P < 0.05) signaling pathway. More importantly, the analysis of intestinal flora showed LZ increased the abundance of Firmicutes (P < 0.05) and the ratio of Firmicutes to Bacteroidota (P = 0.09) at the phylum level, and increased the abundance of Clostridium_sensu_stricto_1 (P < 0.05) and reduced the abundance of Olsenella and Prevotella (P < 0.05) at the genus level. In short, this study proved that LZ could effectively improve the growth performance, relieve inflammation and improve the intestinal barrier function of weaned piglets. These findings provided an important theoretical basis for the application of LZ in pig production.

Garlic essential oil supplementation modulates colonic microbiota compositions and regulates immune response in weaned piglets.

The objective of this study was to investigate the colonic microbiome compositions and immune response and reveal their correlations in weaned piglets fed with garlic essential oil (GEO). Twelve 21-day-old crossbred piglets with the same parity and similar weight (BW = 7.07 ± 0.37 Kg) were randomly divided into control and experimental groups based on BW and sex, which fed either a basal diet (CON group), or a basal diet supplemented with 1.5 g/kg GEO (GEO group). UHPLC-QE-MS showed the main component of GEO were belonged to carbohydrates, organic acid, flavonoids, phenylpropanoids and terpenoids. GEO decreased serum IL-1ß, IL-8 content and the down-regulated mRNA expression of IFN-γ, TLR2 in jejunal mucosa but increased serum IgG, IL-4 content and up-regulated the mRNA expression of IL-4, IL-1ß, TNF-α in ileal mucosa. What's more, the metagenomic analysis demonstrated that GEO increased the abundance of Bacteroidetes, Euryarchaeota and Spirochaetes, while decreased the abundance of Firmicutes and Actinobacteria at Phylum level and Selenomonas_boris, Selenomonadaceae_bacterium_DSM_108025, Clostridiales_bacterium and Phascolarctobacterium_succinatutens at species level. Notably, the main function pathway of virulence factor (VFDB) enriched in GEO group were Fibronection-binding protein, Zn++ metallophrotease and Capsular polysaccharide, while the main function pathway of VFDB enriched in CON group were heme biosynthesis, Lap and FeoAB. Spearman correlation analysis indicated the Spirochaetes had a positive association with IL-6 and IL-4. Acinobacteria was positively correlated with IL-1ß, while negative with the IL-6; In addition, Euryarchaeota had a positive correlation with IL-4, but a negative correlation with IL-1ß; Tenericutes was negative with IL-8; Phascolarcolarctobacterium_succinatutens and was negative with IL-6; Ruminococcaceae_bacterium was negative with TNF-α. While Selenomonadaceae_bacterium_DSM_108025 had a positive correlation with IL-8. In conclusion, our results uncovered that immune regulation effects of GEO may be associated with the microbiome compositions in response to GEO.