Predictive value of hematologic parameters and clinicopathological features of poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma.

PURPOSE: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are rare, aggressive thyroid cancers with poor prognosis. At present, there are a limited number of research reports on PDTC and ATC. The study aimed to analysis the predictive value of hematologic parameters and clinicopathological features of PDTC and ATC. METHODS: This study retrospectively analyzed 67 patients at Tianjin Medical University Cancer Hospital from 2007 to 2019. We analyzed the clinicopathological features and survival outcomes of PDTC and ATC. RESULTS: This study showed that positive D-dimer, a high NLR, and a high PLR were more common in death patients. At the end of follow-up, 22 (32.8%) patients were alive at the time of study and 45 (67.2%) patients died from thyroid carcinoma. Disease-related death rates were 93.8% in ATC and 42.9% in the PDTC group. The median overall survival (OS) was 2.5 (0.3-84) months for patients with ATC, and 56 (3-113) months of PDTC patients. Univariate analysis showed that age at diagnosis and surgery were associations with OS in ATC patients, what's more, age at diagnosis, a high NLR, a high PLR, and positive D-dimer were associations with OS in PDTC patients. Multivariate analysis revealed that age at diagnosis was an independent association with OS in ATC patients. CONCLUSIONS: The hematologic parameters and clinicopathological features may provide predictive value of prognosis for patients with PTDC and ATC.

PFC/M1 activation and excitability: a longitudinal cohort study on fatigue symptoms in healthcare workers post-COVID-19.

BACKGROUND: Fatigue is one of the most common neurological symptoms reported post coronavirus disease 2019 (COVID-19) infection. In order to establish effective early intervention strategies, more emphasis should be placed on the correlation between fatigue and cortical neurophysiological changes, especially in healthcare workers, who are at a heightened risk of COVID-19 infection. METHODS: A prospective cohort study was conducted involving 29 COVID-19 medical workers and 24 healthy controls. The assessment included fatigue, sleep and health quality, psychological status, and physical capacity. Functional near-infrared spectroscopy (fNIRS) was employed to detect activation of brain regions. Bilateral primary motor cortex (M1) excitabilities were measured using single- and paired-pulse transcranial magnetic stimulation. Outcomes were assessed at 1, 3, and 6 months into the disease course. RESULTS: At 1-month post-COVID-19 infection, 37.9% of patients experienced severe fatigue symptoms, dropping to 10.3% at 3 months. Interestingly, the remarkable decreased activation/excitability of bilateral prefrontal lobe (PFC) and M1 were closely linked to fatigue symptoms after COVID-19. Notably, greater increase in M1 region excitability correlated with more significant fatigue improvement. Re-infected patients exhibited lower levels of brain activation and excitability compared to single-infection patients. CONCLUSIONS: Both single infection and reinfection of COVID-19 lead to decreased activation and excitability of the PFC and M1. The degree of excitability improvement in the M1 region correlates with a greater recovery in fatigue. Based on these findings, targeted interventions to enhance and regulate the excitability of M1 may represent a novel strategy for COVID-19 early rehabilitation. TRIAL REGISTRATION: The Ethics Review Committee of Xijing Hospital, No. KY20232051-F-1; www.chictr.org.cn , ChiCTR2300068444.

Serum CD44 levels in early pregnancy and its genetic variants for increased risk of gestational diabetes mellitus in Chinese pregnant women.

This study aimed to explore associations of serum cluster of differentiation 44 (CD44) levels and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational week). Binary conditional logistic regressions were performed to examine associations of serum CD44 levels and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 levels in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 levels and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12-3.40 & 1.95, 1.05-3.61). Furthermore, after adjustment for serum CD44 levels, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98-3.48). In conclusion, serum CD44 levels and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. SIGNIFICANCE: Recent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 plays a causal role in occurrence of GDM. Specifically, it remains unknown whether serum CD44 levels in early pregnancy and its genetic variants can predict the later occurrence of GDM. In this study, we found that high serum CD44 levels in early pregnancy and its genetic variants were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 levels and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms.

Targeting Lactobacillus johnsonii to reverse chronic kidney disease.

Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1-5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.

The first high-altitude autotetraploid haplotype-resolved genome assembled (Rhododendron nivale subsp. boreale) provides new insights into mountaintop adaptation.

BACKGROUND: Rhododendron nivale subsp. boreale Philipson et M. N. Philipson is an alpine woody species with ornamental qualities that serve as the predominant species in mountainous scrub habitats found at an altitude of ∼4,200 m. As a high-altitude woody polyploid, this species may serve as a model to understand how plants adapt to alpine environments. Despite its ecological significance, the lack of genomic resources has hindered a comprehensive understanding of its evolutionary and adaptive characteristics in high-altitude mountainous environments. FINDINGS: We sequenced and assembled the genome of R. nivale subsp. boreale, an assembly of the first subgenus Rhododendron and the first high-altitude woody flowering tetraploid, contributing an important genomic resource for alpine woody flora. The assembly included 52 pseudochromosomes (scaffold N50 = 42.93 Mb; BUSCO = 98.8%; QV = 45.51; S-AQI = 98.69), which belonged to 4 haplotypes, harboring 127,810 predicted protein-coding genes. Conjoint k-mer analysis, collinearity assessment, and phylogenetic investigation corroborated autotetraploid identity. Comparative genomic analysis revealed that R. nivale subsp. boreale originated as a neopolyploid of R. nivale and underwent 2 rounds of ancient polyploidy events. Transcriptional expression analysis showed that differences in expression between alleles were common and randomly distributed in the genome. We identified extended gene families and signatures of positive selection that are involved not only in adaptation to the mountaintop ecosystem (response to stress and developmental regulation) but also in autotetraploid reproduction (meiotic stabilization). Additionally, the expression levels of the (group VII ethylene response factor transcription factors) ERF VIIs were significantly higher than the mean global gene expression. We suspect that these changes have enabled the success of this species at high altitudes. CONCLUSIONS: We assembled the first high-altitude autopolyploid genome and achieved chromosome-level assembly within the subgenus Rhododendron. In addition, a high-altitude adaptation strategy of R. nivale subsp. boreale was reasonably speculated. This study provides valuable data for the exploration of alpine mountaintop adaptations and the correlation between extreme environments and species polyploidization.

A comparative study of the relationship between time in range assessed by self-monitoring of blood glucose and continuous glucose monitoring with microalbuminuria outcome, HOMA-IR and HOMA-ß test.

AIMS: To compare the time in range (TIR) obtained from self-monitoring of blood glucose (SMBG) with that obtained from continuous glucose monitoring (CGM), and explore the relationship of TIR with microalbuminuria outcome, HOMA-IR and HOMA-ß test. METHODS: We recruited 400 patients with type 2 diabetes to carry out blood glucose monitoring by both SMBG and CGM for 3 consecutive days. TIR, TAR, TBR and other blood glucose variation indices were calculated respectively through the glucose data achieved from SMBG and CGM. The HOMA-IR and HOMA-ß test was evaluated by an oral glucose tolerance test. Urinary microalbumin-to-creatinine ratio completed in the laboratory. RESULTS: The median (25 %, 75 % quartile) of TIRCGM and TIRSMBG were 74.94(44.90, 88.04) and 70.83(46.88, 87.50) respectively, and there was no significant difference, p = 0.489; For every 1 % increase in TIRCGM, the risk of microalbuminuria decreased by 1.6 % (95%CI:0.973, 0.995, p = 0.006) and for every 1 % increase in TIRSMBG, the risk of microalbuminuria decreased by 1.3 % (95%CI:0.975, 0.999, p = 0.033). Stepwise multiple linear regression analysis showed an independent positive correlation between TIR (including TIRCGM and TIRSBMG) and LnDI30 and LnDI120 levels (p = 0.000). CONCLUSIONS: The TIR calculated by SMBG was highly consistent with that reported by CGM and was significantly associated with the risk of microalbuminuria and the HOMA-ß. Higher TIR quartiles were associated with lower incidence of microalbuminuria as well as higher lever of HOMA-ß. For patients with limited CGM application, SMBG-derived TIR may be an alternative to CGM-derived TIR, to assess blood glucose control.

Chiral Ligand-Decorated Rhodium Nanoparticles Incorporated in Covalent Organic Framework for Asymmetric Catalysis.

While metal nanoparticles (NPs) have demonstrated their great potential in catalysis, introducing chiral microenvironment around metal NPs to achieve efficient conversion and high enantioselectivity remains a long-standing challenge. In this work, tiny Rh NPs, modified by chiral diene ligands (Lx) bearing diverse functional groups, are incorporated into a covalent organic framework (COF) for the asymmetric 1,4-addition reactions between arylboronic acids and nitroalkenes. Though Rh NPs hosted in the COF are inactive, decorating Rh NPs with Lx creates the active Rh-Lx interface and induces high activity. Moreover, chiral microenvironment modulation around Rh NPs by altering the groups on chiral diene ligands greatly optimizes the enantioselectivity (up to 95.6% ee). Mechanistic investigations indicate that the formation of hydrogen-bonding interaction between Lx and nitroalkenes plays critical roles in the resulting enantioselectivity. This work highlights the significance of chiral microenvironment modulation around metal NPs by chiral ligand decoration for heterogeneous asymmetric catalysis.

Bioinspired Capillary Transistors.

Inspired by the unidirectional liquid spreading on Nepenthes peristome, Araucaria leaf, butterfly wings, etc., various microfluidic devices have been developed for water collection, irrigation, physical/chemical reaction, and oil-water separation. Despite extensive progress, most natural and artificial structures fail to enhance the Laplace pressure difference or capillary force, thus suffering from a low unidirectional capillary height (<30 mm). In this work, asymmetric re-entrant structures with long overhangs and connected forward/lateral microchannels are fabricated by 3D printing, resulting in a significantly increased unidirectional capillary height of 102.3 mm for water, which approximately corresponds to the theoretical limit. The overhangs can partially overlap the forward microchannels of the front structures without direct contact, thus enhancing the Laplace pressure difference and capillary force simultaneously. Based on asymmetric and symmetric re-entrant structures, capillary transistors are proposed and realized to programmably adjust the capillary direction, height, and width, which are envisioned to function as switches/valves and amplifiers/attenuators for highly efficient liquid patterning, desalination, and biochemical microreaction in 3D space.

A Rapid Nanofocusing Method for a Deep-Sea Gene Sequencing Microscope Based on Critical Illumination.

In the deep-sea environment, the volume available for an in-situ gene sequencer is severely limited. In addition, optical imaging systems are subject to real-time, large-scale defocusing problems caused by ambient temperature fluctuations and vibrational perturbations. To address these challenges, we propose an edge detection algorithm for defocused images based on grayscale gradients and establish a defocus state detection model with nanometer resolution capabilities by relying on the inherent critical illumination light field. The model has been applied to a prototype deep-sea gene sequencing microscope with a 20× objective. It has demonstrated the ability to focus within a dynamic range of ±40 µm with an accuracy of 200 nm by a single iteration within 160 ms. By increasing the number of iterations and exposures, the focusing accuracy can be refined to 78 nm within a dynamic range of ±100 µm within 1.2 s. Notably, unlike conventional photoelectric hill-climbing, this method requires no additional hardware and meets the wide dynamic range, speed, and high-accuracy autofocusing requirements of deep-sea gene sequencing in a compact form factor.

[Applications of high performance liquid chromatography-mass spectrometry in proteomics].

Proteomics profiling plays an important role in biomedical studies. Proteomics studies are much more complicated than genome research, mainly because of the complexity and diversity of proteomic samples. High performance liquid chromatography-mass spectrometry (HPLC-MS) is a fundamental tool in proteomics research owing to its high speed, resolution, and sensitivity. Proteomics research targets from the peptides and individual proteins to larger protein complexes, the molecular weight of which gradually increases, leading to sustained increases in structural and compositional complexity and alterations in molecular properties. Therefore, the selection of various separation strategies and stationary-phase parameters is crucial when dealing with the different targets in proteomics research for in-depth proteomics analysis. This article provides an overview of commonly used chromatographic-separation strategies in the laboratory, including reversed-phase liquid chromatography (RPLC), hydrophilic interaction liquid chromatography (HILIC), hydrophobic interaction chromatography (HIC), ion-exchange chromatography (IEC), and size-exclusion chromatography (SEC), as well as their applications and selectivity in the context of various biomacromolecules. At present, no single chromatographic or electrophoretic technology features the peak capacity required to resolve such complex mixtures into individual components. Multidimensional liquid chromatography (MDLC), which combines different orthogonal separation modes with MS, plays an important role in proteomics research. In the MDLC strategy, IEC, together with RPLC, remains the most widely used separation mode in proteomics analysis; other chromatographic methods are also frequently used for peptide/protein fractionation. MDLC technologies and their applications in a variety of proteomics analyses have undergone great development. Two strategies in MDLC separation systems are mainly used in proteomics profiling: the "bottom-up" approach and the "top-down" approach. The "shotgun" method is a typical "bottom-up" strategy that is based on the RPLC or MDLC separation of whole-protein-sample digests coupled with MS; it is an excellent technique for identifying a large number of proteins. "Top-down" analysis is based on the separation of intact proteins and provides their detailed molecular information; thus, this technique may be advantageous for analyzing the post-translational modifications (PTMs) of proteins. In this paper, the "bottom-up" "top-down" and protein-protein interaction (PPI) analyses of proteome samples are briefly reviewed. The diverse combinations of different chromatographic modes used to set up MDLC systems are described, and compatibility issues between mobile phases and analytes, between mobile phases and MS, and between mobile phases in different separation modes in multidimensional chromatography are analyzed. Novel developments in MDLC techniques, such as high-abundance protein depletion and chromatography arrays, are further discussed. In this review, the solutions proposed by researchers when encountering compatibility issues are emphasized. Moreover, the applications of HPLC-MS combined with various sample pretreatment methods in the study of exosomal and single-cell proteomics are examined. During exosome isolation, the combined use of ultracentrifugation and SEC can yield exosomes of higher purity. The use of SEC with ultra-large-pore-size packing materials (200 nm) enables the isolation of exosomal subgroups, and proteomics studies have revealed significant differences in protein composition and function between these subgroups. In the field of single-cell proteomics, researchers have addressed challenges related to reducing sample processing volumes, preventing sample loss, and avoiding contamination during sample preparation. Innovative methods and improvements, such as the utilization of capillaries for sample processing and microchips as platforms to minimize the contact area of the droplets, have been proposed. The integration of these techniques with HPLC-MS shows some progress. In summary, this article focuses on the recent advances in HPLC-MS technology for proteomics analysis and provides a comprehensive reference for future research in the field of proteomics.

Potential impact of NOTCH1 activation on venetoclax sensitivity in chronic lymphocytic Leukaemia: In vitro insights and clinical implications.

Despite significant progress in treating chronic lymphocytic leukaemia (CLL), resistance to therapy remains challenging. NOTCH1 activation, common in CLL, confers adverse prognosis. This study explores the impact of NOTCH1 signalling on venetoclax sensitivity in vitro. Although NOTCH1 activation minimally impaired the susceptibility of CLL cells to venetoclax, ex vivo cell competition studies reveal that cells with constitutive NOTCH1 activation outgrew their wild-type counterparts in the presence of ongoing venetoclax exposure. Our findings suggest that while NOTCH1 activation is insufficient to confer venetoclax refractoriness, there is enhanced potential for cells with NOTCH1 activation to escape and thus become fully resistant to venetoclax.

Fermented Gastrodia elata Bl. Alleviates Cognitive Deficits by Regulating Neurotransmitters and Gut Microbiota in D-Gal/AlCl3-Induced Alzheimer's Disease-like Mice.

Alzheimer's disease (AD) is a common neurological disease with recognition ability loss symptoms and a major contributor to dementia cases worldwide. Gastrodia elata Bl. (GE), a food of medicine-food homology, has been reported to have a mitigating effect on memory and learning ability decline. However, the effect of GE fermented by Lactobacillus plantarum, Acetobacter pasteurianus, and Saccharomyces (FGE) on alleviating cognitive deficits in AD was not studied. Mice were randomly divided into six groups, control, model, donepezil, low, medium, and high doses of FGE, and D-Galactose/Aluminum chloride (D-Gal/AlCl3) was used to establish an AD-like mouse model. The results indicated that FGE could improve the production of neurotransmitters and relieve oxidative stress damage in AD-like mice, which was evidenced by the declined levels of amyloid-ß (Aß), Tau, P-Tau, acetylcholinesterase (AchE), and malondialdehyde (MDA), and increased acetylcholine (Ach), choline acetyltransferase (ChAT), and superoxide dismutase (SOD) levels in brain tissue. Notably, FGE could enhance the richness of the gut microbiota, especially for beneficial bacteria such as Lachnospira and Lactobacillus. Non-target metabolomics results indicated that FGE could affect neurotransmitter levels by regulating amino acid metabolic pathways to improve AD symptoms. The FGE possessed an ameliorative effect on AD by regulating neurotransmitters, oxidative stress levels, and gut microbiota and could be considered a good candidate for ameliorating AD.

Association between glioma and neurodegenerative diseases risk: a two-sample bi-directional Mendelian randomization analysis.

Background: Earlier observational studies have demonstrated a correlation between glioma and the risk of neurodegenerative diseases (NDs), but the causality and direction of their associations remain unclear. The objective of this study was to ascertain the causal link between glioma and NDs using Mendelian randomization (MR) methodology. Methods: Genome-wide association study (GWAS) data were used in a two-sample bi-directional MR analysis. From the largest meta-analysis GWAS, encompassing 18,169 controls and 12,488 cases, summary statistics data on gliomas was extracted. Summarized statistics for NDs, including Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) were obtained from the GWAS of European ancestry. Inverse variance weighted (IVW) method was elected as the core MR approach with weighted median (WM) method and MR-Egger method as complementary methods. In addition, sensitivity analyses were performed. A Bonferroni correction was used to correct the results. Results: Genetically predicted glioma had been related to decreased risk of AD. Specifically, for all glioma (IVW: OR = 0.93, 95% CI = 0.90-0.96, p = 4.88 × 10-6) and glioblastoma (GBM) (IVW: OR = 0.93, 95% CI = 0.91-0.95, p = 5.11 × 10-9). We also found that genetically predicted all glioma has a suggestive causative association with MS (IVW: OR = 0.90, 95% CI = 0.81-1.00, p = 0.045). There was no evidence of causal association between glioma and ALS or PD. According to the results of reverse MR analysis, no discernible causal connection of NDs was found on glioma. Sensitivity analyses validated the robustness of the above associations. Conclusion: We report evidence in support of potential causal associations of different glioma subtypes with AD and MS. More studies are required to uncover the underlying mechanisms of these findings.

[Spatial Prediction and Influencing Factors Analysis of Soil Salinization in Coastal Area Based on MGWR].

Quantitative analysis of the spatial non-stationary characteristics of soil salinization influencing factors and the prediction of its spatial distribution are of great significance for the rational use of coastal saline soil resources and the formulation of local prevention and control measures. In this study, the Hekou District of Dongying City, Shandong Province, was used as the study area, and the descriptive statistics of soil salinization status were conducted using classical statistical methods. Spatial autocorrelation theory was used to explore the characteristics of global and local spatial structure of soil salinization in the study area. Influential factors related to soil salinity were selected, and multivariate linear regression （MLR）, geographically weighted regression （GWR）, and multi-scale geographically weighted regression （MGWR） methods were used to model and predict the spatial distribution of soil salinity in the study area and to analyze the spatial heterogeneity of the effects of different influencing factors on soil salinity. The results showed that： ① The mean value of soil salinity in the study area was 5.84 g·kg-1, indicating severe salinization, with a global Moran's I index of 0.19 （P<0.00） and obvious spatial aggregation characteristics. ② Among the three models, the MGWR model had the highest modeling accuracy. Compared with that of the MLR model, the Radj2 of GWR and MGWR improved by 0.05 and 0.07, respectively, and the RSS decreased by 210.13 and 179.95, respectively. ③ The results of MGWR regression showed that the spatial distribution of soil salinity appeared to be mainly affected by the middle soil salinity, soil clay content, and vegetation cover from the mean values of standardized regression coefficients of different influencing factors. Different influencing factors had significant spatial non-stationary characteristics on soil salinization. ④ The results of the spatial distribution prediction of soil salinity in MGWR showed that the areas of high soil salinity （≥6 g·kg-1） were mainly distributed in the northern part of the study area, with an overall spatial trend of decreasing from the coast to the interior. The results of the study can be used as a reference for the analysis and predictive mapping of factors affecting soil salinization in the county and on a larger scale using MGWR.

Temporal metabolomics analysis reveals the metabolic patterns in goat cumulus cells during oocyte maturation.

Cumulus cells play a crucial role in the oocyte growth and maturation processes through providing necessary nutrients and growth signals by gap junction communication. However, a global overview of metabolic events in goat cumulus cells is still lacking. In the present study, we collected cumulus cells from goat cumulus-oocyte complexes (COCs) at different developmental stages. Metabolomics analysis was performed to investigate the global metabolic patterns in cumulus cells during oocyte in vitro maturation. In particular, we revealed the several significantly altered metabolic pathways and metaboliccharacteristics in goat cumulus cells, including the accumulation of fatty acids, steroid hormones metabolism, active catabolism of arginine during meiotic resumption, and a progressive decline in nucleotide metabolism. In conclusion, the dataset generated by our metabolomic profiling will provide valuable information to understand the key metabolic pathways and metabolites involved in COCs development.

Introducing Hydrogen-Bonding Microenvironment in Close Proximity to Single-Atom Sites for Boosting Photocatalytic Hydrogen Production.

Inspired by enzymatic catalysis, it is crucial to construct hydrogen-bonding-rich microenvironment around catalytic sites; unfortunately, its precise construction and understanding how the distance between such microenvironment and catalytic sites affects the catalysis remain significantly challenging. In this work, a series of metal-organic framework (MOF)-based single-atom Ru1 catalysts, namely, Ru1/UiO-67-X (X = -H, -m-(NH2)2, -o-(NH2)2), have been synthesized, where the distance between the hydrogen-bonding microenvironment and Ru1 sites is modulated by altering the location of amino groups. The -NH2 group can form hydrogen bonds with H2O, constituting a unique microenvironment that causes an increased water concentration around the Ru1 sites. Remarkably, Ru1/UiO-67-o-(NH2)2 displays a superior photocatalytic hydrogen production rate, ∼4.6 and ∼146.6 times of Ru1/UiO-67-m-(NH2)2 and Ru1/UiO-67, respectively. Both experimental and computational results suggest that the close proximity of amino groups to the Ru1 sites in Ru1/UiO-67-o-(NH2)2 improves charge transfer and H2O dissociation, accounting for the promoted photocatalytic hydrogen production.

Tailoring Catalysis of Encapsulated Pt Nanoparticles by Pore Wall Engineering of Covalent Organic Frameworks.

While supported metal nanoparticles (NPs) have shown significant promise in heterogeneous catalysis, precise control over their interaction with the support, which profoundly impacts their catalytic performance, remains a significant challenge. In this study, Pt NPs are incorporated into thioether-functionalized covalent organic frameworks (denoted COF-Sx), enabling precise control over the size and electronic state of Pt NPs by adjusting the thioether density dangling on the COF pore walls. Notably, the resulting Pt@COF-Sx demonstrate exceptional selectivity (>99%) in catalytic hydrogenation of p-chloronitrobenzene to p-chloroaniline, in sharp contrast to the poor selectivity of Pt NPs embedded in thioether-free COFs. Furthermore, the conversion over Pt@COF-Sx exhibits a volcano-type curve as the thioether density increases, due to the corresponding change of accessible Pt sites. This work provides an effective approach to regulating the catalysis of metal NPs via their microenvironment modulation, with the aid of rational design and precise tailoring of support structure.

AhR ligands from LGG metabolites promote piglet intestinal ILC3 activation and IL-22 secretion to inhibit PEDV infection.

In maintaining organismal homeostasis, gut immunity plays a crucial role. The coordination between the microbiota and the immune system through bidirectional interactions regulates the impact of microorganisms on the host. Our research focused on understanding the relationships between substantial changes in jejunal intestinal flora and metabolites and intestinal immunity during porcine epidemic diarrhea virus (PEDV) infection in piglets. We discovered that Lactobacillus rhamnosus GG (LGG) could effectively prevent PEDV infection in piglets. Further investigation revealed that LGG metabolites interact with type 3 innate lymphoid cells (ILC3s) in the jejunum of piglets through the aryl hydrocarbon receptor (AhR). This interaction promotes the activation of ILC3s and the production of interleukin-22 (IL-22). Subsequently, IL-22 facilitates the proliferation of IPEC-J2 cells and activates the STAT3 signaling pathway, thereby preventing PEDV infection. Moreover, the AhR receptor influences various cell types within organoids, including intestinal stem cells (ISCs), Paneth cells, and enterocytes, to promote their growth and development, suggesting that AhR has a broad impact on intestinal health. In conclusion, our study demonstrated the ability of LGG to modulate intestinal immunity and effectively prevent PEDV infection in piglets. These findings highlight the potential application of LGG as a preventive measure against viral infections in livestock.IMPORTANCEWe observed high expression of the AhR receptor on pig and human ILC3s, although its expression was negligible in mouse ILC3s. ILC3s are closely related to the gut microbiota, particularly the secretion of IL-22 stimulated by microbial signals, which plays a crucial regulatory role in intestinal immunity. In our study, we found that metabolites produced by beneficial gut bacteria interact with ILC3s through AhR, thereby maintaining intestinal immune homeostasis in pigs. Moreover, LGG feeding can enhance the activation of ILC3s and promote IL-22 secretion in the intestines of piglets, ultimately preventing PEDV infection.

METTL3 regulates thyroid cancer differentiation and chemosensitivity by modulating PAX8.

Background: Thyroid cancer (TC) is a common endocrine cancer with a favourable prognosis. However, poor patient prognosis due to TC dedifferentiation is becoming an urgent challenge. Recently, methyltransferase-like 3 (METTL3)-mediated N6 -methyladenosine (m6A) modification has been demonstrated to play an important role in the occurrence and progression of various cancers and a tumour suppressor role in TC. However, the mechanism of METTL3 in TC remains unclear. Methods: The correlation between METTL3 and prognosis in TC patients was evaluated by immunohistochemistry. Mettl3fl/flBrafV600ETPO-cre TC mouse models and RNA-seq were used to investigate the underlying molecular mechanism, which was further validated by in vitro experiments. The target gene of METTL3 was identified, and the complete m6A modification process was described. The phenomenon of low expression of METTL3 in TC was explained by identifying miRNAs that regulate METTL3. Results: We observed that METTL3 expression was negatively associated with tumour progression and poor prognosis in TC. Mechanistically, silencing METTL3 promoted the progression and dedifferentiation of papillary thyroid carcinoma (PTC) both in vivo and in vitro. Moreover, overexpressing METTL3 promoted the sensitivity of PTC and anaplastic thyroid cancer (ATC) cells to chemotherapeutic drugs and iodine-131 (131I) administration. Overall, the METTL3/PAX8/YTHDC1 axis has been revealed to play a pivotal role in repressing tumour occurrence, and is antagonized by miR-493-5p.

Directional surface reconstruction of C and S Co-Doped Co2VO4/CoP for the cooperative enhancement of hydrogen production via seawater electrolysis.

The endeavor to architect bifunctional electrocatalysts that exhibit both exceptional activity and durability heralds an era of boundless potential for the comprehensive electrolysis of seawater, an aspiration that, nevertheless, poses a substantial challenge. Within this work, we describe the precise engineering of a three-dimensional interconnected nanoparticle system named SCdoped Co2VO4/CoP (SCCo2VO4), achieved through a meticulously arranged hydrothermal treatment sequence followed by gas-phase carbonization and phosphorization. The resulting SCCo2VO4 electrode exhibits outstanding bifunctional electrocatalytic stability, attributed to the strategic anionic doping and abundant heterogeneous interfaces. Doping not only adjusts the electronic structure, enhancing electron transfer efficiency but also optimizes the surface-active sites. This electrode prodigiously necessitated an extraordinarily minimal overpotential of merely 92 and 350 mV to attain current densities of 10 and 50 mA cm-2 for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively, in 1 M KOH solution. Noteworthily, when integrated into an electrolyzer for the exhaustive splitting of seawater, the SCP-Co2VO4 manifested an exceptionally low cell voltage of 2.08 V@50 mA cm-2 and showcased a durability that eclipses that of most hitherto documented nickel-based bifunctional materials. Further elucidation through Density Functional Theory (DFT) analyses underscored that anion doping and the inherent heterostructure adeptly optimize the Gibbs free energy of intermediates comprising hydrogen, chlorine, and oxygen (manifested as OH, O, OOH) within the HER and OER paradigms, thus propelling the electrochemical kinetics of seawater splitting to unprecedented velocities. These revelations unfurl a pioneering design philosophy for the creation of cost-effective yet superior catalysts aimed at the holistic division of water molecules, charting a course towards the realization of efficient and sustainable hydrogen production methodologies.