Morphological and Transcriptomic Analyses Reveal the Toxicological Mechanism and Risk of Nitrate Exposure in Bufo gargarizans Embryos.

In recent years, nitrate (NO3-N) pollution in water bodies has been increasing due to the excessive use of nitrogen-based fertilizers. Exposure to NO3-N during the development of amphibian embryos may have lasting effects on the growth and development of individuals and even threaten their survival, but the toxicity mechanism of NO3-N in amphibian embryos prior to thyroid morphogenesis remains unclear. In the present study, Bufo gargarizans was selected as the model organism to investigate the toxic effects of 10 mg/L and 100 mg/L NO3-N exposure (N10 and N100) on amphibian embryos using methimazole (MMI) and exogenous thyroxine (T4) as the reference groups. We found that T4, MMI, N10 and N100 inhibited B. gargarizans embryo growth and development, with MMI and N100 showing the earliest and strongest effects. Transcriptome analysis revealed that MMI and NO3-N (especially N100) significantly downregulated genes related to thyroid morphogenesis and cholesterol metabolism, while upregulating genes related to inflammation and apoptosis. Together, these results contribute to a deeper understanding of the complex mechanisms by which NO3-N disrupts B. gargarizans embryonic development, reveal the potential risks of NO3-N pollution to other aquatic organisms, and provide insights into the conservation of a broader ecosystem.

Pollution characteristics and release mechanism of microplastics in a typical end-of-life vehicle (ELV) recycling base, East China.

Microplastics (MPs) is a novel and significant pollution due to its eco-environmental hazards and ubiquity. In end-of-life vehicle (ELV) recycling base, MPs are widely distributed but have rare reported in scientific literature. In this study, a comprehensive analysis of MPs was conducted in a typical ELV recycling base. MPs were found in all samples at different sampling sites and environmental mediums. A total of 34 polymer types were detected by µ-FTIR, and the main polymers include PE-PP, ABS, polyester resin, nylon, and PEU plastic. MPs were released from the crushing, tearing, and breaking of plastic parts in ELVs. They were in high content in ground dust, with the abundance of 737-29,021 p/5 g D (the average abundance of 5552 ± 6435 p/5 g D). The abundance, shape, color, and size of MPs are related with functional areas of ELV recycling. Heavy metals could be adsorbed on MPs, and their contents on MPs have a significant correlation with those in the corresponding dust samples. At last, some specific MPs control measures, such as changing transportation mode, using dust-proof cloths, and equipping dust removal equipment, have been put forward.

Atherosclerotic cardiovascular disease risk profile of patients with chronic hepatitis B treated with tenofovir alafenamide or tenofovir disoproxil fumarate for 96 weeks.

BACKGROUND: Patients with chronic hepatitis B (CHB) who switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) show changes in lipid profiles. AIM: To evaluate how these changes affect cardiovascular risk. METHODS: This pooled analysis, based on two large prospective studies, evaluated fasting lipid profiles of patients with CHB who were treated with TAF 25 mg/day or TDF 300 mg/day for 96 weeks. Patients who fulfilled the American College of Cardiology criteria (age 40-79 years, high-density lipoprotein [HDL] 20-100 mg/dL, total cholesterol [TC] 130-320 mg/dL and systolic blood pressure 90-200 mmHg) required to assess 10-year atherosclerotic cardiovascular disease (ASCVD) risk with baseline lipid data and at least one post-baseline measurement were included in the ASCVD-risk population. The 10-year ASCVD risk was calculated for patients in this population, and changes from baseline to Week 96 were assessed using intermediate- (≥7.5%) and high-risk (≥20%) cut-offs. RESULTS: Among 1632 patients, 620 (38%) met the criteria for the ASCVD-risk population. At Week 96, fasting levels of all lipids, except TC:HDL ratio, were lower with TDF than TAF. No significant increase was observed in overall ASCVD risk or in any ASCVD-risk categories during the 96-week treatment period compared with baseline. A similar proportion of patients in the TAF and TDF treatment groups (1.3% and 2.3%, respectively; p = 0.34) reported cardiovascular events. CONCLUSION: Despite on-treatment differences in lipid profiles with TAF and TDF, predicted cardiovascular risk and clinical events were similar for both groups after 96 weeks.

Effects of perchlorate and exogenous T4 exposures on body condition and endochondral ossification of Rana chensinensis tadpoles.

Perchlorate, as an endocrine-disrupting chemical (EDC), is largely produced and used in the military, fireworks, fertilizers, and other industries and widely exists in water. Although perchlorate is known to destroy the normal function of thyroid hormones (THs) in amphibians and interfere with their growth and development, the impact of TH levels caused by sodium perchlorate (NaClO4) on endochondral ossification and skeletal development is poorly investigated, and the underlying molecular mechanism has not been clarified. The present study aimed to explore the potential effects of NaClO4 and exogenous thyroxine (T4) on the skeletal development of Rana chensinensis tadpoles and elucidate the related molecular mechanisms. Our results showed that histological changes occurred to the femur and tibia-fibula of tadpoles raised in 250 µg/L NaClO4 and 5 µg/L exogenous T4, and the length of their hindlimbs was significantly reduced. In addition, exogenous T4 exposure significantly interfered with the expression of Dio3, TRß, MMP9, MMP13, and Runx2, inhibiting the endochondral ossification process. Therefore, we provide robust evidence that the changes in TH levels caused by NaClO4 and exogenous T4 will adversely affect the endochondral ossification and skeletal development of R. chensinensis tadpoles.

Construction of a backpropagation starlight atmospheric refraction model based on ray tracing.

The atmospheric refraction model is a vital part of the refraction navigation system. A more accurate model needs to be constructed for the navigation algorithm design and simulation verification. Based on the Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics/Sounding of the Atmosphere using Broadband Emission Radiometry (TIMED/SABER) dataset and the geometrical ray propagation law, a ray tracing algorithm is proposed to calculate the atmospheric refraction angles. Moreover, a neural network starlight atmospheric refraction model (BP model) is constructed to better describe the relationship between time, location, and refraction angle. Compared with the experimental data, the bias error of the backpropagation (BP) model is 1.06 ' ' , which is better than the 3.75 ' ' of the traditional model. It indicates that the BP model is exact and has important guiding significance for the starlight refraction navigation technology.

Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B.

Background & Aims: Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB. Methods: The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated. Results: Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 (p <0.001) vs. 0.56 (p = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 (p <0.001) vs. 0.58 (p = 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively). Conclusions: This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis. Impact and implications: Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB. Clinical trial numbers: NCT01940341; NCT02836249; NCT01940471; NCT02836236.

Electrodeposited copper enhanced removal of 2,4-dichlorophenol in batch and flow reaction in Cu@CC-PS-MFC system.

Combination of microbial fuel cell (MFC) and advanced oxidation process (AOP) is promising for pollutant removal. In this paper, Cu0-loaded carbon cloth cathode by electrodeposition (Cu@CC-PS-MFC) was applied to enhance 2,4-dichlorophenol (2,4-DCP) degradation based on persulfate (PS) activation in microbial fuel cell. Cu0 exhibited a typical structure of face-centered cubic metal polyhedron on carbon cloth. The removal of 2,4-DCP by Cu@CC-PS-MFC (75.6%) was enhanced by more than 50% compared to CC-PS-MFC (49.2%) after 1 h of reaction. 30 mg/L 2,4-DCP in Cu@CC-PS-MFC was completely removed and achieved a high mineralization (80.6%) after 9 h of reaction under optimized condition with low dissolved copper ion concentration (0.615 mg/L). Meanwhile, more than 90% removal of 2,4-DCP was stably achieved with flow operation condition (hydraulic residence time of 7.2 h). The change of copper valent state Cu0/Cu2O/CuO was the main mechanism of PS activation with main reactive species of O•H and O21. The bioanode of MFC enhanced the in-situ regeneration of ≡Cu+ and ≡Cu0 on the catalyst surface by transporting electrons, which was believed to contribute to good catalyst lifetime and excellent 2,4-DCP removal. Electrodeposited copper contributes to the enhanced degradation of 2,4-DCP with energy recovery at the same time which can further broaden the application MFC.

Long-term Treatment With Tenofovir Alafenamide for Chronic Hepatitis B Results in High Rates of Viral Suppression and Favorable Renal and Bone Safety.

OBJECTIVES: Results from two Phase 3 studies, through 2 years, in chronic hepatitis B infection (CHB) showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. Here, we report updated results through 5 years. METHODS: Patients with HBeAg-negative or -positive CHB with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years. Efficacy (antiviral, biochemical, serologic), resistance (deep sequencing of polymerase/reverse transcriptase and phenotyping), and safety, including renal and bone parameters, were evaluated by pooled analyses. RESULTS: Of 1298 randomized and treated patients, 866 receiving TAF (DB and OL) and 432 receiving TDF with rollover to OL TAF at year 2 (n = 180; TDF→TAF3y) or year 3 (n = 202; TDF→TAF2y) were included. Fifty (4%) TDF patients who discontinued during DB were excluded. At year 5, 85%, 83%, and 90% achieved HBV DNA < 29 IU/mL (missing = failure) in the TAF, TDF→TAF3y, and TDF→TAF2y groups, respectively; no patient developed TAF or TDF resistance. Median eGFR (by Cockcroft-Gault) declined < 2.5 mL/min, and mean declines of < 1% in hip and spine bone mineral density were seen at year 5 in the TAF group; patients in the TDF→TAF groups had improvements in these parameters at year 5 after switching to OL TAF. CONCLUSIONS: Long-term TAF treatment resulted in high rates of viral suppression, no resistance, and favorable renal and bone safety.

Effects of perchlorate and exogenous T4 on growth, development and tail resorption of Rana chensinensis.

Endocrine disruptors have been demonstrated to exert adverse effects on growth and development of amphibians by disrupting hormone levels. Tail resorption, which is one of the most remarkable events during amphibian metamorphosis, is closely associated with thyroid hormones levels. However, limited research has been conducted on the effects of endocrine disruptors on tail resorption in amphibians. This study explored the effects of NaClO4 and T4 on the growth, development and tail resorption during the metamorphosis of Rana Chensinensis. The results demonstrated that exposure to NaClO4 led to an increase in body size and a delay in metamorphosis of R. Chensinensis tadpoles. Histological analysis revealed that both NaClO4 and exogenous T4 exposure resulted in thyroid gland injury, and NaClO4 treatment delayed the degradation of notochord and muscles, thereby delaying tail resorption. Moreover, transcriptome sequencing results showed that apoptosis-related genes (APAF1, BAX and CASP6) and cell component degradation-related genes (MMP9 and MMP13) were highly expressed in the T4 exposure group, and the expression of oxidative stress-related genes (SOD and CAT) was higher in the NaClO4 exposure group. Taken together, both NaClO4 and exogenous T4 affect tail resorption in R. Chensinensis, thereby affecting their adaptation to terrestrial life. The present study will not only provide a reference for future experimental research on the effects of other endocrine disruptors on the growth, development and tail resorption of amphibians but will also provide insights into environmental protection and ecological risk assessment.

Impairment of bile acid metabolism and altered composition by lead and copper in Bufo gargarizans tadpoles.

Lead (Pb) and copper (Cu) are two common heavy metal contaminants in environments, and liver is recognized as one of the main target organs for toxicity of Pb and Cu in animal organisms. Bile acids play a critical role in regulating hepatic metabolic homeostasis by activating farnesoid X receptor (Fxr). However, there were few studies on the interactions between bile acids and liver pathology caused by heavy metals. In this work, the histopathological changes, targeted metabolome and transcriptome responses in the liver of Bufo gargarizans tadpoles to Pb and/or Cu were examined. We found that exposure to Pb and/or Cu altered the hepatic bile acid profile, resulting in increased hydrophobicity and toxicity of the bile acid pool. And the expression of genes involved in bile acid metabolism and their downstream signaling pathways in the liver were significantly altered by Pb and/or Cu exposure. The alteration of bile acid profiles and the expression of genes related to bile acid metabolism might induce oxidative stress and inflammation, ultimately inducing hepatocyte injury observed in the histological sections. To our knowledge, this is the first study to provide histological, biochemical, and molecular evidence for establishing the link between Pb and Cu exposure, disturbances in hepatic bile acid metabolism, and liver injury.

Regulation mechanisms underlying tail resorption in Bufo gargarizans metamorphosis.

Anurans have been excellent organisms for studying amphibian metamorphosis. Tail resorption is a remarkable event that occurs during amphibian metamorphosis. Although tail resorption has been previously studied in other anurans like Xenopus laevis and Rana chensinensis, there is no report on Bufo gargarizans. This paper thus explored the mechanism of tail resorption during metamorphosis in Bufo gargarizans tadpoles through some biological research methods. Histological results showed that the tail tissues of tadpoles gradually degraded as metamorphosis progressed. RNA sequencing analysis was performed to examine the expression level and functional enrichment of differentially expressed genes in the tail. In addition, we analyzed the mRNA expression levels of genes related to tail resorption by quantitative real-time polymerase chain reaction. We also speculated on three pathways that participate in the regulation of tail resorption based on the above results. The present study might provide a theoretical basis and novel insights for further research of complex molecular mechanisms of tail resorption in amphibians.

Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection (ALLIANCE): a double-blind, multicentre, randomised controlled, phase 3 non-inferiority trial.

BACKGROUND: For most adults with HIV-1 and hepatitis B virus (HBV) coinfection, initial recommended treatment is a tenofovir-containing antiretroviral regimen, but no randomised studies have compared tenofovir disoproxil fumarate with tenofovir alafenamide. We aimed to investigate whether bictegravir, emtricitabine, and tenofovir alafenamide is non-inferior to dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for viral suppression in individuals with HIV-1 and HBV coinfection at 48 and 96 weeks. METHODS: We did this randomised, double-blind, active-controlled, phase 3, non-inferiority trial at 46 outpatient centres in China, Dominican Republic, Hong Kong, Japan, Malaysia, South Korea, Spain, Taiwan, Thailand, Turkey, and the USA. Eligible participants were treatment-naive adults (aged ≥18 years) with plasma HIV-1 RNA of at least 500 copies per mL and plasma HBV DNA of at least 2000 IU/mL. Participants were randomly assigned (1:1) to receive daily oral bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or dolutegravir 50 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg, each with corresponding matching placebo. Randomisation was stratified by hepatitis B e antigen (HBeAg) status (positive vs negative), HBV DNA (<8 vs ≥8 log10 IU/mL), and CD4 count (<50 vs ≥50 cells per µL) at screening. All investigators, participants, and staff providing treatment, assessing outcomes, and collecting data were masked to study treatment for 96 weeks. Coprimary endpoints were the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL (defined by the US Food and Drug Administration snapshot algorithm) and plasma HBV DNA less than 29 IU/mL (using the missing-equals-failure approach) at week 48, with a prespecified non-inferiority margin of -12%. Coprimary endpoints were assessed in the full analysis set, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline HIV-1 RNA or HBV DNA result while on study drug. Safety endpoints were assessed in all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03547908. FINDINGS: Between May 30, 2018 and March 16, 2021, 381 participants were screened, of whom 243 initiated treatment (121 in the receive bictegravir, emtricitabine, and tenofovir alafenamide group; 122 in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group). At week 48, both endpoints met the criteria for non-inferiority: 113 (95%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 111 (91%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HIV-1 RNA less than 50 copies per mL (difference 4·1, 95% CI -2·5 to 10·8; p=0·21), and 75 (63%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus 53 (43%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HBV DNA suppression (difference 16·6, 5·9 to 27·3; nominal p=0·0023). Drug-related adverse events up to week 96 occurred in 35 (29%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 34 (28%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group. One (1%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group reported a serious adverse event (cryptococcal meningitis attributed to immune reconstitution inflammatory syndrome) that was deemed to be treatment-related. INTERPRETATION: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is an effective therapy for adults with HIV-1 and HBV coinfection starting antiviral therapy. FUNDING: Gilead Sciences.

Detachment of Dodecane from Silica Surfaces with Variable Surface Chemistry Studied Using Molecular Dynamics Simulation.

The adsorption and detachment processes of n-dodecane (C12H26) molecules were studied on silica surfaces with variable surface chemistry (Q2, Q3, Q4 environments), using molecular dynamics simulations. The area density of the silanol groups varied from 9.4 to 0 per nm2. The shrinking of the oil-water-solid contact line was a key step for the oil detachment, due to water diffusion on the three-phase contact line. The simulation results showed that oil detachment was easier and faster on a perfect Q3 silica surface which had (≡Si(OH))-type silanol groups, due to the H-bond formation between the water and silanol groups. When the surfaces contained more Q2 crystalline type which had (≡Si(OH)2)-type silanol groups, less oil detached, due to the formations of H-bonds among the silanol groups. There were no silanol groups on the Si-OH 0 surface. Water cannot diffuse on the water-oil-silica contact line, and oil cannot detach from the Q4 surface. The detachment efficiency of oil from the silica surface not only depended on the area density, but also on the types of silanol groups. The density and type of silanol groups depend on the crystal cleavage plane, particle size, roughness, and humidity.

Fate of 15N-labelled urea as affected by long-term manure substitution.

Quantifying the fate of fertilizer nitrogen (N) is essential to develop more sustainable agricultural fertilization practices. However, the fate of chemical fertilizer N, particularly in long-term manure substitution treatment regimes, is not fully understood. The present study aimed to investigate the fate of 15N-labelled urea in a chemical fertilizer treatment (CF, 240 kg 15N ha-1) and N manure 50 % substitution treatment (1/2N + M, 120 kg 15N ha-1 + 120 kg manure N ha-1) in two continuous crop seasons, based on a 10-year long-term experiment in the North China Plain (NCP). The results showed that manure substitution greatly enhanced 15N use efficiency (15NUE) (39.9 % vs. 31.3 %) and suppressed 15N loss (6.9 % vs. 7.5 %) compared with the CF treatment in the first crop. However, the N2O emissions factor in the 1/2N + M treatment was increased by 0.1 % (0.5 kg 15N ha-1 for CF vs. 0.4 kg 15N ha-1 for 1/2N + M) compared with the CF treatment, although N leaching and NH3 volatilization rates decreased by 0.2 % (10.8 kg 15N ha-1 for CF vs. 5.1 kg 15N ha-1 for 1/2N + M) and 0.5 % (6.6 kg 15N ha-1 for CF vs. 2.8 kg 15N ha-1 for 1/2N + M), respectively. In which, only NH3 volatilization presented significantly difference between treatments. It is important to note that in the second crop, the residual 15N in soil (0-20 cm) remained mostly in the soil for the CF (79.1 %) and the 1/2N + M treatment (85.3 %), and contributed less to crop N uptake (3.3 % vs. 0.8 %) and leached losses (2.2 % vs. 0.6 %). This proved that manure substitution could enhance the stabilization of chemical N. These results suggested that long-term manure substitution effectively increases NUE, suppresses N loss, and improves N stabilization in soil, but negative impacts such as N2O emissions due to climate change should be investigated further.

Studies of a novel bone-targeted nano drug delivery system with a HAP core-PSI coating structure for tanshinol injection.

Tanshinol (Tan) has good therapeutic effects on osteoporosis, fracture, and bone trauma repair. However, it is easily oxidised, has low bioavailability and a short half-life. To solve these problems, the study aimed to develop a novel bone-targeted nano-sustained-release drug delivery system PSI-HAPs for the systemic administration of Tan. This proposed system has hydroxyapatite (HAP) as the core to load drug and polysuccinimide (PSI), PEG-PSI (Polyethylene glycol, PEG), and ALN-PEG-PSI (Alendronate sodium, ALN) as the coating materials to form nanoparticles. The article examines the various PSI-HAPs' entrapping efficiency (EE, %), drug loading capacity (DLC, %), and distribution to determine the best PSI-HAP formulation in vivo. The in vivo experiment showed that the ALN-PEG-PSI-HAP (ALN-PEG/PSI molar ratio = 1:20) was the best preparation due to its higher distribution on bone (120 h) and lower distribution in the other tissues. The determined preparation was a uniformly spherical or sphere-like nanoparticle with a negative zeta potential. Additionally, it exhibited pH-sensitive drug release in PBS based on an in vitro drug release test. The proposed PSI-HAP preparations were prepared in the water solution using a facile preparation process without ultrasound, heating, and other conditions, which can significantly affect the stability of drugs.

Real-world effectiveness and factors associated with effectiveness of inactivated SARS-CoV-2 vaccines: a systematic review and meta-regression analysis.

BACKGROUND: The two inactivated SARS-CoV-2 vaccines, CoronaVac and BBIBP-CorV, have been widely used to control the COVID-19 pandemic. The influence of multiple factors on inactivated vaccine effectiveness (VE) during long-term use and against variants is not well understood. METHODS: We selected published or preprinted articles from PubMed, Embase, Scopus, Web of Science, medRxiv, BioRxiv, and the WHO COVID-19 database by 31 August 2022. We included observational studies that assessed the VE of completed primary series or homologous booster against SARS-CoV-2 infection or severe COVID-19. We used DerSimonian and Laird random-effects models to calculate pooled estimates and conducted multiple meta-regression with an information theoretic approach based on Akaike's Information Criterion to select the model and identify the factors associated with VE. RESULTS: Fifty-one eligible studies with 151 estimates were included. For prevention of infection, VE associated with study region, variants, and time since vaccination; VE was significantly decreased against Omicron compared to Alpha (P = 0.021), primary series VE was 52.8% (95% CI, 43.3 to 60.7%) against Delta and 16.4% (95% CI, 9.5 to 22.8%) against Omicron, and booster dose VE was 65.2% (95% CI, 48.3 to 76.6%) against Delta and 20.3% (95% CI, 10.5 to 28.0%) against Omicron; primary VE decreased significantly after 180 days (P = 0.022). For the prevention of severe COVID-19, VE associated with vaccine doses, age, study region, variants, study design, and study population type; booster VE increased significantly (P = 0.001) compared to primary; though VE decreased significantly against Gamma (P = 0.034), Delta (P = 0.001), and Omicron (P = 0.001) compared to Alpha, primary and booster VEs were all above 60% against each variant. CONCLUSIONS: Inactivated vaccine protection against SARS-CoV-2 infection was moderate, decreased significantly after 6 months following primary vaccination, and was restored by booster vaccination. VE against severe COVID-19 was greatest after boosting and did not decrease over time, sustained for over 6 months after the primary series, and more evidence is needed to assess the duration of booster VE. VE varied by variants, most notably against Omicron. It is necessary to ensure booster vaccination of everyone eligible for SARS-CoV-2 vaccines and continue monitoring virus evolution and VE. TRIAL REGISTRATION: PROSPERO, CRD42022353272.

Effects of temperature on metamorphosis and endochondral ossification in Rana chensinensis tadpoles.

Temperature is one of the important factors affecting the growth, development, and metamorphosis of amphibians. Endochondral ossification during metamorphosis plays a crucial role in amphibian survival and adaptation on land. In this study, we explored the effects of different temperature treatments on the growth, development, and endochondral ossification of Rana chensinensis tadpoles during metamorphosis. The results showed that high temperature exposure may affect the skeletal development of tadpoles during metamorphosis, such as reduction of bone length and ossification of limbs, thyroid gland damage and change of ossification-related genes expression levels，and ultimately affect the movement and survival of tadpoles in the terrestrial environment. These results provide an experimental reference for further research on the effects of temperature on amphibian growth and development and provide an important theoretical basis for the decline of the amphibian population caused by temperature.

Comparison of the characteristics of gut microbiota response to lead in Bufo gargarizans tadpole at different developmental stages.

In amphibians, lead (Pb) exposure could alter the composition and structure of gut microbiota, but changes involving microbiota of several successive phases following Pb exposure have been less studied. In the present study, we compared the effects of Pb exposure on morphological parameters and gut microbiota of Bufo gargarizans at Gosner stage (Gs) 33, Gs36, and Gs42. Our results showed that total length (TL), snout-vent length (SVL), and body wet weight (TW) of B. gargarizans at Gs33, as well as TL and SVL at Gs42, were significantly increased after Pb exposure. In addition, high-throughput sequencing analysis indicated that gut microbiota has distinct responses to Pb exposure at different developmental stages. The diversity of gut microbiota was significantly reduced under Pb exposure at Gs33, while it was significantly increased at Gs42. In terms of community composition, Spirochaetota, Armatimonadota, and Patescibacteria appeared in the control groups at Gs42, but not after Pb treatment. Furthermore, functional prediction indicated that the relative abundance of metabolism pathway was significantly decreased at Gs33 and Gs36, and significantly increased at Gs42. Our results fill an important knowledge gap and provide comparative information on the gut microbiota of tadpoles at different developmental stages following Pb exposure.

Effects of temperature on intestinal microbiota and lipid metabolism in Rana chensinensis tadpoles.

Climate change such as global warming is considered a major threat to amphibians. The guts of amphibians are home to trillions of microbes, which are key regulators of gastrointestinal digestion and play a crucial role in lipid metabolites. The aim of this study was to evaluate the effect of temperature change on intestinal microbiota and lipid metabolism in Rana chensinensis tadpoles. Morphological and intestinal microbiota data of R. chensinensis larvae exposed to different temperatures (15 °C, 21 °C, and 26 °C) were measured. The results show that the warm temperature causes histological damage to the intestinal epithelium. In addition, temperature treatments alter the diversity and composition of gut microbes in R. chensinensis tadpoles. At the phylum level of intestinal microbial community, Campilobacterota was detected only in the warm group. At the genera level, unclassified_f__Enterobacteriaceae was markedly declined in the warm group but was notably enriched in the cold group. For lipid metabolism-related genes, the expression levels of GPR109A, HDAC1, and APOA-I decreased significantly in both warm and cold treatment groups, while the expression levels of CLPS and LIPASE increased significantly. Collectively, these observations demonstrated that warm and cold temperatures may reduce the immune capacity of tadpoles by changing the composition of intestinal microorganisms and the expression of genes related to lipid metabolism, affecting the survival of tadpoles.

Research Progress in the Synthesis of Carbon Dots and Their Application in Food Analysis.

Food safety is connected to public health, making it crucial to protecting people's health. Food analysis and detection can assure food quality and effectively reduce the entry of harmful foods into the market. Carbon dots (CDs) are an excellent choice for food analysis and detection attributable to their advantages of good optical properties, water solubility, high chemical stability, easy functionalization, excellent bleaching resistance, low toxicity, and good biocompatibility. This paper focuses on the optical properties, synthesis methods, and applications of CDs in food analysis and detection, including the recent advances in food nutritional composition analysis and food quality detection, such as food additives, heavy metal ions, foodborne pathogens, harmful organic pollutants, and pH value. Moreover, this review also discusses the potentially toxic effects, current challenges, and prospects of CDs in basic research and applications. We hope that this review can provide valuable information to lay a foundation for subsequent research on CDs and promote the exploration of CDs-based sensing for future food detection.