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Juan-Min Zha,1,* Mei Zhang,1,* Tao Wang,2,* Hua-Shan Li,1,2,* Quan-Yao Ban,1,* Mei Liu,1 Xue-Xue Jiang,1 Shi-Ying Guo,2 Jing Wang,2 Ya-Ru Zhou,2 Yu-Hong Liu,2 Wei-Qi He,1,2 Hong Xu1 1Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China; 2Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei-Qi He; Hong Xu, Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-6588-3545, Email whe@suda.edu.cn; hongxusuda@outlook.comObjective: This cross-sectional study aimed to explore the association of overweight and inflammatory indicators with breast cancer risk in Chinese patients.Methods: Weight, height, and peripheral blood inflammatory indicators, including white blood cell count (WBC), neutrophil count (NE), lymphocyte count (LY), platelet count (PLT) and the concentration of hypersensitivity C-reactive protein (hsCRP), were collected in 383 patients with benign breast lumps (non-cancer) and 358 patients with malignant breast tumors (cancer) at the First Affiliated Hospital of Soochow University, China, from March 2018 to July 2020. Body mass index (BMI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were determined according to the ratio equation. The correlations among overweight, inflammatory indicators, and the proportion of non-cancer or cancer cases were analyzed.Results: BMI is associated with an increased breast cancer risk. Compared with non-cancer patients, the average WBC count, NE count, NLR, and level of hsCRP were significantly higher in cancer patients. The level of hsCRP was closely associated with the size of malignant breast tumors.Conclusion: We conclude that overweight and high levels of hsCRP may serve as putative risk factors for malignant breast tumors in Chinese women.Keywords: breast cancer, body mass index, overweight, chronic inflammation, inflammatory indicator

Objective: Adverse birth outcomes and the maternal severity of influenza in pregnancy are well documented but information on pertussis is limited., Design: Population-based linkage data were collected during 2001-2016., Setting: New South Wales, Australia., Population or Sample: A total of 1 453 037 singleton births., Methods: Cox regression was used to estimate the associations between pertussis or influenza during pregnancy and birth outcomes with adjustment of covariates., Main Outcome Measures: Adverse birth outcomes (preterm birth and low birth weight)., Results: Among 1 453 037 singleton births over 16 years, we identified pertussis in 925 (49; 5.3% hospitalised) and influenza in 2850 (1092; 38.3% hospitalised) women during pregnancy. Cases of pertussis were similarly distributed by trimester (32% 3rd) whereas 46% of influenza cases were in the 3rd trimester. Younger age, previous birth, and being overseas-born were associated with both pertussis and influenza, whereas identifying as Aboriginal or Torres Strait Islander, hypertension or diabetes before and during pregnancy, and a number of other factors were only associated with influenza. Both pertussis and influenza in pregnancy were associated with increased risk of preterm birth (pertussis: aHR = 1.30, 95% CI 1.01-1.68; influenza: aHR = 1.56, 95% CI 1.36-1.79) and these increased risks were greater when infections in the period within 2 weeks of birth were considered (pertussis: aHR = 2.36, 95% CI 1.26-4.41; influenza: aHR = 2.29, 95% CI 1.78-2.96)., Conclusions: Maternal pertussis and influenza infections close to the time of birth were associated with adverse birth outcomes. These findings highlight the benefits of vaccination during pregnancy., (© 2024 John Wiley & Sons Ltd.)

Objectives: We aimed to estimate the prevalence of multiple developmental disabilities, identify associated characteristics, and examine trends among American children from 2016 to 2022., Study Design: This was a cross-sectional study., Methods: Using the National Survey of Children's Health data from 2016 to 2022, we estimated the prevalence of multiple developmental disabilities among children aged 3-17 years. Multiple developmental disabilities were defined as two or more concurrent disabilities from 12 common disabilities. Trends were investigated using log-linear regression. Multivariate log-binominal regression was used to compare the prevalence prior to the COVID-19 pandemic (2016-2019) with prevalence during the COVID-19 pandemic (2020-2022)., Results: From 239,534 eligible children (mean age = 10.1 years; male = 51.7%), we found the overall prevalence of multiple developmental disabilities was 10.6%. The most predominant phenotype was attention-deficit/hyperactivity disorder concurrent with behavioural problems (2.1%). Higher prevalence was found among boys, non-Hispanic black children, those from low-household-income families and from families with lower education levels. Prevalence of multiple developmental disabilities increased from 9.8% in 2016 to 11.5% in 2022 (P = 0.014) with significantly higher prevalence during COVID-19 pandemic than before (11.2% vs 10.1%). These increases were found consistently across most sociodemographic groups., Conclusions: Children from certain socio-disadvantaged groups were disproportionally affected by multiple developmental disabilities, highlighting the need for targeted strategies to improve health. The increasing prevalence during the pandemic suggests the need for ongoing monitoring of the trend and the impact of these conditions., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study aims to assess the prevalence of Autism Spectrum Disorder (ASD) and its treatment. The study population was children aged 3-17 years with information on current ASD from National Survey of Children's Health, 2016-2022. Analysis of treatment was also conducted within the population of children with a current ASD diagnosis. A multivariate log-binomial regression model was used to assess the change of current ASD prevalence and ASD treatment by two study period (prior to COVID-19 pandemic: 2016-2019; during COVID-19 pandemic: 2020-22) and sociodemographic information. Compared to the current ASD at 2.5% in 2016, it increased to 3.6% in 2022. The treatment has decreased from 70.5% in 2016 to 61.6% in 2022 for any treatment and from 27.2% in 2016 to 20.4% in 2022 for medication treatment. Compared to children from 2016-2019, children from the following group were more likely to have ASD diagnosis during the pandemic (2020-2022), including those aged 3-5 years (aPR = 1.66, 95%CI 1.29-2.13), non-Hispanic white children, children from family with above national family income, and those with private insurance. However, medication treatment almost halved during the pandemic for non-Hispanic black children (aPR = 0.49, 95%CI 0.26-0.93) and children born overseas. In conclusion, higher prevalence of ASD might indicate a better awareness of ASD. The reduction in treatment correlates to the health service disruption caused by the pandemic, highlighting the needs of policy efforts to improve treatment for ASD., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Background: Accumulating evidence has shown that the NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in the inflammatory cascades involved in the development of acute pancreatitis (AP). However, the specific agonist responsible for activating the NLRP3 inflammasome in this process has not yet been identified. The purpose of this study is to clarify whether heparan sulfate (HS) works as an NLRP3 inflammasome activator to evoke inflammatory cascades in the progression of AP., Methods: Two experimental mouse models of AP were utilized to investigate the pro-inflammatory activity of HS in the development of AP by measuring the secretion of inflammatory cytokines and the neutrophil infiltration in pancreatic tissue. The ability of HS to activate the NLRP3 inflammasome was evaluated both in vitro and in vivo. The nuclear factor kappa B (NF-κB)-mediated expression of NLRP3 inflammasome components in response to HS treatment was determined to decipher the role of HS in transcriptional priming of NLRP3 inflammasome. Furthermore, HS-triggered deubiquitination of NLRP3 was analyzed to reveal the promoting effect of HS on the NLRP3 inflammasome priming via a non-transcriptional pathway., Results: High plasma level of HS was observed with a positive correlation to that of inflammatory cytokines in AP mice. Administration of HS to mice resulted in an exacerbated inflammatory profile, while reducing HS production by an inhibitor of heparanase significantly attenuated inflammatory response. Pharmacological inhibition or genetic deletion of NLRP3 substantially suppressed the HS-stimulated elevation of IL-1β levels in AP mice. The in vitro data demonstrated that HS primarily serves as a priming signal for the activation of the NLRP3 inflammasome. HS possesses the ability to increase the transcriptional activity of NF-κB and TLR4/NF-κB-driven transcriptional pathway is employed for NLRP3 inflammasome priming. Moreover, HS-induced deubiquitination of NLRP3 is another pathway responsible for non-transcriptional priming of NLRP3 inflammasome., Conclusions: Our current work has unveiled HS as a new activator of the NLRP3 inflammasome responsible for the secondary inflammatory cascades during the development of AP, highlighting the HS-NLRP3 pathway as a potential target for future preventive and therapeutic approaches of AP., (© 2024. Japanese Society of Gastroenterology.)

Background: Childhood infection might be associated with adverse child development and neurocognitive outcomes, but the results have been inconsistent., Methods: Two population-based record-linkage cohorts of all singleton children born at term in New South Wales, Australia, from 2001 to 2014, were set up and followed up to 2019 for developmental outcome (N=276 454) and school performance (N=644 291). The primary outcome was developmentally high risk (DHR) at age 4-6 years and numeracy and reading below the national minimum standard at age 7-9 years. Cox regression was used to assess the association of childhood infection ascertained from hospital records with each outcome adjusting for maternal, birth and child characteristics, and sensitivity analyses were conducted assessing E-values and sibling analysis for discordant exposure., Results: A higher proportion of children with an infection-related hospitalisation were DHR (10.9% vs 8.7%) and had numeracy (3.7% vs 2.7%) and reading results (4.3% vs 3.1%) below the national minimum standard, compared with those without infection-related hospitalisation. In the multivariable analysis, children with infection-related hospitalisation were more likely to be DHR (adjusted HR 1.12, 95% CI 1.08 to 1.15) and have numeracy (adjusted HR 1.22, 95% CI 1.18 to 1.26) and reading results (adjusted HR 1.16, 95% CI 1.12 to 1.20) below the national minimum standard. However, these results may be impacted by unmeasured confounding, based on E-values of 1.48-1.74, and minimal association with education outcome was found in the sibling analysis., Conclusions: Infection-related hospitalisation was modestly associated with adverse child development and school performance, but the association may be explained by shared familial factors, particularly in those with most socioeconomic disadvantages., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Colorectal cancer is a prevalent malignancy, with advanced and metastatic forms exhibiting poor treatment outcomes and high relapse rates. To enhance patient outcomes, a comprehensive understanding of the pathophysiological processes and the development of targeted therapies are imperative. The high heterogeneity of colorectal cancer demands precise and personalized treatment strategies. Colorectal cancer organoids, a three-dimensional in vitro model, have emerged as a valuable tool for replicating tumor biology and exhibit promise in scientific research, disease modeling, drug screening, and personalized medicine. In this review, we present an overview of colorectal cancer organoids and explore their applications in research and personalized medicine, while also discussing potential future developments in this field.

Objectives: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH., Methods: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test., Results: Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction., Conclusion: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care., Methods: Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures., Results: A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14])., Conclusion: PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hossain et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Prostate cancer (PCa) ranks as the second most prevalent malignancy among males worldwide at present, and its prevalence keeps rising. Focal therapy not only results in tumor necrosis but also encourages the release of autoantigens originating from the tumor into the bloodstream and activates the host immune system to effectively fight the tumor. However, focal therapy alone may not achieve the total ablation of cancer cells and may cause locoregional recurrence. Immunotherapy, by boosting the body's immune response, destroys tumor cells and prevents immune escape. Recent studies show that focal therapy combined with immunotherapy can produce a better clinical efficacy by enhancing the initial immune response, especially for low- to intermediate-risk confined PCa. This article offers some fresh perspectives on the management of PCa by reviewing the etiology and progression of the malignancy, focal therapeutic options, and advantages and vista of focal therapy combined with immunotherapy.

Microplastics are an emerging contaminant that can persist in the environment for extended periods， posing risks to ecological systems. Recently， microplastic pollution has emerged as a major global environmental problem. In order to ensure accurate and scientific evaluation of the ecological risks associated with microplastic pollution， it is of paramount importance to improve the simplicity and reliability of microplastic identification， systematically analyze the pollution characteristics of microplastics in various environmental media， and clarify their environmental impacts. Machine learning technology has gained widespread attention in microplastic research by learning and analyzing large volumes of data to establish result evaluation or prediction models. The use of machine learning can enhance the automation and identification efficiency of visual and spectral identification of microplastics， provide scientific support for tracing the sources of microplastic pollution， and help reveal the complex environmental effects of microplastics. This review provides a summary of the application characteristics and limitations of machine learning in the aforementioned areas by reviewing the progress made in research that employs machine learning technology in microplastic identification and environmental risk assessment. Furthermore， the findings of the review will provide suggestions and prospects for the development and application of machine learning in related areas.

Typical small organic dyes exhibit excellent UV absorption capabilities and are commonly used as additives to shield plastic films from photoaging. However, their tendency to decompose easily and migrate rapidly within a polymer matrix limits their service life. Herein we prepared g-C 3 N 4 nanosheets and fabricated g-C 3 N 4 /PBAT films to investigate the effects of g-C 3 N 4 on UV shielding and plasticizing of a biodegradable PBAT film. Photophysical characterizations revealed that an improved UV light barrier performance was achieved on g-C 3 N 4 /PBAT films compared to pure PBAT. Furthermore, the photoaging results show that g-C 3 N 4 can stably exist in the PBAT matrix, enabling the aged g-C 3 N 4 /PBAT films to maintain their effective UV shielding ability, whereas the aged benzophenone (UV-0)/PBAT film shows a substantial decrease in UV light absorption due to the photodecomposition of UV-0. Additionally, g-C 3 N 4 acted as a reinforcing material for PBAT, as evidenced by the approximately 1.5-fold increase in longitudinal tear strength and 1.6-fold increase in tensile strength of g-C 3 N 4 /PBAT films compared to pure PBAT. Remarkably, even after 100 hours of photoaging, the aged g-C 3 N 4 /PBAT films retained their favorable mechanical properties. This study highlights the potential of g-C 3 N 4 as a new type of UV shield additive for future practical applications in protecting biodegradable plastic from photoaging., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Simple and rapid tools for screening high-risk patients for perioperative neurocognitive disorders (PNDs) are urgently needed to improve patient outcomes. We developed an online tool with machine-learning algorithms using routine variables based on multicenter data., Methods: The entire dataset was composed of 49,768 surgical patients from 3 representative academic hospitals in China. Surgical patients older than 45 years, those undergoing general anesthesia, and those without a history of PND were enrolled. When the patient's discharge diagnosis was PND, the patient was in the PND group. Patients in the non-PND group were randomly extracted from the big data platform according to the surgical type, age, and source of data in the PND group with a ratio of 3:1. After data preprocessing and feature selection, general linear model (GLM), artificial neural network (ANN), and naive Bayes (NB) were used for model development and evaluation. Model performance was evaluated by the area under the receiver operating characteristic curve (ROCAUC), the area under the precision-recall curve (PRAUC), the Brier score, the index of prediction accuracy (IPA), sensitivity, specificity, etc. The model was also externally validated on the multiparameter intelligent monitoring in intensive care (MIMIC) Ⅳ database. Afterward, we developed an online visualization tool to preoperatively predict patients' risk of developing PND based on the models with the best performance., Results: A total of 1051 patients (242 PND and 809 non-PND) and 2884 patients (6.2% patients with PND) were analyzed on multicenter data (model development, test [internal validation], external validation-1) and MIMIC Ⅳ dataset (external validation-2). The model performance based on GLM was much better than that based on ANN and NB. The best-performing GLM model on validation-1 dataset achieved ROCAUC (0.874; 95% confidence interval [CI], 0.833-0.915), PRAUC (0.685; 95% CI, 0.584-0.786), sensitivity (72.6%; 95% CI, 61.4%-81.5%), specificity (84.4%; 95% CI, 79.3%-88.4%), Brier score (0.131), and IPA (44.7%), and of which the ROCAUC (0.761, 95% CI, 0.712-0.809), the PRAUC (0.475, 95% CI, 0.370-0.581), Brier score (0.053), and IPA (76.8%) on validation-2 dataset. Afterward, we developed an online tool (https://pnd-predictive-model-dynnom.shinyapps.io/ DynNomapp/) with 10 routine variables for preoperatively screening high-risk patients., Conclusions: We developed a simple and rapid online tool to preoperatively screen patients' risk of PND using GLM based on multicenter data, which may help medical staff's decision-making regarding perioperative management strategies to improve patient outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

Solar-driven electrochemical NO 3 - reduction reaction (NO 3 - RR) is a clean and sustainable strategy that can convert pollutant NO 3 - in wastewater to value-added NH 3 . In recent years, cobalt oxides-based catalysts have shown their intrinsic catalytic properties toward NO 3 - RR but still have room for improvement through catalyst design. Coupling metal oxides with noble metal has been demonstrated to improve electrochemical catalytic efficiency. Here, we use Au species to tune the surface structure of Co 3 O 4 and improve the efficiency of NO 3 - RR to NH 3 . The obtained Au nanocrystals-Co 3 O 4 catalyst exhibited an onset potential of 0.54 V vs RHE, NH 3 yield rate of 27.86 µg/h·cm 2 , and Faradaic efficiency (FE) of 83.1% at 0.437 V vs RHE in an H-cell, which is much higher than Au small species (Au clusters or single atoms)-Co 3 O 4 (15.12 µg/h·cm 2 ) and pure Co 3 O 4 (11.38 µg/h·cm 2 ), respectively. Combined experiments with theory calculations, we attributed the enhanced performance of Au nanocrystals-Co 3 O 4 to the reduced energy barrier of *NO hydrogenation to the *NHO and suppression of HER, which originated from the charge transfer from Au to Co 3 O 4 . Using an amorphous silicon triple-junction (a-Si TJ) as the solar cell and an anion exchange membrane electrolyzer (AME), an unassisted solar-driven NO 3 - RR to NH 3 prototype was realized with a yield rate of 4.65 mg/h and FE of 92.1%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this review is to examine the association between proton pump inhibitors (PPIs) and neurological and/or psychiatric disorders in adults., Introduction: The association between PPIs and neurological and/or psychiatric disorders remains unclear, despite the widespread use of the medications. A systematic review is required to investigate the risk of developing neurological and/or psychiatric disorders following the use of PPIs., Inclusion Criteria: Studies including participants aged ≥18 years and using any PPIs, including participants with comorbid conditions or using other medications, will be considered for inclusion. Randomized controlled trials, quasi-experimental studies, and observational studies examining the association of neurological and/or psychiatric disorders with the use of PPIs among adults will be included., Methods: MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases will be searched from inception until the present. Two authors will independently screen and review the titles, abstracts, and full texts. The methodological quality of included studies will be assessed using the JBI critical appraisal checklists. Study characteristics, populations, type and duration of PPI usage, status of existing neurological and/or psychiatric disorders, comorbidity conditions, use of other medications, identification of neurological and/or psychiatric disorders (International Classification of Diseases codes vs others), and estimation of the associated neurological and/or psychiatric disorders will be extracted. Studies will be pooled using statistical meta-analysis where available; otherwise, the findings will be presented in narrative format. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading the certainty of evidence will be followed., Review Registration: PROSPERO CRD42022355543., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 JBI.)

Background: Respiratory infections including influenza and pertussis are associated with significant morbidity and mortality in mothers and newborns. Vaccination during pregnancy against influenza and pertussis is recommended for all women but data on uptake in Australia is limited., Methods: We conducted a retrospective population-based cohort study in Australia's largest state, New South Wales (NSW), using a Perinatal Data Collection (PDC). Data included demographic, pregnancy, and birth details including pertussis and influenza vaccination during pregnancy for all women giving birth between 01 January 2016 and 31 December 2020. We used descriptive statistics to assess uptake of influenza and pertussis vaccination during pregnancy and Poisson loglinear regression to estimate associations between maternal characteristics and vaccine receipt., Results: During 2016-2020, there were 477,776 births (mean maternal age 32.25 years). In 176,255 (36.9%) births the mother received both vaccines; 202,922 (42.5%) influenza and 315,620 (66.1%) pertussis vaccine. From 2016 to 2020, reported coverage increased from 26.7% to 58.7% for influenza and 43.1% to 78.8% for pertussis, respectively. After adjustment, characteristics associated with lower likelihood of receiving influenza and pertussis vaccination included: younger age (<30 years), being born in Australia/New Zealand, from lower socio-economic strata, having previous pregnancies, being later to first antenatal care, utilising the public hospital care model, smoking, having chronic hypertension and BMI > 25 kg/m 2 ., Conclusions: While reported coverage of both influenza and pertussis vaccine in birthing women in NSW has increased over time, disparities in coverage exist and they highlight areas where evidence-based interventions to improve maternal vaccination could be targeted., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nusrat Homaira reports a relationship with Merck Sharp & Dohme UK Ltd that includes: consulting or advisory. Nusrat Homaira reports a relationship with Sanofi that includes: consulting or advisory., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Nafamostat mesilate (NM), a synthetic broad-spectrum serine protease inhibitor, has been commonly used for treating acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases (such as thrombin, trypsin, kallikrein, plasmin, coagulation factors, and complement factors) is generally believed to be responsible for the anti-inflammatory effects of NM, the precise target and molecular mechanism underlying its anti-inflammatory activity in AP treatment remain largely unknown., Methods: The protection of NM against pancreatic injury and inhibitory effect on the NOD-like receptor protein 3 (NLRP3) inflammasome activation were investigated in an experimental mouse model of AP. To decipher the molecular mechanism of NM, the effects of NM on nuclear factor kappa B (NF-κB) activity and NF-κB mediated NLRP3 inflammasome priming were examined in lipopolysaccharide (LPS)-primed THP-1 cells. Additionally, the potential of NM to block the activity of histone deacetylase 6 (HDAC6) and disrupt the association between HDAC6 and NLRP3 was also evaluated., Results: NM significantly suppressed NLRP3 inflammasome activation in the pancreas, leading to a reduction in pancreatic inflammation and prevention of pancreatic injury during AP. NM was found to interact with HDAC6 and effectively inhibit its function. This property allowed NM to influence HDAC6-dependent NF-κB transcriptional activity, thereby blocking NF-κB-driven transcriptional priming of the NLRP3 inflammasome. Furthermore, NM exhibited the potential to interfere the association between HDAC6 and NLRP3, impeding HDAC6-mediated intracellular transport of NLRP3 and ultimately preventing NLRP3 inflammasome activation., Conclusions: Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NM in the treatment of AP, highlighting its promising application in the prevention of NLRP3 inflammasome-associated inflammatory pathological damage., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Although species can arise through hybridization, compelling evidence for hybrid speciation has been reported only rarely in animals. Here, we present phylogenomic analyses on genomes from 12 macaque species and show that the fascicularis group originated from an ancient hybridization between the sinica and silenus groups ~3.45 to 3.56 million years ago. The X chromosomes and low-recombination regions exhibited equal contributions from each parental lineage, suggesting that they were less affected by subsequent backcrossing and hence could have played an important role in maintaining hybrid integrity. We identified many reproduction-associated genes that could have contributed to the development of the mixed sexual phenotypes characteristic of the fascicularis group. The phylogeny within the silenus group was also resolved, and functional experimentation confirmed that all extant Western silenus species are susceptible to HIV-1 infection. Our study provides novel insights into macaque evolution and reveals a hybrid speciation event that has occurred only very rarely in primates.

HIV-1 is a highly host-specific retrovirus that infects humans but not most nonhuman primates. Thus, the lack of a suitable primate model that can be directly infected with HIV-1 hinders HIV-1/AIDS research. In the previous study, we have found that the northern pig-tailed macaques (NPMs) are susceptible to HIV-1 infection but show a nonpathogenic state. In this study, to understand this macaque-HIV-1 interaction, we assembled a de novo genome and longitudinal transcriptome for this species during the course of HIV-1 infection. Using comparative genomic analysis, a positively selected gene, Toll-like receptor 8, was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an interferon-stimulated gene, interferon alpha inducible protein 27, was upregulated in acute HIV-1 infection and acquired an enhanced ability to inhibit HIV-1 replication compared with its human ortholog. These findings coincide with the observation of persistently downregulated immune activation and low viral replication and can partially explain the AIDS-free state in this macaque following HIV-1 infection. This study identified a number of unexplored host genes that may hamper HIV-1 replication and pathogenicity in NPMs and provided new insights into the host defense mechanisms in cross-species infection of HIV-1. This work will facilitate the adoption of NPM as a feasible animal model for HIV-1/AIDS research., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Objectives: To determine the association between after-hours consultations and the likelihood of antibiotic prescribing for self-limiting upper respiratory tract infections (URTIs) in primary care practices., Design: A cross-sectional analysis using Australian national primary-care practice data (MedicineInsight) between February 1, 2016 and January 31, 2019., Setting: Nationwide primary-care practices across Australia., Participants: Adult and pediatric patients who visited primary care practices for first-time URTIs., Methods: We estimated the proportion of first-time URTI episodes for which antibiotic prescribing occurred on the same day (immediate prescribing) using diagnoses and prescription records in the electronic primary-care database. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the likelihood of antibiotic prescribing by the time of primary care visits were calculated using generalized estimating equations., Results: Among 357,287 URTI episodes, antibiotics were prescribed in 172,605 episodes (48.3%). After adjusting for patients' demographics, practice characteristics, and seasons, we detected a higher likelihood of antibiotic prescribing on weekends compared to weekdays (OR, 1.42; 95% CI, 1.39-1.45) and on national public holidays compared to nonholidays (OR, 1.23; 95% CI, 1.17-1.29). When we controlled for patient presentation and diagnosis, the association between antibiotic prescribing and after-hours consultations remained significant: weekend versus weekdays (OR, 1.37; 95% CI, 1.33-1.41) and holidays versus nonholidays (OR, 1.10; 95% CI, 1.03-1.18)., Conclusions: Primary-care consultations on weekends and public holidays were associated with a higher likelihood of immediate antibiotic prescribing for self-limiting URTIs in primary care. This finding might be attributed to lower resourcing in after-hours health care.

Background: Administrative health data has been used extensively to examine congenital heart disease (CHD). However, the accuracy and completeness of these data must be assessed., Objectives: To use data linkage of multiple administrative data sources to examine the validity of identifying CHD cases recorded in hospital discharge data., Methods: We identified all liveborn infants born 2013-2017 in New South Wales, Australia with a CHD diagnosis up to age one, recorded in hospital discharge data. Using record linkage to multiple data sources, the diagnosis of CHD was compared with five reference standards: (i) multiple hospital admissions containing CHD diagnosis; (ii) receiving a cardiac procedure; (iii) CHD diagnosis in the Register of Congenital Conditions; (iv) cardiac-related outpatient health service recorded; and/or (v) cardiac-related cause of death. Positive predictive values (PPV) comparing CHD diagnosis with the reference standards were estimated by CHD severity and for specific phenotypes., Results: Of 485,239 liveborn infants, there were 4043 infants with a CHD diagnosis identified in hospital discharge data (8.3 per 1000 live births). The PPV for any CHD identified in any of the five methods was 62.8% (95% confidence interval [CI] 60.9, 64.8), with PPV higher for severe CHD at 94.1% (95% CI 88.2, 100). Infant characteristics associated with higher PPVs included lower birthweight, presence of a syndrome or non-cardiac congenital anomaly, born to mothers aged <20 years and residing in disadvantaged areas., Conclusion: Using data linkage of multiple datasets is a novel and cost-effective method to examine the validity of CHD diagnoses recorded in one dataset. These results can be incorporated into bias analyses in future studies of CHD., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Tetherin prevents viral cross-species transmission by inhibiting the release of multiple enveloped viruses from infected cells. With the evolution of simian immunodeficiency virus of chimpanzees (SIVcpz), a pandemic human immunodeficiency virus type 1 (HIV-1) precursor, its Vpu protein can antagonize human tetherin (hTetherin). Macaca leonina (northern pig-tailed macaque [NPM]) is susceptible to HIV-1, but host-specific restriction factors limit virus replication in vivo . In this study, we isolated the virus from NPMs infected with strain stHIV-1sv (with a macaque-adapted HIV-1 env gene from simian-human immunodeficiency virus SHIV-KB9, a vif gene replaced by SIVmac239, and other genes originating from HIV-1 NL4.3 ) and found that a single acidic amino acid substitution (G53D) in Vpu could increase its ability to degrade the tetherin of macaques (mTetherin) mainly through the proteasome pathway, resulting in an enhanced release and resistance to interferon inhibition of the mutant stHIV-1sv strain, with no influence on the other functions of Vpu. IMPORTANCE HIV-1 has obvious host specificity, which has greatly hindered the construction of animal models and severely restricted the development of HIV-1 vaccines and drugs. To overcome this barrier, we attempted to isolate the virus from NPMs infected with stHIV-1sv, search for a strain with an adaptive mutation in NPMs, and develop a more appropriate nonhuman primate model of HIV-1. This is the first report identifying HIV-1 adaptations in NPMs. It suggests that while tetherin may limit HIV-1 cross-species transmission, the Vpu protein in HIV-1 can overcome this species barrier through adaptive mutation, increasing viral replication in the new host. This finding will be beneficial to building an appropriate animal model for HIV-1 infection and promoting the development of HIV-1 vaccines and drugs.

Background: Evidence regarding the association between acute respiratory infections during pregnancy and congenital anomalies in babies, is limited and conflicting. The aim of this study was to examine the association between acute respiratory infections during the first trimester of pregnancy and congenital anomalies in babies using record linkage., Methods: We linked a perinatal register to hospitalisation and disease notifications in the Australian state of New South Wales (NSW) between 2001 to 2016. We quantified the risk of congenital anomalies, identified from the babies' linked hospital record in relation to notifiable respiratory and other infections during pregnancy using generalized Estimating Equations (GEE) adjusted for maternal sociodemographic and other characteristics., Results: Of 1,453,037 birth records identified from the perinatal register between 2001 and 2016, 11,710 (0.81%) mothers were hospitalised for acute respiratory infection, 2850 (0.20%) had influenza and 1011 (0.07%) had high risk infections (a record of cytomegalovirus, rubella, herpes simplex, herpes zoster, toxoplasmosis, syphilis, chickenpox (varicella) and zika) during the pregnancy. During the first trimester, acute respiratory infection, influenza and high-risk infections were reported by 1547 (0.11%), 399 (0.03%) and 129 (0.01%) mothers. There were 15,644 (1.08%) babies reported with major congenital anomalies, 2242 (0.15%) with cleft lip/ plate, 7770 (0.53%) with all major cardiovascular anomalies and 1746 (0.12%) with selected major cardiovascular anomalies. The rate of selected major cardiovascular anomalies was significantly higher if the mother had an acute respiratory infection during the first trimester of pregnancy (AOR 3.64, 95% CI 1.73 to 7.66). The rates of all major congenital anomalies and all major cardiovascular anomalies were also higher if the mother had an acute respiratory infection during the first trimester of pregnancy, however the difference was no statistically significant. Influenza during the first trimester was not associated with major congenital anomalies, selected major cardiovascular anomalies or all major cardiovascular anomalies in this study., Conclusion: This large population-based study found severe acute respiratory infection in first trimester of pregnancy was associated with a higher risk of selected major cardiovascular anomalies in babies. These findings support measures to prevent acute respiratory infections in pregnant women including through vaccination., (© 2023. The Author(s).)

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging bunyavirus, causes severe fever with thrombocytopenia syndrome (SFTS), with a high fatality rate of 20%-30%. At present, however, the pathogenesis of SFTSV remains largely unclear and no specific therapeutics or vaccines against its infection are currently available. Therefore, animal models that can faithfully recapitulate human disease are important to help understand and treat SFTSV infection. Here, we infected seven Chinese rhesus macaques ( Macaca mulatta ) with SFTSV. Virological and immunological changes were monitored over 28 days post-infection. Results showed that mild symptoms appeared in the macaques, including slight fever, thrombocytopenia, leukocytopenia, increased aspartate aminotransferase (AST) and creatine kinase (CK) in the blood. Viral replication was persistently detectable in lymphoid tissues and bone marrow even after viremia disappeared. Immunocyte detection showed that the number of T cells (mainly CD8 + T cells), B cells, natural killer (NK) cells, and monocytes decreased during infection. In detail, effector memory CD8 + T cells declined but showed increased activation, while both the number and activation of effector memory CD4 + T cells increased significantly. Furthermore, activated memory B cells decreased, while CD80 + /CD86 + B cells and resting memory B cells (CD27 + CD21 + ) increased significantly. Intermediate monocytes (CD14 + CD16 + ) increased, while myeloid dendritic cells (mDCs) rather than plasmacytoid dendritic cells (pDCs) markedly declined during early infection. Cytokines, including interleukin-6 (IL-6), interferon-inducible protein-10 (IP-10), and macrophage inflammatory protein 1 (MCP-1), were substantially elevated in blood and were correlated with activated CD4 + T cells, B cells, CD16 + CD56 + NK cells, CD14 + CD16 + monocytes during infection. Thus, this study demonstrates that Chinese rhesus macaques infected with SFTSV resemble mild clinical symptoms of human SFTS and provides detailed virological and immunological parameters in macaques for understanding the pathogenesis of SFTSV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Huang, He, He, Wang, Lin, Zhao, Zheng and Pang.)

This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18-35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007-2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%-25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18-22 years (VE = 64%) and 23-27 years (65%). Among participants aged 18-22 years vaccinated before sexual debut, the VE was 47% (23%-64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%-77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5-10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.

Background: Evidence on the effectiveness of influenza vaccine in preventing antibiotic prescriptions for influenza-like illness (ILI) in adults is limited., Methods: A primary care-based case-control study was conducted to estimate influenza vaccine effectiveness (VE) against influenza-like illness (ILI) and antibiotic prescribing for ILI in adults aged ≥40 years. Cases were patients diagnosed with ILI from 1 st June to 30 th September in each year, 2015-2018; a subset of those with ILI prescribed antibiotics was also defined. Controls were patients attending a practice who did not receive an ILI diagnosis. Generalised estimating equations were used to calculate adjusted VE overall, by age (<65 versus ≥65 years) and comorbidity status., Results: The number of ILI cases varied from 558 in 2018 to 2901 in 2017 and controls from 86618 in 2015 to 136763 in 2017. Over 4 years the pooled estimate of VE was 24% (95%CI, 11% to 34%) against ILI and 15% (95%CI, -3% to 29%) against antibiotic prescription for ILI. Influenza vaccine was effective in reducing ILI with an associated antibiotic prescriptions in patients aged <65 years (VE=23%, 95%CI, 3% to 38%) and if no comorbidities were recorded (VE=22%, 95%CI, 1% to 39%) but not in other subgroups., Conclusions: Influenza vaccine reduced the likelihood of antibiotic prescriptions for ILI in low-risk adults (40-64 years and those without comorbidities)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: We aimed to compare the analgesic effect and incidence of lower limb weakness of transmuscular quadratus lumborum (TQL) block via subfascial approach with that via extrafascial after laparoscopic cholecystectomy (LC)., Methods: Eighty patients undergoing LC were randomized to receive ultrasound-guided bilateral TQL block via subfascial (subfascial group) or extrafascial (extrafascial group) using 30 mL of 0.33% ropivacaine unilaterally. Pain scores of port sites while rest and coughing at 1, 6, 12, 24, 36, and 48 hours postoperatively as primary outcome were compared. Modified Lovett Rating Scale, ambulatory dependency, and rescue analgesia requirement was also compared., Results: The pain score of the subxiphoid and of the right subcostal port site for up to the postoperative 36 hours (2 [1 to 2]) and 24 hours (2 [2 to 3]) in the subfascial group was significantly lower than that in extrafascial group (2 [2 to 2] and 3 [2.25 to 4]). Up to postoperative 24 hours, the rescue analgesia requirement in subfascial group was significantly lower than that in extrafascial group, namely less fentanyl consumption and parecoxib (1.3 [±5.5] μg vs. 5.6 [±10.6] μg; 17.5% vs. 37.5%). The ratio of patients with LRS score of 6 at postoperative 1 hour (65.0%), and with dependent ambulation at postoperative 1 and 6 hours in subfascial group (15.0% and 0.0%) was significantly lower than that in extrafascial group (10.0%, 80.0%, and 17.5%)., Conclusion: TQL block via subfascial had the advantages of better analgesic effect and less lower limbs weakness after LC over that via extrafascial., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants., (© 2022. The Author(s).)

Aims: This study aims to compare estimates of primary liver cancer mortality from World Health Organization (WHO), Global Burden Disease (GBD) and Global Cancer Observatory (GCO)., Methods: Liver cancer mortality was extracted from WHO, GBD and GCO for 92 countries for the most recent year. Age-standardized rate (ASR) was computed and used for current comparisons across the three data sources. Temporal trend for 75 countries was analysed and compared between WHO and GBD from 1990 to 2019 using joinpoint regression. Average annual percentage change for the most recent 10 years was used as indicator for change., Results: The estimates of ASR were quite consistent across the three data sources, but most similar estimates were found between WHO and GCO in both region and country levels. The differences in ASR were negatively correlated with completeness of cause-of-death registration, human development index and proportion of liver cancer because of alcohol consumption. Consistent trends of ASR were found from 35 countries between WHO and GBD in the most recent 10 years. However, opposite trends were found from 10 countries with five from Southern America, four from Europe and one from Asia. Of the 18 countries for projection, opposite trends between WHO and GBD were found from seven countries., Conclusion: While the ASR of primary liver cancer mortality was comparable across the three data sources, most similar estimates were found between WHO and GCO. The opposite trends found from 10 countries between WHO and GBD raised concerns of true patterns in these countries., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Litter decomposition is one of the most important ecosystem processes, which plays a critical role in regu-lating nutrient cycling and energy flow in terrestrial ecosystems. The influence of litter inputs on soil microbial community is helpful for understanding the relationship between soil microbial diversity and terrestrial ecosystem function. We conducted a meta-analysis to examine how litter inputs affect soil microbial activity (fungi, bacteria, actinomycetes) and microbial biomass carbon, nitrogen in China. The results showed that compared with non-litter input, soil microbial biomass carbon and nitrogen were significantly increased by 3.9% and 4.4% respectively after litter inputs. Soil fungal PLFA, bacterial PLFA, and total microbial PLFA were increased by 4.0%, 3.1% and 2.4%, respectively. The effects of litter inputs differed significantly with climatic region, annual precipitation, vege-tation type, and soil pH. Under different climate conditions, the responses of soil microbe showed the trend of subtropical monsoon climatic region > temperate monsoon climatic region > temperate continental climatic region, which increased first and then decreased with increasing annual precipitation. Under different vegetation types, the responses of soil microbes showed the trend of broad-leaved forest > grassland ≈ mixed forest > coniferous forest.

Dynamic regulation of intestinal epithelial cell (IEC) differentiation is crucial for both homeostasis and the response to helminth infection. SIRT6 belongs to the NAD + -dependent deacetylases and has established diverse roles in aging, metabolism and disease. Here, we report that IEC Sirt6 deletion leads to impaired tuft cell development and type 2 immunity in response to helminth infection, thereby resulting in compromised worm expulsion. Conversely, after helminth infection, IEC SIRT6 transgenic mice exhibit enhanced epithelial remodeling process and more efficient worm clearance. Mechanistically, Sirt6 ablation causes elevated Socs3 expression, and subsequently attenuated tyrosine 641 phosphorylation of STAT6 in IECs. Notably, intestinal epithelial overexpression of constitutively activated STAT6 (STAT6vt) in mice is sufficient to induce the expansion of tuft and goblet cell linage. Furthermore, epithelial STAT6vt overexpression remarkedly reverses the defects in intestinal epithelial remodeling caused by Sirt6 ablation. Our results reveal a novel function of SIRT6 in regulating intestinal epithelial remodeling and mucosal type 2 immunity in response to helminth infection., (© 2022. The Author(s).)

Two new species of eriophyoid mites are described and illustrated from Guangxi, China: Acaphylla quercus sp. nov. collected on Quercus glauca Thunb. (Fagaceae), Rhyncaphytoptus miliusius sp. nov. collected on Miliusa sinensis Finet Gagnep. (Annonaceae). We further report Cecidodectes euzonus Nalepa, 1917, collected on Trema tomentosa (Roxb.) H.Hara (Cannabaceae), for the first time from China. All the species are vagrants on lower leaf surface causing no apparent damage to their host plants.

Erectile dysfunction (ED) is closely associated with smooth muscle dysfunction, but its underlying mechanisms remains incompletely understood. We here reported that the reduced expression of myosin phosphatase target subunit 1 (MYPT1), the main regulatory unit of myosin light chain phosphatase, was critical for the development of vasculogenic ED. Male MYPT1 knockout mice had reduced fertility and the penises displayed impaired erections as evidenced by reduced intracavernous pressure (ICP). The penile smooth muscles of the knockout mice displayed enhanced response to G-Protein Couple Receptor agonism and depolarization contractility and resistant relaxation. We further identified a natural compound lotusine that increased the MYPT1 expression by inhibiting SIAH1/2 E3 ligases-mediated protein degradation. This compound sufficiently restored the ICP and improved histological characters of the penile artery of Mypt1 haploinsufficiency mice. In diabetic ED mice (db/db), the decreased expression of MYPT1 was measured, and ICP was improved by lotusine treatment. We conclude that the reduction of MYPT1 is the major pathogenic factor of vasculogenic ED. The restoration of MYPT1 by lotusine improved the function of injured penile smooth muscles, and could be a novel strategy for ED therapy., (© 2022. The Author(s).)

Studies have shown that interferon (IFN)-α has an inhibitory effect on human immunodeficiency virus type 1 (HIV-1) replication in the acute infection stage, but its role in chronic infection is still unclear. We previously established a nonpathogenic HIV-1 and pathogenic simian immunodeficiency virus (SIV) model in northern pig-tailed macaques (NPMs, Macaca leonina). In the current study, we detected viral RNA and DNA in various tissues (axillary lymph nodes (LNs), inguinal LNs, and spleen) in HIV-1 NL4-3 - and SIV mac239 -infected NPM during the chronic stage of infection. Results indicated that the levels of viral DNA and RNA were higher in the tested tissues (LNs and spleen) of the SIV mac239 -infected NPMs than in the HIV-1 NL4-3 infected NPMs. Furthermore, IFN-α expression was higher in the HIV-infected tissues than in the SIV-infected controls. The HIV restriction factors induced by IFN-α (i.e., tetherin and MX2), as well as inflammatory factors IFN-γ, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), were analyzed using real-time polymerase chain reaction (PCR) and immunofluorescence staining assays. Results showed that their expression levels were much higher in the HIV-infected tissues than in the SIV-infected controls. These findings were confirmed by in vitro experiments on healthy NPM peripheral blood mononuclear cells infected with HIV-1 NL4-3 , which showed lower viral replication, higher IFN-α expression, and an antiviral status. This study demonstrated that HIV-1 infection, but not SIV mac239 infection, in NPMs caused higher expression of IFN-α and induced a higher antiviral status. This may be one of the reasons why HIV-1 cannot replicate at a high level or develop into AIDS in NPMs., Competing Interests: Declaration of competing interest All authors in this study have no conflicts of interest., (Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Inflammatory bowel disease (IBD) is a chronic relapsing-remitting inflammatory disease of the gastrointestinal tract. Patients are usually diagnosed in adolescence and early adulthood and need lifelong treatment. In recent years, it has been found that diet plays an important role in the pathogenesis of IBD. Diet can change intestinal barrier function, affect the structure and function of intestinal flora, and promote immune disorder, thus promoting inflammation. Many patients believe that diet plays a role in the onset and treatment of the disease and changes their diet spontaneously. This review provides some insights into how nutraceuticals regulate intestinal immune homeostasis and improve intestinal barrier function. We reviewed the research results of dietary fiber, polyphenols, bioactive peptides, and other nutraceuticals in the prevention and treatment of IBD and sought better alternative or supplementary treatment methods for IBD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ban, Liu, Ding, Chen, Lin, Zha and He.)

Background and Aims: Hepatitis B vaccine has been included in the infant immunization schedule since 1991 in the United States. We aimed to assess its effectiveness against HBV infection and its impact on mortality., Approach and Results: The study population was participants aged 6+ years with an HBV vaccination history and an HBV serologic test from the National Health and Nutrition Examination Survey, 1999-2018. Participants aged 18+ years with linked mortality records from 1999-2014 were followed for mortality analysis. Multivariable logistic regression was used to compute vaccine effectiveness (VE) overall, by year of birth, and by age. Cox regression was used to estimate HRs for all-cause, cancer-related, and cardiovascular disease-related mortality. A total of 64,107 participants were included in the main analysis, with 29,600 (40.7%) having completed HBV vaccination (three or more doses, vaccinated). The highest vaccination uptake was found among those born after 1991, at 86.5%. Vaccinated participants had higher prevalence of vaccine-induced immunity than the unvaccinated (47.2% vs. 7.4%). Among those born after 1991, VE was found at 58% (95% CI, 18%-79%) overall and 85% for those aged ≥20 years (mean age, 22), whereas no effect was found among those born prior to 1990. HBV vaccination was associated with reduced risk of all-cause mortality (HR, 0.78; 95% CI, 0.68-0.90) and cancer-related mortality (HR, 0.76; 95% CI, 0.58-1.00) but not for cardiovascular disease-related mortality., Conclusions: In the universal infant vaccination era, the HBV vaccine has shown substantial effectiveness against HBV infection and maintained strong protection for 20 years. It was also associated with reduced risk of all-cause and cancer-related mortality., (© 2021 American Association for the Study of Liver Diseases.)

Background: Regular monitoring and treatment of chronic hepatitis B (CHB) are known to reduce the risk of hepatocellular carcinoma. We sought to describe patterns of monitoring and treatment among adults diagnosed with CHB in Australia., Methods: Population-based prospective cohort study of Australian adults aged 45 + years followed by record-linkage to hepatitis B notifications, monitoring and treatment. Proportions of those with CHB who: had viral load test; were dispensed antiviral treatment; and had ultrasound surveillance were estimated. The characteristics associated with viral load test and ultrasound surveillance were examined using logistic regression., Results: A total of 576 adults with CHB were identified. From 2008 to 2015, 14.8% (85/576) had at least one viral load test recorded every 2 years and 19.1% (110/576) had at least one antiviral treatment recorded, 19.9% (58/292) had at least one ultrasound recorded every year among those eligible for ultrasound surveillance. A record of having at least one viral load test every 2 years was more likely among adults born in Asia compared to Australian-born (21.4% vs 8.6%), those notified in more recent years compared to earlier years, and those on antiviral treatment compared to not on treatment. Increasing proportions of cases had records of at least one viral load test over time (2008: 10.5%, 2015: 27.2%) and at least one antiviral treatment (2008: 3.0%, 2015: 18.5%)., Conclusions: In Australian adults, estimates of care interventions for CHB management have increased over time but still fall short of targets recommended in the National Hepatitis B Strategy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Poly-(butylene adipate-co-terephthalate) (PBAT) has become one of the most prevalent biodegradable plastic film materials owing to its good degradability, mechanical properties, and processability. However, the degradation time of this material was too fast and the functional period was short, which limited its application. Herein, three new tropolone-based UV absorbers (UVA-1C, UVA-4C and UVA-6C) were rationally designed and blended into PBAT. The PBAT/UVA films that formed were used against UV aging and prolonged the functional period of PBAT film. The three new absorbers were synthesized by bridging two tropolones using three different organic chains with different flexibility. Among them, the UVA-6C showed the strongest UV absorbance at around 238 nm and 320 nm. Consequently, the PBAT/UVA-6C film showed an extended validity period of 240 h in the Xenon lamp aging machine and a prolonged functional period of 8 d during the field application test when compared to pure PBAT. More importantly, a 7.8% increase in the maize yield was obtained under PBAT/UVA-6C film relative to pure PBAT film. Obviously, the novel prepared UVA-6C compound is a good candidate for UV absorption in PBAT, which makes PBAT/UVA-6C film more advantageous over pure PBAT in practical applications as biodegradable agricultural film.

Backgrounds: This study investigated the global incidence and mortality of cervical cancer, its predictors, the temporal trend by country and age., Methods: Data from Global Cancer Observatory 2020 for 185 countries was used to estimate current cervical cancer incidence and mortality and their associations with predictors by linear regression analysis. Estimated age-standardized rates (ASR) and average annual percentage changes (AAPC) from cancer registries for up to 53 countries through 2018 were used for trend analysis by joinpoint regression., Results: Wide variations in cervical cancer were observed globally with the highest rates of incidence and mortality in East Africa (ASR, 40.1 and 28.6). The incidence and mortality of cervical cancer were positively associated with human papillomavirus, human immunodeficiency virus infection and negatively associated with cervical cancer screening coverage. In the most recent 5 years, reduction of incidence and mortality was found from 22 (AAPC, -11.2 to -0.5) and 27 countries (-21.5 to -0.3). Increase of incidence and mortality was found from 13 (1.7 to 6.5) and 5 (0.3 to 1.8) countries. Comparing to women aged above 50 years, increasing incidence were additionally found among women under age 50 years from 9 countries (ranging from 0.2 in Denmark to 3.8 in Sweden)., Conclusions: While most countries with cancer registry have shown reduction in cervical cancer incidence and mortality, the increasing incidence among younger women from some developed countries warrants further implementation of effective cancer screening., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Glycosylation inactivation is one of the important macrolide resistance mechanisms. The accumulated evidences attributed glycosylation inactivation to a glucosylation modification at the inactivation sites of macrolides. Whether other glycosylation modifications lead to macrolides inactivation is unclear. Herein, we demonstrated that varied glycosylation modifications could cause inactivation of midecamycin, a 16-membered macrolide antibiotic used clinically and agriculturally. Specifically, an actinomycetic glycosyltransferase (GT) OleD was selected for its glycodiversification capacity towards midecamycin. OleD was demonstrated to recognize UDP-D-glucose, UDP-D-xylose, UDP-galactose, UDP-rhamnose and UDP- N -acetylglucosamine to yield corresponding midecamycin 2'- O -glycosides, most of which displayed low yields. Protein engineering of OleD was thus performed to improve its conversions towards sugar donors. Q327F was the most favorable variant with seven times the conversion enhancement towards UDP- N -acetylglucosamine. Likewise, Q327A exhibited 30% conversion enhancement towards UDP-D-xylose. Potent biocatalysts for midecamycin glycosylation were thus obtained through protein engineering. Wild OleD, Q327F and Q327A were used as biocatalysts for scale-up preparation of midecamycin 2'- O -glucopyranoside, midecamycin 2'- O -GlcNAc and midecamycin 2'- O -xylopyranoside. In contrast to midecamycin, these midecamycin 2'- O -glycosides displayed no antimicrobial activities. These evidences suggested that besides glucosylation, other glycosylation patterns also could inactivate midecamycin, providing a new inactivation mechanism for midecamycin resistance. Cumulatively, glycosylation inactivation of midecamycin was independent of the type of attached sugar moieties at its inactivation site.

Baicalin has been reported to have ameliorative effects on nerve-induced hypoxic ischemia injury; however, its role in the NLRP3 inflammasome-dependent inflammatory response during cerebral ischemia-reperfusion remains unclear. To investigate the molecular mechanisms involved in baicalin alleviating cerebral ischemia-reperfusion injury, we investigated the AMPK signaling pathway which regulates NLRP3 inflammasome activity. SD rats were treated with baicalin at doses of 100 mg/kg and 200 mg/kg, respectively, after middle cerebral artery occlusion at 2 h and reperfusion for 24 h (MCAO/R). MCAO/R treatment significantly increased cerebral infarct volume, changed the ultrastructure of nerve cells, and activated the NLRP3 inflammasome, manifesting as significantly increased expression of NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18. Our results demonstrated that baicalin treatment effectively reversed these phenomena in a dose-dependent manner. Additionally, inhibition of NLRP3 expression was found to promote the neuroprotective effects of baicalin on cortical neurons. Furthermore, baicalin remarkably increased the expression of p-AMPK following oxygen glucose deprivation/reperfusion (OGD/R). The expression of the NLRP3 inflammasome was also increased when the AMPK pathway was blocked by compound C. Taken together, our findings reveal that baicalin reduces the activity of the NLRP3 inflammasome and consequently inhibits cerebral ischemia-reperfusion injury through activation of the AMPK signaling pathway., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cryptosporidium is an enteric apicomplexan parasite, which can infect multiple mammals including livestock and wildlife. Tibetan Antelope ( Pantholops hodgsonii ) is one of the most famous wildlife species, that belongs to the first class protected wild animals in China. However, it has not been known whether Tibetan Antelope is infected with Cryptosporidium so far. The objective of the present study was to determine the prevalence and characterization of Cryptosporidium species infection in Tibetan Antelope and the corresponding species by using molecular biological method. In the current study, a total of 627 fecal samples were randomly collected from Tibetan Antelope in the Tibet Autonomous Region (2019-2020), and were examined by PCR amplification of the small subunit ribosomal RNA (SSU rRNA) gene. Among 627 samples, 19 (3.03%, 19/627) were examined as Cryptosporidium -positive, with 7 (2.33%, 7/300) in females and 12 (3.67%, 12/327) in males. The analysis of SSU rRNA gene sequence suggested that only two Cryptosporidium species, namely, C. xiaoi and C. ubiquitum , were identified in this study. This is the first evidence for an existence of Cryptosporidium in Tibetan Antelope. These findings extend the host range for Cryptosporidium spp. and also provide important data support for prevention and control of Cryptosporidium infection in Tibetan Antelope., Competing Interests: Author CL is employed by Shandong New Hope Liuhe Group Co., Ltd., and Qingdao Jiazhi Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qin, Sun, Lyu, Zhu, Wang, Ma, Zhao, Lan and He.)

Background: This study aims to investigate the temporal trend as well as the burden of primary liver cancer among Mongol and non-Mongol in China., Materials and Methods: The registered data from up to 20 monitoring points in the periods of 2008 to 2015 in Inner Mongolia were used to calculate and model the trend of liver cancer among Mongol and non-Mongol using log-linear regression. Logistic regression was used to characterise the risk of liver cancer by using hospitalization records from 2008 to 2017., Results: Over the study period, significant reduction of liver cancer mortality was found among non-Mongol population (4.8/100,000 from 23.7/100,000 to 18.9/100,000, p=0.04), while the increase of liver cancer mortality was observed among the Mongolian population (8.4/100,000 from 10.7/100,000 to 19.1/100,000, p=0.02), particularly the Mongol from East (25.5/100,000 from 11.2/100,000 to 36.7/100,000, p=0.005). Comparing to the non-Mongol patients with primary liver cancer, the Mongolian patients were more likely to be from East Inner Mongolia (aOR=3.65, 95% CI:2.75-4.87) and those residing in urban area (aOR=2.11, 95%CI: 1.55-2.91). In 2015, a total of 3056 primary liver cancer deaths could be converted if the four known risk factors (HBV, Hepatitis C Virus, alcohol consumption and smoking) could be prevented. HBV remained to be the leading risk factor of liver cancer (PAF=56%, contributing to 2616 deaths) with the highest among the Mongol from East (PAF=65.1%, contributing to 763 deaths)., Conclusion: The continuing increase of primary liver cancer among Mongol suggested further interventions were needed to combat its burden.

Aims: This study aims to assess the trend of hepatitis B virus (HBV)-attributable liver cancer as well as the impact of HBV vaccine on it., Methods: We retrieved data from Global Burden Disease study to estimate trends of HBV-attributable liver cancer by region and age from 1990 to 2017 and HBV vaccine data from World Health Organization to assess its impact on these trends for children (0-14 years), adolescents and young adults (15-29 years). Change of cancer cases, age-standardized incidence rate (ASR) and estimated annual percentage change (EAPC) were used to quantify the trends of HBV-attributable liver cancer., Results: In this study, reduction in HBV-attributable cancer incident cases was found among children (from 2080 to 1430), adolescents and young adults (from 10 890 to 9090). In terms of ASR, overall reduction was observed globally by an average of -0.45% (95% CI: -0.62 to -0.29) per year in the same period. The highest reduction in ASR was found in adolescents and young adults with EAPC of -3.02 (95% CI: -3.57 to -2.46). Although the ASR has decreased from all the five regions with universal HBV immunization programme, it has increased in the region without universal vaccination and the highest increase was found among children with EAPC of 1.97 (95% CI: 1.71-2.23)., Conclusion: Significant reduction in HBV-attributable liver cancer among children was mainly because of the universal HBV vaccination. However, the increasing trend of HBV-attributable liver cancer in region without universal HBV vaccination suggested the necessity of introducing universal immunization., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)