Tea tree oil inhibits hydrogen sulfide-induced oxidative damage in chicken lungs through CYP450s/ROS pathway.

A large amount of hydrogen sulfide (H2S) is produced in the process of chicken breeding, which can cause serious inflammation and oxidative damage to the respiratory system of chickens. Tea tree oil (TTO) has antioxidant and anti-inflammatory properties. No studies have been reported on the use of TTO in H2S-induced lung injury in chickens. Therefore, in this study, 240 one-day-old Roman pink laying hens were randomly and equally divided into 3 groups: control group (CON), H2S exposure group (AVG, containing H2S), and TTO treatment group (TTG, containing H2S and 0.02 mL/L TTO) to establish an experimental model of TTO treatment with H2S exposure for a period of 42 d. Hematoxylin and eosin (H&E) staining was used to detect lung histopathology. Gene expression profiles were analyzed using transcriptomics. The underlying mechanism of the amelioration of lung injury by TTO was further revealed by antioxidant enzyme assays and qRT-PCR. The results showed that H2S exposure induced significant gene expression of CYP450s (CYP1B1 and CYP1C1) (P < 0.05), and caused intense oxidative stress, apoptosis and inflammation compared with CON. TTO could reduce ROS production and enhance antioxidant capacity (SOD, CAT, T-AOC, and GSH-PX) by regulating the CYP450s/ROS pathway (P < 0.05). Compared with the control group, the treatment group showed significantly decreased expression of apoptotic (Caspase-8, Caspase-3, Bid and Fas) (P < 0.05) and inflammatory (IL-4, IL-16, NF-κB, TNF-α and IFN-γ) (P < 0.05) factors in the lung. This study revealed that TTO regulated CYP450s/ROS pathway to alleviate H2S-induced lung injury in chickens. These results enrich the theory of the action mechanism of TTO on H2S-exposed chicken lungs and are of great value for the treatment of H2S-exposed animals.

Construction and alidation of a severity prediction model for acute pancreatitis based on CT severity index: A retrospective case-control study.

To construct and internally and externally validate a nomogram model for predicting the severity of acute pancreatitis (AP) based on the CT severity index (CTSI).A retrospective analysis of clinical data from 200 AP patients diagnosed at the Hefei Third Clinical College of Anhui Medical University from June 2019 to June 2022 was conducted. Patients were classified into non-severe acute pancreatitis (NSAP, n = 135) and severe acute pancreatitis (SAP, n = 65) based on final clinical diagnosis. Differences in CTSI, general clinical features, and laboratory indicators between the two groups were compared. The LASSO regression model was used to select variables that might affect the severity of AP, and these variables were analyzed using multivariate logistic regression. A nomogram model was constructed using R software, and its AUC value was calculated. The accuracy and practicality of the model were evaluated using calibration curves, Hosmer-Lemeshow test, and decision curve analysis (DCA), with internal validation performed using the bootstrap method. Finally, 60 AP patients treated in the same hospital from July 2022 to December 2023 were selected for external validation.LASSO regression identified CTSI, BUN, D-D, NLR, and Ascites as five predictive factors. Unconditional binary logistic regression analysis showed that CTSI (OR = 2.141, 95%CI:1.369-3.504), BUN (OR = 1.378, 95%CI:1.026-1.959), NLR (OR = 1.370, 95%CI:1.016-1.906), D-D (OR = 1.500, 95%CI:1.112-2.110), and Ascites (OR = 5.517, 95%CI:1.217-2.993) were independent factors influencing SAP. The established prediction model had a C-index of 0.962, indicating high accuracy. Calibration curves demonstrated good consistency between predicted survival rates and actual survival rates. The C-indexes for internal and external validation were 0.935 and 0.901, respectively, with calibration curves close to the ideal line.The model based on CTSI and clinical indicators can effectively predict the severity of AP, providing a scientific basis for clinical decision-making by physicians.

Assessment of potential adverse events following the 2022-2023 seasonal influenza vaccines among U.S. adults aged 65 years and older.

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years. METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively. CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

Coupled Pacific Rim megadroughts contributed to the fall of the Ming Dynasty's capital in 1644 CE.

Historical documents provide evidence for regional droughts preceding the political turmoil and fall of Beijing in 1644 CE, when more than 20 million people died in northern China during the late Ming famine period. However, the role climate and environmental changes may have played in this pivotal event in Chinese history remains unclear. Here, we provide tree-ring evidence of persistent megadroughts from 1576 to 1593 CE and from 1624 to 1643 CE in northern China, which coincided with exceptionally cold summers just before the fall of Beijing. Our analysis reveals that these regional hydroclimatic extremes are part of a series of megadroughts along the Pacific Rim, which not only impacted the ecology and society of monsoonal northern China, but likely also exacerbated external geopolitical and economic pressures. This finding is corroborated by last millennium reanalysis data and numerical climate model simulations revealing internally driven Pacific sea surface temperature variations and the predominance of decadal scale La Niña-like conditions to be responsible for precipitation decreases over northern China, as well as extensive monsoon regions in the Americas. These teleconnection patterns provide a mechanistic explanation for reoccurring drought spells during the late Ming Dynasty and the environmental framework fostering the fall of Beijing in 1644 CE, and the subsequent demise of the Ming Dynasty.

Safety of Ancestral Monovalent BNT162b2, mRNA-1273, and NVX-CoV2373 COVID-19 Vaccines in US Children Aged 6 Months to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes after COVID-19 vaccination in the US pediatric population. Design, Setting, and Participants: This cohort study evaluated 21 prespecified health outcomes after exposure before early 2023 to BNT162b2, mRNA-1273, or NVX-CoV2373 ancestral monovalent COVID-19 vaccines in children aged 6 months to 17 years by applying a near-real-time monitoring framework using health care data from 3 commercial claims databases in the US (Optum [through April 2023], Carelon Research [through March 2023], and CVS Health [through February 2023]). Increased rates of each outcome after vaccination were compared with annual historical rates from January 1 to December 31, 2019, and January 1 to December 31, 2020, as well as between April 1 and December 31, 2020. Exposure: Receipt of an ancestral monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-19 vaccine dose identified through administrative claims data linked with Immunization Information Systems data. Main Outcomes and Measures: Twenty-one prespecified health outcomes, of which 15 underwent sequential testing and 6 were only monitored descriptively due to lack of historical rates. Results: Among 4 102 016 vaccinated enrollees aged 6 months to 17 years, 2 058 142 (50.2%) were male and 3 901 370 (95.1%) lived in an urban area. Thirteen of 15 sequentially tested outcomes did not meet the threshold for a statistical signal. Statistical signals were detected for myocarditis or pericarditis after BNT162b2 vaccination in children aged 12 to 17 years and seizure after vaccination with BNT162b2 and mRNA-1273 in children aged 2 to 4 or 5 years. However, in post hoc sensitivity analyses, a statistical signal for seizure was observed only after mRNA-1273 when 2019 background rates were selected; no statistical signal was observed when 2022 rates were selected. Conclusions and Relevance: In this cohort study of pediatric enrollees across 3 commercial health insurance databases, statistical signals detected for myocarditis or pericarditis after BNT162b2 (ages 12-17 years) were consistent with previous reports, and seizures after BNT162b2 (ages 2-4 years) and mRNA-1273 vaccinations (ages 2-5 years) should be further investigated in a robust epidemiologic study with confounding adjustment. The US Food and Drug Administration concludes that the known and potential benefits of COVID-19 vaccination outweigh the known and potential risks of COVID-19 infection.

Thermal Air Oxidation-Mediated Synchronous Coordination and Carbonation of Lanthanum on Biochar toward Phosphorus Adsorption from Wastewater.

Biochar has attracted increasing attention as the sustainable and structure-tunable carrier for lanthanum (La) species for diverse applications. Carbonated La species possesses a higher biocompatibility and a lower leaching potential than other commonly used La species, while less attention is paid on the application of carbonated La in phosphorus (P) adsorption. Herein, thermal air oxidation (TAO) was applied as a novel strategy for synchronously tuning the coordination environment and chemical species of La on biochar surface. The results demonstrated that TAO induced the coordination of La with oxidation-generated oxygenated functional groups (OFGs) and carbonation of La species by the oxidation-generated CO2 on the biochar surface. The batch adsorption results showed that the Qm of resultant biochar remarkably increased from 68.92 to 132.49 mg/g at 1 g/L dosage. It also showed a robust adsorption stability in pH 2-6, a strong resistance to the co-existing Cl-, SO42-, NO3-, CO32-, or HCO3-, a stable adsorption recyclability, and an ultralow La leaching potential. The P adsorption was dominated by ligand exchange-induced inner-sphere complexation. In practical swine wastewater, the resultant biochar composite (1 g/L) removed 99.87% of P from 92.3 to 0.12 mg/L at a practical pH of 7.12. The density functional theory calculation further revealed the significant role of the binding of carbonated La by the biochar surface OFGs in reducing the P adsorption energies, indicating the synergism between the oxygenated biochar carrier and the carbonated La in P adsorption. Finally, this study provided a novel route to synchronously tune the coordination environment and chemical species of La on biochar via a facile TAO process for high-efficient P adsorption from wastewater.

Evaluation of potential adverse events following COVID-19 mRNA vaccination among adults aged 65 years and older: Two self-controlled studies in the U.S.

BACKGROUND: Our near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevation in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluation of potential associations. METHODS: We conducted two self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged ≥ 65 years. Adjusted incidence rate ratio (IRRs) and 95 % confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following monovalent booster doses for AMI, PE, ITP, Bell's Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri). RESULTS: The primary series study included 3,360,981 individuals who received 6,388,542 primary series doses; the booster study included 6,156,100 individuals with one monovalent booster dose. The AMI IRR following BNT162b2 primary series and booster was 1.04 (95 % CI: 0.91 to 1.18) and 1.06 (95 % CI: 1.003 to 1.12), respectively; for mRNA-1273 primary series and booster, 1.01 (95 % CI: 0.82 to 1.26) and 1.05 (95 % CI: 0.998 to 1.11), respectively. The hospital inpatient PE IRR following BNT162b2 primary series and booster was 1.19 (95 % CI: 1.03 to 1.38) and 0.86 (95 % CI: 0.78 to 0.95), respectively; for mRNA-1273 primary series and booster, 1.15 (95 % CI: 0.94 to 1.41) and 0.87 (95 % CI: 0.79 to 0.96), respectively. The studies' results do not support that exposure to COVID-19 mRNA vaccines elevate the risk of ITP, DIC, Myo/Peri, and BP. CONCLUSION: We did not find an increased risk for AMI, ITP, DIC, BP, and Myo/Peri and there was not consistent evidence for PE after exposure to COVID-19 mRNA primary series or monovalent booster vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the U.S. elderly population.

Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination offers early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the US pediatric population aged 5 to 17 years. Design, Setting, and Participants: This population-based study was conducted under a public health surveillance mandate from the US Food and Drug Administration. Participants aged 5 to 17 years were included if they received BNT162b2 COVID-19 vaccination through mid 2022 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window until the COVID-19 vaccination. Surveillance of 20 prespecified health outcomes was conducted in near real time within a cohort of vaccinated individuals from the earliest Emergency Use Authorization date for the BNT162b2 vaccination (December 11, 2020) and was expanded as more pediatric age groups received authorization through May and June 2022. All 20 health outcomes were monitored descriptively, 13 of which additionally underwent sequential testing. For these 13 health outcomes, the increased risk of each outcome after vaccination was compared with a historical baseline with adjustments for repeated looks at the data as well as a claims processing delay. A sequential testing approach was used, which declared a safety signal when the log likelihood ratio comparing the observed rate ratio against the null hypothesis exceeded a critical value. Exposure: Exposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (dose 1 + dose 2), and dose-specific secondary analyses were conducted. Follow-up time was censored for death, disenrollment, end of the outcome-specific risk window, end of the study period, or a receipt of a subsequent vaccine dose. Main Outcomes: Twenty prespecified health outcomes: 13 were assessed using sequential testing and 7 were monitored descriptively because of a lack of historical comparator data. Results: This study included 3 017 352 enrollees aged 5 to 17 years. Of the enrollees across all 3 databases, 1 510 817 (50.1%) were males, 1 506 499 (49.9%) were females, and 2 867 436 (95.0%) lived in an urban area. In the primary sequential analyses, a safety signal was observed only for myocarditis or pericarditis after primary series vaccination with BNT162b2 in the age group 12 to 17 years across all 3 databases. No safety signals were observed for the 12 other outcomes assessed using sequential testing. Conclusions and Relevance: Among 20 health outcomes that were monitored in near real time, a safety signal was identified for only myocarditis or pericarditis. Consistent with other published reports, these results provide additional evidence that COVID-19 vaccines are safe in children.

A critical review on the development of lanthanum-engineered biochar for environmental applications.

Biochar and lanthanum (La) have been widely used in environment. However, there is a lack of knowledge and perspective on the development of La-engineered biochar (LEB) for environmental applications. This review shows that LEBs with a variety of La species via pre-/post-doping routes are developed for environmental applications. Specifically, precipitation, gelation, and calcination are the common sub-processes involved in the pre-/post-doping of La on the resultant LEB. The dominant La species for LEBs is La(OH)3, which is formed through precipitation of La ions with various bases. Various La carbonates, e.g., LaOHCO3, La2(CO3)3, La2CO5, and NaLa(CO3)2, are also involved in the preparation of LEBs. The LEBs are high-efficient in the adsorption of phosphate, arsenic, antimonate and fluoride ions, attributed to the strong affinity of La to oxyanions and Lewis hard base. Lanthanum is also favorable for co-doping with transition metal species to further enhance the performances in adsorption or catalysis. This review also analyzes the prospects and future challenges for the preparation and application of LEBs in environment. Finally, this review is beneficial to inspire new breakthroughs on the preparation and environmental application of LEBs.

Surveillance of COVID-19 vaccine safety among elderly persons aged 65 years and older.

BACKGROUND: Monitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public. METHODS: We evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. FINDINGS: Four outcomes met the threshold for a statistical signal following BNT162b2 vaccination including pulmonary embolism (PE; RR = 1.54), acute myocardial infarction (AMI; RR = 1.42), disseminated intravascular coagulation (DIC; RR = 1.91), and immune thrombocytopenia (ITP; RR = 1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the mRNA-1273 or Ad26 COV2.S vaccines. INTERPRETATION: This early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following BNT162b2 vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.

Background rates of adverse events of special interest for COVID-19 vaccine safety monitoring in the United States, 2019-2020.

BACKGROUND: The U.S. Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination. Historical incidence rates (IRs) of AESI are comparators to evaluate safety. METHODS: We estimated IRs of 17 AESI in six administrative claims databases from January 1, 2019, to December 11, 2020: Medicare claims for adults ≥ 65 years and commercial claims (Blue Health Intelligence®, CVS Health, HealthCore Integrated Research Database, IBM® MarketScan® Commercial Database, Optum pre-adjudicated claims) for adults < 65 years. IRs were estimated by sex, age, race/ethnicity (Medicare), and nursing home residency (Medicare) in 2019 and for specific periods in 2020. RESULTS: The study included >100 million enrollees annually. In 2019, rates of most AESI increased with age. However, compared with commercially insured adults, Medicare enrollees had lower IRs of anaphylaxis (11 vs 12-19 per 100,000 person-years), appendicitis (80 vs 117-155), and narcolepsy (38 vs 41-53). Rates were higher in males than females for most AESI across databases and varied by race/ethnicity and nursing home status (Medicare). Acute myocardial infarction (Medicare) and anaphylaxis (all databases) IRs varied by season. IRs of most AESI were lower during March-May 2020 compared with March-May 2019 but returned to pre-pandemic levels after May 2020. However, rates of Bell's palsy, Guillain-Barré syndrome, narcolepsy, and hemorrhagic/non-hemorrhagic stroke remained lower in multiple databases after May 2020, whereas some AESI (e.g., disseminated intravascular coagulation) exhibited higher rates after May 2020 compared with 2019. CONCLUSION: AESI background rates varied by database and demographics and fluctuated in March-December 2020, but most returned to pre-pandemic levels after May 2020. It is critical to standardize demographics and consider seasonal and other trends when comparing historical rates with post-vaccination AESI rates in the same database to evaluate COVID-19 vaccine safety.

Interfacial engineering of heterostructured Fe-Ni3S2/Ni(OH)2 nanosheets with tailored d-band center for enhanced oxygen evolution catalysis.

Hydrogen production by electrochemical water splitting suffers from high kinetic barriers in the anodic oxygen evolution reaction (OER), which limits the overall efficiency. Herein, we report a structural and electronic engineering strategy by integrating self-standing Fe-doped Ni3S2 (denoted by Fe-Ni3S2) nanosheet arrays with Ni(OH)2 subunits to form heterostructured Fe-Ni3S2/Ni(OH)2 on a Ni Foam substrate. The strong electronic interaction between the Fe-Ni3S2 and Ni(OH)2 constituents contributes abundant catalytic sites and ensures high electron transfer. Moreover, the combined experimental and theoretical study revealed that the coupling of Ni(OH)2 onto the Fe-Ni3S2 is favorable for lowering the activation energy of water oxidation for favorable OER kinetics and upshifting the Ni d-band center to facilitate the adsorption of O-containing intermediates. Consequently, the optimized Fe-Ni3S2/Ni(OH)2 hybrid catalyst exhibits excellent OER performance in alkaline electrolytes with an ultralow overpotential of 202 mV at 10 mA cm-2, a small Tafel slope of 50.6 mV dec-1, and long-term durability under high current density (0.25 A cm-2) for up to 60 h without significant deactivation. Moreover, a two-electrode Fe-Ni3S2/Ni(OH)2||Pt/C electrolyzer requires only a low voltage of 1.54 V at 10 mA cm-2 for overall water splitting. This study emphasizes the importance of interface and surface engineering in achieving highly efficient electrocatalysts.

Study on Boundary Layer and Surface Hardness of Carbon Black in Natural Rubber Using Atomic Force Microscopy.

The mechanical properties and wear resistance of carbon black/natural rubber (CB/NR) composites are significantly influenced by the degree of CB dispersion in rubber. Here, we present a novel reinforcement theory using atomic force microscopy (AFM) to quantify the adhesive thickness of rubber molecules around the CB particles as well as the height, area, and volume in NR. The thickness of the bonded rubber (BR) was found to vary between 3 and 7 nm depending on the values of the nitrogen surface area (NSA) for CB. This indicates that a higher BR content is a result of a higher CB NSA with a smaller particle size, showing a higher number of active positions to anchor rubber molecules. The nanoindentation of AFM was used to determine the surface hardness of CB in NR; the value decreases with increasing BR height. In this study, we demonstrate a well-defined reinforcement mechanism of CB in NR with the factors of BR, surface hardness, 100%/300% modulus, and tensile strength.

Converting a Non-Porous Rare-Earth Metal-Organic Framework into a Porous Yttrium-Based NH2UiO-66 Network via a Linker Exchange Approach.

The solvent-assisted linker exchange (SALE) method was used to produce amino-functionalized yttrium-based UiO-66 [NH2UiO-66(Y)], which is not obtainable via a direct synthetic method. Remarkably, SALE not only produced relatively highly porous NH2UiO-66(Y) from completely non-porous 3,3-bpdc-Y but also changed the network topology from 8-connected bcu in 3,3-bpdc-Y to 12-connected fcu in NH2UiO-66(Y). Based on our knowledge, this is one of the rare cases where SALE changes the whole network topology of the resulting metal-organic framework. NH2UiO-66(Y) also showed promising ability for selective detection of Cu2+ at a low concentration.

Near real-time surveillance of safety outcomes in US COVID-19 vaccine recipients aged 12 to 64 years.

BACKGROUND: Active monitoring of safety outcomes following COVID-19 vaccination is critical to understand vaccine safety and can provide early detection of rare outcomes not identified in pre-licensure trials. We present findings from an early warning rapid surveillance system in three large commercial insurance databases including more than 16 million vaccinated individuals. METHODS: We evaluated 17 outcomes of interest following COVID-19 vaccination among individuals aged 12-64 years in Optum, HealthCore, and CVS Health databases from December 11, 2020, through January 22, 2022, January 7, 2022, and December 31, 2021, respectively. We conducted biweekly or monthly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. FINDINGS: Among 17 outcomes evaluated, 15 did not meet the threshold for statistical signal in any of the three databases. Myocarditis/pericarditis met the statistical threshold for a signal following BNT162b2 in two of three databases (RRs: 1.83-2.47). Anaphylaxis met the statistical threshold for a signal in all three databases following BNT162b2 vaccination (RRs: 4.48-10.86) and mRNA-1273 vaccination (RRs: 7.64-12.40). DISCUSSION: Consistent with published literature, our near-real time monitoring of 17 adverse outcomes following COVID-19 vaccinations identified signals for myocarditis/pericarditis and anaphylaxis following mRNA COVID-19 vaccinations. The method is intended for early detection of safety signals, and results do not imply a causal effect. Results of this study should be interpreted in the context of the method's utility and limitations, and the validity of detected signals must be evaluated in fully adjusted epidemiologic studies.

Drug Delivery Using Hydrophilic Metal-Organic Frameworks (MOFs): Effect of Structure Properties of MOFs on Biological Behavior of Carriers.

To study the influence of pore structural properties of metal-organic frameworks (MOFs) on drug adsorption and delivery, we synthesized two MOF termed TMU-6(RL1) {[Zn(oba)(RL1)0.5]n·(DMF)1.5} and TMU-21(RL2) {[Zn(oba)(RL2)0.5]n·(DMF)1.5} with amine basic N-donor pillars containing phenyl or naphthyl cores with various hydrophilic properties around the main center of the reaction. TG, IR, XPS, and PXRD analyses were used to extensively characterize the MOFs. The synthesized carriers showed high adsorption efficiency, stability, and controlled release. As an anticancer drug, Nimesulide (Nim) was adsorbed to MOFs using multiple adsorption mechanisms, such as Hostπ-πGuest interaction and HostN-H···OGuest hydrogen bonds. Moreover, Hirshfeld surface analysis showed when the benzene core was replaced with the naphthalene core, the percentage of intermolecular interactions of π···π and N···H by amine sites in TMU-21(RL2) decreased compared with TMU-6(RL1), while the percentage of these interactions with guest molecules increased. The results showed that changes in the hydrophobicity/hydrophilicity properties of MOFs would alter their ability to adsorb Nim in the pore of the frameworks. In vitro anticancer studies also showed that the cytotoxicity of Nim in MOFs@Nim composites against human cervical cancer cell line (HeLa cells) and human colon cancer cell line (HT-29 cells) is much higher than that of free Nim. Generally, based on the results, it can be said that the biological behavior of carriers can be regulated by adjusting the structure properties of MOFs.

The Effects of Green Intellectual Capital on Green Innovation: A Green Supply Chain Integration Perspective.

To demonstrate how green innovation (GI) effectively occurs, this study examines the effects of green intellectual capital (GIC) on GI from the perspective of green supply chain integration (GSCI). Based on a natural-resource-based view and knowledge-based view, the authors constructed an intermediary model of GIC-GSCI-GI, and analyzed the effects of green absorptive ability (GAA) and relationship learning ability (RLA) as moderators. An empirical survey of 328 Chinese manufacturing companies was conducted. Our results indicate that three dimensions of GIC positively impact GI. The mediating effects of internal and external GSCI exist in the relationship between GIC and GI. The moderating effects of GAA and RLA in these effects were also verified. Our study provides further empirical evidence for the relationship between GIC and GI, highlights the effects of companies' internal and external abilities on GI, and suggests new ways and implementation contexts for GI.

Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases.

BACKGROUND: Several passive surveillance systems reported increased risks of myocarditis or pericarditis, or both, after COVID-19 mRNA vaccination, especially in young men. We used active surveillance from large health-care databases to quantify and enable the direct comparison of the risk of myocarditis or pericarditis, or both, after mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) vaccinations. METHODS: We conducted a retrospective cohort study, examining the primary outcome of myocarditis or pericarditis, or both, identified using the International Classification of Diseases diagnosis codes, occurring 1-7 days post-vaccination, evaluated in COVID-19 mRNA vaccinees aged 18-64 years using health plan claims databases in the USA. Observed (O) incidence rates were compared with expected (E) incidence rates estimated from historical cohorts by each database. We used multivariate Poisson regression to estimate the adjusted incidence rates, specific to each brand of vaccine, and incidence rate ratios (IRRs) comparing mRNA-1273 and BNT162b2. We used meta-analyses to pool the adjusted incidence rates and IRRs across databases. FINDINGS: A total of 411 myocarditis or pericarditis, or both, events were observed among 15 148 369 people aged 18-64 years who received 16 912 716 doses of BNT162b2 and 10 631 554 doses of mRNA-1273. Among men aged 18-25 years, the pooled incidence rate was highest after the second dose, at 1·71 (95% CI 1·31 to 2·23) per 100 000 person-days for BNT162b2 and 2·17 (1·55 to 3·04) per 100 000 person-days for mRNA-1273. The pooled IRR in the head-to-head comparison of the two mRNA vaccines was 1·43 (95% CI 0·88 to 2·34), with an excess risk of 27·80 per million doses (-21·88 to 77·48) in mRNA-1273 recipients compared with BNT162b2. INTERPRETATION: An increased risk of myocarditis or pericarditis was observed after COVID-19 mRNA vaccination and was highest in men aged 18-25 years after a second dose of the vaccine. However, the incidence was rare. These results do not indicate a statistically significant risk difference between mRNA-1273 and BNT162b2, but it should not be ruled out that a difference might exist. Our study results, along with the benefit-risk profile, continue to support vaccination using either of the two mRNA vaccines. FUNDING: US Food and Drug Administration.

[Research progress on camptothecin and its derivative nano-prodrugs based on tumor microenvironment response].

Nano-prodrug, one of the most widely used nano-formulation at present, has excellent efficacies in tumor treatment with high potential and clinical value. Camptothecin and its derivatives have broad prospects in the preparation of prodrugs for the treatment of tumors. Given the special microenvironment of tumors, including partial acidity, high concentration of reactive oxygen species, high concentration of glutathione and enzyme concentration, a large number of tumor microenvironment-responsive camptothecin and its derivative prodrugs were prepared. This paper classified them from the microenvironment response types and drug release characteristics, reviewed the research progress of camptothecin and its derivative prodrugs based on safety and clinical trials, and analyzed the existing problems and deficiencies, hoping to provide references for the development of camptothecin and its derivatives.

Results of the osteochondral autologous transplantation for treatment of osteochondral lesions of the talus with harvesting from the ipsilateral talar articular facets.

PURPOSE: There are few studies on the clinical outcomes of osteochondral autologous transplantation (OAT) harvesting from local talar non-weight-bearing articular facets for the treatment of osteochondral lesions of the talus (OLTs). The purpose of this study was to review the short- to midterm outcomes of our patients who were treated with OAT harvesting from ipsilateral talar articular facets for OLTs. METHODS: Between December 2010 and November 2018, 24 patients were enrolled in this study. There were 16 males and eight females with an average age of 39.1 years and a follow-up period of 50.9 months. The clinical results were evaluated according to the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and the visual analogue scale (VAS) score. Pre-operative plain radiographs and magnetic resonance imaging (MRI) scans, post-operative radiographs, and X-ray and computed tomography (CT) scans at the last follow-up were observed. RESULTS: There was a significant improvement in the AOFAS score from 61.3 ± 19.0 pre-operatively to 84.9 ± 9.2 post-operatively (P < 0.001). The VAS score improved from 6.1 ± 2.3 to 2.0 ± 1.4 at the last follow-up (P < 0.001). Twenty-one patients (87.5%) were satisfied with their clinical results. By the last follow-up CT scan, there was bone cyst formation at the donor sites in three patients, at the recipient sites in five patients and at both sites in five patients. Two patients (8.3%) underwent re-operation with arthroscopic debridement because of medial gutter hypertrophic soft tissue impingement. CONCLUSION: OAT harvesting from the ipsilateral talar articular facet showed satisfactory results. The mean post-operative VAS score and AOFAS ankle-hindfoot score improved significantly. Post-operative impingement around the osteotomy site was the main complication and reason for re-operation after the index procedure. In addition, bone cysts at the recipient and/or donor site(s) were found with a large percentage under CT. Therefore, longer follow-up is necessary to determine the long-term clinical results for this technique.