Insights into tissue accumulation, depletion, and health risk assessment of clopidol in poultry.

Clopidol is extensively used in livestock farming and residues of this antibiotic can persist in animal tissues, posing a risk to humans and the environment. In this study, we investigated the depletion of clopidol in various edible tissues of chickens (muscle, liver, kidney, fat, and eggs) using liquid chromatography-tandem mass spectrometry after the administration of a clopidol-contaminated diet (at 250 mg kg-1 for the high (1x) dose). After 14 d of exposure, the clopidol concentrations were highest in eggs (median: 9.83 mg/kg), followed by liver (3.56 mg/kg), kidney (3.01 mg/kg), muscle (1.56 mg/kg), and fat (0.727 mg/kg) at low exposure group, indicating that clopidol accumulated primarily in eggs rather than the other edible tissues. In addition, the maternal transfer ratios were estimated, and the transfer efficiencies of clopidol in muscle (egg-to-tissue ratio, ETR:1.81) and fat (2.06-58.2) were higher than those in liver (0.731-31.1) and kidney (0.832-38.9). Furthermore, we conducted a cumulative risk assessment for clopidol in edible chicken tissues using the hazard quotient (HQ) method. This assessment revealed that the exposure levels for Korean consumers pose an acceptable risk. However, for eggs from the 1x dose exposure group, the HQ values were greater than 1 for all age groups, particularly for young children (<18 y), suggesting that the higher daily consumption of eggs combined with the higher clopidol residues in eggs resulted in higher HQ values, which requires further attention. The findings of this study can assist in the management and monitoring of clopidol residues in chicken tissues and eggs.

Meta-analysis of Palliative Care on End-stage Quality of Life in Cancer Patients.

Objective: This study aimed to investigate the impact of palliative care on the quality of life, depressive state, and physical and psychological symptoms of patients with end-stage cancer. Methods: A systematic literature search of PubMed, Embase, and Scopus databases was conducted for randomized controlled trials (RCTs) published from May 2000 to June 2023, focusing on the impact of palliative care on end-stage cancer patients. The search utilized terms such as "palliative care," "cancer/tumor/malignancy," "terminal/end-stage/advanced," to identify studies meeting our inclusion criteria. Selected RCTs were evaluated for quality, and relevant data were extracted for meta-analysis. Results: Meta-analysis of 16 RCTs revealed that palliative care significantly improved depressive states [OR=-0.88, 95%CI (-1.55, -0.20), P = .01] and alleviated physical and psychological symptoms [OR=-2.38, 95%CI (-3.95, -0.81), P = .003] in end-stage cancer patients compared to conventional oncology care. However, the improvement in overall quality of life was not statistically significant (P > .05). Conclusion: Palliative care significantly enhances the mental and physical well-being of end-stage cancer patients by reducing depressive states and symptom burden, although its impact on overall quality of life requires further exploration.

Risk assessment of exposure to 12 kinds of mycotoxins through consumption of Pericarpium Citri Reticulatae collected from Three Gorges Reservoir area of China.

A method for simultaneous determination of 12 mycotoxins in Pericarpium Citri Reticulataeby HPLC-MS/MS was established to analyze the residues of mycotoxins, inwhich from Three Gorges Reservoir area of China, including AFB1, AFB2, AFG1, AFG2, T-2, FB1, FB2, FB3, ZEN, OTA, OTB and DON.In addition, a probabilistic assessment model based on Monte Carlo simulation method was established in combination with pollution data, and the health risk assessment was carried out by the exposure limit method (MOE).The results showed that the method with strong specificity, good linearity and accurate recovery was established and could be used for the determination of 12 mycotoxins in Pericarpium Citri Reticulatae.In general, the total pollution rate of different degrees of pollution in the 36 batches of Pericarpium Citri Reticulatae sampleswas 75 %. It should be noted thatthe proportion of positive samplescontaminated by one toxin was the highest (59.26 %), and the detection rate of FB3 in Pericarpium Citri Reticulataewas the highest (66.67%), followed by AFG1 (44.44 %), indicating that the medicinal material polluted by AFG1 and AFB3 alone or simultaneously was more serious. Specifically, the detection rate of mycotoxins in Chongqing was the highest (92.31%) on account of the high temperature and humidity in Chongqing, followed by Southeast of Sichuan (83.33%) and West of Hubei (45.45%).On the other hand, the MOE of AFB1 and AFB2 calculated were both greater than 10000, indicating that the health risk of AFB1 and AFB2 exposure caused by taking Pericarpium Citri Reticulatae was low, but the risk of high intake population was higher than that of conventional intake population, which needed to be paid attention to. This study can provide a reference for the safety assessment of clinical medication of Pericarpium Citri Reticulatae inThree Gorges Reservoir area.

Effects of enzymatic hydrolysis technology on the physicochemical properties and biological activities of American ginseng beverages.

American ginseng (Panax quinquefolius L.) contains various biological macromolecules, such as polysaccharides, saponins, and proteins, which have various pharmacological activities, including antioxidant, anti-inflammatory, and hypoglycemic effects. Consequently, the utilization of novel processing technologies developed an American ginseng beverage to meet people's health needs and the preferences of young people. This study was the first to use American ginseng as a primary raw material, utilizing a three-step enzymatic hydrolysis approach with cellulase, pectinase, amylase, maltase, and flavor protease enzymes to prepare an American ginseng beverage. The basic nutritional and active ingredient contents of the product were determined. The antioxidant activity of enzymatic beverages was evaluated by calculating the free radical clearance rates of DPPH and ABTS, and the effect of enzymatic beverages on α-glucosidase activity was also tested. The anti-inflammatory activity of RAW264.7 cells induced by LPS was evaluated by measuring the production of NO, TNF-α, and IL-6 during the enzymatic hydrolysis process. The results indicated that the nutritional components of American ginseng beverage products met the beverage industry standards. Moreover, the application of enzymatic hydrolysis technology had improved the antioxidant and anti-inflammatory activities of American ginseng beverages. In addition, the enzymatic beverage of American ginseng exhibited certain hypoglycemic activity. Consequently, the established enzymatic hydrolysis technology provided a reference for the production of other beverage products.

A novel hybrid model for species distribution prediction using neural networks and Grey Wolf Optimizer algorithm.

Neural networks are frequently employed to model species distribution through backpropagation methods, known as backpropagation neural networks (BPNN). However, the complex structure of BPNN introduces parameter settings challenges, such as the determination of connection weights, which can affect the accuracy of model simulation. In this paper, we integrated the Grey Wolf Optimizer (GWO) algorithm, renowned for its excellent global search capacity and rapid convergence, to enhance the performance of BPNN. Then we obtained a novel hybrid algorithm, the Grey Wolf Optimizer algorithm optimized backpropagation neural networks algorithm (GNNA), designed for predicting species' potential distribution. We also compared the GNNA with four prevalent species distribution models (SDMs), namely the generalized boosting model (GBM), generalized linear model (GLM), maximum entropy (MaxEnt), and random forest (RF). These models were evaluated using three evaluation metrics: the area under the receiver operating characteristic curve, Cohen's kappa, and the true skill statistic, across 23 varied species. Additionally, we examined the predictive accuracy concerning spatial distribution. The results showed that the predictive performance of GNNA was significantly improved compared to BPNN, was significantly better than that of GLM and GBM, and was even comparable to that of MaxEnt and RF in predicting species distributions with small sample sizes. Furthermore, the GNNA demonstrates exceptional powers in forecasting the potential non-native distribution of invasive plant species.

A PAM hydrogel surface-coated hydroponic bamboo evaporator with efficient thermal utilization for solar evaporation.

Solar-driven interfacial water purification emerges as a sustainable technology for seawater desalination and wastewater treatment to address the challenge of water scarcity. Currently, the energy losses via radiation and convection to surrounding environment minimize its energy efficiency. Therefore, it is necessary to develop strategies to minimize the heat losses for efficient water purification. Here, a novel evaporator was developed through the in situ gelation of PAM hydrogel on the surface carbonized hydroponic bamboo (PSC) to promote energy efficiency. The inherent porous and layered network structures of bamboo, in synergy with the functional hydration capacity of PAM hydrogel, facilitated adequate water transportation, while reducing evaporation enthalpy. The PAM hydrogel firmly covered on the photothermal layer surface effectively minimized the radiation and convection heat losses, while further harvesting those thermal energy that would otherwise dissipate into the surrounding environment. The reduced thermal conductivity of PSC served as a thermal insulator as well, obstructing heat transfer to bulk water and thus diminishing conduction losses. Consequently, the rational designed PSC could efficiently convert solar energy to purified water, leading to the evaporation of 2.09 kg m-2 h-1, the energy efficiency of 87.6 % under one sun irradiation, and yielding 9.6 kg m-2 fresh water over 11 h outdoor operation. Moreover, the PSC also performs excellent salt rejection, and long-term stability at outdoor experiment. These results demonstrated high and stable solar evaporation performance could be achieved if turning heat losses into a way of extra energy extraction to further enhance the evaporation performance. This strategy appears to be a promising strategy for effective thermal energy management and practical application.

Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway.

The current study aimed to assess the effectiveness of pharmacological intervention with Platycodin D (PD), a critically active compound isolated from the roots of Platycodon grandiflorum, in mitigating cardiotoxicity in a murine model of type 2 diabetes-induced cardiac injury and in H9c2 cells in vitro. Following oral administration for 4 weeks, PD (2.5 mg/kg) significantly suppressed the elevation of fasting blood glucose (FBG) levels, improved dyslipidemia, and effectively inhibited the rise of the cardiac injury markers creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT). PD treatment could ameliorate energy metabolism disorders induced by impaired glucose uptake by activating AMPK protein expression in the DCM mouse model, thereby promoting the GLUT4 transporter and further activating autophagy-related proteins. Furthermore, in vitro experiments demonstrated that PD exerted a concentration-dependent increase in cell viability while also inhibiting palmitic acid and glucose (HG-PA)-stimulated H9c2 cytotoxicity and activating AMPK protein expression. Notably, the AMPK activator AICAR (1 mM) was observed to upregulate the expression of AMPK in H9c2 cells after high-glucose and -fat exposure. Meanwhile, we used AMPK inhibitor Compound C (20 µM) to investigate the effect of PD activation of AMPK on cells. In addition, the molecular docking approach was employed to dock PD with AMPK, revealing a binding energy of -8.2 kcal/mol and indicating a tight interaction between the components and the target. PD could reduce the expression of autophagy-related protein p62, reduce the accumulation of autophagy products, promote the flow of autophagy, and improve myocardial cell injury. In conclusion, it has been demonstrated that PD effectively inhibits cardiac injury-induced type 2 diabetes in mice and enhances energy metabolism in HG-PA-stimulated H9c2 cells by activating the AMPK signaling pathway. These findings collectively unveil the potential cardioprotective effects of PD via modulation of the AMPK signaling pathway.

Restoring thalamocortical circuit dysfunction by correcting HCN channelopathy in Shank3 mutant mice.

Thalamocortical (TC) circuits are essential for sensory information processing. Clinical and preclinical studies of autism spectrum disorders (ASDs) have highlighted abnormal thalamic development and TC circuit dysfunction. However, mechanistic understanding of how TC dysfunction contributes to behavioral abnormalities in ASDs is limited. Here, our study on a Shank3 mouse model of ASD reveals TC neuron hyperexcitability with excessive burst firing and a temporal mismatch relationship with slow cortical rhythms during sleep. These TC electrophysiological alterations and the consequent sensory hypersensitivity and sleep fragmentation in Shank3 mutant mice are causally linked to HCN2 channelopathy. Restoring HCN2 function early in postnatal development via a viral approach or lamotrigine (LTG) ameliorates sensory and sleep problems. A retrospective case series also supports beneficial effects of LTG treatment on sensory behavior in ASD patients. Our study identifies a clinically relevant circuit mechanism and proposes a targeted molecular intervention for ASD-related behavioral impairments.

Generation of transgene-free canker-resistant Citrus sinensis cv. Hamlin in the T0 generation through Cas12a/CBE co-editing.

Citrus canker disease affects citrus production. This disease is caused by Xanthomonas citri subsp. citri (Xcc). Previous studies confirmed that during Xcc infection, PthA4, a transcriptional activator like effector (TALE), is translocated from the pathogen to host plant cells. PthA4 binds to the effector binding elements (EBEs) in the promoter region of canker susceptibility gene LOB1 (EBEPthA4-LOBP) to activate its expression and subsequently cause canker symptoms. Previously, the Cas12a/CBE co-editing method was employed to disrupt EBEPthA4-LOBP of pummelo, which is highly homozygous. However, most commercial citrus cultivars are heterozygous hybrids and more difficult to generate homozygous/biallelic mutants. Here, we employed Cas12a/CBE co-editing method to edit EBEPthA4-LOBP of Hamlin (Citrus sinensis), a commercial heterozygous hybrid citrus cultivar grown worldwide. Binary vector GFP-p1380N-ttLbCas12a:LOBP1-mPBE:ALS2:ALS1 was constructed and shown to be functional via Xcc-facilitated agroinfiltration in Hamlin leaves. This construct allows the selection of transgene-free regenerants via GFP, edits ALS to generate chlorsulfuron-resistant regenerants as a selection marker for genome editing resulting from transient expression of the T-DNA via nCas9-mPBE:ALS2:ALS1, and edits gene(s) of interest (i.e., EBEPthA4-LOBP in this study) through ttLbCas12a, thus creating transgene-free citrus. Totally, 77 plantlets were produced. Among them, 8 plantlets were transgenic plants (#HamGFP1 - #HamGFP8), 4 plantlets were transgene-free (#HamNoGFP1 - #HamNoGFP4), and the rest were wild type. Among 4 transgene-free plantlets, three lines (#HamNoGFP1, #HamNoGFP2 and #HamNoGFP3) contained biallelic mutations in EBEpthA4, and one line (#HamNoGFP4) had homozygous mutations in EBEpthA4. We achieved 5.2% transgene-free homozygous/biallelic mutation efficiency for EBEPthA4-LOBP in C. sinensis cv. Hamlin, compared to 1.9% mutation efficiency for pummelo in a previous study. Importantly, the four transgene-free plantlets and 3 transgenic plantlets that survived were resistant against citrus canker. Taken together, Cas12a/CBE co-editing method has been successfully used to generate transgene-free canker-resistant C. sinensis cv. Hamlin in the T0 generation via biallelic/homozygous editing of EBEpthA4 of the canker susceptibility gene LOB1.

Oral-gut microbial transmission promotes diabetic coronary heart disease.

BACKGROUND: Diabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic coronary heart disease (DCHD). Simultaneously, we aim to establish a causal link between the diabetes-driven oral-gut microbiota axis and increased susceptibility to diabetic myocardial ischemia-reperfusion injury (MIRI). METHODS: We comprehensively investigated the microbial landscape in the oral and gut microbiota in DCHD using a discovery cohort (n = 183) and a validation chohort (n = 68). Systematically obtained oral (tongue-coating) and fecal specimens were subjected to metagenomic sequencing and qPCR analysis, respectively, to holistically characterize the microbial consortia. Next, we induced diabetic MIRI by administering streptozotocin to C57BL/6 mice and subsequently investigated the potential mechanisms of the oral-gut microbiota axis through antibiotic pre-treatment followed by gavage with specific bacterial strains (Fusobacterium nucleatum or fecal microbiota from DCHD patients) to C57BL/6 mice. RESULTS: Specific microbial signatures such as oral Fusobacterium nucleatum and gut Lactobacillus, Eubacterium, and Roseburia faecis, were identified as potential microbial biomarkers in DCHD. We further validated that oral Fusobacterium nucleatum and gut Lactobacillus are increased in DCHD patients, with a positive correlation between the two. Experimental evidence revealed that in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage indicated by TTC, HE, TUNEL staining, all of which contributed to exacerbated MIRI. CONCLUSION: Our findings not only uncover dysregulation of the oral-gut microbiota axis in diabetes patients but also highlight the pivotal intermediary role of the increased abundance of oral F. nucleatum and gut Lactobacillus in exacerbating MIRI. Targeting the oral-gut microbiota axis emerges as a potent strategy for preventing and treating DCHD. Oral-gut microbial transmission constitutes an intermediate mechanism by which diabetes influences myocardial injury, offering new insights into preventing acute events in diabetic patients with coronary heart disease.

Integrated Full-Length Transcriptomics and Metabolomics Reveal Glycosyltransferase Involved in the Biosynthesis of Flavonol Glycosides in Laportea bulbifera.

Many species of the Urticaceae family are important cultivated fiber plants that are known for their economic and industrial values. However, their secondary metabolite profiles and associated biosynthetic mechanisms have not been well-studied. Using Laportea bulbifera as a model, we conducted widely targeted metabolomics, which revealed 523 secondary metabolites, including a unique accumulation of flavonol glycosides in bulblet. Through full-length transcriptomic and RNA-seq analyses, the related genes in the flavonoid biosynthesis pathway were identified. Finally, weighted gene correlation network analysis and functional characterization revealed four LbUGTs, including LbUGT78AE1, LbUGT72CT1, LbUGT71BX1, and LbUGT71BX2, can catalyze the glycosylation of flavonol aglycones (kaempferol, myricetin, gossypetin, and quercetagetin) using UDP-Gal and UDP-Glu as the sugar donors. LbUGT78AE1 and LbUGT72CT1 showed substrate promiscuity, whereas LbUGT71BX1 and LbUGT71BX2 exhibited different substrate and sugar donor selectivity. These results provide a genetic resource for studying Laportea in the Urticaceae family, as well as key enzymes responsible for the metabolism of valuable flavonoid glycosides.

Multi-omics analysis reveals promiscuous O-glycosyltransferases involved in the diversity of flavonoid glycosides in Periploca forrestii (Apocynaceae).

Flavonoid glycosides are widespread in plants, and are of great interest owing to their diverse biological activities and effectiveness in preventing chronic diseases. Periploca forrestii, a renowned medicinal plant of the Apocynaceae family, contains diverse flavonoid glycosides and is clinically used to treat rheumatoid arthritis and traumatic injuries. However, the mechanisms underlying the biosynthesis of these flavonoid glycosides have not yet been elucidated. In this study, we used widely targeted metabolomics and full-length transcriptome sequencing to identify flavonoid diversity and biosynthetic genes in P. forrestii. A total of 120 flavonoid glycosides, including 21 C-, 96 O-, and 3 C/O-glycosides, were identified and annotated. Based on 24,123 full-length coding sequences, 99 uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) were identified and classified into 14 groups. Biochemical assays revealed that four UGTs exhibited O-glycosyltransferase activity toward apigenin and luteolin. Among them, PfUGT74B4 and PfUGT92A8 were highly promiscuous and exhibited multisite O-glycosylation or consecutive glycosylation activities toward various flavonoid aglycones. These four glycosyltransferases may significantly contribute to the diversity of flavonoid glycosides in P. forrestii. Our findings provide a valuable genetic resource for further studies on P. forrestii and insights into the metabolic engineering of bioactive flavonoid glycosides.

[Photochemical Mechanism and Control Strategy Optimization for Summertime Ozone Pollution in Yining City].

To explore the formation mechanism of the ozone （O3） and emission reduction strategy in a northwestern city， an extensive field campaign was conducted in summertime in 2021 in Yining City， in which the 0-D box model incorporating the latest explicit chemical mechanism （MCMv3.3.1） was applied for the first time to quantify the O3-NOx-VOCs sensitivity and formulate a precise O3 control strategy in this city. The results showed that： ① the three indicators ï¼»i.e.， O3 formation potential （OFP）， ·OH reaction rate （k·OH）， and relative incremental reactivity （RIR）］ jointly indicated that alkenes， oxygenated volatile organic compounds （OVOCs）， and aromatics were the highest contributors among anthropogenic volatile organic compounds （AVOC） to O3 formation， and the contribution of biogenic volatile organic compounds （BVOC） also could not be ignored. Additionally， the results based on RIR calculation implied that that the acetaldehyde， ethylene， and propylene were the most sensitive individual VOCs species in Yining City. ② The in-situ photochemical O3 variations were primarily influenced by the local photochemical production and export process horizontally to downwind areas or vertically to the upper layer， and the reaction pathways of HO2·+ NO and ·OH + NO2 contributed the most to the gross Ox photochemical production （60%） and photochemical destruction production （53%）， respectively. Hence， the reduction in local emissions for O3 precursors was more essential to alleviate O3 pollution in this city. ③ The outcome based on RIR（NOx） / RIR（AVOC） and EKMA jointly suggested that the photochemical regime in this city can be considered a transitional regime that was also nearly a VOCs-limited regime. Detailed mechanism modeling based on multiple scenarios further suggested that the NOx and VOCs synergic emission reduction strategies was helpful to alleviate O3 pollution. These results are useful to provide policy-related guidance for other cities facing similar O3 pollution in northwest China.

miR-34b-3p-mediated regulation of STC2 and FN1 enhances chemosensitivity and inhibits proliferation in cervical cancer.

Dysregulation of microRNA (miRNA) expression in cancer is a significant factor contributing to the progression of chemoresistance. The objective of this study is to explore the underlying mechanisms by which miR-34b-3p regulates chemoresistance in cervical cancer (CC). Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues. In this study, we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin (DDP). Subsequently, miR-34b-3p mimics are transfected into SiHa/DDP cells. It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation, migration, and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death. Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2 and FN1 in SiHa/DDP cells, contrary to the expression pattern of miR-34b-3p. Moreover, STC2 and FN1 contribute to DDP resistance, proliferation, migration, invasion, and decreased apoptosis in CC cells. Through dual-luciferase assay analysis, we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC. Finally, rescue experiments demonstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance, proliferation, migration and invasion in CC cells. In conclusion, our findings support the role of miR-34b-3p as a tumor suppressor in CC. This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.

Identification of flavor peptides based on virtual screening and molecular docking from Hypsizygus marmoreuss.

Hypsizygus marmoreuss is an under-explored source of flavor peptides that can enhance the flavor of NaCl or MSG, allowing products to be reformulated in line with reduction policies. This study utilized advanced techniques, including UPLC-Q-TOF MS/MS and molecular docking, to identify H. marmoreuss peptides. Sensory evaluations revealed 10 peptides with pronounced umami flavors and seven with dominantly salty tastes. VLPVPQK scored highest for umami intensity (5.2), and EGNPAHQK for salty intensity (6.2). Further investigation influenced by 0.35 % MSG or 0.35 % NaCl exposed peptides with elevated umami and salty thresholds. LDSPATPEK, VVEGEPSLK, and QKLPEKPER had umami-enhancing thresholds of 0.18, 0.18, and 0.35 mM, while LDSPATPEK and VVEGEPSLK had similar thresholds for salt (0.09 mM). Molecular docking revealed that taste receptor proteins interacted with umami peptides through hydrogen, carbon-hydrogen, alkyl, and van der Waals forces. Specific amino acids in the umami receptor T1R1 had roles in bonding with umami peptides through hydrogen and carbon-hydrogen interactions. In conclusion, molecular docking proved to be an effective and efficient method for flavor peptide screening. Further, this study demonstrated that flavor peptides from H. marmoreuss had the capacity to enhance NaCl and MSG flavours and might be useful tools for reformulation, reducing salt and MSG contents.

Novel Pathogenic Mutation of P209L in TRPC6 Gene Causes Adult Focal Segmental Glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a leading kidney disease, clinically associated with proteinuria and progressive renal failure. The occurrence of this disease is partly related to gene mutations. We describe a single affected family member who presented with FSGS. We used high-throughput sequencing, sanger sequencing to identify the pathogenic mutations, and a systems genetics analysis in the BXD mice was conducted to explore the genetic regulatory mechanisms of pathogenic genes in the development of FSGS. We identified high urinary protein (++++) and creatinine levels (149 µmol/L) in a 29-year-old male diagnosed with a 5-year history of grade 2 hypertension. Histopathology of the kidney biopsy showed stromal hyperplasia at the glomerular segmental sclerosis and endothelial cell vacuolation degeneration. Whole-exome sequencing followed by Sanger sequencing revealed a heterozygous missense mutation (c.643C > T) in exon 2 of TRPC6, leading to the substitution of arginine with tryptophan at position 215 (p.Arg215Trp). Systems genetics analysis of the 53 BXD mice kidney transcriptomes identified Pygm as the upstream regulator of Trpc6. Those two genes are jointly involved in the regulation of FSGS mainly via Wnt and Hippo signaling pathways. We present a novel variant in the TRPC6 gene that causes FSGS. Moreover, our data suggested TRPC6 works with PYGM, as well as Wnt and Hippo signaling pathways to regulate renal function, which could guide future clinical prevention and targeted treatment for FSGS outcomes.

Dentin surface modification by MDP to improve dentin bonding stability: Topological enhancement and mineralization of collagen structure in hybrid layers.

Decades of research have been conducted on 10-Methacryloyloxydecyl dihydrogen phosphate (MDP) through numerous studies. The mechanisms by which its residual calcium salts benefit dentin bonding remain undetermined. The objective of the research was to investigate the role and process of remaining calcium salts in the priming procedure and their capacity for remineralization. The investigation focused on the variations in topological structure, mechanical properties, and chemical interactions between the main agent and the dentin surface. Two adhesive modes including prime-and-rinse(P&R) and prime-and-nonrinse (P&NR) utilized to evaluate the bonding performance and remineralization ability. The findings indicated that both P&R and P&NR methods could eliminate the smear-layer, uncover dentinal-tubules, and generate a textured/rough surface on the dentin. Collagen fibrils exhibited a greater presence of inorganic minerals in the P&NR mode. Compared to control group, both P&R and P&NR groups improved immediate and aging bond strength significantly (P < 0.05). AFM and 3D-STORM revealed MDP and its residual calcium salts distributed in collagen fibrils and expanded collagen matrix. In the P&NR group, TEM revealed that the dentin collagen matrix experienced some remineralization, and there was also mineralization within the collagen fibrils embedded in the bonding interface. Thus, MDP priming improved dentin bonding stability. Residual calcium salts of P&NR process can enhance topological structure of the collagen matrix and induce intrafibrillar mineralization.

Analysis of etiology and clinical features of spontaneous downbeat nystagmus: a retrospective study.

Objective: To investigate the topical diagnosis, possible etiology and mechanism of spontaneous downbeat nystagmus (sDBN) patients with dizziness/vertigo. Methods: The clinical features of dizziness/vertigo patients accompanied with DBN were retrospectively reviewed in the Vertigo Center of our hospital from January 2018 to March 2021. The clinical features of dizziness/vertigo patients accompanied with DBN were reviewed. Comprehensive VNG, bithermal caloric testing, video-head-impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP), head magnetic resonance imaging (MRI), three-dimensional fluid-attenuated incersion recovery magnetic resonance imaging (3D-FLAIR MRI) in the inner ear, serum immunology and other examinations were to determine the lesion site, and analyze its possible etiology and mechanism. Results: A total of 54 patients were included. Among them, 70.4% (n = 38) of DBN patients were diagnosed with episodic vestibular syndrome (EVS), 22.2% (n = 12) with chronic vestibular syndrome (CVS), and 7.4% (n = 4) with acute vestibular syndrome (AVS). Among all the patients, 51.9% of DBN patients had clear etiology, with central lesions of 29.6% and peripheral diseases of 22.2%. The most common diseases in DBN patients were cerebellar lesions (13.0%, n = 7) and vestibular migraine (13.0%, n = 7), followed by benign positional paroxysmal vertigo (7.4%, n = 4) and drug-related dizziness/vertigo (5.6%, n = 3). The other 48.1% of the patients had unknown etiology. 53.8% (14/26) of patients with idiopathic DBN had decreased semicircular canal function, with 42.9% (6/14) decreased posterior semicircular canal function. The posterior semicircular canal gain in DBN patients decreased compared to the anterior semicircular canal in the same conjugate plane. Patients with peripheral DBN were more prone to horizontal/torsional nystagmus during positional testing. Conclusion: In our study, DBN patients have a relative decrease in posterior semicircular canal gain, which is possibly a particular result found in a subset of downbeat nystagmus patients. The changes in nystagmus during positional testing may be helpful in distinguishing between peripheral and central causes.

Turn-on Near-Infrared Phosphorescent Recognition of Anion Based on Self-Assembly of Cyclometalated Platinum Complexes That Induce Oncosis and Monitor Living Cells.

The design of bio-responsive functional molecular materials that can undergo self-assembly to form nanostructures within cells in response to cellular endogenous stimuli and the clarification of their prospective reaction mechanisms are of paramount significance. This work aims to elucidate the spatiotemporal generation of subcellular nanostructures and their influence on cellular functionality. Three sets of cyclometalated platinum complexes have been designed and synthesized as near-infrared phosphorescent turn-on probes for specific anions based on dynamic self-assembly in aqueous solution. The augmentation of the quantity of aromatic rings in the NN bidentate ligand of the complex modifies both the intensity of the intermolecular Pt-Pt interaction and the capacity to generate self-assembled nanowires with near-infrared emission. Besides, we explored the impact of the CN ligand's substituent effect on anion recognition, which revealed that complexes with electron-absorbing F atom substitution exhibit superior selectivity for Br-. These complexes display vivid green turn-on luminescence upon interaction with cellular biomolecules, enabling dynamic monitoring of their subcellular distribution and their interaction on diverse conditions. Furthermore, our complexes were observed to induce oncosis in cancer cells, underscoring the potential of our work in facilitating in vitro diagnosis and developing effective theranostic agents for cancer therapy.

Economic level, environmental regulation, and new energy industry development.

Using panel data of 30 provinces and new energy (NE)-listed enterprises in China from 2011 to 2020, this paper uses basic model to research the impact of various environmental policies in China on NE industry development firstly. Then, using economic level as a threshold variable, a threshold model was constructed to research the impact of economic level on the relationship between environmental regulation and NE industry development. The research results show that firstly, various environmental policies in China have significantly promoted the development of the NE industry. This is mainly manifested in two aspects. One is environmental regulations significantly increased the NE industry output value and profit, the other is environmental regulations enhanced the NE industry growth potential. Secondly, the regional economic level has a significant impact on the relationship between environmental regulations and NE industry development. The promotion effect of environmental regulations on NE industry development depends on the regional economic level. When the regional economic level exceeds the threshold, the promoting effect of environmental regulations on NE industry development significantly increases. The reason is that a weak economic foundation will affect investment in the NE industry. Insufficient capital investment will inevitably seriously hinder the development of the NE industry. Thirdly, residents' education status, financial support, and NE industry agglomeration degree have a positive impact on the development of the NE industry, while population size has no significant impact on NE industry development.