Phosphatidic acid modulates MPK3- and MPK6-mediated hypoxia signaling in Arabidopsis.

Phosphatidic acid (PA) is an important lipid essential for several aspects of plant development and biotic and abiotic stress responses. We previously suggested that submergence induces PA accumulation in Arabidopsis thaliana; however, the molecular mechanism underlying PA-mediated regulation of submergence-induced hypoxia signaling remains unknown. Here, we showed that in Arabidopsis, loss of the phospholipase D (PLD) proteins PLDα1 and PLDδ leads to hypersensitivity to hypoxia, but increased tolerance to submergence. This enhanced tolerance is likely due to improvement of PA-mediated membrane integrity. PA bound to the mitogen-activated protein kinase 3 (MPK3) and MPK6 in vitro and contributed to hypoxia-induced phosphorylation of MPK3 and MPK6 in vivo. Moreover, mpk3 and mpk6 mutants were more sensitive to hypoxia and submergence stress compared with wild type, and fully suppressed the submergence-tolerant phenotypes of pldα1 and pldδ mutants. MPK3 and MPK6 interacted with and phosphorylated RELATED TO AP2.12, a master transcription factor in the hypoxia signaling pathway, and modulated its activity. In addition, MPK3 and MPK6 formed a regulatory feedback loop with PLDα1 and/or PLDδ to regulate PLD stability and submergence-induced PA production. Thus, our findings demonstrate that PA modulates plant tolerance to submergence via both membrane integrity and MPK3/6-mediated hypoxia signaling in Arabidopsis.

Cardiac-specific PFKFB3 overexpression prevents diabetic cardiomyopathy via enhancing OPA1 stabilization mediated by K6-linked ubiquitination.

Diabetic cardiomyopathy (DCM) is a prevalent complication of type 2 diabetes (T2D). 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a glycolysis regulator. However, the potential effects of PFKFB3 in the DCM remain unclear. In comparison to db/m mice, PFKFB3 levels decreased in the hearts of db/db mice. Cardiac-specific PFKFB3 overexpression inhibited myocardial oxidative stress and cardiomyocyte apoptosis, suppressed mitochondrial fragmentation, and partly restored mitochondrial function in db/db mice. Moreover, PFKFB3 overexpression stimulated glycolysis. Interestingly, based on the inhibition of glycolysis, PFKFB3 overexpression still suppressed oxidative stress and apoptosis of cardiomyocytes in vitro, which indicated that PFKFB3 overexpression could alleviate DCM independent of glycolysis. Using mass spectrometry combined with co-immunoprecipitation, we identified optic atrophy 1 (OPA1) interacting with PFKFB3. In db/db mice, the knockdown of OPA1 receded the effects of PFKFB3 overexpression in alleviating cardiac remodeling and dysfunction. Mechanistically, PFKFB3 stabilized OPA1 expression by promoting E3 ligase NEDD4L-mediated atypical K6-linked polyubiquitination and thus prevented the degradation of OPA1 by the proteasomal pathway. Our study indicates that PFKFB3/OPA1 could be potential therapeutic targets for DCM.

Microwave Ablation versus Surgical Resection for US-detected Multifocal T1N0M0 Papillary Thyroid Carcinoma: A 10-Center Study.

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.

A Tumor-Specific Cascade-Activating Smart Prodrug System for Enhanced Targeted Therapy.

Developing intelligently targeted drugs with low side effects is urgent for cancer treatment. Toward this goal, a tumor-specific cascade-activating smart prodrug system consisting of a G-quadruplex(G4)-modulated tumor-targeted DNA vehicle and a well-designed cellular stimuli-responsive ligand-drug conjugates (LDCs) is proposed. An original "donor-acceptor" binary fluorescent ligand, with ultrahigh affinity, brightness, and photostability, is engineered to tightly bind G4 structures and significantly improve the nuclease resistance of the DNA vehicle, which serves as a bridge contributing to the construction of the prodrug system, named ApG4/LDCs. Sodium nitroprusside and doxorubicin are loaded into ApG4/LDCs in one pot and generate nitric oxide and superoxide anion in response to cancer cellular environments, which in cascade generates peroxynitrite to cause DNA damage while promoting the self-monitored drug release to achieve enhanced targeted therapy. Such a cascade activation and self-reinforcement process is executed only when the prodrug system targets the tumor tissue followed by cell uptake, showing significant antitumor efficacy and greatly weakening the damage to normal tissues. Given the unique features, the innovative strategy for prodrug design may open a new door to precision disease treatment.

G-Quadruplex-Programmed Versatile Nanorobot Combined with Chemotherapy and Gene Therapy for Synergistic Targeted Therapy.

Developing synergistic targeted therapeutics to improve treatment efficacy while reducing side effects has proven promising for anticancer therapies, but how to conveniently modulate multidrug cooperation remains a challenge. Here, a novel synergistic strategy using a G-quadruplex-programmed versatile nanorobot (G4VN) containing two subunits of DNAzyme (DzG4) and ligand-drug conjugates (LDCs) is proposed to precisely target tumors and then execute both gene silencing and chemotherapy. As the core module of this nanorobot, a well-designed G4 responding to a high level of K+ in tumor microenvironment smartly kills three birds with one stone, which makes two TfR aptamers proximate to improve their efficiency of targeting tumor cells, and in situ activates a split 10-23 DNAzyme to downregulate target mRNA expression, meanwhile promotes the cell uptake of a GSH-responsive LDCs to enhance drug efficacy. Such a design enables a potently synergistic anticancer therapy with low side effects in vivo, showing great promise for broad applications in precision disease treatment.

Selective N-Alkylation of Aminobenzenesulfonamides with Alcohols for the Synthesis of Amino-(N-alkyl)benzenesulfonamides Catalyzed by a Metal-Ligand Bifunctional Ruthenium Catalyst.

[(p-Cymene)Ru(2,2'-bpyO)(H2O)] was proven to be an efficient catalyst for the synthesis of amino-(N-alkyl)benzenesulfonamides via selective N-alkylation of aminobenzenesulfonamides with alcohols. It was confirmed that functional groups in the bpy ligand are crucial for the activity of catalysts. Furthermore, the utilization of this catalytic system for the preparation of a biologically active compound was presented.

The interactions of subcellular organelles in pulmonary fibrosis induced by carbon black nanoparticles: a comprehensive review.

Owing to the widespread use and improper emissions of carbon black nanoparticles (CBNPs), the adverse effects of CBNPs on human health have attracted much attention. In toxicological research, carbon black is frequently utilized as a negative control because of its low toxicity and poor solubility. However, recent studies have indicated that inhalation exposure to CBNPs could be a risk factor for severe and prolonged pulmonary inflammation and fibrosis. At present, the pathogenesis of pulmonary fibrosis induced by CBNPs is still not fully elucidated, but it is known that with small particle size and large surface area, CBNPs are more easily ingested by cells, leading to organelle damage and abnormal interactions between organelles. Damaged organelle and abnormal organelles interactions lead to cell structure and function disorders, which is one of the important factors in the development and occurrence of various diseases, including pulmonary fibrosis. This review offers a comprehensive analysis of organelle structure, function, and interaction mechanisms, while also summarizing the research advancements in organelles and organelle interactions in CBNPs-induced pulmonary fibrosis.

[Association of polymorphisms in SEC16B, DNAJC27, FTO and MC4R genes with overweight and obesity in Han preschool children].

OBJECTIVE: To investigate the association of polymorphisms in SEC16B rs633715, DNAJC27 rs713586, FTO rs11642015 and MC4R rs6567160 with overweight and obesity in Han Chinese preschool children. METHODS: A total of 749 Han Chinese preschool children from Henan and Guizhou Province of Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack were selected for the study and divided into an overweight and obese group and a normal control group in 2022. rs633715, rs713586, rs11642015 and rs6567160 were genotyped using Kompetitive allele-specific PCR(KASP) technology. The distribution of genotypic polymorphisms was compared using the χ~2 test. The association between the four loci and overweight and obesity in preschool children was analyzed using a multifactorial logistic regression model. RESULTS: The statistical analysis revealed a significant disparity(P<0.05) in the distribution of genotypic polymorphisms of rs633715 and rs6567160 among preschoolers in Henan and Guizhou Province. CC heterozygous mutant and recessive models at rs633715 locus were associated with susceptibility to overweight and obesity in preschool children [OR and 95% CI 2.915(1.163-7.305), and 2.997(1.226-7.323), respectively, both P<0.05]. TC heterozygous mutant and dominant models at rs713586 locus were also associated susceptibility to overweight and obesity in preschool children(OR and 95% CI were 2.362(1.054-5.289)and 2.362(1.054-5.289), respectively, both P<0.05). rs11642015 and rs6567160 loci were not associated with susceptibility to overweight and obesity in preschool children(P>0.05). The result of the analysis of the cumulative effect of rs633715 and rs713586 showed that the number of genotypes carrying the risk genotype was positively associated with the risk of overweight and obesity in preschool children(P_(trend)<0.01). CONCLUSION: Among Han Chinese preschool children, SEC16B rs633715 and DNAJC27 rs713586 were associated with susceptibility to overweight and obesity in preschool children. Moreover, rs633715 and rs713586 had a cumulative effect on susceptibility to overweight and obesity in preschool children, the number of risk genotypes carried was positively associated with childhood overweight and obesity risk.

Proximity-Enhanced Electrochemiluminescence Sensing Platform for Effective Capturing of Exosomes and Probing Internal MicroRNAs Involved in Cancer Cell Apoptosis.

Exosomal microRNAs (miRNAs) play critical regulatory roles in many cellular processes, and so how to probe them has attracted increasing interest. Here we propose an aptamer-functionalized dimeric framework nucleic acid (FNA) nanoplatform for effective capture of exosomes and directly probing internal miRNAs with electrochemiluminescence (ECL) detection, not requiring RNA extraction in conventional counterparts. A CD63 protein-binding aptamer is tethered to one of the FNA structures, allowing exosomes to be immobilized there and release internal miRNAs after lysis. The target miRNA induces the formation of a Y-shaped junction on another FNA structure in a close proximity state, which benefits the loading of covalently hemin-modified spherical nucleic acid enzymes for enhanced ECL readout in the luminol-H2O2 system. In this facile way, the ultrasensitive detection of exosomal miR-21 from cancer cells is accomplished and then used for cell apoptosis analysis, indicating that the oncogene miR-21 negatively participates in the regulation of the apoptotic process; namely, downregulating the miR-21 level is unbeneficial for cancer cell growth.

Poaceae-specific ß-1,3;1,4-d-glucans link jasmonate signalling to OsLecRK1-mediated defence response during rice-brown planthopper interactions.

Brown planthopper (BPH, Nilaparvata lugens), a highly destructive insect pest, poses a serious threat to rice (Oryza sativa) production worldwide. Jasmonates are key phytohormones that regulate plant defences against BPH; however, the molecular link between jasmonates and BPH responses in rice remains largely unknown. Here, we discovered a Poaceae-specific metabolite, mixed-linkage ß-1,3;1,4-d-glucan (MLG), which contributes to jasmonate-mediated BPH resistance. MLG levels in rice significantly increased upon BPH attack. Overexpressing OsCslF6, which encodes a glucan synthase that catalyses MLG biosynthesis, significantly enhanced BPH resistance and cell wall thickness in vascular bundles, whereas knockout of OsCslF6 reduced BPH resistance and vascular wall thickness. OsMYC2, a master transcription factor of jasmonate signalling, directly controlled the upregulation of OsCslF6 in response to BPH feeding. The AT-rich domain of the OsCslF6 promoter varies in rice varieties from different locations and natural variants in this domain were associated with BPH resistance. MLG-derived oligosaccharides bound to the plasma membrane-anchored LECTIN RECEPTOR KINASE1 OsLecRK1 and modulated its activity. Thus, our findings suggest that the OsMYC2-OsCslF6 module regulates pest resistance by modulating MLG production to enhance vascular wall thickness and OsLecRK1-mediated defence signalling during rice-BPH interactions.

Freestanding narrowband terahertz filters based on aluminum foil.

Terahertz (THz) filters with high transmission coefficient (T) in the passband and frequency selectivity are critical in numerous applications such as astronomical detection and next-generation wireless communication. Freestanding bandpass filters eliminate the Fabry-Pérot effect of substrate, thus providing a promising choice for cascaded THz metasurfaces. However, the freestanding bandpass filters (BPFs) using the traditional fabrication process are costly and fragile. Here, we demonstrate a methodology to fabricate THz BPFs using aluminum (Al) foils. We designed a series of filters with center frequencies below 2 THz and manufacture them on 2-inch Al foils with various thicknesses. By optimizing the geometry, T of the filter at the center frequency is over 92%, and the relative full-width half maxima (FWHM) is as narrow as 9%. The responses of BPFs show that "cross-shaped" structures are insensitive to the polarization direction. The simple and low-cost fabrication process of the freestanding BPFs promise their widespread applications in THz systems.

VLPs containing stalk domain and ectodomain of matrix protein 2 of influenza induce protection in mice.

BACKGROUND: As a result of antigenic drift, current influenza vaccines provide limited protection against circulating influenza viruses, and vaccines with broad cross protection are urgently needed. Hemagglutinin stalk domain and ectodomain of matrix protein 2 are highly conserved among influenza viruses and have great potential for use as a universal vaccine. METHODS: In this study, we co-expressed the stalk domain and M2e on the surface of cell membranes and generated chimeric and standard virus-like particles of influenza to improve antigen immunogenicity. We subsequently immunized BALB/c mice through intranasal and intramuscular routes. RESULTS: Data obtained demonstrated that vaccination with VLPs elicited high levels of serum-specific IgG (approximately 30-fold higher than that obtained with soluble protein), induced increased ADCC activity to the influenza virus, and enhanced T cell as well as mucosal immune responses. Furthermore, mice immunized by VLP had elevated level of mucosal HA and 4M2e specific IgA titers and cytokine production as compared to mice immunized with soluble protein. Additionally, the VLP-immunized group exhibited long-lasting humoral antibody responses and effectively reduced lung viral titers after the challenge. Compared to the 4M2e-VLP and mHA-VLP groups, the chimeric VLP group experienced cross-protection against the lethal challenge with homologous and heterologous viruses. The stalk domain specific antibody conferred better protection than the 4M2e specific antibody. CONCLUSION: Our findings demonstrated that the chimeric VLPs anchored with the stalk domain and M2e showed efficacy in reducing viral loads after the influenza virus challenge in the mice model. This antibody can be used in humans to broadly protect against a variety of influenza virus subtypes. The chimeric VLPs represent a novel approach to increase antigen immunogenicity and are promising candidates for a universal influenza vaccine.

Efficacy and safety of microwave ablation for the treatment of multifocal versus unifocal T1N0M0 papillary thyroid carcinoma: a propensity-matched multicentre retrospective study.

OBJECTIVES: Microwave ablation (MWA) has been widely used for unifocal papillary thyroid carcinoma (U-PTC) and has recently been preliminarily used in multifocal papillary thyroid carcinoma (M-PTC). However, the efficacy and safety of MWA for M-PTC have not been investigated in large samples. The aim of the present study was to evaluate the efficacy and safety of MWA for M-PTC and compare them with MWA for U-PTC. MATERIALS AND METHODS: This retrospective multicentre study enrolled 504 patients (376 females) who underwent MWA for U-PTC (340 cases) or M-PTC (164 cases) from Jan 2015 to Dec 2020. The median age of the patients was 43 years (age range, 20-80 years). Propensity score matching (PSM) was used to balance the baseline characteristics between M-PTC group and U-PTC group. The tumour progression, tumour disappearance, and complication rates were compared between the two groups. RESULTS: The complete ablation was achieved in all enrolled cases in one session. According to the statistical results, no significant differences were shown in tumour progression-free survival (p  = 0.29) or cumulative tumour progression rate (6.7% vs. 4.3%, p  = 0.33) between the M-PTC and U-PTC groups during the follow-up time. However, the tumour disappearance rate in the M-PTC group was lower in the U-PTC group (40.9% vs. 62.8%, p < 0.001), and tumour disappearance was slower in the M-PTC group (p < 0.001). The complication rate showed no significant difference (3.0% vs. 4.9%, p  = 0.571). CONCLUSIONS: MWA is an effective and safe treatment for selected patients with M-PTC, and the prognosis is similar to that of U-PTC. CLINICAL RELEVANCE STATEMENT: The present study provided evidence that compared with unifocal papillary thyroid cancer, microwave ablation could also treat multifocal T1N0M0 papillary thyroid cancer safely with similar clinical outcome, which could promote the application of minimally invasive treatment for papillary thyroid cancer. KEY RESULTS: • Microwave ablation for multifocal and unifocal T1N0M0 papillary thyroid carcinoma had similar tumour progression rates after propensity score matching (6.7% vs. 4.3%, p = 0.33). • The tumour disappearance rate in the multifocal group was lower than that in the unifocal group (40.9% vs. 62.8%, p < 0.001), and tumour disappearance was slower in the multifocal group (p < 0.001). • Tumour size, number, and location were not risk factors for tumour progression in the multifocal papillary thyroid cancer group.

Sensitively detecting endogenous homocysteine in human serum and cardiomyocytes with a specific fluorescent probe.

The elevated level of homocysteine (Hcy) in circulating blood is generally regarded as a risk factor for a variety of diseases including acute myocardial infarction (AMI), but there is no clear answer to whether circulating Hcy can be used for AMI diagnosis. To address it, here we have designed a tetraazacycle-based fluorescent probe for sensitive detection of endogenous Hcy in AMI patients' serum and cardiomyocytes, showing a perfect selectivity over other biothiols (e.g. Cys and GSH). It mainly relies on the formation of a stable six-membered ring structure when this probe responds to Hcy, which is accompanied by a weakening of photoinduced electron transfer (PET) that induces a sharp increase in the fluorescence emission. In this way, Hcy can be probed in biofluids with high sensitivity. We then employed this fluorescent sensor to statistically analyze the levels of Hcy in human circulating blood, indicating a big difference between AMI patients and the healthy participants. To tell whether such a difference is applicable to AMI diagnosis, we further compare the expression levels of Hcy in cardiomyocytes and other tissue cells. It reveals a lower level of endogenous Hcy in cardiomyocytes, implying no direct relationship between the elevated Hcy and cardiomyocyte damage. This observation suggests that Hcy in circulating blood cannot be utilized as a potential biomarker for AMI diagnosis, although it is proven as a risk factor for this disease.

Hexaazatrinaphthalene-Based Covalent Triazine Framework-Supported Rhodium(III) Complex: A Recyclable Heterogeneous Catalyst for the Reductive Amination of Ketones to Primary Amines.

The development of efficient and recyclable heterogeneous catalysts is an important topic. Herein, a rhodium(III) complex Cp*Rh@HATN-CTF was synthesized by the coordinative immobilization of [Cp*RhCl2]2 on a hexaazatrinaphthalene-based covalent triazine framework. In the presence of Cp*Rh@HATN-CTF (1 mo l% Rh), a series of primary amines could be obtained via the reductive amination of ketones in high yields. Moreover, catalytic activity of Cp*Rh@HATN-CTF is well maintained during six runs. The present catalytic system was also applied for the large scale preparation of a biologically active compound. It would facilitate the development of CTF-supported transition metal catalysts for sustainable chemistry.

Growth, immunity and transcriptome response to different stocking densities in Litopenaeus vannamei.

The effects of different stocking densities on Litopenaeus vannamei were investigated from the aspects of growth performance, immune response and transcriptome in this experiment. L. vannamei (initial body weight: 0.30 ± 0.02 g) were reared for 8 weeks at three stocking densities of 100 (LSD), 200 (MSD) and 300 (HSD) shrimp/m³, respectively. The results showed that the survival rate (SR), final body weight (FBW), weight gain rate (WGR), specific growth ratio (SGR) and protein efficiency ratio (PER) of L. vannamei significantly decreased, while the feed factor (FCR) significantly increased with the increase of stocking density. After Vibrio parahemolyticus infection, the SR of L. vannamei in the HSD group was significantly lower than that in the LSD and MSD groups. Increasing stocking density significantly increased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lysozyme (LYS) while significantly decreased the activities of catalase (CAT) and phenol oxidase (PO) in the serum of L. vannamei. Similar changes of the gene expression as the activities of immune enzymes were found in the hemocytes. Pairwise comparison between the LSD, MSD and HSD group in the transcriptome analysis identified that there were 304, 1376 and 2083 differentially expressed genes (DEGs) in LSD vs MSD, MSD vs HSD and LSD vs HSD, respectively. Among them, most of the immune-related DEGs were down-regulated and metabolism-related DEGs were up-regulated with the increasing stocking density. In addition, KEGG enrichment pathway analysis revealed that several immune and metabolic related pathways including PI3K-Akt signaling pathway and AMPK signaling pathway were significantly enriched. Of these, the PI3K-Akt signaling pathway had the most DEGs and was also the most significantly enriched pathway. Furthermore, 16 DEGs (such as FOXO, PCK2 and CTSC, etc.) and partial immune enzyme activity (such as AST, CAT and PO, etc.) changes were closely correlated with the increase of stocking density when partial immune-related DEGs and immune-related enzymes were analyzed jointly. All these results indicated that changes in stocking density had a significant effect on the growth performance, immunity and transcriptome of L. vannamei.

The enhancement effect of low-dose dietary lipopolysaccharide on the growth and immunity of Litopenaeus vannamei, and transcriptome analysis.

In this study, the effects of dietary lipopolysaccharide (LPS) on Litopenaeus vannamei were investigated to determine whether LPS could play a role as a potential immunostimulant in shrimp. L. vannamei with an initial body weight of 0.30 ± 0.02 g were fed a diet containing LPS at doses of 0, 0.2, 1, 5, 25 or 125 mg kg-1 for eight weeks (groups LPS0, LPS0.2, LPS1, LPS5, LPS25 and LPS125, respectively). After eight weeks of feeding, the growth performance, immunity and transcriptome response of L. vannamei were analysed. Only dietary LPS at 0.2 and 1 mg kg-1 resulted in a significant increase in the growth of L. vannamei (P < 0.05). According to the weight gain rate (WGR) and specific growth rate (SGR), the optimum dietary LPS level was 2.462 and 2.455 mg kg-1, respectively. When compared with the control group, the survival rate (SR) of L. vannamei in the LPS0.2 group was significantly increased after white spot syndrome virus (WSSV) infection and the SR of L. vannamei in the LPS1 group was significantly increased after Vibrio parahaemolyticus infection (both P < 0.05). Compared with the LPS0 group, immune enzyme activity in the serum of L. vannamei could be significantly increased and the content of maleic dialdehyde (MDA) significantly decreased by dietary LPS. Transcriptome analysis of the haemocytes of L. vannamei identified 399 up-regulated differentially expressed genes (DEGs) and 5000 down-regulated DEGs in the LPS0.2 compared to the control group. Most of the DEGs were significantly enriched in the following pathways: phosphatidylinositol signalling, Wnt signalling, Jak-STAT signalling and inositol phosphate metabolism. In conclusion, this study revealed that diets supplemented with low-dose LPS had positive effects on the growth and immunity of L. vannamei.

Unraveling the flexible aromaticity of C13H9+/0/-: a 2D superatomic-molecule theory.

Phenalenyl (C13H9) is the smallest triangular unit of a graphene nanosheet, and has been experimentally verified to be stable in radical (C13H9˙), cationic (C13H9+), and anionic (C13H9-) states. All these three species feature high symmetry and stability as well as delocalized π electrons, a visible sign of aromaticity, but their aromatic origin remains a challenge. This work reports new chemical insights into the π electrons of C13H9+/0/- and deciphers their aromaticity using a recently emerged two-dimensional (2D) superatomic-molecule theory. 12π-C13H9+, 13π-C13H9˙, and 14π-C13H9- are seen as triangular 2D superatomic molecules ◊O3, ◊O3-, and ◊O32-, respectively, where ◊O denotes a 2D benzenoid superatom bearing 4 π electrons. Visualized superatomic Lewis structures show that each ◊O can dynamically adjust its π electrons to satisfy the superatomic sextet rule of benzene via superatomic lone pairs and covalent bonds. C13H9+/0/- are representatives of adaptive aromaticity in the 2D superatomic-molecule system, exhibiting flexible π electronic structures to achieve shell-closure. Moreover, we specially adopt a progressive methodology to study the evolution of 2D periodic materials, by applying this theory to the similar family of C6H3N7, C18H6N22 and graphitic carbon nitride (g-C3N4) crystals, and meanwhile accounting for the special stability of g-C3N4. This work enriches 2D superatomic bonding chemistry and provides a useful strategy to design new 2D functional nanostructured materials.

The validity and IRT psychometric analysis of Chinese version of Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10).

OBJECTIVE: The doctor-patient relationship (DPR) plays a crucial role in the Chinese healthcare system, functioning to improve medical quality and reduce medical costs. This study examined the psychometric properties of the Chinese version of the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) among general hospital inpatients in China. METHODS: The research recruited 38 resident doctors responsible for 120 participants, and factor analyses were used to assess the construct validity of the scale. Convergent validity was evaluated by examining the correlation between DDPRQ-10 and depressive symptoms, burnout, and self-efficacy, using the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Maslach Burnout Inventory (MBI). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) frameworks were used to estimate the parameters of each item. RESULTS: The Chinese version of DDPRQ-10 showed satisfactory internal consistency (Cronbach's alpha = 0.931), and fitted in a modified two-factor model of positive feelings and negative feelings (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, SRMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). Significant correlations with PHQ-9 with DDPRQ-10 and both subscales were revealed (r = 0.293 ~ 0.333, p < .001), while DDPRQ-10 score also significantly correlated with doctors' MBI score (r = -0.467, p < .001). The MIRT model of full scale and IRT models of both subscales showed high discrimination of all items (a = 2.30 ~ 10.18), and the test information within the range of low-quality relationship was relatively high. CONCLUSION: The Chinese version of DDPRQ-10 displayed satisfactory reliability and validity and thus was appropriate for measuring the DPR in Chinese medical settings.

The toxic effect of bisphenol AF and nanoplastic coexposure in parental and offspring generation zebrafish.

Microplastics (MPs) and bisphenol AF (BPAF) are two environmental pollutants that usually coexist in the natural environment. Studies of MPs or BPAF have gradually increased in recent years, but few studies have focused on the combination toxic effects. In this study, the subchronic model of adult zebrafish was exposed to 1 mg/L nanolevel microplastics and 200 µg/L BPAF for 45 days; the parental zebrafish were spawning every 3 days during exposure, and the effects of continuous poisoning were examined on the offspring after 1-9 spawns. The results showed that single BPAF exposure or BPAF and nanoplastic coexposure can both decrease the number of eggs laid and the locomotor behavior of parental zebrafish and impact the hatching rate, mortality, body length and locomotor behavior of offspring zebrafish, especially in 7-9 spawn. BPAF were accumulated in parental zebrafish intestinal in 334.62 ng/g in BPAF group and 594.52 ng/g in nm+BPAF group, and accumulated in whole offspring zebrafish for 281.6 ng/g in BPAF group and 321.46 ng/g in nm+BPAF group. Neurodevelopmental, inflammation, apoptosis and oxidative stress-related genes were also significantly increased after 7-9 spawn. In addition, the exacerbated accumulation in the BPAF+nm group in parental and offspring zebrafish may be the reason for the accelerated toxic effect in the present research. In this study, we investigated the combined effects of nanoplastics and BPAF on parental and offspring zebrafish in the aquatic environment to identify the accumulative toxic effects and provide new experimental support for assessing the effects of coexposure on aquatic organisms.