Stabilization of Organic Cations in Lead Halide Perovskite Solar Cells Using Phosphine Oxides Derivatives.

Preventing ion migration in perovskite photovoltaics is key to achieving stable and efficient devices. The activation energy for ion migration is affected by the chemical environment surrounding the ions. Thus, the migration of organic cations in lead halide perovskites can be mitigated by engineering their local interactions, for example through hydrogen bonding. Ion migration also leads to ionic losses via interfacial reactions. Undesirable reactivities of the organic cations can be eliminated by introducing protecting groups. In this work, we report bis(2-oxo-3-oxazolidinyl) phosphinic chloride (BOP-Cl) as a perovskite ink additive with the following benefits: (1) The phosphoryl and two oxo groups form six-membered intermolecular hydrogen-bonded rings with the formamidinium cation (FA), mitigating ion migrations. (2) The hydrogen bonding reduces the electrophilicity of the ammonium protons by donating electron density, therefore reducing its reactivity with the surface oxygen on the metal oxide. Furthermore, the molecule can react to form a protecting group on the nucleophilic oxygen at the tin oxide transport layer surface through the elimination of chlorine. As a result, we achieve perovskite solar cells with an efficiency of 25.0% and improved MPP stability T93 = 1200 h at 40-45 °C compared to a control device (T86 = 550 h). In addition, we show a negative correlation between the strength of hydrogen bonding of different phosphine oxide derivatives to the organic cations and the degree of metastable behavior (e.g., initial burn-in) of the device.

Effect of metabolic dysfunction-associated steatotic liver disease on BNT162b2 immunogenicity against the severe acute respiratory syndrome coronavirus 2 omicron variant.

BACKGROUND AND AIM: We aimed to investigate the effect of metabolic dysfunction-associated steatotic liver disease (MASLD) on three-dose BNT162b2 immunogenicity to the omicron variant. METHODS: Adult recipients of three doses of BNT162b2 were prospectively recruited between May and December 2021. The serology of the neutralizing antibody by live virus microneutralization (vMN) to the omicron variant was measured at baseline, day 180, and day 360 after the first dose. The primary outcome was seroconversion (vMN titer ≥ 10) at day 360. Exposure of interest was MASLD, defined as hepatic steatosis (controlled attenuation parameter ≥ 248 dB/m on transient elastography) plus at least one of five cardiometabolic risk factors. Subjects with prior COVID-19 were excluded. A multivariable logistic regression model was used to derive the adjusted odds ratio of seroconversion with MASLD by adjusting for age, sex, antibiotic use, and proton pump inhibitor use. RESULTS: One hundred forty-eight BNT162b2 recipients (male: 48 [32.4%]; median age: 51.0 years [interquartile range, IQR: 44.5-57.3]) were recruited. The median time from the first dose to the third dose was 8.5 months (IQR: 7.9-8.9). MASLD subjects had a lower seroconversion rate than non-MASLD ones (89.6% vs 99.0%; P = 0.007). MASLD was the only independent risk factor for seroconversion (adjusted odds ratio: 0.051, 95% confidence interval: 0.002-0.440). Subgroup analysis of immunogenicity at 4 months after the third dose shows significantly lower vMN titer (13.06 [IQR: 7.69-22.20] vs 33.49 [IQR: 24.05-46.53]; P = 0.004) and seroconversion rate (76.9% vs 97.4%; P = 0.016) in MASLD than non-MASLD subjects, but not within 4 months from the third dose (vMN titer: 46.87 [IQR: 33.12-66.02] vs 41.86 [IQR: 34.47-50.91], P = 0.240; seroconversion rate: 94.3% vs 100%, P = 0.131). CONCLUSION: Metabolic dysfunction-associated steatotic liver disease was a risk factor for poorer immunogenicity to the omicron variant, with a more pronounced waning effect compared among three-dose BNT162b2 recipients.

Introgression of an adult-plant powdery mildew resistance gene Pm4VL from Dasypyrum villosum chromosome 4V into bread wheat.

Powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) seriously threatens wheat production worldwide. It is imperative to identify novel resistance genes from wheat and its wild relatives to control this disease by host resistance. Dasypyrum villosum (2n = 2x = 14, VV) is a relative of wheat and harbors novel genes for resistance against multi-fungal diseases. In the present study, we developed a complete set of new wheat-D. villosum disomic introgression lines through genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH) and molecular markers analysis, including four disomic substitution lines (2n=42) containing respectively chromosomes 1V#6, 2V#6, 3V#6, and 6V#6, and four disomic addition lines (2n=44) containing respectively chromosomes 4V#6, 5V#6, 6V#6 and 7V#6. These lines were subsequently evaluated for their responses to a mixture Bgt isolates at both seedling and adult-plant stages. Results showed that introgression lines containing chromosomes 3V#6, 5V#6, and 6V#6 exhibited resistance at both seedling and adult-plant stages, whereas the chromosome 4V#6 disomic addition line NAU4V#6-1 exhibited a high level of adult plant resistance to powdery mildew. Moreover, two translocation lines were further developed from the progenies of NAU4V#6-1 and the Ph1b mutation line NAU0686-ph1b. They were T4DL·4V#6S whole-arm translocation line NAU4V#6-2 and T7DL·7DS-4V#6L small-fragment translocation line NAU4V#6-3. Powdery mildew tests of the two lines confirmed the presence of an adult-plant powdery mildew resistance gene, Pm4VL, located on the terminal segment of chromosome arm 4V#6L (FL 0.6-1.00). In comparison with the recurrent parent NAU0686 plants, the T7DL·7DS-4V#6L translocation line NAU4V#6-3 showed no obvious negative effect on yield-related traits, providing a new germplasm in breeding for resistance.

Human-induced pluripotent stem cell-derived hepatocyte platform in modeling of SARS-CoV-2 infection.

Background and Aim: Currently, SARS-CoV-2 is still spreading rapidly and globally. A large proportion of patients with COVID-19 developed liver injuries. The human-induced pluripotent stem cell (iPSC)-derived hepatocytes recapitulate primary human hepatocytes and have been widely used in studies of liver diseases. Methods: To explore the susceptibility of hepatocytes to SARS-CoV-2, we differentiated iPSCs to functional hepatocytes and tried infecting them with different MOI (1, 0.1, 0.01) of SARS-CoV-2. Results: The iPSC-derived hepatocytes are highly susceptible to virus infection, even at 0.01 MOI. Other than the ancestral strain, iHeps also support the replication of SARS-CoV-2 variants including alpha, beta, theta, and delta. More interestingly, the ACE2 expression significantly upregulated after infection, suggesting a vicious cycle between virus infection and liver injury. Conclusions: The iPSC-derived hepatocytes can support the replication of SARS-CoV-2, and this platform could be used to investigate the SARS-CoV-2 hepatotropism and hepatic pathogenic mechanisms.

Clinical and Economic Burden of Severe Asthma With Low Blood Eosinophil Counts.

BACKGROUND: Type 2 low-severe asthma phenotype is often a result of corticosteroid-overtreated type 2 disease owing to persistent symptoms, often unrelated to asthma and unlikely to respond to high-dose corticosteroid treatment. OBJECTIVE: This study aimed to characterize patients with severe asthma with low eosinophil counts (<300 cells/µL) and describe their disease burden and treatment across health care settings in the United Kingdom. METHODS: A retrospective cohort study of patients with severe asthma using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients according to the latest blood eosinophil count (BEC). Clinical characteristics, treatment patterns, outcomes, and health care resource use were described by baseline BEC (≤150 and >150 to <300 cells/µL). RESULTS: Analysis included 701 (CPRD-HES) and 1,546 (UKSAR) patients; 60.5% and 59.4% had BECs 150 cells/µL or less at baseline, respectively. Across BEC groups, the proportion with uncontrolled asthma (two or more exacerbations) at follow-up (12 months after the index) was 5.4% in CPRD-HES and 45.2% in UKSAR. Maintenance oral corticosteroid use remained high across BEC groups (CPRD-HES: 29.4%; UKSAR: 51.7%), symptom control remained poor (>200 µg short-acting ß2 agonist or >500 µg terbutaline/d in CPRD-HES: 48.8%; median Asthma Control Questionnaire-6 score in UKSAR: 2.0 [range, 1.0-3.3]). Health care resource use was similar across BEC groups. CONCLUSIONS: Most patients managed in primary care experienced infrequent exacerbations, whereas UKSAR patients had frequent exacerbations. Large proportions of both patient groups had poor symptom control and continued to receive high levels of maintenance oral corticosteroids, increasing the risk of corticosteroid-induced morbidity. These data highlight the need for rigorous assessment of underlying disease pathology to guide appropriate treatment.

Effect of non-uniform root salt distribution on the ion distribution and growth of the halophyte Suaeda salsa.

Soil salinity in the root rhizosphere is highly heterogeneous in natural environments. Suaeda salsa L. is a highly salt-adapted halophyte, but it is unclear how S. salsa responds to non-uniform salinity conditions. The results of the root-splitting experiment showed that the increase in root dry weight in the low salt side (50/350-50) root of S. salsa may be associated with relative increases in root morphology. The concentration of Na+, Cl-, K+, the Na+ efflux and the expression of SsSOS1 in the low salt side root were higher than that of uniform low salt treatment. The expression of SsPIP1-4, SsPIP2-1, SsNRT1.1 and SsNRT2.1 were upregulated, which increased water and NO3- uptake in the low salt side root compared to uniform low salt treatment. In conclusion, under non-uniform salt treatment, the increased Na+ efflux, water and NO3- uptake from the low salt side root can alleviate salt stress in S. salsa.

Transferring an Adult-Plant Stripe-Rust Resistance Gene Yr7VS from Chromosome 7V of Dasypyrum villosum (L.) to Bread Wheat.

Stripe rust (Puccinia striiformis West. f.sp. tritici, Pst) is a destructive disease that seriously threatens wheat production globally. Exploring novel resistance genes for use in wheat breeding is an urgent need, as continuous Pst evolution frequently leads to a breakdown of host resistance. Here, we identified a set of wheat-Dasypyrum villosum 01I139 (V#6) disomic introgression lines for the purpose of determining their responses to a mixture of Pst isolates CYR32, CYR33 and CYR34 at both seedling and adult-plant stages. The results showed that all introgression lines exhibited high susceptibility at the seedling stage, with infection-type (IT) scores in the range of 6-8, whereas, for chromosomes 5V#6 and 7V#6, disomic addition lines NAU5V#6-1 and NAU7V#6-1 displayed high resistance at the adult-plant stage, indicating that adult-plant resistance (APR) genes were located on them. Further, in order to transfer the stripe-rust resistance on chromosome 7V#6, four new wheat-D. villosum introgression lines were identified, by the use of molecular cytogenetic approaches, from the self-pollinated seeds of 7D and 7V#6, in double monosomic line NAU7V#6-2. Among them, NAU7V#6-3 and NAU7V#6-4 were t7V#6L and t7V#6S monosomic addition lines, and NAU7V#6-5 and NAU7V#6-6 were homozygous T7DS·7V#6L and T7DL·7V#6S whole-arm translocation lines. Stripe-rust tests and genetic analyses of chromosome 7V#6 introgression lines revealed a dominant APR gene designated as Yr7VS on the chromosome arm 7V#6S. Comparison with the homozygous T7DL·7V#6S translocation line and the recurrent parent NAU0686 showed no significant differences in yield-related traits. Thus, T7DL·7V#6S whole-arm translocation with the APR gene Yr7VS provided a valuable germplasm for breeding for resistance.

Integrating pyriproxyfen into the incompatible insect technique enhances mosquito population suppression efficiency and eliminates the risk of population replacement.

BACKGROUND: The incompatible insect technique (IIT) has been used for Aedes mosquito population suppression to curb the transmission of dengue. However, its wide application is limited owing to the low output of male mosquitoes and the risk of population replacement from the release of fertile Wolbachia-infected females. This study aims to improve IIT efficiency for broader adoption. RESULTS: We assessed the impact of 10% pyriproxyfen (PPF) sticky powder exposure on Wolbachia (from Culex molestus)-transinfected Aedes albopictus Guangzhou line (GUA line) (GC) mosquitoes. We found that the exposure caused chronic toxicity in adult mosquitoes without affecting the cytoplasmic incompatibility (CI)-inducing capability of males. The PPF-contaminated GC females exhibited significant sterilization and the ability to disseminate lethal doses of PPF to breeding sites. Subsequently, we conducted a field trial combining PPF with IIT aiming to suppress the Ae. albopictus population. This combined approach, termed boosted IIT (BIIT), showed a notable enhancement in population suppression efficiency. The improved efficacy of BIIT was attributed to the dispersion of PPF particles in the field via the released PPF-contaminated male mosquitoes. During the BIIT field trial, no Wolbachia wPip-positive Ae. albopictus larvae were detected, indicating the effective elimination of the risk of Wolbachia-induced population replacement. Additionally, the field trial of BIIT against Ae. albopictus resulted in the suppression of the nontarget mosquito species Culex quinquefasciatus. CONCLUSION: Our results highlight the remarkable efficiency and feasibility of combining IIT with PPF in suppressing mosquito populations, facilitating the widespread implementation of IIT-based management of mosquito-borne diseases. © 2024 Society of Chemical Industry.

Plasma immune profiling combined with machine learning contributes to diagnosis and prognosis of active pulmonary tuberculosis.

Tuberculosis (TB) remains one of the deadliest chronic infectious diseases globally. Early diagnosis not only prevents the spread of TB but also ensures effective treatment. However, the absence of non-sputum-based diagnostic tests often leads to delayed TB diagnoses. Inflammation is a hallmark of TB, we aimed to identify biomarkers associated with TB based on immune profiling. We collected 222 plasma samples from healthy controls (HCs), disease controls (non-TB pneumonia; PN), patients with TB (TB), and cured TB cases (RxTB). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure the levels of 92 immune proteins. Based on differential analysis and the correlation with TB severity, we selected 9 biomarkers (CXCL9, PDL1, CDCP1, CCL28, CCL23, CCL19, MMP1, IFNγ and TRANCE) and explored their diagnostic capabilities through 7 machine learning methods. We identified combination of these 9 biomarkers that distinguish TB cases from controls with an area under the receiver operating characteristic curve (AUROC) of 0.89-0.99, with a sensitivity of 82-93% at a specificity of 88-92%. Moreover, the model excels in distinguishing severe TB cases, achieving AUROC exceeding 0.95, sensitivities and specificities exceeding 93.3%. In summary, utilizing targeted proteomics and machine learning, we identified a 9 plasma proteins signature that demonstrates significant potential for accurate TB diagnosis and clinical outcome prediction.

[Spatiotemporal Simulation and Prediction of Soil Organic Carbon Density in Gannan Grassland Under Future Climate Scenarios].

To study the temporal and spatial distribution characteristics of soil organic carbon density in grassland and explore the relationship between organic carbon density and influencing factors is of great significance to the management and maintenance of grassland ecosystems in Gannan Autonomous Prefecture, which is conducive to realizing the goal of "double carbon," promoting carbon sink, and mitigating climate change. Taking Gannan Tibetan Autonomous Prefecture of Gansu Province as the research object, based on data from two CMIP6 future climate scenarios (SSP126 and SSP585), the CENTURY model was used to simulate and predict the temporal and spatial changes in soil organic carbon density in grassland of Gannan during 2023-2100. The main conclusions were as follows:① From 2023 to 2100, total organic carbon density, slow organic carbon density, and inert organic carbon density all showed a downward trend, whereas active organic carbon density fluctuated first and then increased. Meanwhile, the total organic carbon density, active organic carbon density, slow organic carbon density, and inert organic carbon density under the SSP585 scenario were higher than those under the SSP126 scenario. ② Mann-Kendall mutation analysis showed that the abrupt change in the difference of soil total organic carbon density (Δsomtc) occurred in 2030. The abrupt change in the difference of soil active carbon density (Δsom1c) occurred in 2027. ③ During the study period, the average soil organic carbon density of Gannan grassland was 7 505.69 g·m-2 under the SSP126 scenario and 7 551.87 g·m-2 under the SSP585 scenario. Gannan grassland soil organic carbon density was higher in the west and lower in the east, and the coefficient of variation was relatively stable. ④ The results of partial correlation analysis showed that precipitation was positively correlated with soil organic carbon density, whereas temperature was significantly negatively correlated with soil organic carbon density under future climate scenarios. ⑤ The results of the Theil-Sen Median trend analysis and Mann-Kendall test showed that under the two climate scenarios, the soil organic carbon density in Gannan showed an overall downward trend, in which Luqu County showed the fastest downward trend and Dibe County showed the slowest.

Proteomics appending a complementary dimension to precision oncotherapy.

Recent advances in high-throughput proteomic profiling technologies have facilitated the precise quantification of numerous proteins across multiple specimens concurrently. Researchers have the opportunity to comprehensively analyze the molecular signatures in plentiful medical specimens or disease pattern cell lines. Along with advances in data analysis and integration, proteomics data could be efficiently consolidated and employed to recognize precise elementary molecular mechanisms and decode individual biomarkers, guiding the precision treatment of tumors. Herein, we review a broad array of proteomics technologies and the progress and methods for the integration of proteomics data and further discuss how to better merge proteomics in precision medicine and clinical settings.

Photoactivated disinfection procedure for denture stomatitis in diabetic rats.

Objective: To study the efficacy of PADTM Plus-based photoactivated disinfection (PAD) for treating denture stomatitis (DS) in diabetic rats by establishing a diabetic rat DS model. Methods: The diabetic rat DS model was developed by randomly selecting 2-month-old male Sprague-Dawley rats and dividing them into four groups. The palate and denture surfaces of rats in the PAD groups were incubated with 1 mg/mL toluidine blue O for 1 min each, followed by a 1-min exposure to 750-mW light-emitting diode light. The PAD-1 group received one radiation treatment, and the PAD-2 group received three radiation treatments over 5 days with a 1-day interval. The nystatin (NYS) group received treatment for 5 days with a suspension of NYS of 100,000 IU. The infection group did not receive any treatment. In each group, assessments included an inflammation score of the palate, tests for fungal load, histological evaluation, and immunohistochemical detection of interleukin-17 (IL-17) and tumor necrosis factor (TNF-α) conducted 1 and 7 days following the conclusion of treatment. Results: One day after treatment, the fungal load on the palate and dentures, as well as the mean optical density values of IL-17 and TNF-α, were found to be greater in the infection group than in the other three treatment groups (P < 0.05). On the 7th day after treatment, these values were significantly higher in the infection group than in the PAD-2 and NYS groups (P < 0.05). Importantly, there were no differences between the infection and PAD-1 groups nor between the PAD-2 and NYS groups (P > 0.05). Conclusions: PAD effectively reduced the fungal load and the expressions of IL-17 and TNF-α in the palate and denture of diabetic DS rats. The efficacy of multiple-light treatments was superior to that of single-light treatments and similar to that of NYS.

A rare case of TFEB/6p21/VEGFA-amplified renal cell carcinoma diagnosed by whole-exome sequencing: clinicopathological and genetic feature report and literature review.

BACKGROUND: TFEB/6p21/VEGFA-amplified renal cell carcinoma (RCC) is rare and difficult to diagnose, with diverse histological patterns and immunohistochemical and poorly defined molecular genetic characteristics. CASE PRESENTATION: We report a case of a 63-year-old male admitted in 2017 with complex histomorphology, three morphological features of clear cell, eosinophilic and papillary RCC and resembling areas of glomerular and tubular formation. The immunophenotype also showed a mixture of CD10 and P504s. RCC with a high suspicion of collision tumors was indicated according to the 2014 WHO classification system; no precise diagnosis was possible. The patient was diagnosed at a different hospital with poorly differentiated lung squamous cell carcinoma one year after RCC surgery. We exploited molecular technology advances to retrospectively investigate the patient's molecular genetic alterations by whole-exome sequencing. The results revealed a 6p21 amplification in VEGFA and TFEB gene acquisition absent in other RCC subtypes. Clear cell, papillary, chromophobe, TFE3-translocation, eosinophilic solid and cystic RCC were excluded. Strong TFEB and Melan-A protein positivity prompted rediagnosis as TFEB/6p21/VEGFA-amplified RCC as per 2022 WHO classification. TMB-L (low tumor mutational load), CCND3 gene acquisition and MRE11A and ATM gene deletion mutations indicated sensitivity to PD-1/PD-L1 inhibitor combinations and the FDA-approved targeted agents Niraparib (Grade C), Olaparib (Grade C), Rucaparib (Grade C) and Talazoparib (Class C). GO (Gene Ontology) and KEGG enrichment analyses revealed major mutations and abnormal CNVs in genes involved in biological processes such as the TGF-ß, Hippo, E-cadherin, lysosomal biogenesis and autophagy signaling pathways, biofilm synthesis cell adhesion substance metabolism regulation and others. We compared TFEB/6p21/VEGFA-amplified with TFEB-translocated RCC; significant differences in disease onset age, histological patterns, pathological stages, clinical prognoses, and genetic characteristics were revealed. CONCLUSION: We clarified the patient's challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.

An ensemble deep learning diagnostic system for determining Clinical Activity Scores in thyroid-associated ophthalmopathy: integrating multi-view multimodal images from anterior segment slit-lamp photographs and facial images.

Background: Thyroid-associated ophthalmopathy (TAO) is the most prevalent autoimmune orbital condition, significantly impacting patients' appearance and quality of life. Early and accurate identification of active TAO along with timely treatment can enhance prognosis and reduce the occurrence of severe cases. Although the Clinical Activity Score (CAS) serves as an effective assessment system for TAO, it is susceptible to assessor experience bias. This study aimed to develop an ensemble deep learning system that combines anterior segment slit-lamp photographs of patients with facial images to simulate expert assessment of TAO. Method: The study included 156 patients with TAO who underwent detailed diagnosis and treatment at Shanxi Eye Hospital Affiliated to Shanxi Medical University from May 2020 to September 2023. Anterior segment slit-lamp photographs and facial images were used as different modalities and analyzed from multiple perspectives. Two ophthalmologists with more than 10 years of clinical experience independently determined the reference CAS for each image. An ensemble deep learning model based on the residual network was constructed under supervised learning to predict five key inflammatory signs (redness of the eyelids and conjunctiva, and swelling of the eyelids, conjunctiva, and caruncle or plica) associated with TAO, and to integrate these objective signs with two subjective symptoms (spontaneous retrobulbar pain and pain on attempted upward or downward gaze) in order to assess TAO activity. Results: The proposed model achieved 0.906 accuracy, 0.833 specificity, 0.906 precision, 0.906 recall, and 0.906 F1-score in active TAO diagnosis, demonstrating advanced performance in predicting CAS and TAO activity signs compared to conventional single-view unimodal approaches. The integration of multiple views and modalities, encompassing both anterior segment slit-lamp photographs and facial images, significantly improved the prediction accuracy of the model for TAO activity and CAS. Conclusion: The ensemble multi-view multimodal deep learning system developed in this study can more accurately assess the clinical activity of TAO than traditional methods that solely rely on facial images. This innovative approach is intended to enhance the efficiency of TAO activity assessment, providing a novel means for its comprehensive, early, and precise evaluation.

Characterization of Probiotic Properties and Whole-Genome Analysis of Lactobacillus johnsonii N5 and N7 Isolated from Swine.

In our previous microbiome profiling analysis, Lactobacillus (L.) johnsonii was suggested to contribute to resistance against chronic heat stress-induced diarrhea in weaned piglets. Forty-nine L. johnsonii strains were isolated from these heat stress-resistant piglets, and their probiotic properties were assessed. Strains N5 and N7 exhibited a high survival rate in acidic and bile environments, along with an antagonistic effect against Salmonella. To identify genes potentially involved in these observed probiotic properties, the complete genome sequences of N5 and N7 were determined using a combination of Illumina and nanopore sequencing. The genomes of strains N5 and N7 were found to be highly conserved, with two N5-specific and four N7-specific genes identified. Multiple genes involved in gastrointestinal environment adaptation and probiotic properties, including acidic and bile stress tolerance, anti-inflammation, CAZymes, and utilization and biosynthesis of carbohydrate compounds, were identified in both genomes. Comparative genome analysis of the two genomes and 17 available complete L. johnsonii genomes revealed 101 genes specifically harbored by strains N5 and N7, several of which were implicated in potential probiotic properties. Overall, this study provides novel insights into the genetic basis of niche adaptation and probiotic properties, as well as the genome diversity of L. johnsonii.

Association between Gut Microbiota Composition and Long-Term Vaccine Immunogenicity following Three Doses of CoronaVac.

BACKGROUND: Neutralizing antibody level wanes with time after COVID-19 vaccination. We aimed to study the relationship between baseline gut microbiota and immunogenicity after three doses of CoronaVac. METHODS: This was a prospective cohort study recruiting three-dose CoronaVac recipients from two centers in Hong Kong. Blood samples were collected at baseline and one year post-first dose for virus microneutralization (vMN) assays to determine neutralization titers. The primary outcome was high immune response (defined as with vMN titer ≥ 40). Shotgun DNA metagenomic sequencing of baseline fecal samples identified potential bacterial species and metabolic pathways using Linear Discriminant Analysis Effect Size (LEfSe) analysis. Univariate and multivariable logistic regression models were used to identify high response predictors. RESULTS: In total, 36 subjects were recruited (median age: 52.7 years [IQR: 47.9-56.4]; male: 14 [38.9%]), and 18 had low immune response at one year post-first dose vaccination. Eubacterium rectale (log10LDA score = 4.15, p = 0.001; relative abundance of 1.4% vs. 0, p = 0.002), Collinsella aerofaciens (log10LDA score = 3.31, p = 0.037; 0.39% vs. 0.18%, p = 0.038), and Streptococcus salivarius (log10LDA score = 2.79, p = 0.021; 0.05% vs. 0.02%, p = 0.022) were enriched in low responders. The aOR of high immune response with E. rectale, C. aerofaciens, and S. salivarius was 0.03 (95% CI: 9.56 × 10-4-0.32), 0.03 (95% CI: 4.47 × 10-4-0.59), and 10.19 (95% CI: 0.81-323.88), respectively. S. salivarius had a positive correlation with pathways enriched in high responders like incomplete reductive TCA cycle (log10LDA score = 2.23). C. aerofaciens similarly correlated with amino acid biosynthesis-related pathways. These pathways all showed anti-inflammation functions. CONCLUSION: E. rectale,C. aerofaciens, and S. salivarius correlated with poorer long-term immunogenicity following three doses of CoronaVac.

Degradation of Poly(ethylene terephthalate) Catalyzed by Nonmetallic Dibasic Ionic Liquids under UV Radiation.

Nonmetallic ionic liquids (ILs) exhibit unique advantages in catalyzing poly (ethylene terephthalate) (PET) glycolysis, but usually require longer reaction times. We found that exposure to UV radiation can accelerate the glycolysis reaction and significantly reduce the reaction time. In this work, we synthesized five nonmetallic dibasic ILs, and their glycolysis catalytic activity was investigated. 1,8-diazabicyclo [5,4,0] undec-7-ene imidazole ([HDBU]Im) exhibited better catalytic performance. Meanwhile, UV radiation is used as a reinforcement method to improve the PET glycolysis efficiency. Under optimal conditions (5 g PET, 20 g ethylene glycol (EG), 0.25 g [HDBU]Im, 10,000 µW·cm-2 UV radiation reacted for 90 min at 185 °C), the PET conversion and BHET yield were 100% and 88.9%, respectively. Based on the UV-visible spectrum, it was found that UV radiation can activate the C=O in PET. Hence, the incorporation of UV radiation can considerably diminish the activation energy of the reaction, shortening the reaction time of PET degradation. Finally, a possible reaction mechanism of [HDBU]Im-catalyzed PET glycolysis under UV radiation was proposed.

Interaction and antiviral treatment of coinfection between SARS-CoV-2 and influenza in vitro.

BACKGROUND: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has lasted for three years. Coinfection with seasonal influenza may occur resulting in more severe diseases. The interaction between these two viruses for infection and the effect of antiviral treatment remains unclear. METHODS: A SARS-CoV-2 and influenza H1N1 coinfection model on Calu-3 cell line was established, upon which the simultaneous and sequential coinfection was evaluated by comparing the viral load. The efficacy of molnupiravir and baloxavir against individual virus and coinfection were also studied. RESULTS: The replication of SARS-CoV-2 was significantly interfered when the influenza virus was infected simultaneously or in advance (p < 0.05). On the contrary, the replication of the influenza virus was not affected by the SARS-CoV-2. Molnupiravir monotherapy had significant inhibitory effect on SARS-CoV-2 when the concentration reached to 6.25 µM but did not show any significant anti-influenza activity. Baloxavir was effective against influenza within the dosage range and showed significant effect of anti-SARS-CoV-2 at 16 µM. In the treatment of coinfection, molnupiravir had significant effect for SARS-CoV-2 from 6.25 µM to 100 µM and inhibited H1N1 at 100 µM (p < 0.05). The tested dosage range of baloxavir can inhibit H1N1 significantly (p < 0.05), while at the highest concentration of baloxavir did not further inhibit SARS-CoV-2, and the replication of SARS-CoV-2 significantly increased in lower concentrations. Combination treatment can effectively inhibit influenza H1N1 and SARS-CoV-2 replication during coinfection. Compared with molnupiravir or baloxavir monotherapy, combination therapy was more effective in less dosage to inhibit the replication of both viruses. CONCLUSIONS: In coinfection, the replication of SARS-CoV-2 would be interfered by influenza H1N1. Compared with molnupiravir or baloxavir monotherapy, treatment with a combination of molnupiravir and baloxavir should be considered for early treatment in patients with SARS-CoV-2 and influenza coinfection.

Nanoplastics aggravated TDCIPP-induced transgenerational developmental neurotoxicity in zebrafish depending on the involvement of the dopamine signaling pathway.

Plastics pose a hazard to the environment. Although plastics have toxicity, microplastics (MPs) and nanoplastics (NPs) are capable of interacting with the rest pollutants in the environment, so they serve as the carriers and interact with organic pollutants to modulate their toxicity, thus resulting in unpredictable ecological risks. PS-NPs and TDCIPP were used expose from 2 h post-fertilization (hpf) to 150 days post-fertilization (dpf) to determine the bioaccumulation of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and its potential effects on neurodevelopment in F1 zebrafish (Danio rerio) offspring under the action of polystyrene nano plastics (PS-NPs). The exposure groups were assigned to TDCIPP (0, 0.4, 2 or 10 µg/L) alone group and the PS-NPs (100 µg/L) and TDCIPP co-exposed group. F1 embryos were collected and grown in clean water to 5 dpf post-fertilization. PS-NPs facilitated the bioaccumulation of TDCIPP in the gut, gill, head，gonad and liver of zebrafish in a sex-dependent manner and promoted the transfer of TDCIPP to their offspring, thus contributing to PS-NPs aggravated the inhibition of offspring development and neurobehavior of TDCIPP-induced. In comparison with TDCIPP exposure alone, the combination could notably down-regulate the levels of the dopamine neurotransmitter, whereas the levels of serotonin or acetylcholine were not notably different. This result was achieved probably because PS-NPs interfered with the TDCIPP neurotoxic response of zebrafish F1 offspring not through the serotonin or acetylcholine neurotransmitter pathway. The increased transfer of TDCIPP to the offspring under the action of PS-NPs increased TDCIPP-induced transgenerational developmental neurotoxicity, which was proven by a further up-regulation/down-regulation the key gene and protein expression related to dopamine synthesis, transport, and metabolism in F1 larvae, in contrast to TDCIPP exposure alone. The above findings suggested that dopaminergic signaling involvement could be conducive to the transgenerational neurodevelopmental toxicity of F1 larval upon parental early co-exposure to PS-NPs and TDCIPP.

[Occurrence Characteristic and Risk Assessment of Microplastics in Sishui River (Xingyang Section)].

Urban rivers are the main receptors and transporters of microplastic pollution. Understanding the occurrence and environmental risk of microplastics in urban rivers can provide theoretical basis for further control of microplastic pollution. The Sishui River, a tributary of the Yellow River, was selected as the research object. A total of nine water samples were collected from sewage outlets of the Sishui River (Xingyang section). The microplastics in the collected samples were characterized by their sizes, shapes, and colors using a microscope. It was found that microplastics were mostly in the form of transparent fibers and fragments in the water body of sewage outlets, of which the size below 500 µm was relatively high. In addition, PET and PE polymers were identified as the main types using a laser infrared imager. The correlation analysis showed that there was a significant correlation between the PET and PE, indicating that they were similar in origin. The results of the environmental risk assessment showed that the type of microplastics was the main factor affecting the assessment results, whereas the risk values of six sewage samples containing PVC were high. However, the value of pollution load index revealed a low risk level of pollutants in the study area.