Biodegradable Plant Oil-Based Bioadhesive with Ultrastrong Wet-Tissue Adhesion for Instant Sealing Hemostasis.

The key to saving lives is to achieve instant and effective sealing hemostasis in the event of emergency bleeding. Herein, a plant oil-based EMTA/Zn2+ bioadhesive is prepared by a facile reaction of epoxidized soybean oil (ESO) with methacrylic acid (MAA) and tannic acid (TA), followed by the addition of zinc ions for coordination with TA. The EMTA/Zn2+ bioadhesive can be rapidly cured in situ at the wound site through photo-cross-linking under ultraviolet (UV) light-emitting diode (LED) irradiation within 30 s, achieving ultrastrong wet-tissue adhesion performance of 92.4 and 51.8 kPa to porcine skin and aortic skin after 7 days underwater, respectively. Especially, the EMTA/Zn2+ bioadhesive exhibits outstanding sealing performance in vitro with the high burst pressure of 525 mmHg (70 kPa) and 337.5 mmHg (45 kPa) to porcine skin and aortic skin, respectively. Moreover, the EMTA/Zn2+ bioadhesive not only has outstanding hemocompatibility and good biodegradability but also exhibits excellent cytocompatibility and antibacterial properties. Notably, the EMTA/Zn2+ bioadhesive has remarkable instant sealing hemostatic ability for hemorrhaging liver in vivo. Therefore, the prepared plant oil-based EMTA/Zn2+ bioadhesive can serve as a charming alternative candidate for instant sealing hemostasis in clinical applications, especially in traumatic internal organs and arterial bleeding.

Reductions in renin-angiotensin system inhibitors following hospitalization for heart failure.

AIMS: Limited data are available that evaluate the efficacy of renin-angiotensin system inhibitor (RASI) dose-reduction in older adults with heart failure with reduced ejection fraction following a heart failure hospitalization. METHODS AND RESULTS: We examined a 5% random sample of Medicare beneficiaries with prescription coverage who were discharged to home following a hospitalization for heart failure with reduced ejection fraction between 1 January 2007 and 30 June 2018 and were treated with RASI prior to hospitalization. We classified patients into three mutually exclusive groups based on RASI dosage before (prescription fills up to 90 days prior to) and after a hospitalization (prescription fills up to 365 days that were most proximate to the discharge date as possible)-same/increased dose, dose-reduction, and discontinuation. We examined associations between RASI prescribing patterns and outcomes (mortality and all-cause readmission at 30 days and 1 year) using Cox proportional hazards models. Among 12 794 unique older adults, 36.8% experienced a RASI reduction following their hospitalization for HFrEF-15.7% had a dose-reduction and 21.1% had a discontinuation. Neither dose-reduction nor discontinuation was associated with 30-day mortality. Discontinuation was associated 1-year mortality, 30-day all-cause readmission, and 1-year all-cause readmission, whereas dose-reduction was not. CONCLUSION: RASI dose-reduction occurs in 1 out of 7 HF hospitalizations. In contrast to RASI discontinuation, RASI dose-reduction was not associated with adverse short or long-term outcomes. These findings indicate that RASI dose-reduction is preferred over RASI discontinuation in selected situations where RASI reduction is needed.

Predicted Cardiovascular Risk by the PREVENT Equations in US Adults With Stage 1 Hypertension.

BACKGROUND: The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends initiation of antihypertensive medication for adults with stage 1 hypertension (systolic blood pressure, 130-139 mm Hg, or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10% estimated by the pooled cohort equations (PCEs). In 2023, the American Heart Association published the predicting risk of cardiovascular disease events (PREVENT) equations to estimate ASCVD and total cardiovascular disease risk. METHODS: We analyzed US National Health and Nutrition Examination Survey data from 2013 to 2020 for 1703 adults aged 30 to 79 years without self-reported cardiovascular disease with stage 1 hypertension. We estimated 10-year ASCVD risk by the PCEs and 10-year ASCVD and total cardiovascular disease risk by the base PREVENT equations. Analyses were weighted to represent noninstitutionalized US adults with stage 1 hypertension. RESULTS: Mean 10-year ASCVD risk was 5.4% (95% CI, 5.0%-5.9%) and 2.9% (95% CI, 2.7%-3.1%) using the PCEs and PREVENT equations, respectively. The proportion with 10-year ASCVD risk of 10% to <15% and ≥15% was 8.1% and 7.8% estimated by the PCEs, respectively, and 3.0% and 0.3% estimated by the PREVENT equations, respectively. No participants had a 10-year ASCVD risk ≥10% on the PREVENT equations and <10% on the PCEs, while 12.5% had a 10-year ASCVD risk ≥10% on the PCEs and <10% on the PREVENT equations. The mean 10-year total cardiovascular disease risk estimated by the PREVENT equations was lower than the mean 10-year ASCVD risk on the PCEs. CONCLUSIONS: Among US adults with stage 1 hypertension, the 10-year predicted ASCVD risk estimated by the PREVENT equations was approximately half the risk estimated by the PCEs.

Oregano Essential Oil in Livestock and Veterinary Medicine.

With a growing global concern over food safety and animal welfare issues, the livestock and veterinary industries are undergoing unprecedented changes. These changes have not only brought challenges within each industry, but also brought unprecedented opportunities for development. In this context, the search for natural and safe products that can effectively replace traditional veterinary drugs has become an important research direction in the fields of animal husbandry and veterinary medicine. Oregano essential oil (OEO), as a natural extract, is gradually emerging in the fields of animal husbandry and veterinary medicine with its unique antibacterial, antioxidant, and multiple other biological activities. OEO not only has a wide antibacterial spectrum, effectively fighting against a variety of pathogenic microorganisms, but also, because of its natural properties, helps us to avoid traditional veterinary drugs that may bring drug residues or cause drug resistance problems. This indicates OEO has great application potential in animal disease treatment, animal growth promotion, and animal welfare improvement. At present, the application of OEO in the fields of animal husbandry and veterinary medicine has achieved preliminary results. Studies have shown that adding OEO to animal feed can significantly improve the growth performance and health status of animals and reduce the occurrence of disease. At the same time, pharmacokinetic studies in animals show that the absorption, distribution, metabolism, and excretion processes of OEO in animals shows good bioavailability. In summary, oregano essential oil (OEO), as a substitute for natural veterinary drugs with broad application prospects, is gradually becoming a research hotspot in the field of animal husbandry and veterinary medicine. In the future, we look forward to further tapping the potential of OEO through more research and practice and making greater contributions to the sustainable development of the livestock and veterinary industries.

Epidemiological Investigation of Goose Astrovirus in Hebei Province, China, 2019-2021.

The goose astrovirus (GAstV), a key pathogen causing visceral gout and high mortality in geese, has spread widely in China, with frequent outbreaks in recent years. Outbreaks and transmissions of this virus have been reported across China, causing considerable economic losses to the goose industry worldwide, with losses exceeding tens of billions in China alone. However, there is still no effective prevention strategy against this virus. Therefore, continuous monitoring of the genetic diversity of dominant GAstV strains is crucial for developing targeted vaccines and appropriate therapeutics. As a crucial region for goose breeding in China, Hebei Province has previously lacked reports on the epidemiology of GAstV. Hence, investigating the epidemiology of GAstV in Hebei Province is highly important. From January 2019 to December 2021, 474 samples suspected of having a GAstV infection were collected in Hebei Province in this study. Through detailed histological observations, pathological examinations, virus isolation and identification, and genetic diversity analysis, we found that GAstV-2 has become the predominant circulating genotype. However, the presence of GAstV-1 and mixed infections cannot be ignored and should receive increased attention. The findings of this study not only deepened our understanding of GAstV in waterfowl in China but also provided scientific evidence for developing effective prevention and control measures, thereby promoting the healthy development of the goose industry in China.

Urea-formaldehyde resin room temperature phosphorescent material with ultra-long afterglow and adjustable phosphorescence performance.

Organic room-temperature phosphorescence materials have attracted extensive attention, but their development is limited by the stability and processibility. Herein, based on the on-line derivatization strategy, we report the urea-formaldehyde room-temperature phosphorescence materials which are constructed by polycondensation of aromatic diamines with urea and formaldehyde. Excitingly, urea-formaldehyde room-temperature phosphorescence materials achieve phosphor lifetime up to 3326 ms. There may be two ways to enhance phosphorescence performance, one is that the polycondensation of aromatic diamine with urea and formaldehyde promotes spin-orbit coupling, and another is that the imidazole derivatives derived from the condensation of aromatic o-diamine with formaldehyde maintains low levels of energy level difference and spin-orbit coupling, thus achieving ultra-long afterglow. Surprisingly, urea-formaldehyde room-temperature phosphorescence materials exhibit tunable phosphorescence emission in electrostatic field. Accordingly, 1,4-phenylenediamine, urea, and formaldehyde are copolymerized and self-assembled into phosphorescence microspheres with different electrostatic potential strengths. By mixing 1 wt% 1,4-phenylenediamine polycondensation microspheres with 1,4-phenylenediamine free microspheres, phosphor lifetime of the composite could be regulated from 27 ms to 123 ms. Moreover, vulcanization process enables precise shaping of urea-formaldehyde room-temperature phosphorescence materials. This work not only demonstrates that urea-formaldehyde room-temperature phosphorescence materials are promising candidates for organic phosphors, but also exhibits the phenomenon of electrostatically regulated phosphorescence.

Persistence and Adherence to PCSK9 Inhibitor Monoclonal Antibodies Versus Ezetimibe in Real-World Settings.

INTRODUCTION: The cardiovascular disease risk reduction benefits of proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (PCSK9i mAb) and ezetimibe are dependent on remaining on treatment and being persistent and adherent. We estimated the percentage of patients on therapy, persistent and adherent at 182 and 365 days among US adults with health insurance who initiated a PCSK9i mAb (n = 16,588) or ezetimibe (n = 83,086) between July 2015 and December 2019. METHODS: Using pharmacy fill claims, being on therapy was defined as having a day of medication supply in the last 60 of 182 and 365 days following treatment initiation, being persistent was defined as not having a gap of 60 days or more between the last day of supply from one prescription fill and the next fill, and being adherent was defined by having medication available to take on ≥ 80% of the 182 and 365 days following treatment initiation. We estimated multivariable-adjusted risk ratios for being persistent and adherent comparing patients initiating PCSK9i mAb versus ezetimibe using Poisson regression. RESULTS: At 182 days following initiation, 80% and 68% were on therapy and 76% and 64% were persistent among patients who initiated a PCSK9i mAb and ezetimibe, respectively. Among patients who were on therapy and persistent at 182 days following initiation, 88% and 81% of those who initiated a PCSK9i mAb and ezetimibe, respectively, were on therapy at 365 days. Among those on therapy and persistent at 182 days following initiation, being persistent and being adherent at 365 days were each more common among PCSK9i mAb versus ezetimibe initiators (persistent: 82% versus 76%, multivariable-adjusted risk ratio 1.07; 95% confidence interval [CI] 1.06-1.08; adherent: 74% versus 71%, multivariable-adjusted risk ratio 1.02; 95% CI 1.01-1.03). CONCLUSIONS: These data suggest approaches to increase persistence and adherence to PCSK9i mAb and ezetimibe should be implemented prior to or within 182 days following treatment initiation.

Trends in the Prevalence of Multiple Chronic Conditions Among US Adults With Hypertension From 1999-2000 Through 2017-2020.

BACKGROUND: The prevalence of many chronic conditions has increased among US adults. Many adults with hypertension have other chronic conditions. METHODS: We estimated changes in the age-adjusted prevalence of multiple (≥3) chronic conditions, not including hypertension, using data from the National Health and Nutrition Examination Survey, from 1999-2000 to 2017-2020, among US adults with (n = 24,851) and without (n = 24,337 hypertension. Hypertension included systolic blood pressure (BP) ≥130 mm Hg, diastolic BP ≥80 mm Hg, or antihypertensive medication use. We studied 14 chronic conditions: arthritis, asthma, cancer, coronary heart disease, chronic kidney disease, depression, diabetes, dyslipidemia, hepatitis B, hepatitis C, heart failure, lung disease, obesity, and stroke. RESULTS: From 1999-2000 to 2017-2020, the age-adjusted mean number of chronic conditions increased more among US adults with vs. without hypertension (2.2 to 2.8 vs. 1.7 to 2.0; P-interaction <0.001). Also, the age-adjusted prevalence of multiple chronic conditions increased from 39.0% to 52.0% among US adults with hypertension and from 26.0% to 30.0% among US adults without hypertension (P-interaction = 0.022). In 2017-2020, after age, gender, and race/ethnicity adjustment, US adults with hypertension were 1.94 (95% confidence interval: 1.72-2.18) times as likely to have multiple chronic conditions compared to those without hypertension. In 2017-2020, dyslipidemia, obesity, and arthritis were the most common 3 co-occurring chronic conditions among US adults with and without hypertension (age-adjusted prevalence 16.5% and 3.1%, respectively). CONCLUSIONS: In 2017-2020, more than half of US adults with hypertension had ≥3 additional chronic conditions, a substantial increase from 20 years ago.

Comparing PCSK9 Monoclonal Antibody Treatment Strategies Following Myocardial Infarction Using Negative Control Outcomes: A Target Trial Emulation Study.

BACKGROUND: Initiation of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9 mAb) for lipid-lowering following myocardial infarction (MI) is likely affected by patients' prognostic factors, potentially leading to bias when comparing real-world treatment effects. METHODS: Using target-trial emulation, we assessed potential confounding when comparing two treatment strategies post-MI: initiation of PCSK9 mAb within 1 year and no initiation of PCSK9 mAb. We identified MI hospitalizations during July 2015-June 2020 for patients aged ≥18 years in Optum's de-identified Clinformatics Data Mart (CDM) and MarketScan, and those aged ≥66 in the US Medicare claims database. We estimated a 3-year counterfactual cumulative risk and risk difference (RD) for 10 negative control outcomes using the clone-censor-weight approach to address time-varying confounding and immortal person-time. RESULTS: PCSK9 mAb initiation within 1-year post-MI was low (0.7% in MarketScan and 0.4% in both CDM and Medicare databases). In CDM, there was a lower risk for cancer (RD = -3.6% [95% CI: -4.3%, -2.9%]), decubitus ulcer (RD = -7.7% [95% CI: -11.8%, -3.7%]), fracture (RD = -8.1% [95% CI: -9.6%, -6.6%]), influenza vaccine (RD = -9.3% [95% CI: -17.5%, -1.1%]), and visual test (RD = -0.6% [95% CI: -0.7%, -0.6%]) under the PCSK9 mAb initiation versus no initiation strategy. Similar differences persisted in the MarketScan and Medicare databases. In each database, ezetimibe and low-density lipoprotein testing were unbalanced between treatment strategies. CONCLUSION: A comparative effectiveness study of these treatments using the current approach would likely bias results due to the low number of PCSK9 mAb initiators.

Comparison of B cells' immune response induced by PEDV virulent and attenuated strains.

Porcine epidemic diarrhea virus (PEDV) is an acute, highly contagious enterovirus that infects pigs of all ages. The B cells are important for antigen presentation, antibody production, and cytokine secretion to resist infection. However, the role of B cells in PEDV infection remains unclear. In this study, the effects of PEDV virulent (QY2016) and attenuated strains (CV777) on B cells sorted from neonatal piglets, nursery piglets, and gilts were investigated. The results showed that PEDV-QY2016 and PEDV-CV777 could significantly increase the expression of CD54 and CD27 in B cells from neonatal piglets. The percentages of CD80, MHC II, and IgM expressed on neonatal piglet B cells infected with PEDV-QY2016 were significantly lower than those expressed on the B cells infected with PEDV-CV777. Both PEDV-QY2016 and PEDV-CV777 could stimulate IFN-α and GM-CSF secretions in neonatal piglet B cells; IL-1, IFN-α, and IL-4 secretion in nursery piglet B cells; and IL-1, TGF-ß secretion, and GM-CSF in gilt B cells. Furthermore, both PEDV-QY2016 and PEDV-CV777 could induce the secretion of IgA, IgM, and IgG in nursery piglet B cells but could not induce the secretion of IgA, IgM, and IgG in neonatal piglet B cells. The secretion of IgA, IgM, and IgG was significantly higher by the PEDV-CV777 strains infected B cells than those by the PEDV-QY2016 strains infected gilt B cells. In conclusion, the surface molecule expression, cytokine secretion, and antibody production of B cells induced by PEDV are closely related to the ages of pigs and the virulence of the PEDV strain.

Modified photoanode by in situ growth of covalent organic frameworks on BiVO4 for oxygen evolution reaction.

The development of efficient oxygen evolution reaction (OER) catalysts is of great significance because the water oxidation reaction at the photoanode is the rate-determining step in photoelectrocatalytic (PEC) water splitting. Herein, two hybrid photoanodes named BiVO4/COF-Azo and BiVO4/COF-Ben were prepared by in situ solvothermal growth on a modified BiVO4 photoanode. Characterization results revealed that the Azo and Ben COFs could match with BiVO4 well to form heterojunctions, which could effectively enhance the separation efficiency of photogenerated carriers. Also, the smaller impedance of the composite photoanodes and faster kinetics of the water oxidation reaction promoted the charge transmission and enhanced the reaction efficiency of the surface-reaching holes, respectively. As a result, the composite photoanodes exhibited a larger photocurrent and more negative onset potential compared to the pristine BiVO4. This work not only provides a new strategy to construct efficient hybrid photoanodes, but also expands the applications of COFs.

ε-Polylysine organic ultra-long room-temperature phosphorescent materials based on phosphorescent molecule doping.

Achieving long-lived room-temperature phosphorescence from pure organic amorphous polymers is attractive, and afterglow materials with colour-tunable and multiple-stimuli-responsive afterglow are particularly important, but only few materials with these characteristics have been reported so far. Herein, a facile and general method is reported to construct a series of ε-polylysine (ε-PL)-based afterglow materials with tunable colour (from blue to red) and long life. By doping guest molecules into ε-PL to obtain composite materials, the polymer matrix provides a rigid environment for luminescent groups, resulting in amorphous polymers with different RTPs. In this system, the materials even have impressive humidity-stimulated responses, and the phosphorescence emission exhibits excitation-dependent and time-dependent properties. The humidity-responsive afterglow is caused by the destruction of hydrogen bonds and quenching of triplet excitons. The time-dependent afterglow should stem from the formation of diversified RTP emissive species with comparable but different lifetimes. 9,10-diaminophene has Ex-De properties in the film doping state. With the change of excitation wavelength (254 nm to 365 nm), the emission wavelength shifts from 461 nm to 530 nm, accompanied by the change of emission colour from blue to green. In addition, the phosphorescence life of the film is the longest, up to 2504.7 ms, and the afterglow lasts up to 15 s, which is conducive to its applications in anti-counterfeiting and information encryption.

Structural insights into human organic cation transporter 1 transport and inhibition.

The human organic cation transporter 1 (hOCT1), also known as SLC22A1, is integral to hepatic uptake of structurally diversified endogenous and exogenous organic cations, influencing both metabolism and drug pharmacokinetics. hOCT1 has been implicated in the therapeutic dynamics of many drugs, making interactions with hOCT1 a key consideration in novel drug development and drug-drug interactions. Notably, metformin, the frontline medication for type 2 diabetes, is a prominent hOCT1 substrate. Conversely, hOCT1 can be inhibited by agents such as spironolactone, a steroid analog inhibitor of the aldosterone receptor, necessitating a deep understanding of hOCT1-drug interactions in the development of new pharmacological treatments. Despite extensive study, specifics of hOCT1 transport and inhibition mechanisms remain elusive at the molecular level. Here, we present cryo-electron microscopy structures of the hOCT1-metformin complex in three distinct conformational states - outward open, outward occluded, and inward occluded as well as substrate-free hOCT1 in both partially and fully open states. We also present hOCT1 in complex with spironolactone in both outward and inward facing conformations. These structures provide atomic-level insights into the dynamic metformin transfer process via hOCT1 and the mechanism by which spironolactone inhibits it. Additionally, we identify a 'YER' motif critical for the conformational flexibility of hOCT1 and likely other SLC22 family transporters. Our findings significantly advance the understanding of hOCT1 molecular function and offer a foundational framework for the design of new therapeutic agents targeting this transporter.

Trends in All-Cause, Cardiovascular, and Noncardiovascular Mortality Among US Adults With Hypertension.

BACKGROUND: Death certificate data indicate that hypertension may have increased as a contributing cause of death among US adults. Hypertension is not commonly recorded on death certificates although it contributes to a substantial proportion of cardiovascular disease (CVD) deaths. METHODS: We estimated changes in all-cause, CVD, and non-CVD mortality over 5 years of follow-up among 4 cohorts of US adults with hypertension using mortality follow-up data from National Health and Nutrition Examination Survey III in 1988 to 1994, and National Health and Nutrition Examination Survey cycles from 1999 to 2000 through 2015 to 2016 (n=20 927). Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or antihypertensive medication use. Participants were grouped according to the date of their National Health and Nutrition Examination Survey study visit (1988-1994, 1999-2004, 2005-2010, 2011-2016). RESULTS: There were 2646, 1048, and 1598 all-cause, CVD, and non-CVD deaths, respectively. After age, gender, and race/ethnicity adjustment and compared with the 1988 to 1994 cohort, the hazard ratio of all-cause mortality was 0.88 (95% CI, 0.76-1.01) for the 1999 to 2004 cohort, 0.82 (95% CI, 0.70-0.95) for the 2005 to 2010 cohort, and 0.89 (95% CI, 0.75-1.05) for the 2011 to 2016 cohort (P trend=0.123). The age, gender, and race/ethnicity-adjusted hazard ratios for CVD mortality compared with the 1988 to 1994 cohort were 0.74 (95% CI, 0.60-0.90) for the 1999 to 2004 cohort, 0.61 (95% CI, 0.50-0.74) for the 2005 to 2010 cohort, and 0.57 (95% CI, 0.44-0.74) for the 2011 to 2016 cohort (P trend <0.001). There was no evidence of a change in CVD mortality between the 2005 to 2010 and 2011 to 2016 cohorts (P=0.661). Noncardiovascular mortality did not decline over the study period (P trend=0.145). CONCLUSIONS: The decline in CVD mortality among US adults with hypertension stalled after 2005 to 2010.

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus.

Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation.

Monocarboxylate transporter 1 (MCT1) exhibits essential roles in cellular metabolism and energy supply. Although MCT1 is highly expressed in activated B cells, it is not clear how MCT1-governed monocarboxylates transportation is functionally coupled to antibody production during the glucose metabolism. Here, we report that B cell-lineage deficiency of MCT1 significantly influences the class-switch recombination (CSR), rendering impaired IgG antibody responses in Mct1f/fMb1Cre mice after immunization. Metabolic flux reveals that glucose metabolism is significantly reprogrammed from glycolysis to oxidative phosphorylation in Mct1-deficient B cells upon activation. Consistently, activation-induced cytidine deaminase (AID), is severely suppressed in Mct1-deficient B cells due to the decreased level of pyruvate metabolite. Mechanistically, MCT1 is required to maintain the optimal concentration of pyruvate to secure the sufficient acetylation of H3K27 for the elevated transcription of AID in activated B cells. Clinically, we found that MCT1 expression levels are significantly upregulated in systemic lupus erythematosus patients, and Mct1 deficiency can alleviate the symptoms of bm12-induced murine lupus model. Collectively, these results demonstrate that MCT1-mediated pyruvate metabolism is required for IgG antibody CSR through an epigenetic dependent AID transcription, revealing MCT1 as a potential target for vaccine development and SLE disease treatment.

Multimorbidity is associated with lower total 24-hour movement activity among US adults.

Objective: Having chronic conditions may result in reduced physical and cognitive function but less is known about multimorbidity with daily movement. We examined the association of multimorbidity and device-measured total daily movement in a nationally representative sample of US adults aged ≥ 30 years from the 2011-2014 National Health and Nutrition Examination Surveys. Methods: Any multimorbidity (≥2 conditions) and complex multimorbidity (≥3 conditions across ≥ 3 body systems) were quantified using 16 chronic conditions via self-report and/or clinical thresholds. Total movement over 24-hours (Monitor-Independent Movement Summary units [MIMS-units]) was measured using a wrist-worn device (ActiGraph GT3X). Multivariable linear regression examined the association of 1) each chronic condition, 2) number of conditions, 3) any multimorbidity, and 4) complex multimorbidity with total movement. Covariates included age, gender, race/ethnicity, educational attainment, and smoking status. Results: Among US adults (N = 7304, mean age: 53.2 ± 0.34 years, 53.2% female, 69.4% Non-Hispanic White), 62.2% had any multimorbidity with 34.2% having complex multimorbidity. After adjustment, a higher number of chronic conditions was associated with incrementally lower total movement (ß MIMS-units [95% CI] compared to those with no chronic conditions; one: -419 [-772, -66], two: -605 [-933, -278], three: -1201 [-1506, -895], four: -1908 [-2351, -1465], 5+: -2972 [-3384, -2560]). Complex multimorbidity presence was associated with -1709 (95% CI: -2062, -1357) and -1269 (-1620, -918) lower total movement compared to those without multimorbidity and multimorbidity but not complex, respectively. Conclusions: Multimorbidity was associated with lower 24-h movement among US adults and may be helpful for identifying adults at risk for low movement.

Hydroxy-Rich Covalent Organic Framework for the Efficient Catalysis of the Cycloaddition of CO2.

The cycloaddition of CO2 with epoxides to cyclic carbonates is one of the most promising and green pathways for CO2 utilization, and the development of highly efficient catalysts remains a challenge. In this work, a novel hydroxy-rich covalent organic framework (TFPB-DHBD-COF) was synthesized, and it served as an efficient heterogeneous catalyst for the reaction of CO2 with 1,2-epoxybutane under mild conditions, providing the desired products in 90% conversion. The abundant hydroxy groups in the pore channels of TFPB-DHBD-COF could not only activate epoxides and CO2 via hydrogen bonding but also obviously enhance its stability through intramolecular five-membered ring hydrogen bonding. Thus, this COF also exhibited outstanding stability and tolerance for diverse substrates. Undoubtedly, this work has enriched the application of tailored COFs in the activation and utilization of CO2.

Identification, Typing, and Drug Resistance Analysis of Escherichia coli in Two Different Types of Broiler Farms in Hebei Province.

Hebei Province is an important area for breeding broiler chickens in China, but the antimicrobial resistance and prevalence of Escherichia coli (E. coli) are still unclear. A total of 180 cloacal samples from broiler farms in Hebei Province were collected and used for the isolation and identification of E. coli. The isolates were subjected to resistance phenotyping, resistance profiling, and genotyping, and some multiresistant strains were subjected to multilocus sequence typing (MLST). The results showed that 175 strains were isolated. Among both types of broiler farms, the ampicillin resistance rate was the highest, and the meropenem resistance rate was the lowest. Serious multiresistance was present in both types of broiler farms. Thirty strains of multidrug-resistant E. coli were typed by MLST to obtain a total of 18 ST types, with ST10 being the most prevalent. This study was to simply analyze the antimicrobial resistance and prevalence of E. coli in broiler chickens in Hebei Province after the implementation of the pilot work program of action to reduce the use of veterinary antimicrobials in standard farms (SFs) and nonstandard farms (NSFs). This study will provide a research basis and data support for the prevention and control of E. coli in Hebei.