Effects of single and combined urinary polycyclic aromatic hydrocarbon effects on lung function in the U.S. adult population.

BACKGROUND: The impact of polycyclic aromatic hydrocarbons (PAHs) on lung function has garnered attention, but studies mostly focus on individual effect. This study investigates urinary PAH metabolites as biomarkers of exposure and assesses the relationships between single and combined exposures to nine urinary PAH metabolites and lung function in adults. METHODS: Data from 4040 adults in the 2007-2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. Weighted generalized linear models estimated the effects of individual PAH metabolites on lung function. Additionally, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were employed to evaluate the combined impacts of multiple PAH metabolites. RESULTS: Analyses of individual PAH metabolites revealed negative associations with lung function, excluding forced vital capacity (FVC). The WQS, qgcomp, and BKMR models consistently showed that exposure to multiple PAH metabolites was associated with lung function decrease. WQS indicated that 2-hydroxynaphthalene (2-NAP) was the largest contributor to the reductions in forced expiratory volume in 1 s (FEV1), FVC, peak expiratory flow (PEF), and forced expiratory flow from 25 to 75% of FVC (PEF25-75%). Additionally, 1-hydroxypyrene (1-PYR) was the primary PAH metabolite contributing to the decreases in FEV1/FVC and fractional exhaled nitric oxide (FeNO). The combined effect of urinary PAH metabolites did not affect FVC in the current smokers or FeNO in nonsmokers, but decreased FEV1/FVC in current smokers. CONCLUSION: This study strengthens the negative relationships between multiple PAH metabolites exposure and lung function in adults. Given the limitations of this study, including the lack of knowledge of other exposure pathways and the uncertainty of urinary metabolites, further research is necessary to explore the mechanisms underlying these associations and to address the limitations in exposure assessment.

Carbon-metal versus metal-metal synergistic mechanism of ethylene electro-oxidation via electrolysis of water on TM2N6 sites in graphene.

Acetaldehyde (AA) and ethylene oxide (EO) are important fine chemicals, and are also substrates with wide applications for high-value chemical products. Direct electrocatalytic oxidation of ethylene to AA and EO can avoid the untoward effects from harmful byproducts and high energy emissions. The most central intermediate state is the co-adsorption and coupling of ethylene and active oxygen intermediates (*O) at the active site(s), which is restricted by two factors: the stability of the *O intermediate generated during the electrolysis of water on the active site at a certain applied potential and pH range; and the lower kinetic energy barriers of the oxidation process based on the thermo-migration barrier from the *O intermediate to produce AA/EO. The benefit of two adjacent active atoms is more promising, since diverse adsorption and flexible catalytic sites may be provided for elementary reaction steps. Motivated by this strategy, we explored the feasibility of various homonuclear TM2N6@graphenes with dual-atomic-site catalysts (DASCs) for ethylene electro-oxidation through first-principles calculations via thermodynamic evaluation, analysis of the surface Pourbaix diagram, and kinetic evaluation. Two reaction mechanisms through C-TM versus TM-TM synergism were determined. Between them, a TM-TM mechanism on 4 TM2N6@graphenes and a C-TM mechanism on 5 TM2N6@graphenes are built. All 5 TM2N6@graphenes through the C-TM mechanism exhibit lower kinetic energy barriers for AA and EO generation than the 4 TM2N6@graphenes through the TM-TM mechanism. In particular, Pd2N6@graphene exhibits the most excellent catalytic activity, with energy barriers for generating AA and EO of only 0.02 and 0.65 eV at an applied potential of 1.77 V vs. RHE for the generation of an active oxygen intermediate. Electronic structure analysis indicates that the intrinsic C-TM mechanism is more advantageous than the TM-TM mechanism for ethylene electro-oxidation, and this study also provides valuable clues for further experimental exploration.

Phylogenomics, taxonomy and morphological characters of the Microdochiaceae (Xylariales, Sordariomycetes).

Species of the family Microdochiaceae (Xylariales, Sordariomycetes) have been reported from worldwide, and collected from different plant hosts. The proposed new genus and two new species, viz., Macroidriella gen. nov., M.bambusae sp. nov. and Microdochiumaustrale sp. nov., are based on multi-locus phylogenies from a combined dataset of ITS rDNA, LSU, RPB2 and TUB2 with morphological characteristics. Microdochiumsinense has been collected from diseased leaves of Phragmitesaustralis and this is the first report of the fungus on this host plant. Simultaneously, we annotated 10,372 to 11,863 genes, identified 4,909 single-copy orthologous genes, and conducted phylogenomic analysis based on genomic data. A gene family analysis was performed and it will expand the understanding of the evolutionary history and biodiversity of the Microdochiaceae. The detailed descriptions and illustrations of species are provided.

Further screening of SNP loci of eggshell translucency related genes and evaluation of genetic effects.

Eggshell translucency is a widespread issue in the field of egg quality. Previous research has established that the heritability of eggshell translucency is relatively low or moderate. Scientists have also successfully identified SNP loci related to eggshell translucency on different chromosomes by using gene chips and single-variant GWAS. However, the specific impact of single or multiple genes on the trait of eggshell translucency remains unknown. In an effort to investigate this, we examined 170 SNPs associated with eggshell translucency obtained by our research group. We selected 966 half-sibling laying hens from 2 generations in 3 pure lines: Dwarf Layer-White, Rhode Island Red-White Strain, and Rhode Island Red. Eggs were collected from each hen over a period of 5 consecutive days, and eggshell translucency was measured using a grading method in which the hens were divided into 2 groups: an opaque group and a translucent group. We collected blood samples from the laying hens and extracted DNA. Time of flight mass spectrometry (TOF-MS) was used for genotyping to identify SNP loci that influence the trait of eggshell translucency. The results of our analysis revealed that using TOF-MS in 3 chicken strains, we were able to eliminate loci with low gene polymorphism, genetic effect contribution less than 1%, and deviation from Hardy-Weinberg equilibrium. Ultimately, 5 SNPs (Affx-50362599, rs15050262, rs312943734, rs316121113, and rs317389181) were identified on chromosomes 1, 5, and 19. Additionally, nine candidate genes (DCN, BTG1, ZFP92, POU2F1, NUCB2, FTL, GGNBP2, ACACA, and TADA2A) were found to be associated with these SNPs. No linkage disequilibrium relationship was observed between the 2 pairs of SNP loci on chromosomes 1 and 19. Based on previous studies on the formation mechanism of eggshell translucency, we hypothesize that NUCB2, FTL, and ACACA genes may be affecting the eggshell structure through different mechanisms, such as increase the water permeability or make thin of eggshell membrane, which promote moisture or part of other egg contents and ultimately lead to the formation of eggshell translucency. These findings validate and identify five SNP loci that regulate the translucency trait, and provide molecular markers for breeding non-translucent populations. Furthermore, this study serves as a reference for further investigation of the genetic regulatory mechanisms underlying eggshell translucency.

Pyrene-Alkyne-Based Conjugated Porous Polymers with Skeleton Distortion-Mediated ⋠O2 - and 1O2 Generation for High-Selectivity Organic Photosynthesis.

Reactive oxygen species (ROS) play a crucial role in determining photocatalytic reaction pathways, intermediate species, and product selectivity. However, research on ROS regulation in polymer photocatalysts is still in its early stages. Herein, we successfully achieved series of modulations to the skeleton of Pyrene-alkyne-based (Tetraethynylpyrene (TEPY)) conjugated porous polymers (CPPs) by altering the linkers (1,4-dibromobenzene (BE), 4,4'-dibromobiphenyl (IP), and 3,3'-dibromobiphenyl (BP)). Experiments combined with theoretical calculations indicate that BE-TEPY exhibits a planar structure with minimal exciton binding energy, which favors exciton dissociation followed by charge transfer with adsorbed O2 to produce ⋅O2 -. Thus BE-TEPY shows optimal photocatalytic activity for phenylboronic acid oxidation and [3+2] cycloaddition. Conversely, the skeleton of BP-TEPY is significantly distorted. Its planar conjugation decreases, intersystem crossing (ISC) efficiency increases, which makes it more prone for resonance energy transfer to generate 1O2. Therefore, BP-TEPY displays best photocatalytic activity in [4+2] cycloaddition and thioanisole oxidation. Both above reactant conversion and its product selectivity exceed 99 %. This work systematically reveals the intrinsic structure-activity relationship among the skeleton structure of CPPs, excitonic behavior, and selective generation of ROS, providing new insights for the rational design of highly efficient and selective CPPs photocatalysts.

The efficacy and safety of molidustat for anemia in dialysis-dependent and non-dialysis-dependent chronic kidney disease patients: A systematic review and meta-analysis.

Objective: Molidustat is a novel agent investigated for the treatment of anemia in both dialysisdependent (DD) and non-dialysis-dependent (NDD) patients. Its efficacy and safety are still unclear. Methods: We searched five databases to identify randomized controlled trials comparing molidustat to erythropoiesis-stimulating agents (ESAs) or placebo in patients with anemia. Results: Six studies containing 2025 eligible participants were identified. For NDD patients, the change in Hb levels from baseline (ΔHb) was significantly higher for molidustat than for placebo [mean difference (MD) = 1.47 (95 % CI: 1.18 to 1.75), P < 0.00001] and ΔHb was also significantly higher for molidustat than for ESAs [MD = 0.25 (95 % CI 0.09 to 0.40), P = 0.002]. For NDD patients, Δhepcidin was significantly lower for molidustat than for placebo [MD = -20.66 (95 % CI: -31.67 to -9.66), P = 0.0002] and Δhepcidin was also significantly lower for molidustat than for ESAs [MD = -24.51 (95 % CI: -29.12 to -19.90), P < 0.00001]. For NDD patients, Δiron was significantly lower for molidustat than for ESAs [MD = -11.85 (95 % CI: -15.52 to -8.18), P < 0.00001], and ΔTSAT was also significantly lower for molidustat than for ESAs [MD = -5.29 (95 % CI: -6.81 to -3.78), P < 0.00001]. For NDD patients, Δferritin was significantly lower for molidustat than for placebo [MD = -90.01 (95 % CI: -134.77 to -45.25), P < 0.00001]. However, for DD-CKD patients, molidustat showed an effect similar to that of ESAs on increasing the Hb level [MD = -0.18 (95 % CI: -0.47 to 0.11), P = 0.23], Δiron level [MD = 3.78 (95 % CI: -7.21 to 14.76), P = 0.5], Δferritin level [MD = 25.03 (95 % CI: -34.69 to 84.75), P = 0.41], and Δhepcidin level [MD = 1.20 (95 % CI: -4.36 to 6.76), P = 0.67]. For DD-CKD patients, compared with the placebo or ESA group, molidustat showed a significantly higher level on ΔTSAT[MD = 3.88 (95 % CI: 2.10 to 5.65), P < 0.0001] and a slightly increased level on ΔTIBC level [MD = 1.08 (95 % CI: -0.07 to 2.23), P = 0.07]. There was no significant difference in the incidence of severe adverse events (SAEs), death, and cardio-related adverse events between molidustat and the ESAs groups. Conclusions: Moricizine can effectively improves Hb levels in NDD patients and corrects anemia in DD patients without increasing adverse event incidence.

Arbuscular mycorrhizal fungi increased peanut (Arachis hypogaea L.) yield by changing the rhizosphere microbial community structure in saline-alkali soil.

Arbuscular mycorrhizal fungi (AMF) have demonstrated the potential to enhance the saline-alkali tolerance in plants. Nevertheless, the extent to which AMF can ameliorate the tolerance of salt-sensitive plants to alkaline conditions necessitates further investigation. The current study is primarily centered on elucidating the impact of AMF on the growth of the Huayu22 (H22) when cultivated in saline-alkaline soil. We leveraged DNA of rhizosphere microorganisms extracted from saline-alkali soil subjected to AMF treatment and conducted high-throughput sequencing encompassing 16S rRNA gene and ITS sequencing. Our findings from high-throughput sequencing unveiled Proteobacteria and Bacillus as the prevailing phylum and genus within the bacterial population, respectively. Likewise, the predominant fungal phylum and genus were identified as Ascomycota and Haematonectria. It is noteworthy that the relative abundance of Proteobacteria, Actinobacteria, Chloroflexi, Bacteroidetes, and Ascomycota exhibited significant increments subsequent to AMF inoculation. Our investigation into soil enzyme activity revealed a remarkable surge post-AMF inoculation. Notably, the amounts of pathogen growth inhibitory enzymes and organic carbon degrading enzymes rise, as predicted by the putative roles of microbial communities. In saline-alkali soil, inoculation of AMF did boost the yield of H22. Notable improvements were observed in the weight of both 100 fruits and 100 grains, which increased by 20.02% and 22.30%, respectively. Conclusively, this study not only provides a theoretical framework but also furnishes empirical evidence supporting the utilization of AMF as a viable strategy for augmenting the yield of salt-sensitive plants grown in alkaline conditions.

Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis.

BACKGROUND AND AIMS: The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features. METHODS: Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. RESULTS: Elevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs. CONCLUSION: This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.

Selective Encapsulation and Chiral Induction of C60 and C70 Fullerenes by Axially Chiral Porous Aromatic Cages.

Chiral induction has been an important topic in chemistry, not only for its relevance in understanding the mysterious phenomenon of spontaneous symmetry breaking in nature but also due to its critical implications in medicine and the chiral industry. The induced chirality of fullerenes by host-guest interactions has been rarely reported, mainly attributed to their chiral resistance from high symmetry and challenges in their accessibility. Herein, we report two new pairs of chiral porous aromatic cages (PAC), R-PAC-2, S-PAC-2 (with Br substituents) and R-PAC-3, S-PAC-3 (with CH3 substituents) enantiomers. PAC-2, rather than PAC-3, achieves fullerene encapsulation and selective binding of C70 over C60 in fullerene carbon soot. More significantly, the occurrence of chiral induction between R-PAC-2, S-PAC-2 and fullerenes is confirmed by single-crystal X-ray diffraction and the intense CD signal within the absorption region of fullerenes. DFT calculations reveal the contribution of electrostatic effects originating from face-to-face arene-fullerene interactions dominate C70 selectivity and elucidate the substituent effect on fullerene encapsulation. The disturbance from the differential interactions between fullerene and surrounding chiral cages on the intrinsic highly symmetric electronic structure of fullerene could be the primary reason accounting for the induced chirality of fullerene.

Estimation of genetic parameters of eggshell translucency and production traits in different genotypes of laying hens.

The translucency of eggshells is a ubiquitous appearance problem caused by moisture translocation and the accumulation of egg contents into the eggshell ultrastructure. Previous studies have mainly investigated the causes of eggshell translucency from nutritional and environmental perspectives. However, little is known of the effect of genetics the causes of eggshell translucency on hen production performance. To evaluate the genetic parameters of eggshell translucency and other production performance indicators, we performed an experiment on 3 pure hen lines: 624 Dwarf Layer-White, 1,612 Rhode Island Red, and 813 Rhode Island Red-White. We collected eggs from each hen over 5 d and measured eggshell translucent level (TL) using the grading method. Additionally we measured indicators of each hen during the laying period, including age at laying of the first egg (AFE), body weight at laying of the first egg (BWFE), weight of the first egg (FEW), body weight at 40 wk (BW40), egg weight at 40 wk (EW40), egg production up to 40 wk of age (EN), and calculated the genetic parameters among the indicators. The results showed that the estimated heritability of TL in the 3 genotypes were 0.30, 0.24, and 0.20, respectively, suggesting a low or moderate level of heritability. We found a positive correlation between TL and AFE, with genetic correlation coefficients 0.19 to 0.41, and negative genetic correlation between TL and EN, with correlation coefficient -0.36 to -0.19. Additionally, we observed positive correlation exists between AFE and FEW, BWFE and FEW, and BW40 and EW40; and negative correlation between AFE and EN in the 3 pure lines. These results enriched the research on heritability of eggshell translucency in different hen breeds and demonstrated moderate or low heritability of the indicator. Furthermore, eggshell translucency was negatively affected by AFE and EN. Our results provide a valuable reference for predicting selection response of eggshell translucency and production performance in brood hens, and locating the genes regulating eggshell translucency.

Advanced treatment of secondary effluent from wastewater treatment plant by a newly isolated microalga Desmodesmus sp. SNN1.

Secondary effluents contain considerable amounts of nitrogen and phosphorous, which if dumped untreated can cause eutrophication of the receiving water bodies. Microalgae can remove these nutrients and other pollutants from the wastewater effluents and play an effective role in the secondary effluent treatment. In this study, six microalgae strains (SNN1, SNN2, SNN3, SNN4, SNS1, and SNS2) were isolated and screened from the water and mud of Yingxue Lake of Shandong Jianzhu University, and their efficiencies for the removal of COD, NH4 +-N, TN, and TP in the secondary effluent were assessed. By comparing the growth performances and nutrient removal ability of algal strains in domestic sewage, we found that SNN1 (identified and named as Desmodesmus sp. SNN1) has the highest efficiency for biomass accumulation and sewage purification. Hence, the algal strain SNN1 was selected for further screening and optimization experiments. The strain showed higher biomass yield and better nutrient removal rate when the pH of secondary effluent was 9.0 and the initial inoculum concentration (optical density at 680 nm) of algal strain was 0.4. After 12 days of treatment, the concentrations of COD, NH4 +-N, TN, and TP in the secondary effluent were 31.79, 0.008, 8.631, and 0.069 mg/L, respectively. Therefore, SNN1 with the removal rates of 52.69% (COD), 99.99% (NH4 +-N), 89.09% (TN), and 94.64% (TP) displayed its high potential in nutrient removal. In addition, it also yielded 5.30 mg/L of chlorophyll a and 168.33 mg/L of lipids. These results demonstrated that this strain exhibited an effective treatment capacity for secondary effluent and microalgal oil production. This study is helpful to provide a strategy for the resource utilization of secondary effluent and the conservation of freshwater resources required by microalgae culture.

Fascinating Electrocatalysts with Dispersed Di-Metals in MN3 -M'N4 Moiety as Two Active Sites Separately for N2 and CO2 Reduction Reactions and Jointly for CN Coupling and Urea Production.

The idealized urea electrocatalyst is crucial to boost the CN coupling reaction and simultaneously suppress their isolated reduction process after adsorbing N2 and CO2 molecules. Therefore, the dispersed MN3 -M'N4 moiety is investigated systematically, including 26 homonuclear and 650 heteronuclear di-metal systems. After, 205 stable systems are selected using lowest-energy principle and ab initio molecular dynamics simulations. According to three possible pathways, NCON, CO, and OCOH to produce urea, a five-step high-throughput screening method for excellent catalytic activity and a five-aspect high-throughput screening strategy for outstanding catalytic selectivity are proposed, respectively. The potential determined steps and the limiting potential through three pathways are identified. The data indicates both CO pathway and OCOH pathway are more competitive at lower Gibbs free energy. Significantly, the most favorite RuN3 -CoN4 combination possesses an extremely low limiting potential of -0.80 V for urea production, meanwhile it exists a strong foundation for experimental preparation. This work not only broadens electrocatalytic potentiality of developing di-metals as two active sites, but also provides a feasible high-throughput screening recipe for urea production.

Theoretical Insight on the High Reactivity of Reductive Elimination of NiIII Based on Energy- and Electron-Transfer Mechanisms.

Iridium/nickel (Ir/Ni) metallaphotoredox dual catalysis overcomes the challenging reductive elimination (RE) of Ni(II) species and has made a breakthrough progress to construct a wide range of C-X (X = C, N, S, and P) bonds. However, the corresponding reaction mechanisms are still ambiguous and controversial because the systematic research on the nature of this synergistic catalysis is not sufficient. Herein, IrIII/NiII and IrIII/Ni0 metallaphotoredox catalysis have been theoretically explored taking the aryl esterification reaction of benzoic acid and aryl bromide as an example by a combination of density functional theory (DFT), molecular dynamics, and time-dependent DFT computations. It is found that an electron-transfer mechanism is applicable to IrIII/NiII metallaphotoredox catalysis, but an energy-transfer mechanism is applicable to IrIII/Ni0 combination. The IrIII/NiII metallaphotoredox catalysis succeeds to construct a NiI-NiIII catalytic cycle to avoid the challenging RE of Ni(II) species, while the RE occurs from triplet excited-state Ni(II) species in the IrIII/Ni0 metallaphotoredox catalysis. In addition, the lower lowest unoccupied molecular orbital energy level of Ni(III) species than that of Ni(II) species accelerates RE from Ni(III) one. The triplet excited-state Ni(II) species can resemble a Ni(III) center, considering the metal-to-ligand charge transfer character to promote the RE.

Integrated Network Pharmacology Analysis and Experimental Validation to Investigate the Molecular Mechanism of Triptolide in the Treatment of Membranous Nephropathy.

Background: Triptolide, a major active ingredient isolated from Tripterygium wilfordii Hook f., is effective in the treatment of membranous nephropathy (MN); however, its pharmacological mechanism of action has not yet been clarified. We applied an approach that integrated network pharmacology and experimental validation to systemically reveal the molecular mechanism of triptolide in the treatment of MN. Methods: First, potential targets of triptolide and the MN-related targets were collected from publicly available database. Then, based on a protein-protein interaction network as well as GO and KEGG pathway enrichment analyses, we constructed target-pathway networks to unravel therapeutic targets and pathways. Moreover, molecular docking was applied to validate the interactions between the triptolide and hub targets. Finally, we induced passive Heymann nephritis (PHN) rat models and validated the possible molecular mechanisms of triptolide against MN. Results: The network pharmacology results showed that 118 intersected targets were identified for triptolide against MN, including mTOR, STAT3, CASP3, EGFR and AKT1. Based on enrichment analysis, signaling pathways such as PI3K/AKT, MAKP, Ras and Rap1 were involved in triptolide treatment of MN. Furthermore, molecular docking confirmed that triptolide could bind with high affinity to the PIK3R1, AKT1 and mTOR, respectively. Then, in vivo experiments indicated that triptolide can reduce 24 h urine protein (P < 0.01) and protect against renal damage in PHN. Serum albumin level was significantly increased and total cholesterol, triglycerides, and low-density lipoprotein levels were decreased by triptolide (P < 0.05). Compared with PHN group, triptolide treatment regulated the PI3K/AKT/mTOR pathway according to Western blot analyses. Conclusion: Triptolide could exert antiproteinuric and renoprotective effects in PHN. The therapeutic mechanism of triptolide may be associated with the regulation of PI3K/AKT/mTOR signaling pathway. This study demonstrates the pharmacological mechanism of triptolide in the treatment of MN and provides scientific evidence for basic and clinical research.

ATF6α contributes to rheumatoid arthritis by inducing inflammatory cytokine production and apoptosis resistance.

Objective: The contribution of activating transcription factor 6α (ATF6α) in rheumatoid arthritis (RA) pathogenesis, especially on fibroblast-like synoviocytes (FLSs), has been suggested by its sensitivity to inflammatory stimulus. However, the exact role and therapeutic potential of ATF6α in RA remains to be fully elucidated. Methods: ATF6α expression was determined in joint tissues and FLS, and gain-of-function and loss-of-function analyses were applied to evaluate the biological roles of ATF6α in RA FLSs. A murine collagen-induced arthritis (CIA) model, combining both gene deletion of ATF6α and treatment with the ATF6α inhibitor Ceapin-A7, was employed. Joint inflammation, tissue destruction, circulating levels of inflammatory cytokines were assessed in CIA mice. Transcriptome sequencing analysis (RNASeq), molecular biology, and biochemical approaches were performed to identify target genes of ATF6α. Results: ATF6α expression was significantly increased in synovium of RA patients and in synovium of mice subjected to CIA. ATF6α silencing or inhibition repressed RA FLSs viability and cytokine production but induced the apoptosis. CIA-model mice with ATF6α deficiency displayed decreased arthritic progression, leading to profound reductions in clinical and proinflammatory markers in the joints. Pharmacological treatment of mice with Ceapin-A7 reduced arthritis severity in CIA models. RNA-sequencing of wild-type and knockdown of ATF6α in RA FLSs revealed a transcriptional program that promotes inflammation and suppresses apoptosis, and subsequent experiments identified Baculoviral IAP Repeat Containing 3 (BIRC3) as the direct target for ATF6α. Conclusion: This study highlights the pathogenic role of ATF6α-BIRC3 axis in RA and identifies a novel pathway for new therapies against RA.

Chiral self-sorting and guest recognition of porous aromatic cages.

The synthesis of ultra-stable chiral porous organic cages (POCs) and their controllable chiral self-sorting at the molecular and supramolecular level remains challening. Herein, we report the design and synthesis of a serial of axially chiral porous aromatic cages (PAC 1-S and 1-R) with high chemical stability. The theoretical and experimental studies on the chiral self-sorting reveal that the exclusive self-recognition on cage formation is an enthalpy-driven process while the chiral narcissistic and self-sorting on supramolecular assembly of racemic cages can be precisely regulated by π-π and C-H…π interactions from different solvents. Regarding the chemical stability, the crystallinity of PAC 1 is maintained in aqueous solvents, such as boiling water, high-concentrated acid and alkali; mixtures of solvents, such as 1 M H2SO4/MeOH/H2O solution, are also tolerated. Investigations on the chiral sensing performance show that PAC 1 enables enantioselective recognition of axially chiral biaryl molecules.

Preclinical evaluation and pilot clinical study of [18F]AlF-NOTA-FAPI-04 for PET imaging of rheumatoid arthritis.

PURPOSE: Fibroblast-like synoviocytes (FLSs) are key effector cells in the inflamed joints of patients with rheumatoid arthritis (RA). Previous studies have suggested that fibroblast activation protein (FAP) is highly expressed in RA-derived FLSs and is a specific marker of activated RA FLSs. In this study, we developed aluminum-[18F]-labeled 1,4,7-triazacyclononane-N,N',N″-triacetic acid-conjugated FAP inhibitor 04 ([18F]AlF-NOTA-FAPI-04) to image RA-FLSs in vitro and arthritic joints in collagen-induced arthritis (CIA) mice and RA patients. METHODS: RA FLSs and NIH3T3 cells transfected with FAP were used to perform in vitro-binding studies. Biodistribution was conducted in normal DBA1 mice. Collagen-induced arthritis (CIA) models with different arthritis scores were subjected to [18F]AlF-NOTA-FAPI-04 and 18F-FDG PET imaging. Histological examinations were performed to evaluate FAP expression and Cy3 dye-labeled FAPI-04(Cy3-FAPI-04) uptake. Blocking studies with excess unlabeled FAPI-04 in CIA mice and NIH3T3 xenografts in immunocompromised mice were used to evaluate the binding specificity of [18F]AlF-NOTA-FAPI-04. Additionally, [18F]AlF-NOTA-FAPI-04 PET imaging was performed on two RA patients. RESULTS: The binding of [18F]AlF-NOTA-FAPI-04 increased significantly in RA FLSs and NIH3T3 cells overexpressing FAP compared to their parental controls (FAP-GFP-NIH3T3 vs. GFP-NIH3T3, 2.40 ± 0.078 vs. 0.297 ± 0.05% AD/105 cells; RA FLSs vs. OA FLSs, 1.54 ± 0.064 vs. 0.343 ± 0.056% AD/105 cells). Compared to 18F-FDG imaging, [18F]AlF-NOTA-FAPI-04 showed high uptake in inflamed joints in the early stage of arthritis, which was positively correlated with the arthritic scores (Pearson r=0.834, P<0.001). In addition, the binding of [18F]AlF-NOTA-FAPI-04 to cells with high FAP expression and the uptake of [18F]AlF-NOTA-FAPI-04 in arthritic joints both could be blocked by excessive unlabeled FAPI-04. Fluorescent staining showed that the intensity of Cy3-FAPI-04 binding to FAP increased accordingly as the expression of FAP protein increased in cells and tissue sections. Furthermore, the uptake of [18F]AlF-NOTA-FAPI-04 in FAP-GFP-NIH3T3 xenografts was significantly higher than that in GFP-NIH3T3 xenograft (35.44 ± 4.27 vs 7.92 ± 1.83% ID/mL). Finally, [18F]AlF-NOTA-FAPI-04 PET/CT imaging in RA patients revealed nonphysiologically high tracer uptake in the synovium of arthritic joints. CONCLUSION: [18F]AlF-NOTA-FAPI-04 is a promising radiotracer for imaging RA FLSs and could potentially complement the current noninvasive diagnostic parameters.

Volunteering among Chinese College Students during the COVID-19 Pandemic.

Volunteering has been found to be not only beneficial to the well-being of recipients but also to the volunteers themselves, particularly from the life course perspective. Although previous studies have identified key factors of volunteering motivation, the literature is less focused on the interplay of public interest and private gains in volunteering motivation. This study used 1871 college students across China to examine how the interplay between public interest and private gains affects general and Coronavirus Disease 2019 (COVID-19)-specific volunteering during the pandemic. The results show that the interplay of these two factors constitutes a dynamic process, depending on the volunteering and time-specific context. Overall, undergraduate students with greater concern for public interest and less preference in private gains had the highest rate of overall volunteering, followed by students with high concern for both public interest and private gains. It is crucial to take both public interest and private gains into account when discussing volunteering opportunities among Chinese college students, which may increase the well-being of students in the long run.

First report of Rhizopus oryzae causing rhizome rot on ginger in China.

Ginger (Zingiber officinale Rosc.) is a herbal plant, widely grown in China for its medicinal and culinary purposes. In July 2020, a new rhizome rot disease was observed on ginger in Laiwu, Shandong Province, China. The disease symptoms were observed on both above-ground and underground plant parts. The above ground stems and leaves becoming withered and yellow, and water-soaked symptoms were observed on the collar region. The diseased rhizomes were poorly developed with brown lesion and eventually they would rot, without offensive odors. Disease incidence was estimated at approximately 5% across the survey area. To isolate the pathogen, tissues from 30 rhizomes were cut from the border between diseased and healthy tissue, surface sterilized in 75% alcohol for 15 s, soaked in 0.1% mercuric chloride for 1 min, washed with sterile distilled water three times, and plated on potato dextrose agar (PDA) at 25°C for 2-3 days. Twenty nine fungal isolates with similar morphological characteristics were obtained and pure cultures were obtained using single spore isolation. The colony of AQJ-1, a representative isolate, on PDA was cottony, fluffy, white, and beige coloration on the reverse side at first, and subsequently many black sporangia were produced. The sporangia were black, sub-globose, and 45.2-181.7 µm (n = 50) in diameter. The sporangiospores were unequal, globose or sub-globose, about 3.2-8.7 × 4.6-12.3µm (n = 50) in diameter. For the molecular characterization, genomic DNA was extracted by modified CTAB method (Niu et al., 2008). Internal transcribed spacer (ITS) region and translation elongation factor 1-alpha (EF-1α) gene were amplified using the primer pairs ITS1/ITS4 (White et al., 1990) and MEF10/MEF4 (Abe et al., 2007), respectively. The ITS and EF-1α sequences of isolate AQJ-1 were submitted to GenBank (MN606288 and MN735220, respectively). The BLASTn analysis of the sequences showed 99%-100% similarity to the sequences of R. oryzae strain CBS 120.12 (MH854609, AB281529, respectively). Therefore, based on morphological and molecular characteristics, isolate AQJ-1 was identified as R. oryzae. For pathogenicity tests, thirty ginger seedlings (Laiwu Big Ginger) were grown for 30 days in plastic pots and removed from the pots and the rhizomes washed in running tap water. The rhizomes of fifteen ginger seedlings were attached to a 7 mm agar disk from a plate containing 2-day-old mycelium, and the other fifteen seedlings were attached to agar disk without mycelium as control. Then the inoculated and control seedlings were planted in pots and were kept in separate chambers in a greenhouse at 25±2 °C. After 14 days, the same symptoms of rhizome rot were observed in all inoculated plants as previously described, and no symptoms were observed on the control plants. The pathogen was re-isolated from symptomatic tissues, and was identified as R. oryzae, which full-filled the Koch's postulates. To our knowledge, this is the first report of R. oryzae causing rhizome rot on ginger in China. This disease may pose a potential threat to ginger production in China.

Euphorbia factor L3 ameliorates rheumatoid arthritis by suppressing the inflammatory response by targeting Rac family small GTPase 1.

Euphorbia factor L3 (EFL3) is extracted from Euphorbia lathyris and is known for its anti-inflammatory properties. This study focused on the potential anti-inflammatory and therapeutic effects of EFL3 on rheumatoid arthritis (RA) using fibroblast-like synoviocytes (FLSs) and arthritis animal models. Functional analysis showed that EFL3 could ameliorate the inflammatory phenotype of FLSs derived from RA patients, as evidenced by the decreases in cell viability, migration, invasion and cytokine production. Luciferase activity, Western blotting and immunofluorescence assays demonstrated that EFL3 inhibited the nuclear translocation of the p65 subunit and the subsequent activation of the nuclear factor kappa-Β (NF-κB) pathway. Furthermore, the therapeutic effects of EFL3 against arthritic progression were evidenced by decreases in joint swelling, arthritis scores, inflammatory factor production, synovial hyperplasia, and bone destruction in collagen-induced arthritis (CIA) and tumor necrosis factor-α (TNF-α) transgenic (TNF-tg) mouse models. Molecular analysis identified Rac family small GTPase 1 (Rac1) as the potential target that was required for EFL3-mediated suppression of the inflammatory RA FLS phenotype. In summary, this study uncovered the therapeutic potential of EFL3 in RA, which suggests its future clinical use.