Formononetin Alleviates Ischemic Acute Kidney Injury by Regulating Macrophage Polarization through KLF6/STAT3 Pathway.

Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-[Formula: see text], and IL-1[Formula: see text]) and macrophage infiltration into the kidneys of AKI mice. In vitro studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-[Formula: see text]. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.

A novel molecular pathway of lipid accumulation in human hepatocytes caused by PFOA and PFOS.

Exposed to ubiquitously perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with non-alcoholic fatty liver disease (NAFLD), yet the underlying molecular mechanism remains elusive. The extrapolation of empirical studies correlating per- and polyfluoroalkyl substance (PFAS) exposure with NAFLD occurrence to real-life exposure was hindered by the limited availability of mechanistic data at environmentally relevant concentrations. Herein, a novel pathway mediating hepatocyte lipid accumulation by PFOA and PFOS at human-relevant dose (<10 µM) was identified by integrating CRISPR-Cas9 genome screening, concentration-dependent transcriptional assay in HepG2 cell and epidemiological data mining. 1) At genetic level, nudt7 showed the highest enriched potency among 569 NAFLD-related genes, and the transcription of nudt7 was significantly downregulated by PFOA and PFOS exposure (<7 µM). 2) At molecular pathway, upon exposure to ≤10-4 µM PFOA and PFOS, the downregulation of nudt7 transcriptional expression triggered the reduction of Ace-CoA hydrolase activity. 3) At cellular level, increased lipids were measured in HepG2 cells with PFOA and PFOS (<2 µM). Overall, we identified a novel mechanism mediated by transcriptional downregulation of nudt7 gene in hepatocellular lipid increase treated with PFOA and PFOS, which could potentially explain the NAFLD occurrence associated with exposure to PFASs in humans.

Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex.

The ring-shaped Cohesin complex, consisting of core subunits Smc1, Smc3, Scc1, and SA2 (or its paralog SA1), topologically entraps two duplicated sister DNA molecules to establish sister chromatid cohesion in S-phase. It remains largely elusive how the Cohesin release factor Wapl binds the Cohesin complex, thereby inducing Cohesin disassociation from mitotic chromosomes to allow proper resolution and separation of sister chromatids. Here, we show that Wapl uses two structural modules containing the FGF motif and the YNARHWN motif, respectively, to simultaneously bind distinct pockets in the extensive composite interface between Scc1 and SA2. Strikingly, only when both docking modules are mutated, Wapl completely loses the ability to bind the Scc1-SA2 interface and release Cohesin, leading to erroneous chromosome segregation in mitosis. Surprisingly, Sororin, which contains a conserved FGF motif and functions as a master antagonist of Wapl in S-phase and G2-phase, does not bind the Scc1-SA2 interface. Moreover, Sgo1, the major protector of Cohesin at mitotic centromeres, can only compete with the FGF motif but not the YNARHWN motif of Wapl for binding Scc1-SA2 interface. Our data uncover the molecular mechanism by which Wapl binds Cohesin to ensure precise chromosome segregation.

Beneficial effects of duck-derived lactic acid bacteria on growth performance and meat quality through modulation of gut histomorphology and intestinal microflora in Muscovy ducks.

Duck-derived lactic acid bacteria (DDL) are a crucial beneficial bacterium in the intestines, contributing significantly to the health of ducks. However, the mechanism by which these DDL improves the growth performance and meat quality of Muscovy duck is not clear. In this study, A total of 800 male Muscovy ducks, initially weighing 50.15 ± 5.37 g, were randomly allocated into 4 groups, each with 4 replicates, consisting of 50 ducks per replicate. The control group consumed deep well water, while the experimental groups were given water supplemented with 1%, 3%, and 5% DDL (1.59×108 CFU/mL). The study duration was 70 d. The results revealed that Muscovy ducks drinks with the DDL significant reduced the feed conversion ratio (FCR) (P < 0.05) and increased the sweetness and richness of duck meat, among which the 5% drinking group has the most significant difference. Further study finding, the DDL significantly increased the height of villi, the ratio of villi height/crypt depth (V/C) on jejunum and colon, and the ratio of acidic mucus, neutral mucus, and glycogen to tissue area in both the duodenum and ileum of Muscovy ducks, and significantly decreased the tunel positive cells. Moreover, DDL significantly enhanced the abundance of genus beneficial bacterium (Bacillus, lentilactobacillus, Bacterodies, Lactobacillus) on duodenum and ileum. Additionally, drink with the DDL elevated the level of IgG in blood and the immune indices of the thymus and the fabricius bursa (P<0.05). Meanwhile, the meat composition analysis demonstrated that Muscovy duck drinks with the DDL raised the level of the saturated fatty acid rate(C12:0), and polyunsaturated fatty acid (C18:2 n-6 and C20:5 n-3,), and the monounsaturated (C18:1 n-7, and C18:1 n-9). Furthermore, correlation analysis finding that the growth performance of Muscovy ducks was positively correlated with the height of villi, the ratio of villi height/crypt depth (V/C), the abundance of genus beneficial bacterium. And the meat quality of Muscovy ducks has positively correlated with genus beneficial bacterium in intestinal, glutamic acid, saturated fatty acid rate and polyunsaturated fatty acid. This finding suggest DDL is an effective strategy to improve the growth performance and meat quality of Muscovy ducks by gut histomorphology and intestinal microflora.

Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.

Optimization of Quartz Sand-Enhanced Coagulation for Sewage Treatment by Response Surface Methodology.

The quartz sand-enhanced coagulation (QSEC) is an improved coagulation method for treating water, which uses quartz sand as a heavy medium to accelerate the sedimentation rate of flocs and reduce the sedimentation time. The factors that influence the QSEC effect and can be controlled manually include the quartz sand dosage, coagulant dosage, sewage pH, stirring time, settling time, etc., and their reasonable setting is critical to the result of water treatment. This paper aimed to study the optimal conditions of QSEC; first, single-factor tests were conducted to explore the optimal range of influencing factors, followed by response surface methodology (RSM) tests to accurately determine the optimum values of significant factors. The results show that the addition of quartz sand did not improve the water quality of the coagulation treatment, it took only 140 s for the floc to sink to the bottom, and the sediment volume only accounted for 12.2% of the total sewage. The quartz sand dosage, the coagulant dosage, and sewage pH all had a significant impact on the coagulation effect, and resulted in inflection points. A QSEC-guiding model was derived through RSM tests, and subsequent model optimization and experimental validation revealed the optimal conditions for treating domestic sewage as follows: the polyaluminum chloride (PAC) dosage, cationic polyacrylamide (CPAM) dosage, the sewage pH, quartz sand dosage, stirring time, and settling time were 0.97 g/L, 2.25 mg/L, 7.22, 2 g/L, 5 min, and 30 min, respectively, and the turbidity of the treated sewage was reduced to 1.15 NTU.

Lycium barbarum polysaccharides regulate the gut microbiota to modulate metabolites in high-fat diet-induced obese rats.

Lycium Barbarum Polysaccharides (LBP) can benefit lipid parameters such as total cholesterol, triglyceride, and high-density lipoprotein levels and upregulate the level of Firmicutes, increase the diversity of gut microbiota and reduce metabolic disorders, finally relieving weight gain of obese rats. But it cannot reverse the outcome of obesity. Over 30 differential metabolites and four pathways are altered by LBP.

A non-canonical role of the inner kinetochore in regulating sister-chromatid cohesion at centromeres.

The 16-subunit Constitutive Centromere-associated Network (CCAN)-based inner kinetochore is well-known for connecting centromeric chromatin to the spindle-binding outer kinetochore. Here, we report a non-canonical role for the inner kinetochore in directly regulating sister-chromatid cohesion at centromeres. We provide biochemical, X-ray crystal structure, and intracellular ectopic localization evidence that the inner kinetochore directly binds cohesin, a ring-shaped multi-subunit complex that holds sister chromatids together from S-phase until anaphase onset. This interaction is mediated by binding of the 5-subunit CENP-OPQUR sub-complex of CCAN to the Scc1-SA2 sub-complex of cohesin. Mutation in the CENP-U subunit of the CENP-OPQUR complex that abolishes its binding to the composite interface between Scc1 and SA2 weakens centromeric cohesion, leading to premature separation of sister chromatids during delayed metaphase. We further show that CENP-U competes with the cohesin release factor Wapl for binding the interface of Scc1-SA2, and that the cohesion-protecting role for CENP-U can be bypassed by depleting Wapl. Taken together, this study reveals an inner kinetochore-bound pool of cohesin, which strengthens centromeric sister-chromatid cohesion to resist metaphase spindle pulling forces.

De novo transcriptome assembly database for 100 tissues from each of seven species of domestic herbivore.

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.

Association between childhood obesity and gut microbiota: 16S rRNA gene sequencing-based cohort study.

BACKGROUND: This study aimed to identify characteristic gut genera in obese and normal-weight children (8-12 years old) using 16S rDNA sequencing. The research aimed to provide insights for mechanistic studies and prevention strategies for childhood obesity. Thirty normal-weight and thirty age- and sex-matched obese children were included. Questionnaires and body measurements were collected, and fecal samples underwent 16S rDNA sequencing. Significant differences in body mass index (BMI) and body-fat percentage were observed between the groups. Analysis of gut microbiota diversity revealed lower α-diversity in obese children. Di-fferences in gut microbiota composition were found between the two groups. Prevotella and Firmicutes were more abundant in the obese group, while Bacteroides and Sanguibacteroides were more prevalent in the control group. AIM: To identify the characteristic gut genera in obese and normal-weight children (8-12-year-old) using 16S rDNA sequencing, and provide a basis for subsequent mechanistic studies and prevention strategies for childhood obesity. METHODS: Thirty each normal-weight, 1:1 matched for age and sex, and obese children, with an obese status from 2020 to 2022, were included in the control and obese groups, respectively. Basic information was collected through questionnaires and body measurements were obtained from both obese and normal-weight children. Fecal samples were collected from both groups and subjected to 16S rDNA sequencing using an Illumina MiSeq sequencing platform for gut microbiota diversity analysis. RESULTS: Significant differences in BMI and body-fat percentage were observed between the two groups. The Ace and Chao1 indices were significantly lower in the obese group than those in the control group, whereas differences were not significant in the Shannon and Simpson indices. Kruskal-Wallis tests indicated significant differences in unweighted and weighted UniFrac distances between the gut microbiota of normal-weight and obese children (P < 0.01), suggesting substantial disparities in both the species and quantity of gut microbiota between the two groups. Prevotella, Firmicutes, Bacteroides, and Sanguibacteroides were more abundant in the obese and control groups, respectively. Heatmap results demonstrated significant differences in the gut microbiota composition between obese and normal-weight children. CONCLUSION: Obese children exhibited lower α-diversity in their gut microbiota than did the normal-weight children. Significant differences were observed in the composition of gut microbiota between obese and normal-weight children.

Duck compound probiotics fermented diet alters the growth performance by shaping the gut morphology, microbiota and metabolism.

Dietary absorption and digestion are influenced by the microbiota, morphology, and digestive enzymes of intestines, and fermentation is a popular and effective technique to enhance animal rearing growth performance. This study aims to explore the pivotal role of Muscovy duck probiotics fermented feedstuff (FF) in altering the growth performance by reshaping gut morphology, microorganisms and metabolism. The findings showed that FF considerably raised the levels of fatty acids (FA) and small peptides (7-19AA) in the diet. Further feeding trial data reveals that FF greatly increased the Muscovy duck average daily gain (ADG) but had no effect on their daily feed intake (DFI), and the FCR significantly dropped (P < 0.05). Additionally, it was evident that FF improved the integrity of the intestinal mucosa in Muscovy duck by increasing villus height, villus height-to-crypt depth ratio, and lowering crypt depth. Then, in comparison to the control group (NC), there was a significant increase in the gene expression of the mucosal tight junction proteins Occludin, Claudin-1, and Zo-1 in the intestine of Muscovy duck. Additionally, there was higher expression of the mucosal transport channels SGLT-1, PepT1, AQP2, AQP3, and AQP10 in the similarly colon site, jejunum, and duodenum. Furthermore, in AB-PAS/PAS-stained duodenum, jejunum, ileum, and similarly colon site, FF markedly increased relative mucus output and goblet cells while decreasing epithelial cell apoptosis. Following 16S sequencing data indicated that the intestinal microbiota was altered and the diversity and richness of gut microbes was greatly enhanced by FF. Particularly, the boost of core probiotics, such as Rothia of duodenum, Limosilactobacillus and Lentilactobacillus of jejunum, Lactococcus and Rothia of ileum, Ligilactobacillus and Entocuccus of similarly colon site, Gallibacterium of caecum. And reduced potentially pathogenic bacteria (Campylobacter, Prevotellaceae, Clostridia-vadinBB60, and Oscillospira). Nontargeted metabolomics assay for intestinal content confirmed an increased organic acids (oxidanesulfonic acid, cholic acid, gallic acid, coumaric acid, pipecollc acid, 13s-hydroxyoctadecadienoic acid) and glycosides metabolites (5-hydroxydantrolene, 3-hydroxyguanfacine glucuronide, acetylleucine, astragalin, xanthosine, taxiphylin, sinapine, denudatine, penylalanyl-tyrosine and phenylalanyl-valine). These findings demonstrated that FF, a viable option to improve Muscovy duck growth performance through reconstructed intestinal morphology, microorganisms, and metabolism, subsequently promoted the gut health and increased diet digestion and absorption. The study that is being presented offers scientific proof that FF might be a useful strategy for improving Muscovy duck growth performance.

Changes in health-promoting metabolites associated with high-altitude adaptation in honey.

The levels of metabolites in honey are influenced by floral origin, production region, and bee species. However, how environmental factors affect honey quality remains unclear. Based on untargeted metabolomics and using UPLC Q-Orbitrap MS, we analyzed 3596 metabolites in 51 honey samples from Yunnan and Shennongjia. Comparative analysis revealed that geniposidic acid, kynurenic acid and caffieine accumulated at significantly different levels between Shennongjia and Yunnan honey. Based on cluster structure analysis, 36 Yunnan honey samples were divided into two distinct groups by altitude. Notably, quercetin, hyperoside, taxifolin, rutin, tryptophan, astragalin and phenylalanine were higher levels in high-altitude honey (>1700 m), whereas abscisic acid was higher levels in low-altitude honey (≤1700 m). Among these, significantly elevated levels of hyperoside, taxfolin, astragalin, and tryptophan were observed in honey collected from high-altitude areas in Shennongjia. Our findings highlight the effect of altitude on honey health-promoting components, providing valuable insights into honey quality.

Bifurcation of bound states in the continuum in periodic structures.

In lossless dielectric structures with a single periodic direction, a bound state in the continuum (BIC) is a special resonant mode with an infinite quality factor (Q factor). The Q factor of a resonant mode near a typical BIC satisfies Q∼1/(ß-ß ∗)2, where ß and ß ∗ are the Bloch wavenumbers of the resonant mode and the BIC, respectively. However, for some special BICs with ß ∗=0 (referred to as super-BICs by some authors), the Q factor satisfies Q ∼ 1/ß6. Although super-BICs are usually obtained by merging a few BICs through tuning a structural parameter, they can be precisely characterized by a mathematical condition. In this Letter, we consider arbitrary perturbations to structures supporting a super-BIC. The perturbation is given by δF(r), where δ is the amplitude and F(r) is the perturbation profile. We show that for a typical F(r), the BICs in the perturbed structure exhibit a pitchfork bifurcation around the super-BIC. The number of BICs changes from one to three as δ passes through zero. However, for some special profiles F(r), there is no bifurcation, i.e., there is only a single BIC for δ around zero. In that case, the super-BIC is not associated with a merging process for which δ is the parameter.

[Effects of Combined Stress of High Density Polyethylene Microplastics and Chlorimuron-ethyl on Soybean Growth and Rhizosphere Bacterial Community].

With the vigorous development of agriculture in China， plastic mulch film and pesticides are widely used in agricultural production. However， the accumulation of microplastics （formed by the degradation of plastic mulch film） and pesticides in soil has also caused many environmental problems. At present， the environmental biological effects of microplastics or pesticides have been reported， but there are few studies on the combined effects on crop growth and the rhizosphere soil bacterial community. Therefore， in this study， the high density polyethylene microplastics （HDPE， 500 mesh） were designed to be co-treated with sulfonylurea herbicide chlorimuron-ethyl to study their effects on soybean growth. In addition， the effects of the combined stress of HDPE and chlorimuron-ethyl on soybean rhizosphere soil bacterial community diversity， structure composition， microbial community network， and soil function were investigated using high-throughput sequencing technology， interaction network， and PICRUSt2 function analysis to clarify the combined toxicity of HDPE and chlorimuron-ethyl to soybean. The results showed that the half-life of chlorimuron-ethyl in soil was prolonged by the 1% HDPE treatment （from 11.5 d to 14.3 d）， and the combined stress of HDPE and chlorimuron-ethyl had more obvious inhibition effects on soybean growth than that of the single pollutant or control. The HiSeq 2 500 sequencing showed that the rhizosphere bacterial community of soybean was composed of 20 phyla and 312 genera under combined stress， the number of phyla and genera was significantly less than that of the control and single pollutant treatment， and the relative abundances of bacteria with potential biological control and plant growth-promoting characteristics （such as Nocardioides and Sphingomonas） were reduced. Alpha diversity analysis showed that the combined stress significantly reduced the richness and diversity of the soybean rhizosphere bacterial community， and Beta diversity analysis showed that the combined stress significantly changed the structure of the bacterial community. The dominant flora of the rhizosphere bacterial community were regulated， and the abundances of secondary functional layers such as amino acid metabolism， energy metabolism， and lipid metabolism were reduced under combined stress by the analysis of LEfSe and PICRUSt2. It was inferred from the network analysis that the combined stress of HDPE and chlorimuron-ethyl reduced the total number of connections and network density of soil bacteria， simplified the network structure， and changed the important flora species to maintain the stability of the network. The results above indicated that the combined stress of HDPE and chlorimuron-ethyl significantly affected the growth of soybean and changed the rhizosphere bacterial community structure， soil function， and network structure. Compared with that of the single pollutant treatment， the potential risk of combined stress was greater. The results of this study can provide guidance for evaluating the ecological risks of polyethylene microplastics and chlorimuron-ethyl and for the remediation of contaminated soil.

Diagnostic performance of intravascular ultrasound-based fractional flow reserve in evaluating of intermediate left main stenosis.

BACKGROUND: The recently introduced ultrasonic flow ratio (UFR), is a novel fast computational method to derive fractional flow reserve (FFR) from intravascular ultrasound (IVUS) images. In the present study, we evaluate the diagnostic performance of UFR in patients with intermediate left main (LM) stenosis. METHODS: This is a prospective, single center study enrolling consecutive patients with presence of intermediated LM lesions (diameter stenosis of 30%-80% by visual estimation) underwent IVUS and FFR measurement. An independent core laboratory assessed offline UFR and IVUS-derived minimal lumen area (MLA) in a blinded fashion. RESULTS: Both UFR and FFR were successfully achieved in 41 LM patients (mean age, 62.0 ± 9.9 years, 46.3% diabetes). An acceptable correlation between UFR and FFR was identified (r = 0.688, P < 0.0001), with an absolute numerical difference of 0.03 (standard difference: 0.01). The area under the curve (AUC) in diagnosis of physiologically significant coronary stenosis for UFR was 0.94 (95% CI: 0.87-1.01), which was significantly higher than angiographic identified stenosis > 50% (AUC = 0.66, P < 0.001) and numerically higher than IVUS-derived MLA (AUC = 0.82; P = 0.09). Patient level diagnostic accuracy, sensitivity and specificity for UFR to identify FFR ≤ 0.80 was 82.9% (95% CI: 70.2-95.7), 93.1% (95% CI: 82.2-100.0), 58.3% (95% CI: 26.3-90.4), respectively. CONCLUSION: In patients with intermediate LM diseases, UFR was proved to be associated with acceptable correlation and high accuracy with pressure wire-based FFR as standard reference. The present study supports the use of UFR for functional evaluation of intermediate LM stenosis.

Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

Penthorum chinense Pursh inhibits ferroptosis in cellular and Caenorhabditis elegans models of Alzheimer's disease.

BACKGROUND: Ferroptosis, a unique type of cell death triggered by iron-dependent lipid peroxidation, plays a critical role in the pathogenesis of Alzheimer's disease (AD), a debilitating condition marked by memory loss and cognitive impairment due to the accumulation of beta-amyloid (Aß) and hyperphosphorylated Tau protein. Increasing evidence suggests that inhibitors of ferroptosis could be groundbreaking in the treatment of AD. METHOD: In this study, we established in vitro ferroptosis using erastin-, RSL-3-, hemin-, and iFSP1-induced PC-12 cells. Using MTT along with Hoechst/PI staining, we assessed cell viability and death. To determine various aspects of ferroptosis, we employed fluorescence probes, including DCFDA, JC-1, C11 BODIPY, Mito-Tracker, and PGSK, to measure ROS production, mitochondrial membrane potential, lipid peroxidation, mitochondrial morphology, and intracellular iron levels. Additionally, Western blotting, biolayer interferometry technology, and shRNA were utilized to investigate the underlying molecular mechanisms. Furthermore, p-CAX APP Swe/Ind- and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, along with Caenorhabditis elegans (C. elegans) strains CL4176, CL2331, and BR5270, were employed to examine ferroptosis in AD models. RESULTS: Here, we conducted a screening of our natural medicine libraries and identified the ethanol extract of Penthorum chinense Pursh (PEE), particularly its ethyl acetate fraction (PEF), displayed inhibitory effects on ferroptosis in cells. Specifically, PEF inhibited the generation of ROS, lipid peroxidation, and intracellular iron levels. Furthermore, PEF demonstrated protective effects against H2O2-induced cell death, ROS production, and mitochondrial damage. Mechanistic investigations unveiled PEF's modulation of intracellular iron accumulation, GPX4 expression and activity, and FSP1 expression. In p-CAX APP Swe/Ind and pRK5-EGFP-Tau P301L overexpressing PC-12 cells, PEF significantly reduced cell death, as well as ROS and lipid peroxidase production. Moreover, PEF ameliorated paralysis and slowing rate in Aß and Tau transgenic C. elegans models, while inhibiting ferroptosis, as evidenced by decreased DHE intensity, lipid peroxidation levels, iron accumulation, and expression of SOD-3 and gst-4. CONCLUSION: Our findings highlight the suppressive effects of PEF on ferroptosis in AD cellular and C. elegans models. This study helps us better understand how ferroptosis affects AD and emphasizes the potential of PCP as a candidate for AD intervention.

A multifactorial study of mass movement in the hilly and gully Loess Plateau based on intensive field surveys and remote sensing techniques.

Mass movements, driven by various non-linearly correlated factors, exhibit high randomness, posing vast difficulties for field observations and subsequent investigations into the underlying mechanisms. In this study 157 mass movement incidents (including collapses, slump and spalling) and their primary influencing factors were surveyed in a small catchment of the hilly and gully Loess Plateau, China, through intensive field investigations and remote sensing techniques. The spatial pattern of mass movement and its relation with the influencing factors were assessed, while the relative impact of different factors was studied using the canonical correlation analysis. Results showed that 1) Mass movements predominantly occurred on gully slopes steeper than 70°. Collapses were the main type of mass movement, accounting for 87.9 % of the number of samples. 2) With regard to the impact of individual factors, rainstorms (rainfall intensity >50 mm day-1) significantly enhanced the occurrence frequency, erosion area and erosion volume of mass movement. The occurrence frequency and erosion area / volume were highest at a soil dry bulk density of 1.34 g cm-3 and 1.54 g cm-3, respectively. Mass movement occurred most frequently on unvegetated or unrooted gully slopes, where the resisting effect of vegetation on mass movement was absent. Gully slopes with smooth rather than rugged profiles were also found to be typical areas of mass movement. The occurrence frequency of mass movement decreased with the elevated topographic wetness index (TWI) and distance to slope top and increased with the distance to channels. 3) For the relative impact of different factors, rainfall and shear strength were key factors facilitating and resisting the onset of mass movement, respectively, while topography exerted the greatest influence on the erosion area and volume. This study revealed the relative influence of different factors on occurrence and scale of mass movement, providing a useful reference for modelling and control of the problem.

Fluorescence emission mechanism for the π-conjugated zwitterion 2,4-Bisimidazolylphenol base on ESIPT: A TDDFT theoretical reconsideration.

Molecules with zwitterionic characteristics exhibit significant potential for utilization in nonlinear optics, optoelectronics, and organic lasers owing to their large dipole moments. Recently, the synthesized compound 2,4-bis (4,5-diphenyl-1H-imidazol-2-yl) phenol (2,4-bImP) by Sakai et al. has been noticed for its unique photochromic properties in solvents [J. Phys. Chem. A, 125 (2021), 4784-4792]. The observed fluorescence in chloroform was attributed to the keto tautomer. Based on the excited state intramolecular proton transfer, the photochromism of 2,4-bImP in chloroform was interpreted as zwitterion production. However, the zwitterion with a specific electronic structure can be in resonance with the conventional neutral structure. The impact of the resonance contribution from the zwitterion and the conventional neutral structure on fluorescence attribution was not taken into account in the previous studies. In this investigation, the ESIPT mechanism of the 2,4-bImP in chloroform has been explored using both the density functional theory and the time-dependent density functional theory. The optimized geometric configuration parameters illustrate the molecular resonant properties. The calculated fluorescence spectra on the basis of the optimization results further corroborate that the fluorescence peaks after proton transfer originates from the resonance of the zwitterionic and the neutral configuration. The zwitterionic nature of the molecule was demonstrated by electrostatic potential and atomic dipole modified Hesfeld atomic charge (ADCH) analysis. Furthermore, the characterization of potential energy curves and IR spectrum further verified the resonance of both the zwitterionic and neutral structures. The results reveal that the 2,4-bImP molecule generates the neutral o-quinoid structure and the zwitterionic structure resonance phenomenon following ESIPT. The aforementioned resonance structure offers novel insights into the ascription of fluorescence. These discoveries establish the theoretical foundation for the exploration and development of zwitterions.

Genome-Wide Identification of bZIP Transcription Factors in Cymbidium ensifolium and Analysis of Their Expression under Low-Temperature Stress.

The basic leucine zipper (bZIP) transcription factors constitute the most widely distributed and conserved eukaryotic family. They play crucial roles in plant growth, development, and responses to both biotic and abiotic stresses, exerting strong regulatory control over the expression of downstream genes. In this study, a genome-wide characterization of the CebZIP transcription factor family was conducted using bioinformatic analysis. Various aspects, including physicochemical properties, phylogenetics, conserved structural domains, gene structures, chromosomal distribution, gene covariance relationships, promoter cis-acting elements, and gene expression patterns, were thoroughly analyzed. A total of 70 CebZIP genes were identified from the C. ensifolium genome, and they were randomly distributed across 18 chromosomes. The phylogenetic tree clustered them into 11 subfamilies, each exhibiting complex gene structures and conserved motifs arranged in a specific order. Nineteen pairs of duplicated genes were identified among the 70 CebZIP genes, with sixteen pairs affected by purifying selection. Cis-acting elements analysis revealed a plethora of regulatory elements associated with stress response, plant hormones, and plant growth and development. Transcriptome and qRT-PCR results demonstrated that the expression of CebZIP genes was universally up-regulated under low temperature conditions. However, the expression patterns varied among different members. This study provides theoretical references for identifying key bZIP genes in C. ensifolium that confer resistance to low-temperature stress, and lays the groundwork for further research into their broader biological functions.