Artificial neural network optimisation of natural deep eutectic solvent extraction process of Danshen-Gegen and cytotoxicity study.

Natural deep eutectic solvents (NaDESs) are environmentally friendly and efficient for the componential extraction of traditional Chinese medicine compared to conventional organic solvents. In this study, NaDES was screened and employed to extract Danshen-Gegen (DG), and the extraction process was optimised by response surface methodology (RSM) and artificial neural networks (ANN) model. Besides, the in vitro security of extracts of DG were evaluated in PC12 cells. As a result, Betaine-Urea (Bet-Ur) was screened as extraction solvent and ANN model was more accurate than RSM model in optimising the extraction parameter. The extraction process optimised by ANN was as follows: 70% NaDES concentration, 80 mg/mL solid to liquid ratio, 67 °C ultrasonic temperature, and 33 min of ultrasonic time. The comprehensive value of extraction yield was 0.7251 ± 0.84%. IC50 of Bet-Ur, NaDES DG extract and aqueous DG extract were 0.15%, 0.3% and 10% (v/v).

Human circular RNA hsa_circ_0000231 clinical diagnostic effectiveness as a new tumor marker in gastric cancer.

BACKGROUND: Owing to the subtlety of initial symptoms associated with gastric cancer (GC), the majority of patients are diagnosed at later stages. Given the absence of reliable diagnostic markers, it is imperative to identify novel markers that exhibit high sensitivity and specificity. Circular RNA, a non-coding RNA, plays an important role in tumorigenesis and development and is well expressed in body fluids. AIMS: In this study, we aimed to identify hsa_circ_0000231 as a new biomarker for the diagnosis of GC and to assess its clinical diagnostic value in serum. METHODS AND RESULTS: The stability and correctness of hsa_circ_0000231 was determined by agarose gel electrophoresis, Rnase R assay and Sanger sequencing. Real-time quantitative polymerase chain reaction (qRT-PCR) was designed to discover the expression level of hsa_circ_0000231 and whether it has dynamic serum monitoring capability. The correlation between hsa_circ_0000231 and clinicopathological parameters was analyzed by collecting clinical and pathological data from GC patients. In addition, diagnostic efficacy was assessed by constructing receiver operating characteristic curves (ROC). Hsa_circ_0000231 exhibits a stable and consistently expressed structure. In GC serum, cells, and tissues, it demonstrates reduced expression levels. Elevated expression levels observed postoperatively suggest its potential for dynamic monitoring. Additionally its expression level correlates with TNM staging and neuro/vascular differentiation. The area under ROC curve (AUC) for hsa_circ_0000231 is 0.781, indicating its superior diagnostic value compared to CEA, CA19-9, and CA72-4. The combination of these four indicators enhances diagnostic accuracy, with an AUC of 0.833. CONCLUSIONS: The stable expression of hsa_circ_0000231 in the serum of gastric cancer patients holds promise as a novel biomarker for both the diagnosis and dynamic monitoring of GC.

Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11.

BACKGROUND: Luteolin (3,4,5,7-tetrahydroxy flavone) is reported to strongly protect from acute carbon tetrachloride (CCl4) -induced liver injury or fibrosis. Ferroptosis can be induced by hepatic injury, and contributes to liver fibrosis development. The exact functional mechanism underlying luteolin inhibition of hepatic injury and whether ferroptosis is involved are unclear. METHODS: Mice model and cell model of liver injury were constructed or induced to explore the effect and molecular mechanisms of Luteolin in the treatment of hepatic injury using CCl4. Cell Counting Kit-8 (CCK-8) and flow cytometry were used to evaluate HepG2 cell viability and apoptosis. The differential expressed genes involved in liver injury were scanned using RNA-seq and confirmed using functional study. Western blot was used to detect the indicators related to ferroptosis. RESULTS: Luteolin attenuated hepatic injury by alleviating cell morphology and decreasing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in vivo mice models, and increasing cell viability, downregulating arachidonate 12-lipoxygenase (ALOX12), cyclooxygenase-2 (COX-2) and P21 protein expression, suppressing apoptosis in vitro cell models. Luteolin also inhibited ferroptosis by stimulating glutathione peroxidase 4 (GPX4) and mitochondrial ferritin (FTMT) protein expression, increasing glutathione (GSH) content, and minimizing Fe2+ and malondialdehyde (MDA) levels. Solute carrier family 7a member 11 (SLC7A11) was identified to be a key regulatory gene that participated in luteolin attenuation of CCl4-induced hepatic injuries in HepG2 cells using Microarray assay. Functional study showed that SLC7A11 can alleviate hepatic injury and ferroptosis. CONCLUSION: Luteolin attenuated CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. SLC7A11 may serve as a novel alternative therapeutic target for hepatic injury.

First report of large-berry coffee (Coffea liberica) anthracnose caused by Colletotrichum kahawae in China.

Large-berry coffee (Coffea liberica) is one of the three cultivated coffee species and a precious breeding germplasm in China (Yan et al, 2019). Anthracnose is a damaging epidemic disease on coffee worldwide (Mohammed et al. 2015). Between June and September 2022, anthracnose was observed on coffee plants in Puer area, Yunnan, China and disease incidence (% plants diseased) of 8.5%-28.2% was recorded in the field. The disease symptoms were observed at all growth stages. Lesions on leaves were circular or oval, with a white to gray central zone outlined by a brown margin and surrounded by a chlorotic halo, Φ5.1-18.5 mm; some lesions extended and coalesced later to form large, blighted areas, leading to complete leaf senescence, defoliation and bare blighted branches on heavily infected trees. The spots on coffee berries were oval or fusiform, sunken and brown-black; diseased berries became gray-black and dried-out but remained on the tree. Leaves with typical anthracnose lesions were collected from fields in Simao ( 22.07°E,100.98°N) to isolate the pathogen. Leaf pieces (5×5mm) from the lesion margin were cut, surface-sterilized with 75% ethanol and 2% NaClO, and cultured on PDA at 25°C. Three isolates with the same colony morphology were obtained by hyphal tip purification. Detached and intact leaves of 6-month coffee seedlings were inoculated with Φ5mm mycelial discs of the isolates. Anthracnose lesions developed on the inoculated leaves, with all 3 isolates, 7d after incubation in a growth chamber (25°C, > 90% RH and lighting 8 h/d at 11000 lux). Pathogens with the same colony morphology as those of the original isolates were re-isolated from the infected tissues of inoculated leaves, thus fulfilling Koch's Postulates. The ITS sequence (PP550861) for the isolate was PCR-amplified and Blast-n analyses showed 100 % (554/554bp) identity to Colletotrichum kahawae LWTJ01; so they were the same population and coded as KFTJ02. The actin (ACT), calmodulin(CAL), glyceraldehydes-3-phosphate dehydrogenase (GAPHD) and histone 3 (HIS3) genes (Qiu et al. 2020) were amplified from one of KFTJ02 isolates, sequenced and deposited in NCBI GenBank (OR842543, OR842544, OR842545 & OR842546). A phylogenetic tree was generated based on the concatenated sequences of the four genes and those of related Colletotrichum spp. using MEGA 6.0 and KFTJ02 clustered in the same clade with C. kahawae IMI319418 on the tree (Bootstrap sup.=88%). When cultured at 25°C on PDA for 7 days, its colonies were near round or ovoid, gray-white, contoured, Φ73.2-80.1 (76.2±2.3)mm or growth rate 10.2-11.1(8.1) mm/d (n=10). The hyphae were hyaline, septated, branching at near right angles. Conidial masses formed 14 days after incubation. The conidia were elliptical, hyaline, monocellular, 10.2-15.5 (12.7±1.06)×3.8-5.2 (4.3±0.52) µm (n=50). The appressoria were black-brown, oval or irregular, 7.8-9.3 (8.5±0.81)µm (n= 50). These morphological characteristics were consistent with those of C. kahawae (Bridge et al, 2008). Therefore, KFTJ02 was identified as C. kahawae, which has been found to infect Camellia oleifera, Areca catechu and Ficus microcarpa (Wei et al, 2023; Zhang et al, 2020; Lin 2023). The coffee berry disease pathogen (C. kahawae) is a quarantine species which has not been recorded and so it is first reported on coffee crops in China. Results of the present study provide important references for further studies on this disease.

Changes and driving factors of microbial community composition and functional groups during the decomposition of Pinus massoniana deadwood.

Clarifying changes in the microbial community in deadwood at different stages of decomposition is crucial for comprehending the role of deadwood in the biogeochemical processes and the sustainability of forest development. However, there have been no reports on the dynamics of microbial community during the decomposition of Pinus massoniana. We used the "space-for-time" substitution to analyze the characteristics of microbial community changes and the key influencing factors in the P. massoniana deadwood during different decomposition stages by 16S and ITS rRNA gene sequencing. The results suggest that the microbial community structure of the early decomposition (decay class I) was significantly different from the other decay classes, while the diversity and richness of the microbial community were the highest in the late decomposition (decay class V). The Linear Discriminant Analysis Effect Size analysis revealed that most bacterial and fungal taxa were significantly enriched in decay classes I and V deadwood. During the initial stages of decomposition, the relative abundance of the bacterial functional group responsible for carbohydrate metabolism was greater than the later stages. As decomposition progressed, the relative abundance of saprophytic fungi gradually decreased, and there was a shift in the comparative abundance of mixed saprophytic-symbiotic fungi from low to high before eventually decreasing. Total organic carbon, total nitrogen, carbon-to-nitrogen ratio, total potassium, total phenol, condensed tannin, lignin, and cellulose were significantly correlated with microbial community structure, with the carbon-to-nitrogen ratio having the greatest effect. Our results indicate that the physicochemical properties of deadwood, microbial community structural composition and functional group changes were related to the decay class, among which the carbon-to-nitrogen ratio may be an important factor affecting the composition and diversity of microbial communities.

Rhythm gene PER1 mediates ferroptosis and lipid metabolism through SREBF2/ALOX15 axis in polycystic ovary syndrome.

OBJECTIVE: This work aimed to investigate the role of rhythm gene PER1 in mediating granulosa cell ferroptosis and lipid metabolism of polycystic ovary syndrome (PCOS). METHODS: We injected dehydroepiandrosterone and Ferrostatin-1 (Fer-1) into mice to explore the mechanism of ferroptosis in PCOS. The effect of PER1 on ferroptosis-like changes in granulosa cells was explored by overexpression of PER1 plasmid transfection and Fer-1 treatment. RESULTS: We found that Fer-1 ameliorated the characteristic polycystic ovary morphology, suppressed ferroptosis in the PCOS mice. PER1 and ALOX15 were highly expressed in PCOS, whereas SREBF2 was lowly expressed. Overexpression of PER1 decreased granulosa cell viability and inhibited proliferation. Meanwhile, overexpression of PER1 increased lipid reactive oxygen species, 4-Hydroxynonenal (4-HNE), Malondialdehyde (MDA), total Fe, and Fe2+ levels in granulosa cells and decreased Glutathione (GSH) content. Fer-1, SREBF2 overexpression, or ALOX15 silencing treatment reversed the effects of PER1 overexpression on granulosa cells. PER1 binds to the SREBF2 promoter and represses SREBF2 transcription. SREBF2 binds to the ALOX15 promoter and represses ALOX15 transcription. Correlation analysis of clinical trials showed that PER1 was positively correlated with total cholesterol, low-density lipoprotein cholesterol, luteinizing hormone, testosterone, 4-HNE, MDA, total Fe, Fe2+, and ALOX15. In contrast, PER1 was negatively correlated with SREBF2, high-density lipoprotein cholesterol, follicle-stimulating hormone, progesterone, and GSH. CONCLUSION: This study demonstrates that the rhythm gene PER1 promotes ferroptosis and dysfunctional lipid metabolism in granulosa cells in PCOS by inhibiting SREBF2/ALOX15 signaling.

Graphene oxide/ε-poly-L-lysine self-assembled functionalized coatings improve the biocompatibility and antibacterial properties of titanium implants.

The construction of an antibacterial biological coating on titanium surface plays an important role in the long-term stability of oral implant restoration. Graphene oxide (GO) has been widely studied because of its excellent antibacterial properties and osteogenic activity. However, striking a balance between its biological toxicity and antibacterial properties remains a significant challenge with GO. ε-poly-L-lysine (PLL) has broad-spectrum antibacterial activity and ultra-high safety performance. Using Layer-by-layer self-assembly technology (LBL), different layers of PLL/GO coatings and GO self-assembly coatings were assembled on the surface of titanium sheet. The materials were characterized using scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and contact angle test. The antibacterial properties of Porphyromonas gingivalis (P.g.) were analyzed through SEM, coated plate experiment, and inhibition zone experiment. CCK-8 was used to determine the cytotoxicity of the material to MC3T3 cells, and zebrafish larvae and embryos were used to determine the developmental toxicity and inflammatory effects of the material. The results show that the combined assembly of 20 layers of GO and PLL exhibits good antibacterial properties and no biological toxicity, suggesting a potential application for a titanium-based implant modification scheme.

Pentraxin-3 and Outcomes in CKD: A Systematic Review and Meta-analysis.

Rationale & Objective: Long pentraxin-3 (PTX-3) serves as a biomarker for prognosticating adverse clinical outcomes in individuals with chronic kidney disease (CKD). The objective of the current meta-analysis was to evaluate the prognostic efficacy of PTX-3 in patients with CKD. In addition, we compared the prognostic effectiveness of PTX-3 and the short pentraxin C-reactive protein (CRP) in the identical cohort of patients with CKD. Study Design: A systematic review and meta-analysis. Setting & Participants: Patients with CKD treated with or without dialysis. Selection Criteria for Studies: A cohort study with a minimum 1-year follow-up. Data Extraction: Risk measurements, adjusted hazard risk with 95% CI, and modified variables. Analytical Approach: To aggregate the adjusted effect estimates, a fixed-effects or random-effects model was employed. Results: Nine studies covering 1,825 patients with CKD were selected in the present review. Six of the 9 studies exclusively included patients receiving hemodialysis. The collected findings indicated that patients with CKD in the highest tertile of PTX-3 demonstrated significantly higher risks of all-cause mortality (HR, 1.92; 95% CI, 1.44-2.56), cardiovascular death (HR, 1.98; 95% CI, 1.28-3.05), infectious death (HR, 5.26; 95% CI, 1.60-17.31), and fatal and nonfatal cardiovascular events (HR, 1.81; 95% CI, 1.35-2.42), as compared with those in the lowest tertile. These significant associations with risk were also observed when effect estimates were presented as per unit change in the PTX-3. Moreover, when comparing the prognostic value of PTX-3 and CRP in the same individuals (5 studies covering 904 patients), PTX-3 proved to be a satisfactory predictor of adverse events in these patients, whereas CRP failed to exhibit such predictive capability, regardless of the type of effect estimate used. Limitations: A relatively small sample size and some heterogeneity. Conclusions: Pentraxin 3 is associated with adverse events in individuals with CKD and may be a more reliable predictor of adverse clinical events than CRP in this population.

Systemic inflammatory markers are useful in predicting the prognosis of patients with CKD. Pentraxin-3 (PTX-3) is an emerging biomarker of inflammation compared with other members of the pentraxin family, such as C-reactive protein (CRP). This meta-analysis evaluated the prognostic value of PTX-3 in predicting adverse outcomes in patients with CKD. Also, we compared the prognostic values between PTX-3 and CRP in the subset of studies with data on CRP. We found that patients with CKD with higher circulating PTX-3 levels had a significantly heightened risk of adverse outcomes compared with those with lower PTX-3 levels. By contrast, CRP did not appear to be a good predictor of adverse events. Pentraxin-3 might be a more reliable prognostic marker than CRP in patients with CKD.

Protective Effects of Isoliquiritigenin and Licochalcone B on the Immunotoxicity of BDE-47: Antioxidant Effects Based on the Activation of the Nrf2 Pathway and Inhibition of the NF-κB Pathway.

2,2',4,4'-Tetrabrominated biphenyl ether (BDE-47) is a polybrominated diphenyl ether (PBDE) homologue that is ubiquitous in biological samples and highly toxic to humans and other organisms. Prior research has confirmed that BDE-47 can induce oxidative damage in RAW264.7 cells, resulting in apoptosis and impaired immune function. The current study mainly focused on how Isoliquiritigenin (ISL) and Licochalcone B (LCB) might protect against BDE-47's immunotoxic effects on RAW264.7 cells. The results show that ISL and LCB could increase phagocytosis, increase the production of MHC-II, and decrease the production of inflammatory factors (TNF-α, IL-6, and IL-1ß) and co-stimulatory factors (CD40, CD80, and CD86), alleviating the immune function impairment caused by BDE-47. Secondly, both ISL and LCB could reduce the expressions of the proteins Bax and Caspase-3, promote the expression of the protein Bcl-2, and reduce the apoptotic rate, alleviating the apoptosis initiated by BDE-47. Additionally, ISL and LCB could increase the levels of antioxidant substances (SOD, CAT, and GSH) and decrease the production of reactive oxygen species (ROS), thereby counteracting the oxidative stress induced by BDE-47. Ultimately, ISL and LCB suppress the NF-κB pathway by down-regulating IKBKB and up-regulating IκB-Alpha in addition to activating the Nrf2 pathway and promoting the production of HO-1 and NQO1. To summarize, BDE-47 causes oxidative damage that can be mitigated by ISL and LCB through the activation of the Nrf2 pathway and inhibition of the NF-κB pathway, which in turn prevents immune function impairment and apoptosis. These findings enrich the current understanding of the toxicological molecular mechanism of BDE-47 and the detoxification mechanism of licorice.

Inequality characteristics and influencing factors of CO2 emissions per capita in Jiangsu Province, China.

Analyzing the inequality characteristics and influencing factors of CO2 emissions per capita (CEPC) is conducive to balancing regional development and CO2 emissions reduction. This study applied the Gini coefficient and Theil index to investigate the CEPC inequalities during 2005-2017 at the county level in Jiangsu Province, China. Considering the spatial spillover and interaction effects, the factors influencing CEPC were analyzed by a hierarchical spatial autoregressive model. The results showed that the inequalities in CEPC first increased and then decreased at the inter-regional, and inter-county levels. The spatial pattern of CEPC was stable, and there was a significantly positive spatial autocorrelation of CEPC at the county level. The High-High type counties were mainly located in Sunan (southern Jiangsu). The spatial interaction effects of the CEPC between the prefecture and county levels indicated that governments at the prefecture level should integrate their county governments to reduce the CEPC. Moreover, carbon intensity, GDP per capita, land urbanization, and industrial structure play an important role in reducing CEPC. Our findings provide a scientific basis for formulating reasonable and effective carbon emission reduction policies.

HP3D-V2V: High-Precision 3D Object Detection Vehicle-to-Vehicle Cooperative Perception Algorithm.

Cooperative perception in the field of connected autonomous vehicles (CAVs) aims to overcome the inherent limitations of single-vehicle perception systems, including long-range occlusion, low resolution, and susceptibility to weather interference. In this regard, we propose a high-precision 3D object detection V2V cooperative perception algorithm. The algorithm utilizes a voxel grid-based statistical filter to effectively denoise point cloud data to obtain clean and reliable data. In addition, we design a feature extraction network based on the fusion of voxels and PointPillars and encode it to generate BEV features, which solves the spatial feature interaction problem lacking in the PointPillars approach and enhances the semantic information of the extracted features. A maximum pooling technique is used to reduce the dimensionality and generate pseudoimages, thereby skipping complex 3D convolutional computation. To facilitate effective feature fusion, we design a feature level-based crossvehicle feature fusion module. Experimental validation is conducted using the OPV2V dataset to assess vehicle coperception performance and compare it with existing mainstream coperception algorithms. Ablation experiments are also carried out to confirm the contributions of this approach. Experimental results show that our architecture achieves lightweighting with a higher average precision (AP) than other existing models.

Directed Surface Reconstruction of Fe Modified Co2VO4 Spinel Oxides for Water Oxidation Catalysts Experiencing Self-Terminating Surface Deterioration.

Affordable highly efficient catalysts for electrochemical oxygen evolution reaction (OER) play pivotal roles in green hydrogen production via water electrolysis. Regarding the non-noble metal-based electrocatalysts, considerable efforts are made to decipher the cation leaching and surface reconstruction; yet, little attention is focused on correlating them with catalytical activity and stability. Herein, in situ reconstruction of Fe-modified Co2VO4 precursor catalyst to form a highly active (Fe,V)-doped CoOOH phase for OER is reported, during which partial leaching of V accelerates the surface reconstruction and the V reserved in the reconstructed CoOOH layer in the form of alkali-resistant V2O3 serves for dynamic charge compensation and prevention of excessive loss of lattice oxygen and Co dissolution. Fe substitution facilitates Co pre-oxidation and endows the catalysts with structural flexibility by elevating O 2p band level; hence, encouraging participation of lattice oxygen in OER. The optimized Co2Fe0.25V0.75O4 electrode can afford current densities of 10 and 500 mA cm-2 at low overpotentials of 205 and 320 mV, respectively, with satisfactory stability over 600 h. By coupling with Pt/C cathode, the assembled alkaline electrolyzer can deliver 500 mA cm-2 at a low cell voltage of 1.798 V, better than that of commercial RuO2 (+) || Pt/C (-).

In situ reconstruction of self-supported NiFeP electrodes for overall water splitting at large current density.

In this study, self-supported NiFeP was fabricated on Ni mesh (NiFeP/NM) via a two-step monopulse electrodeposition and phosphorization strategy. The NiFeP/NM exhibited excellent activity through electrochemical surface reconstruction to generate true active sites, requiring low overpotentials of 349 mV and 310 mV to reach a current density of 500 mA cm-2 for the HER and OER, respectively, and exhibiting satisfactory stability in 6 M NaOH.

GABAergic/Glycinergic and Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes of STXBP1 Encephalopathy.

An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms ( Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as MUNC18-1; Verhage and Sørensen, 2020; John et al., 2021). STXBP1 is an essential protein for presynaptic neurotransmitter release. Its haploinsufficiency is the main disease mechanism and impairs both excitatory and inhibitory neurotransmitter release. However, the disease pathogenesis and cellular origins of the broad spectrum of neurological phenotypes are poorly understood. Here we generate cell type-specific Stxbp1 haploinsufficient male and female mice and show that Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons causes developmental delay, epilepsy, and motor, cognitive, and psychiatric deficits, recapitulating majority of the phenotypes observed in the constitutive Stxbp1 haploinsufficient mice and STXBP1 encephalopathy. In contrast, Stxbp1 haploinsufficiency in glutamatergic neurons results in a small subset of cognitive and seizure phenotypes distinct from those caused by Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons. Thus, the contrasting roles of excitatory and inhibitory signaling reveal GABAergic/glycinergic dysfunction as a key disease mechanism of STXBP1 encephalopathy and suggest the possibility to selectively modulate disease phenotypes by targeting specific neurotransmitter systems.

Zr-Based MOF-545 Metal-Organic Framework Loaded with Highly Dispersed Small Size Ni Nanoparticles for CO2 Methanation.

We report the use of Zr-based metal-organic frameworks (MOFs) MOF-545 and MOF-545(Cu) as supports to prepare catalysts with uniformly and highly dispersed Ni nanoparticles (NPs) for CO2 hydrogenation into CH4. In the first step, we studied the MOF support under catalytic conditions using operando diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, ex situ characterizations (PXRD, XPS, TEM, and EDX-element mapping), and DFT calculations. We showed that the high-temperature conditions undoubtedly confer a potential for catalytic functionality to the solids toward CH4 production, while no role of the Cu could be evidenced. The MOF was shown to be transformed into a catalytically active material, amorphized but still structured with dehydroxylated Zr-oxoclusters, in line with DFT calculations. In the second step, Ni@MOF-545 catalysts were prepared using either impregnation (IM) or double solvent (DS) methods, followed by a dry reduction (R) route under H2 to immobilize Ni NPs. The highest catalytic activity was obtained with the Ni@MOF-545 DS R catalyst (595 mmolCH4 gNi-1 h-1) with 100% CH4 selectivity and 60% CO2 conversion after ∼3 h. The higher catalytic activity of Ni@MOF-545 DS R is a result of much smaller (∼5 nm) and better dispersed Ni NPs than in the IM sample (20-40 nm), the latter exhibiting sintering. The advantages of the encapsulation of Ni NPs by the DS method and of the use of a MOF-545-based support are discussed, highlighting the interest of designing yet-unexplored Zr-based MOFs loaded with Ni NPs for CO2 hydrogenation.

Recurrent Cushing's Disease Caused by a TPIT-Lineage Densely Granulated Corticotroph Pituitary Neuroendocrine Tumor: A Case Report.

INTRODUCTION: Recurrent Cushing's disease (recurrent CD) is an uncommon and intricate clinical form of Cushing's syndrome. However, the connection between the pathological types of ACTH-secreting PitNETs and the clinical signs of recurrent CD remains uncertain. CASE DESCRIPTION: A 64-year-old woman, previously diagnosed with renal carcinoma, was admitted to our hospital due to recent weight gain. Previous endocrine tests indicated fluctuating hypercortisolemia and a recurrent pituitary tumor over the past six years. She underwent two transsphenoidal hypophysectomies, and histopathological analysis of the tumor revealed it as a densely granulated corticotroph tumor (DGCT), a subtype of TPIT-lineage PitNET, accompanied by tumor apoplexy. CONCLUSION: This case highlights the connection between recurrent CD and the pathological subtypes of TPIT-lineage DGCT-PitNETs.

Potentially Massive and Global Non-Pyrogenic Production of Condensed "Black" Carbon through Biomass Oxidation.

With the increased occurrences of wildfires worldwide, there has been an increase in scientific interest surrounding the chemistry of fire-derived "black" carbon (BC). Traditionally, wildfire research has assumed that condensed aromatic carbon (ConAC) is exclusively produced via combustion, and thus, ConAC is equated to BC. However, the lack of correlations between ConAC in soils or rivers and wildfire history suggests that ConAC may be produced non-pyrogenically. Here, we show quantitative evidence that this occurs during the oxidation of biomass with environmentally ubiquitous hydroxyl radicals. Pine wood boards exposed to iron nails and natural weather conditions for 12 years yielded a charcoal-like ConAC-rich material. ConAC was also produced during laboratory oxidations of pine, maple, and brown-rotted oak woods, as well as algae, corn root, and tree bark. Back-of-the-envelope calculations suggest that biomass oxidation could be producing massive non-pyrogenic ConAC fluxes to terrestrial and aquatic environments. These estimates (e.g., 163-182 Tg-ConAC/year to soils) are much higher than the estimated pyrogenic "BC" fluxes (e.g., 128 Tg-ConAC/year to soils) implying that environmental ConAC is primarily non-pyrogenic. This novel perspective suggests that wildfire research trajectories should shift to assessing non-pyrogenic ConAC sources and fluxes, developing new methods for quantifying true BC, and establishing a new view of ConAC as an intermediate species in the biogeochemical processing of biomass during soil humification, aquatic photochemistry, microbial degradation, or mineral-organic matter interactions. We also advise against using BC or pyrogenic carbon (pyC) terminologies for ConAC measured in environmental matrices, unless a pyrogenic source can be confidently assigned.

Danggui Shaoyao San protects cyclophosphamide-induced premature ovarian failure by inhibiting apoptosis and oxidative stress through the regulation of the SIRT1/p53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: It has been reported that apoptosis and oxidative stress are related to cyclophosphamide (CYC)-induced premature ovarian failure (POF). Therefore, anti-apoptotic and anti-oxidative stress treatments exhibit therapeutic efficacy in CYC-induced POF. Danggui Shaoyao San (DSS), which has been extensively used to treat gynecologic diseases, is found to inhibit apoptosis and reduce oxidative stress. However, the roles of DSS in regulating apoptosis and oxidative stress during CYC-induced POF, and its associated mechanisms are still unknown. AIM OF THE STUDY: This work aimed to investigate the roles and mechanisms of DSS in inhibiting apoptosis and oxidative stress in CYC-induced POF. MATERIALS AND METHODS: CYC (75 mg/kg) was intraperitoneally injected in mice to construct the POF mouse model for in vivo study. Thereafter, alterations of body weight, ovary morphology and estrous cycle were monitored to assess the ovarian protective properties of DSS. Serum LH and E2 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was employed for examining ovarian pathological morphology and quantifying follicles in various stages. Meanwhile, TUNEL staining and apoptosis-related proteins were adopted for evaluating apoptosis. Oxidative stress was measured by the levels of ROS, MDA, and 4-HNE. Western blot (WB) assay was performed to detect proteins related to the SIRT1/p53 pathway. KGN cells were used for in vitro experiment. TBHP stimulation was carried out for establishing the oxidative stress-induced apoptosis cell model. Furthermore, MTT assay was employed for evaluating the protection of DSS from TBHP-induced oxidative stress. The anti-apoptotic ability of DSS was evaluated by hoechst/PI staining, JC-1 staining, and apoptosis-related proteins. Additionally, the anti-oxidative stress ability of DSS was measured by detecting the levels of ROS, MDA, and 4-HNE. Proteins related to SIRT1/p53 signaling pathway were also measured using WB and immunofluorescence (IF) staining. Besides, SIRT1 expression was suppressed by EX527 to further investigate the role of SIRT1 in the effects of DSS against apoptosis and oxidative stress. RESULTS: In the in vivo experiment, DSS dose-dependently exerted its anti-apoptotic, anti-oxidative stress, and ovarian protective effects. In addition, apoptosis, apoptosis-related protein and oxidative stress levels were inhibited by DSS treatment. DSS treatment up-regulated SIRT1 and down-regulated p53 expression. From in vitro experiment, it was found that DSS treatment protected KGN cells from TBHP-induced oxidative stress injury. Besides, DSS administration suppressed the apoptosis ratio, apoptosis-related protein levels, mitochondrial membrane potential damage, and oxidative stress. SIRT1 suppression by EX527 abolished the anti-apoptotic, anti-oxidative stress, and ovarian protective effects, as discovered from in vivo and in vitro experiments. CONCLUSIONS: DSS exerts the anti-apoptotic, anti-oxidative stress, and ovarian protective effects in POF mice, and suppresses the apoptosis and oxidative stress of KGN cells through activating SIRT1 and suppressing p53 pathway.

Genomic analysis reveals the population structure and antimicrobial resistance of avian Pasteurella multocida in China.

OBJECTIVES: To investigate the population structure and antimicrobial resistance (AMR) of avian Pasteurella multocida in China. METHODS: Utilizing WGS analysis, we explored the phylogeny using a dataset of 546 genomes, comprising avian P. multocida isolates from China (n = 121), the USA (n = 165), Australia(n = 153), Bangladesh (n = 3) and isolates of other hosts from China (n = 104). We examined the integrative and conjugative element (ICE) structures and the distribution of their components carrying resistance genes, and reconstructed the evolutionary history of A:L1:ST129 (n = 110). RESULTS: The population structure of avian P. multocida in China was dominated by the A:L1:ST129 clone with limited genetic diversity. A:L1:ST129 isolates possessed a broader spectrum of resistance genes at comparatively higher frequencies than those from other hosts and countries. The novel putative ICEs harboured complex resistant clusters that were prevalent in A:L1:ST129. Bayesian analysis predicted that the A:L1:ST129 clone emerged around 1923, and evolved slowly. CONCLUSIONS: A:L1:ST129 appears to possess a host predilection towards avian species in China, posing a potential health threat to other animals. The complex AMR determinants coupled with high frequencies may strengthen the population dominance of A:L1:ST129. The extensive antimicrobial utilization in poultry farming and the mixed rearing practices could have accelerated AMR accumulation in A:L1:ST129. ICEs, together with their resistant clusters, significantly contribute to resistance gene transfer and facilitate the adaptation of A:L1:ST129 to ecological niches. Despite the genetic stability and slow evolution rate, A:L1:ST129 deserves continued monitoring due to its propensity to retain resistance genes, warranting global attention to preclude substantial economic losses.

Effectiveness of the Stress Process Model-Based Program in Dementia Caregiving (DeCare-SPM) for Family Caregivers: A Study Protocol for a Randomized Controlled Trial.

This paper aims to describe a randomized controlled trial protocol evaluating the effectiveness, cost, and process of a stress process model-based program in dementia caregiving (DeCare-SPM) for family caregivers. Family caregivers of individuals with dementia will be recruited from memory clinics and community settings and randomly assigned to either DeCare-SPM or usual care. DeCare-SPM comprises three face-to-face sessions (ie, problem-based coping, emotion-based coping, meaning-based coping), and a fourth session (ie, social support) including weekly telephone-based consultation for four weeks and then monthly face-to-face boosters. Outcomes will be measured at baseline (T0), and at one (T1), three (T2), and six months (T3). The primary outcome is positive aspects of caregiving and secondary outcomes are caregiving (ie, sense of competence, caregiver burden, social support, anxiety, depression, and quality of life), dementia-related (ie, care dependency, neuropsychiatric symptoms, and quality of life), and stress-related biomarkers of blood and saliva. In addition, process and economic evaluations will be performed. Mixed-effects models will be used to assess intervention effects. Content analysis will be performed on the qualitative data. This paper described the protocol for comprehensive evaluation of the effectiveness, cost, and process of the theory-driven DeCare-SPM to inform how and why interventions work. It highlights the need to reduce challenges and enhance the positive aspects of dementia care. The DeCare-SPM will provide evidence-based insights into how to support and empower family caregivers in their important roles, thereby, leading to improved dementia care.