Growth performance, lipid metabolism, and systemic immunity of weaned piglets were altered by buckwheat protein through the modulation of gut microbiota.

Tartary buckwheat protein (BWP) is well known for the wide-spectrum antibacterial activity and the lipid metabolism- regulating property; therefore, BWP can be applied as feed additives to improve the animal's nutritional supply. With the aim to investigate the bioactive actions of the BWP, growth performance, lipid metabolism and systemic immunity of the weaned piglets were measured, and the alterations of pig gut microbiota were also analyzed. According to the results, the growth performances of the weaned piglets which were calculated as the average daily gain (ADG) and the average daily feed intake (ADFI) were significantly increased when compared to the control group. Simultaneously, the serum levels of the total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased, while the levels of high-density lipoprotein cholesterol (HDL-C) were increased in the BWP group. Moreover, the relative abundances of Lactobacillus, Prevotella_9, Subdoligranulum, Blautia, and other potential probiotics in the gut microbiota of weaned piglets were obviously increased in the BWP group. However, the relative abundances of Escherichia-Shigella, Campylobacter, Rikenellaceae_RC9_gut_group and other opportunistic pathogens were obviously decreased in the BWP group. In all, BWP was proved to be able to significantly improve the growth performance, lipid metabolism, and systemic immunity of the weaned piglets, and the specific mechanism might relate to the alterations of the gut microbiota. Therefore, BWP could be explored as a prospective antibiotic alternative for pig feed additives.

Palmitoylation at Residue C221 of Japanese Encephalitis Virus NS2A Protein Contributes to Viral Replication Efficiency and Virulence.

Palmitoylation of viral proteins is crucial for host-virus interactions. In this study, we examined the palmitoylation of Japanese encephalitis virus (JEV) nonstructural protein 2A (NS2A) and observed that NS2A was palmitoylated at the C221 residue of NS2A. Blocking NS2A palmitoylation by introducing a cysteine-to-serine mutation at C221 (NS2A/C221S) impaired JEV replication in vitro and attenuated the virulence of JEV in mice. NS2A/C221S mutation had no effect on NS2A oligomerization and membrane-associated activities, but reduced protein stability and accelerated its degradation through the ubiquitin-proteasome pathway. These observations suggest that NS2A palmitoylation at C221 played a role in its protein stability, thereby contributing to JEV replication efficiency and virulence. Interestingly, the C221 residue undergoing palmitoylation was located at the C-terminal tail (amino acids 195 to 227) and is removed from the full-length NS2A following an internal cleavage processed by viral and/or host proteases during JEV infection. IMPORTANCE An internal cleavage site is present at the C terminus of JEV NS2A. Following occurrence of the internal cleavage, the C-terminal tail (amino acids 195 to 227) is removed from the full-length NS2A. Therefore, it was interesting to discover whether the C-terminal tail contributed to JEV infection. During analysis of viral palmitoylated protein, we observed that NS2A was palmitoylated at the C221 residue located at the C-terminal tail. Blocking NS2A palmitoylation by introducing a cysteine-to-serine mutation at C221 (NS2A/C221S) impaired JEV replication in vitro and attenuated JEV virulence in mice, suggesting that NS2A palmitoylation at C221 contributed to JEV replication and virulence. Based on these findings, we could infer that the C-terminal tail might play a role in the maintenance of JEV replication efficiency and virulence despite its removal from the full-length NS2A at a certain stage of JEV infection.

Polydopamine Enhanced Interactions of Graphene Nanosheets to Fabricate Graphene/Polydopamine Aerogels with Effectively Clear Organic Pollutants.

Graphene/polydopamine aerogels (GPDXAG, where X represents the weight ratio of DA·HCl to GO) were prepared by the chemical reduction of graphene oxide (GO) using dopamine (DA) and l-ascorbic acid as reducing agents. During the gelation process, DA was polymerized to form polydopamine (PDA). The introduction of PDA in the gelation of aerogels led to a deeper reduction of GO and stronger interactions between graphene nanosheets forced by covalent cross-linking and noncovalent bonding including π-π stacking and hydrogen bonding. The weight ratio of DA·HCl to GO influencing the formation and morphology of GPDXAG was explored. With the increasing content of DA in gelation, the reduction of GO and the cross-linking degree of graphene nanosheets were enhanced, and the resulting GPDXAG had a more regular pore distribution. Additionally, introducing PDA into GPDXAG improved its hydrophobicity because of the adhesion of PDA to a network of aerogels. GPDXAG exhibited a higher removal efficiency for organic pollutants than the controlled graphene aerogels (GAG). Specifically, the adsorption capacity of GPDXAG for organic solvents was superior to that of GAG, and organic solvent was completely separated from the oil/water mixture by GPDXAG. The equilibrium adsorption capacity of GPDXAG for malachite green (MG) was measured to be 768.50 mg/g, which was higher than that for methyl orange (MO). In MG/MO mixed solutions, aerogels had obvious adsorption selectivity for the cationic dye. The adsorption mechanism of aerogels for MG was also discussed by simulating adsorption kinetic models and adsorption isothermal models.

Baicalin ameliorates the gut barrier function and intestinal microbiota of broiler chickens.

The deoxynivalenol (DON)-contaminated feeds can impair chicken gut barrier function, disturb the balance of the intestinal microbiota, decrease chicken growth performance and cause major economic loss. With the aim of investigating the ameliorating effects of baicalin on broiler intestinal barrier damage and gut microbiota dysbiosis induced by DON, a total of 150 Arbor Acres broilers are used in the present study. The morphological damage to the duodenum, jejunum, and ileum caused by DON is reversed by treatment with different doses of baicalin, and the expression of tight junction proteins (ZO-1, claudin-1, and occludin) is also significantly increased in the baicalin-treated groups. Moreover, the disturbance of the intestinal microbiota caused by DON-contaminated feed is altered by baicalin treatment. In particular, compared with those in the DON group, the relative abundances of Lactobacillus, Lachnoclostridium, Ruminiclostridium and other beneficial microbes in the baicalin-treated groups are significantly greater. However, the percentage of unclassified_f__Lachnospiraceae in the baicalin-treated groups is significantly decreased in the DON group. Overall, the current results demonstrate that different doses of baicalin can improve broiler intestinal barrier function and the ameliorating effects on broiler intestinal barrier damage may be related to modulations of the intestinal microbiota.

Two Enterococcus faecium Isolates Demonstrated Modulating Effects on the Dysbiosis of Mice Gut Microbiota Induced by Antibiotic Treatment.

Broad-spectrum antibiotics are frequently used to treat bacteria-induced infections, but the overuse of antibiotics may induce the gut microbiota dysbiosis and disrupt gastrointestinal tract function. Probiotics can be applied to restore disturbed gut microbiota and repair abnormal intestinal metabolism. In the present study, two strains of Enterococcus faecium (named DC-K7 and DC-K9) were isolated and characterized from the fecal samples of infant dogs. The genomic features of E. faecium DC-K7 and DC-K9 were analyzed, the carbohydrate-active enzyme (CAZyme)-encoding genes were predicted, and their abilities to produce short-chain fatty acids (SCFAs) were investigated. The bacteriocin-encoding genes in the genome sequences of E. faecium DC-K7 and DC-K9 were analyzed, and the gene cluster of Enterolysin-A, which encoded a 401-amino-acid peptide, was predicted. Moreover, the modulating effects of E. faecium DC-K7 and DC-K9 on the gut microbiota dysbiosis induced by antibiotics were analyzed. The current results demonstrated that oral administrations of E. faecium DC-K7 and DC-K9 could enhance the relative abundances of beneficial microbes and decrease the relative abundances of harmful microbes. Therefore, the isolated E. faecium DC-K7 and DC-K9 were proven to be able to alter the gut microbiota dysbiosis induced by antibiotic treatment.

Various mobile genetic elements carrying optrA in Enterococcus faecium and Enterococcus faecalis isolates from swine within the same farm.

OBJECTIVES: In this study, the distribution of the oxazolidinone/phenicol resistance gene optrA and the mobile genetic elements involved in its dissemination were analysed among enterococcal isolates from a farrow-to-finish swine farm. METHODS: Enterococcus faecium and Enterococcus faecalis isolates were obtained from all pig production stages in the farm. The optrA-carrying E. faecium and E. faecalis isolates were subjected to PFGE and antimicrobial susceptibility testing. Complete sequences of the genetically unrelated optrA-carrying E. faecium and E. faecalis isolates were determined using Illumina HiSeq and MinION platforms. RESULTS: The optrA gene was present in 12.2% (23/188) of the E. faecium and E. faecalis isolates, most of which originated from nursery and finishing stages. The 23 optrA-positive Enterococcus isolates represented 15 PFGE types. WGS of representative isolates of the 15 PFGE types showed that optrA was carried by diverse genetic elements either located in the chromosomal DNA or on plasmids. A novel optrA-bearing genetic element was identified on two distinct multi-resistance plasmids from E. faecium. Two new hybrid plasmids carrying several resistance genes were found in two E. faecalis isolates. pC25-1-like plasmids and chromosomally integrated Tn6674 and Tn6823-like transposons were prevalent in the remaining Enterococcus isolates. CONCLUSIONS: The gene optrA was found in genetically unrelated E. faecium and E. faecalis isolates from the same farm. Analysis of the genetic contexts of optrA suggested that horizontal transfer including different plasmids and transposons played a key role in the dissemination of optrA in this farm.

NS5-V372A and NS5-H386Y variations are responsible for differences in interferon α/ß induction and co-contribute to the replication advantage of Japanese encephalitis virus genotype I over genotype III in ducklings.

Japanese encephalitis virus (JEV) genotype I (GI) replicates more efficiently than genotype III (GIII) in birds, and this difference is considered to be one of the reasons for the JEV genotype shift. In this study, we utilized duck embryo fibroblasts and domestic ducklings as in vitro and in vivo models of a JEV amplifying avian host to identify the viral determinants of the differing replication efficiency between the GI and GIII strains in birds. GI strains induced significantly lower levels of interferon (IFN)-α and ß production than GIII strains, an effect orrelated with the enhanced replication efficiency of GI strains over GIII strains. By using a series of chimeric viruses with exchange of viral structural and non-structural (NS) proteins, we identified NS5 as the viral determinant of the differences in IFN-α and ß induction and replication efficiency between the GI and III strains. NS5 inhibited IFN-α and ß production induced by poly(I:C) stimulation and harbored 11 amino acid variations, of which the NS5-V372A and NS5-H386Y variations were identified to co-contribute to the differences in IFN-α and ß induction and replication efficiency between the strains. The NS5-V372A and NS5-H386Y variations resulted in alterations in the number of hydrogen bonds formed with neighboring residues, which were associated with the different ability of the GI and GIII strains to inhibit IFN-α and ß production. Our findings indicated that the NS5-V372A and NS5-H386Y variations enabled GI strains to inhibit IFN-α and ß production more efficiently than GIII strains for antagonism of the IFN-I mediated antiviral response, thereby leading to the replication and host adaption advantages of GI strains over GIII strains in birds. These findings provide new insight into the molecular basis of the JEV genotype shift.

Comparative analysis of the pulmonary microbiome in healthy and diseased pigs.

The lungs possess an effective antimicrobial system and a strong ability to eliminate microorganisms in healthy organisms, and were once considered sterile. With the development of culture-independent sequencing technology, the richness and diversity of porcine lung microbiota have been gaining attention. In order to study the relationship between lung microbiota and porcine respiratory disease complex (PRDC), the lung microbiota in healthy and diseased swine bronchoalveolar lavage fluids were analyzed and compared using the Illumina MiSeq sequencing platform. The predominant microbial communities of healthy and diseased swine were similar at the phylum level, mainly composed of Proteobacteria, Firmicutes, Tenericutes, and Bacteroidetes. However, the bacterial taxonomic communities of healthy and diseased swine differed at the genus level. The higher relative abundances of Lactococcus, Enterococcus, Staphylococcus, and Lactobacillus genera in healthy swine might provide more benefits for lung health, while the enhanced richness of Streptococcus, Haemophilus, Pasteurella, and Bordetella genera in diseased swine might be closely related to pathogen invasion and the occurrence of respiratory disease. In conclusion, the observed differences in the richness and diversity of lung microbiota can provide novel insights into their relationship with PRDC. Analyses of swine lung microbiota communities might produce an effective strategy for the control and prevention of respiratory tract infections.

Mosquito Defensins Enhance Japanese Encephalitis Virus Infection by Facilitating Virus Adsorption and Entry within the Mosquito.

Japanese encephalitis virus (JEV) is a viral zoonosis that can cause viral encephalitis, death, and disability. Although the Culex mosquito is the primary vector of JEV, little is known about JEV transmission by this kind of mosquito. Here, we found that mosquito defensin facilitated the adsorption of JEV on target cells via the defensin/lipoprotein receptor-related protein 2 (LRP2) axis. Mosquito defensin bound the ED III domain of the viral envelope (E) protein and directly mediated efficient virus adsorption on the target cell surface; the receptor LRP2, which is expressed on the cell surface, affected defensin-dependent adsorption. As a result, mosquito defensin enhanced JEV infection in the salivary gland, increasing the possibility of viral transmission by mosquitoes. These findings demonstrate the novel role of mosquito defensin in JEV infection and the mechanisms through which the virus exploits mosquito defensin for infection and transmission.IMPORTANCE In this study, we observed the complex roles of mosquito defensin in JEV infection; mosquito defensin exhibited a weak antiviral effect but strongly enhanced binding. In the latter, defensin directly binds the ED III domain of the viral E protein and promotes the adsorption of JEV to target cells by interacting with lipoprotein receptor-related protein 2 (LRP2), thus accelerating virus entry. Together, our results indicate that mosquito defensin plays an important role in facilitating JEV infection and potential transmission.

Downregulation of miR-296-3p by highly pathogenic porcine reproductive and respiratory syndrome virus activates the IRF1/TNF-α signaling axis in porcine alveolar macrophages.

Porcine reproductive and respiratory syndrome virus (PRRSV, species Betaarterivirus suid 1 or 2) is a major pathogen affecting pigs on farms throughout the world. miR-296-3p is a multifunctional microRNA involved in the regulation of the inflammatory response in mice and humans. However, little is known about the biological functions of miR-296-3p in pigs. In this study, we used a highly pathogenic PRRSV-2 (species Betaarterivirus suid 2) strain to show that PRRSV infection robustly downregulates the expression of miR-296-3p in porcine alveolar macrophages (PAMs). Furthermore, we demonstrated that overexpression of miR-296-3p increases the replication of highly pathogenic (HP)-PRRSV in PAMs. Notably, the overexpression of miR-296-3p inhibited the induction of TNF-α, even with increased viral replication, compared with that in the HP-PRRSV-infected control group. We also demonstrated that miR-296-3p targets IRF1-facilitated viral infection and modulates the expression of TNF-α in PAMs during HP-PRRSV infection and that IRF1 regulates the expression of TNF-α by activating the TNF promoter via IRF1 response elements. In summary, these findings show that HP-PRRSV infection activates the IRF1/TNF-α signaling axis in PAMs by downregulating host miR-296-3p. This extends our understanding of the inflammatory response induced by HP-PRRSV infection.

Rapid and accurate detection of African swine fever virus by DNA endonuclease-targeted CRISPR trans reporter assay.

The first case of African swine fever (ASF) outbreak in China was reported in a suburban pig farm in Shenyang in 2018. Since then, the rapid spread and extension of ASF has become the most serious threat for the swine industry. Therefore, rapid and accurate detection of African swine fever virus (ASFV) is essential to provide effective strategies to control the disease. In this study, we developed a rapid and accurate ASFV-detection method based on the DNA endonuclease-targeted CRISPR trans reporter (DETECTR) assay. By combining recombinase polymerase amplification with CRISPR-Cas12a proteins, the DETECTR assay demonstrated a minimum detection limit of eight copies with no cross reactivity with other swine viruses. Clinical blood samples were detected by DETECTR assay and showed 100% (30/30) agreement with real-time polymerase chain reaction assay. The rapid and accurate detection of ASFV may facilitate timely eradication measures and strict sanitary procedures to control and prevent the spread of ASF.

Structural and antioxidant analysis of Tartary buckwheat (Fagopyrum tartaricum Gaertn.) 13S globulin.

BACKGROUND: The main component of buckwheat seed storage proteins is 13S globulin. In this study, Tartary buckwheat 13S globulin was separated and its structural features were investigated using Edman sequencing and matrix-assisted laser desorption / ionization time of flight mass spectrometry (MALDI-TOF-MS). The protective effect of its enzymatic hydrolysates against oxidative stress induced by H2 O2 was also evaluated to elucidate the antioxidant mechanism. RESULTS: Results showed that the isolated Tartary buckwheat 13S globulin contained one acidic and one basic subunit, which were linked by a disulfide bond. Six Tartary buckwheat active peptides were obtained from the enzymatic hydrolysates of Tartary buckwheat 13S globulin acidic subunit with a molecular weight of 38 kDa, namely Pep-1, Pep-2, Pep-3, Pep-4, Pep-5, and Pep-6. Pre-treatment of cells with Tartary buckwheat active peptides maintained the redox state balance of HepG2 cells and protected the activity of antioxidant enzymes in HepG2 cells. The Tartary buckwheat active peptides improved oxidative stress in HepG2 cells via the PPAR-α/HO-1 pathway. CONCLUSION: These results provide an insight into the antioxidant mechanism of Tartary buckwheat 13S globulin and suggest that Tartary buckwheat active peptides can be used as a functional ingredient in the food industry. © 2019 Society of Chemical Industry.

Prices, availability and affordability of insulin products: a cross-sectional survey in Shaanxi Province, western China.

OBJECTIVE: To evaluate price, availability and affordability of insulin products in Shaanxi Province, western China. METHODS: We used a simplified and adapted WHO/Health Action International method to obtain the availability and prices of insulin products and five oral anti-diabetic medicines as comparators in public general hospitals and private retail outlets. In addition, we investigated the price components of eight selected insulin products by tracing the supply chain. RESULTS: All three kinds of insulin products, prandial, basal and premixed insulin, are 100% available in public hospitals, and have fairly high availability in the private sector (62.5-68.8%). The prices of most insulin products were higher than international reference prices in both sectors (ranging from 0.95 times to 2.33 times). All insulin products were unaffordable as they would cost 3.5-17.1 days' wage of the lowest-paid government workers in Shaanxi. The manufacturer's markup (selling price), which comprised more than 60% of the final price of all insulin products surveyed, was the largest price component. CONCLUSIONS: Although availability of insulin products was high in public general hospitals and private retail pharmacies, their high price made them unaffordable to diabetes patients, especially low-income patients. The government should increase insurance compensation for those who need these life-saving medicines or decrease the cost of insulin products through negotiation with suppliers.

Early-life food nutrition, microbiota maturation and immune development shape life-long health.

The current knowledge about early-life nutrition and environmental factors that affect the interaction between the symbiotic microbiota and the host immune system has demonstrated novel regulatory target for treating allergic diseases, autoimmune disorders and metabolic syndrome. Various kinds of food nutrients (such as dietary fiber, starch, polyphenols and proteins) can provide energy resources for both intestinal microbiota and the host. The indigestible food components are fermented by the indigenous gut microbiota to produce diverse metabolites, including short-chain fatty acids, bile acids and trimethylamine-N-oxide, which can regulate the host metabolized physiology, immunity homeostasis and health state. Therefore it is commonly believed early-life perturbation of the microbial community structure and the dietary nutrition interference on the child mucosal immunity contribute to the whole life susceptibility to chronic diseases. In all, the combined interrelationship between food ingredients nutrition, intestinal microbiota configurations and host system immunity provides new therapeutic targets to treat various kinds of pathogenic inflammations and chronic diseases.

The Effect of Tartary Buckwheat Flavonoids in Inhibiting the Proliferation of MGC80-3 Cells during Seed Germination.

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is rich in functional compounds such as rutin, quercetin, d-chiro-inositol, dietary fiber, and essential amino acids. Electric field (EF) treatment before sprout germination results in physiological and chemical changes, and some alterations might lead to positive applications in plant seeds. MTT assay showed that the effect of total flavonoids on human gastric cancer cell line MGC80-3 was significantly changed after EF treatment for different germination days (3-7 days). Among them, the total flavonoids of tartary buckwheat (BWTF) on the third day had the most obvious inhibitory effect on MGC80-3 (p < 0.01). In addition, flow cytometry evidenced that different ratios of quercetin and rutin had effects on the proliferation of MGC80-3. The same content of quercetin and rutin had the best effect, reaching 6.18 ± 0.82%. The anti-cancer mechanism was mainly promoted by promoting the expression of apoptotic proteins. The expression of Bax/Bcl-2 and caspase-8 in MGC80-3 cells was mediated by BWTFs. This study has good research value for improving the biological and economic value of tartary buckwheat.

Disparities in out-of-pocket inpatient expenditures in rural Shaanxi Province, western China from 2011 to 2014: a time series analysis.

OBJECTIVE: To investigate the long-term trend of disparity of monthly average out-of-pocket inpatient expenditures (OOP) between areas with different developing levels since the new healthcare reform. METHODS: Time series regression was used to assess the trend of disparities of OOP and monthly average inpatient expenditures (AIE) between areas with different developing levels in rural Shaanxi Province, western China. The data of OOP and AIE in primary health institutions, secondary hospitals, tertiary hospitals and also all levels of the hospital were analysed separately covering the period 2011 through to 2014. RESULTS: The disparity of AIE at all levels of hospitals was increasing (coefficient = 0.003, P = 0.029), and only the disparity of AIE in secondary hospitals was statistical significant (coefficient = 0.003, P = 0.012) when separately considering different levels of the hospital. The disparity of OOP in all levels of the hospital was increasing (coefficient = 0.007, P = 0.001), and the OOP in primary hospitals contributed most of the disparity (coefficient = 0.019, P = 0.000), followed by OOP in secondary (coefficient = 0.008, P = 0.003) and tertiary hospitals (coefficient = 0.004, P = 0.091). CONCLUSIONS: A statistically significant absolute increase in the trend of disparities of OOP and AIE at all levels of hospital was detected after the new healthcare reform in Shaanxi Province, western China. The increase rate of disparity of OOP was bigger than that of AIE. A modified health insurance plan should be proposed to guarantee equity in the future.

Impact of the zero-markup drug policy on hospitalisation expenditure in western rural China: an interrupted time series analysis.

OBJECTIVES: To assess the long-term effects of the introduction of China's zero-markup drug policy on hospitalisation expenditure and hospitalisation expenditures after reimbursement. METHODS: An interrupted time series was used to evaluate the impact of the zero-markup drug policy on hospitalisation expenditure and hospitalisation expenditure after reimbursement at primary health institutions in Fufeng County of Shaanxi Province, western China. Two regression models were developed. Monthly average hospitalisation expenditure and monthly average hospitalisation expenditure after reimbursement in primary health institutions were analysed covering the period 2009 through to 2013. RESULTS: For the monthly average hospitalisation expenditure, the increasing trend was slowed down after the introduction of the zero-markup drug policy (coefficient = -16.49, P = 0.009). For the monthly average hospitalisation expenditure after reimbursement, the increasing trend was slowed down after the introduction of the zero-markup drug policy (coefficient = -10.84, P = 0.064), and a significant decrease in the intercept was noted after the second intervention of changes in reimbursement schemes of the new rural cooperative medical insurance (coefficient = -220.64, P < 0.001). CONCLUSIONS: A statistically significant absolute decrease in the level or trend of monthly average hospitalisation expenditure and monthly average hospitalisation expenditure after reimbursement was detected after the introduction of the zero-markup drug policy in western China. However, hospitalisation expenditure and hospitalisation expenditure after reimbursement were still increasing. More effective policies are needed to prevent these costs from continuing to rise.

A Real-world Study of Denosumab For Reducing Refracture Risk after Percutaneous Vertebral Augmentation.

OBJECTIVE: To investigate the use of anti-osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real-world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real-world scenarios to enhance the management of bone health in OVCF patients. METHODS: This retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55-90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on-treatment and off-treatment groups according to whether they received a second dose of denosumab, with follow-up beginning on the index day (225 days after the first denosumab dose). In this study, the off-treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti-osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed. RESULTS: A total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on-treatment group than in the off-treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on-treatment group than in the off-treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti-osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%-15% taking oral bisphosphonates. CONCLUSION: Postmenopausal women have a high refracture rate and a low proportion of anti-osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.

Multidimensional occurrence and diet risk of emerging contaminants in freshwater with urban agglomerations.

Freshwater systems near highly urbanized areas are extremely susceptible to emerging contaminants (ECs), yet their stereoscopic persistence in aquatic ecosystems and related risks remain largely unknown. Herein, we characterized the multi-mediums distribution of 63 ECs in Baiyangdian Lake, the biggest urban lake in the North of China. We identified variations in the seasonal patterns of aquatic EC levels, which decreased in water and increased in sediment from wet to dry seasons. Surprisingly, higher concentrations and a greater variety of ECs were detected in reeds than in aquatic animals, indicating that plants may contribute to the transferring of ECs. Source analysis indicated that human activity considerably affected the distribution and risk of ECs. The dietary risk of ECs is most pronounced among children following the intake of aquatic products, especially with a relatively higher risk associated with fish consumption. Besides, a comprehensive scoring ranking method was proposed, and 9 ECs, including BPS and macrolide antibiotics, are identified as prioritized control pollutants. These findings highlight the risks associated with aquatic ECs and can facilitate the development of effective management strategies.