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Abstract Carbon-based metal-free catalysts are promising green catalysts for photocatalysis and electrocatalysis due to their low cost and environmental friendliness. A key challenge in utilizing these catalysts is identifying their active sites, given their poor crystallinity and complex structures. Here we demonstrate the key structure of the double-bonded conjugated carbon group as a metal-free active site, enabling efficient O2 photoreduction to H2O2 through a cascaded water oxidation − O2 reduction process. Using ethylenediaminetetraacetic acid as a precursor, we synthesized various carbon-based photocatalysts and analyzed their structural evolution. Under the polymerization conditions of 260 °C to 400 °C, an N-ethyl-2-piperazinone-like structure was formed on the surface of the catalyst, resulting in high photocatalytic H2O2 photoproduction (2884.7 μmol g−1h−1) under visible light. A series of control experiments and theoretical calculations further confirm that the double-bond conjugated carbonyl structure is the key and universal feature of the active site of metal-free photocatalysts.

Cardiometabolic diseases (CMD) are leading causes of death and disability worldwide, with complex pathophysiological mechanisms in which inflammation plays a crucial role. This review aims to elucidate the molecular and cellular mechanisms within the inflammatory microenvironment of atherosclerosis, hypertension and diabetic cardiomyopathy. In atherosclerosis, oxidized low-density lipoprotein (ox-LDL) and pro-inflammatory cytokines such as Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) activate immune cells contributing to foam cell formation and arterial wall thickening. Hypertension involves the activation of the renin-angiotensin system (RAS) alongside oxidative stress-induced endothelial dysfunction and local inflammation mediated by T cells. In diabetic cardiomyopathy, a high-glucose environment leads to the accumulation of advanced glycation end products (AGEs), activating the Receptor for Advanced Glycation Endproducts (RAGE) and triggering inflammatory responses that further damage cardiac and microvascular function. In summary, the inflammatory mechanisms in different types of metabolic cardiovascular diseases are complex and diverse; understanding these mechanisms deeply will aid in developing more effective individualized treatment strategies.

BackgroundMetabolic abnormalities are closely tied to the development of ovarian cancer (OC), yet the relationship between anthropometric indicators as risk indicators for metabolic abnormalities and OC lacks consistency.MethodThe Mendelian randomization (MR) approach is a widely used methodology for determining causal relationships. Our study employed summary statistics from the genome-wide association studies (GWAS), and we used inverse variance weighting (IVW) together with MR-Egger and weighted median (WM) supplementary analyses to assess causal relationships between exposure and outcome. Furthermore, additional sensitivity studies, such as leave-one-out analyses and MR-PRESSO were used to assess the stability of the associations.ResultThe IVW findings demonstrated a causal associations between 10 metabolic factors and an increased risk of OC. Including “Basal metabolic rate” (OR= 1.24, P= 6.86×10-4); “Body fat percentage” (OR= 1.22, P= 8.20×10-3); “Hip circumference” (OR= 1.20, P= 5.92×10-4); “Trunk fat mass” (OR= 1.15, P= 1.03×10-2); “Trunk fat percentage” (OR= 1.25, P= 8.55×10-4); “Waist circumference” (OR= 1.23, P= 3.28×10-3); “Weight” (OR= 1.21, P= 9.82×10-4); “Whole body fat mass” (OR= 1.21, P= 4.90×10-4); “Whole body fat-free mass” (OR= 1.19, P= 4.11×10-3) and “Whole body water mass” (OR= 1.21, P= 1.85×10-3).ConclusionSeveral metabolic markers linked to altered fat accumulation and distribution are significantly associated with an increased risk of OC.

This study examines the economic and environmental impacts of green production practices among farmers. It aims to contribute to sustainable agricultural development, mitigate agricultural non-point source (NPS) pollution, and align environmental protection with economic growth. This paper utilizes survey data from 1345 farm households in the main rice production areas of Jiangxi Province, China, using the example of reduced fertilizer application (RFA) among rice farmers. This study constructs a slack-based measure data envelopment analysis (DEA—SBM) model with undesirable outputs to measure environmental effects and applies an endogenous switching regression model (ESRM) to test the economic and environmental effects of farmers’ adoption of green production technologies. We found the following: (1) The RFA behavior of farmers has a significant positive impact on their net profit per hectare (NPH), helping farmers increase their income, with the increase ranging from 2.05% to 6.54%. (2) Farmers’ RFA behavior has a significant positive impact on agricultural green productivity (AGP), contributing to the improvement of the environment, ranging from 44.09% to 45.35%. (3) A heterogeneity analysis found inconsistencies in the income-enhancing and environmental-enhancing effects at different quantiles of NPH and AGP. Therefore, attention should be placed on improving the agricultural product quality supervision system under the market circulation mechanism, creating land scale conditions conducive to the promotion and application of fertilizer reduction technologies and promoting the implementation of externality internalization compensation systems.

Abstract Despite the accumulating evidence linking the development of Alzheimer’s disease (AD) to the aggregation of Aβ peptides and the emergence of Aβ oligomers, the FDA has approved very few anti-aggregation-based therapies over the past several decades. Here, we report the discovery of an Aβ peptide aggregation inhibitor: an ultra-small nanodot called C3N. C3N nanodots alleviate aggregation-induced neuron cytotoxicity, rescue neuronal death, and prevent neurite damage in vitro. Importantly, they reduce the global cerebral Aβ peptides levels, particularly in fibrillar amyloid plaques, and restore synaptic loss in AD mice. Consequently, these C3N nanodots significantly ameliorate behavioral deficits of APP/PS1 double transgenic male AD mice. Moreover, analysis of critical tissues (e.g., heart, liver, spleen, lung, and kidney) display no obvious pathological damage, suggesting C3N nanodots are biologically safe. Finally, molecular dynamics simulations also reveal the inhibitory mechanisms of C3N nanodots in Aβ peptides aggregation and its potential application against AD.

Abstract Background The ring-shaped cohesin complex is an important factor for the formation of chromatin loops and topologically associating domains (TADs) by loop extrusion. However, the regulation of association between cohesin and chromatin is poorly understood. In this study, we use super-resolution imaging to reveal the unique role of cohesin subunit RAD21 in cohesin loading and chromatin structure regulation. Results We directly visualize that up-regulation of RAD21 leads to excessive chromatin loop extrusion into a vermicelli-like morphology with RAD21 clustered into foci and excessively loaded cohesin bow-tying a TAD to form a beads-on-a-string-type pattern. In contrast, up-regulation of the other four cohesin subunits results in even distributions. Mechanistically, we identify that the essential role of RAD21 is attributed to the RAD21-loader interaction, which facilitates the cohesin loading process rather than increasing the abundance of cohesin complex upon up-regulation of RAD21. Furthermore, Hi-C and genomic analysis reveal how RAD21 up-regulation affects genome-wide higher-order chromatin structure. Accumulated contacts are shown at TAD corners while inter-TAD interactions increase after vermicelli formation. Importantly, we find that in breast cancer cells, the expression of RAD21 is aberrantly high with poor patient survival and RAD21 forms beads in the nucleus. Up-regulated RAD21 in HeLa cells leads to compartment switching and up-regulation of cancer-related genes. Conclusions Our results provide key insights into the molecular mechanism by which RAD21 facilitates the cohesin loading process and provide an explanation to how cohesin and loader work cooperatively to promote chromatin extrusion, which has important implications in construction of three-dimensional genome organization.

Abstract Nasopharyngeal carcinoma (NPC) is a common head and neck malignant with a high incidence in Southern China. Genetic aberrations play a vital role in the pathogenesis, progression and prognosis of NPC. In the present study, we elucidated the underlying mechanism of FAS-AS1 and its genetic variation rs6586163 in NPC. We demonstrated that FAS-AS1 rs6586163 variant genotype carriers were associated with lower risk of NPC (CC vs. AA, OR = 0.645, P = 0.006) and better overall survival (AC + CC vs. AA, HR = 0.667, P = 0.030). Mechanically, rs6586163 increased the transcriptional activity of FAS-AS1 and contributed to ectopic overexpression of FAS-AS1 in NPC. rs6586163 also exhibited an eQTL trait and the genes affected by rs6586163 were enriched in apoptosis related signaling pathway. FAS-AS1 was downregulated in NPC tissues and over-expression of FAS-AS1 was associated with early clinical stage and better short-term treatment efficacy for NPC patients. Overexpression of FAS-AS1 inhibited NPC cell viability and promoted cell apoptosis. GSEA analysis of RNA-seq data suggested FAS-AS1 participate in mitochondria regulation and mRNA alternative splicing. Transmission electron microscopic examination verified that the mitochondria was swelled, the mitochondrial cristae was fragmented or disappeared, and their structures were destroyed in FAS-AS1 overexpressed cells. Furthermore, we identified HSP90AA1, CS, BCL2L1, SOD2 and PPARGC1A as the top 5 hub genes of FAS-AS1 regulated genes involved in mitochondria function. We also proved FAS-AS1 could affect Fas splicing isoform sFas/mFas expression ratio, and apoptotic protein expression, thus leading to increased apoptosis. Our study provided the first evidence that FAS-AS1 and its genetic polymorphism rs6586163 triggered apoptosis in NPC, which might have a potential as new biomarkers for NPC susceptibility and prognosis.

BackgroundPrevious observational studies have investigated the association between endocrine and metabolic factors and idiopathic pulmonary fibrosis (IPF), yet have produced inconsistent results. Therefore, it is imperative to employ the Mendelian randomization (MR) analysis method to conduct a more comprehensive investigation into the impact of endocrine and metabolic factors on IPF.MethodsThe instrumental variables (IVs) for 53 endocrine and metabolic factors were sourced from publicly accessible genome-wide association study (GWAS) databases, with GWAS summary statistics pertaining to IPF employed as the dependent variables. Causal inference analysis encompassed the utilization of three methods: inverse-variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analysis incorporated the implementation of MR-PRESSO and leave-one-out techniques to identify potential pleiotropy and outliers. The presence of horizontal pleiotropy and heterogeneity was evaluated through the MR-Egger intercept and Cochran’s Q statistic, respectively.ResultsThe IVW method results reveal correlations between 11 traits and IPF. After correcting for multiple comparisons, seven traits remain statistically significant. These factors include: “Weight” (OR= 1.44; 95% CI: 1.16, 1.78; P=8.71×10-4), “Body mass index (BMI)” (OR= 1.35; 95% CI: 1.13, 1.62; P=1×10-3), “Whole body fat mass” (OR= 1.40; 95% CI: 1.14, 1.74; P=1.72×10-3), “Waist circumference (WC)” (OR= 1.54; 95% CI: 1.16, 2.05; P=3.08×10-3), “Trunk fat mass (TFM)” (OR=1.35; 95% CI: 1.10,1.65; P=3.45×10-3), “Body fat percentage (BFP)” (OR= 1.55; 95% CI: 1.15,2.08; P=3.86×10-3), “Apoliprotein B (ApoB)” (OR= 0.78; 95% CI: 0.65,0.93; P=5.47×10-3). Additionally, the sensitivity analysis results confirmed the reliability of the MR results.ConclusionThe present study identified causal relationships between seven traits and IPF. Specifically, ApoB exhibited a negative impact on IPF, while the remaining six factors demonstrated a positive impact. These findings offer novel insights into the underlying etiopathological mechanisms associated with IPF.

BackgroundThe existing literature on the relationship of hyperparathyroidism with both blood counts and biochemical indicators primarily comprises observational studies, which have produced inconsistent findings. This study aimed to evaluate the causal relationship between hyperparathyroidism and blood counts and biochemical indicators.MethodsMendelian randomization (MR) analyses were conducted to investigate the associations between hyperparathyroidism and the identified 55 blood counts and biochemical indicators. The genome-wide association study (GWAS) for hyperparathyroidism data was obtained from FinnGen, while the GWASs for the blood counts and biochemical indicators were sourced from the UK Biobank (UKBB).ResultsThe MR analysis using the inverse-variance weighted (IVW) method revealed potential causality between genetically predicted hyperparathyroidism and seven out of 55 blood counts and biochemical indicators. These markers include “Platelet count” (Beta = -0.041; 95% CI: -0.066, -0.016; p = 0.001), “Platelet distribution width (PDW)” (Beta = 0.031; 95% CI: 0.006, 0.056; p = 0.016), “Mean platelet volume (MPV)” (Beta = 0.043; 95% CI: 0.010, 0.076; p = 0.011), “Vitamin D” (Beta = -0.038; 95% CI: -0.063, -0.013; p = 0.003), “Calcium (Ca2+)” (Beta = 0.266; 95% CI: 0.022, 0.509; p = 0.033), “Phosphate” (Beta = -0.114; 95% CI: -0.214, -0.014; p = 0.025), and “Alkaline phosphatase (ALP)” (Beta = 0.030; 95% CI: 0.010, 0.049; p = 0.003).ConclusionThe findings of our study revealed a suggestive causal relationship between hyperparathyroidism and blood cell count as well as biochemical markers. This presents a novel perspective for further investigating the etiology and pathological mechanisms underlying hyperparathyroidism.

RNA N6-melthyladenosine (m6A) can play an important role in regulation of various biological processes. Chicken ovary development is closely related to egg laying performance, which is a process primarily controlled by complex gene regulations. In this study, transcriptome-wide m6A methylation of the Wuhua yellow-feathered chicken ovaries before and after sexual maturation was profiled to identify the potential molecular mechanisms underlying chicken ovary development. The results indicated that m6A levels of mRNAs were altered dramatically during sexual maturity. A total of 1,476 differential m6A peaks were found between these two stages with 662 significantly upregulated methylation peaks and 814 downregulated methylation peaks after sexual maturation. A positive correlation was observed between the m6A peaks and gene expression levels, indicating that m6A may play an important role in regulation of chicken ovary development. Functional enrichment analysis indicated that apoptosis related pathways could be the key molecular regulatory pathway underlying the poor reproductive performance of Wuhua yellow-feathered chicken. Overall, the various pathways and corresponding candidate genes identified here could be useful to facilitate molecular design breeding for improving egg production performance in Chinese local chicken breed, and it might also contribute to the genetic resource protection of valuable avian species.

Abstract Ammonium tetrathiomolybdate (TTM) is a copper chelator in clinical trials for treatment of Wilson’s disease, tumors and other diseases. In the current study, we innovatively discovered that TTM is a novel NRF2 activator and illustrated that autophagy contributed to TTM-induced NRF2 activation. We showed that TTM treatment promoted NRF2 nuclear translocation and upregulated transcription level of NRF2 target genes including HMOX1, GCLM, and SLC7A11 in vascular endothelial cells (HUVECs). Moreover, NRF2 deficiency directly hindered TTM-mediated antioxidative effects. Followingly, we revealed that overexpression of KEAP1, a negative regulator of NRF2, significantly repressed NRF2 activation induced by TTM. Further mutation analysis revealed that KEAP1 Cys151 is a major sensor responsible for TTM-initiated NRF2 signaling, suggesting that KEAP1 is involved in TTM-mediated NRF2 activation. Notably, we found that TTM can trigger autophagy as evidenced by accumulation of autophagosomes, elevation of LC3BI-II/I, increase of LC3 puncta and activation of AMPK/mTOR/ULK1 pathway. Autophagic flux assay indicated that TTM significantly enhanced autophagic flux in HUVECs. Inhibition of autophagy with knockout of autophagy key gene ATG5 resulted in suppression of TTM-induced NRF2 activation. TTM also induced phosphorylation of autophagy receptor SQSTM1 at Ser349, while SQSTM1-deficiency inhibited KEAP1 degradation and blocked NRF2 signaling pathway, suggesting that TTM-induced NRF2 activation is autophagy dependent. As the novel NRF2 activator, TTM protected against sodium arsenite (NaAsO2)-induced oxidative stress and cell death, while NRF2 deficiency weakened TTM antioxidative effects. Finally, we showed that autophagy-dependent NRF2 activation contributed to the protective effects of TTM against NaAsO2-induced oxidative injury, because of ATG5 or SQSTM1 knockout aggravated NaAsO2-induced elevation of HMOX1, cleaved PARP and γH2AX. Taken together, our findings highlight copper chelator TTM is a novel autophagy-dependent NRF2 activator and shed a new light on the cure for oxidative damage-related diseases.

Abstract Background Despite the importance of root decomposition in predicting ecosystem responses to future climate change, the effects of branch order on root decomposition and the feedback to soil still remains poorly understood. Here we separated root samples taken from two tree species (Castanopsis fargesii and Schima superba in subtropical forests along the coastal area in eastern China) into four-order classes (1st–2nd order, 3rd order, 4th order, and 5th order) and conducted a 540-day litterbag incubation experiment in laboratory to examine root mass loss, nutrient release, and the influence on soil during decomposition. Results C. fargesii roots of 1st–2nd and 3rd order decayed more slowly than those of 4th and 5th order, but this pattern was not significant for S. superba. Of all the measured root traits, the decomposition rates correlated best with root C/N ratio, diameter and specific root length (SRL) based on the structural equation modeling. Both tree species and root order exhibited significantly effects on root initial traits. Overall, C. fargesii roots decay faster than S. superba, and this appears to be associated with root initial C quality and N concentration. In addition, root order positively affected root decomposition rates mainly through root diameter and SRL. However, no significant difference was found in C and N content between soils below the litterbag with different-order roots. Conclusions Our findings suggest the effects of branch order on root decomposition are dependent on tree species. Moreover, root morphological properties might also be the controlling factor in root decay besides root chemistry fractions. Overall, the integrative effects should be considered to improve our understanding of the fate of fine-root litter and their contribution to soil C and N pool.

Highlights 1. CuONPs exposure activates NRF2 signaling in vascular endothelial cells and mouse thoracic aorta. 2. KEAP1 is dispensable for NRF2 activation in CuONPs-treated vascular endothelial cells. 3. CuONPs-induced autophagy facilitates NRF2 activation in vascular endothelial cells and mouse thoracic aorta. 4. Autophagy and ubiquitin–proteasome reciprocally regulate NRF2 activation in CuONPs-treated vascular endothelial cells and mouse thoracic aorta.

Highlights 1. CuONPs disturb mitochondrial dynamics and trigger mitophagy in vascular endothelial cells and mouse blood vessel. 2. PINK1/TAX1BP1-mediated mitophagy regulates the removal of excessive ROS and aberrant mitochondria in CuONPs-treated vascular endothelial cells. 3. The mitophagy activator urolithin A attenuates CuONPs-induced vascular endothelial cells death and mice vascular injury.

Abstract Background Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined. Results We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired. Conclusion Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.

Background: Hypoxia is associated with abnormal cell apoptosis in trophoblast cells, which causes fetal growth restriction and related placental pathologies. Few effective methods for the prevention and treatment of placenta-related diseases exist. Natural products and functional foods have always been a rich source of potential anti-apoptotic drugs. Nobiletin (NOB), a hexamethoxyflavonoid derived from the citrus pomace, shows an anti-apoptotic activity, which is a non-toxic constituent of dietary phytochemicals approved by the Food and Drug Administration. However, their effects on hypoxia-induced human trophoblast cells have not been fully studied. Objective: The aim of this study was to investigate the protective effects of NOB on hypoxia-induced apoptosis of human trophoblast JEG-3 and BeWo cells, and their underlying mechanisms. Design: First, the protective effect of NOB on hypoxia-induced apoptosis of JEG-3 and BeWo cells was studied. Cell viability and membrane integrity were determined by CCK-8 assay and lactate dehydrogenase activity, respectively. Real Time Quantitative PCR (RT-qPCR) and Western blot analysis were used to detect the mRNA and protein levels of HIF1α. Propidium iodide (PI)-labeled flow cytometry was used to detect cell cycle distribution. Cell apoptosis was detected by flow cytometry with Annexin V-FITC and PI double staining, and the expression of apoptosis marker protein cl-PARP was detected by Western blot analysis. Then, the molecular mechanism of NOB against apoptosis was investigated. Computer molecular docking and dynamics were used to simulate the interaction between NOB and p53 protein, and this interaction was verified in vitro by Ultraviolet and visible spectrum (UV-visible spectroscopy), fluorescence spectroscopy and circular dichroism. Furthermore, the changes in the expression of p53 signaling pathway genes and proteins were detected by RT-qPCR and Western blot analysis, respectively. Results: Hypoxia treatment resulted in a decreased cell viability and cell membrane integrity in JEG-3 and BeWo cell lines, and an increased expression of HIF1α, cell cycle arrest in the G1 phase, and massive cell apoptosis, which were alleviated after NOB treatment. Molecular docking and dynamics simulations found that NOB spontaneously bonded to human p53 protein, leading to the change of protein conformation. The intermolecular interaction between NOB and human p53 protein was further confirmed by UV-visible spectroscopy, fluorescence spectroscopy and circular dichroism. After the treatment of 100 μM NOB, a down-regulation of mRNA and protein levels of p53 and p21 and an up-regulation of BCL2/BAX mRNA and protein ratio were observed in JEG-3 cells; however, there was also a down-regulation of mRNA and protein levels observed for p53 and p21 in BeWo cells after the treatment of NOB. The BCL2/BAX ratio of BeWo cells did not change after the treatment of 100 μM NOB. Conclusion: NOB attenuated hypoxia-induced apoptosis in JEG-3 and BeWo cell lines and might be a potential functional ingredient to prevent pregnancy-related diseases caused by hypoxia-induced apoptosis. These findings would also suggest the exploration and utilization of citrus resources, and the development of citrus industry.

Dengue virus (DENV) infection is a major global public health concern, and there is no effective vaccine for it. In this study, we describe the design and characterization of three nucleotide-modified mRNA vaccines (prME-mRNA, E80-mRNA, and NS1-mRNA) for DENV-2. Our results showed that vaccination with E80-mRNA alone or a combination of E80-mRNA and NS1-mRNA can induce high levels of neutralizing antibodies and antigen-specific T cell responses; furthermore, these vaccines confer complete protection against DENV-2 challenge in immunocompetent mice. These data provide foundations for further development of a tetravalent DENV vaccine based on nucleotide-modified mRNA.

Abstract As the main organelles for the clearance of damaged proteins and damaged organelles, the function of lysosomes is crucial for maintaining the intracellular homeostasis of long-lived neurons. A stable acidic environment is essential for lysosomes to perform their functions. TMEM175 has been identified as a new K+ channel that is responsible for regulating lysosomal membrane potential and pH stability in neurons. This study aimed to understand the role of TMEM175 in lysosomal function of neurons and neuronal injury following cerebral ischemia-reperfusion (I/R). A middle-cerebral-artery occlusion/reperfusion (MCAO/R) model was established in adult male Sprague-Dawley rats in vivo, and cultured neurons were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic ischemia-reperfusion (I/R) injury in vitro. We found that the protein level of TMEM175 decreased after cerebral I/R injury and that TMEM175 overexpression ameliorated MCAO/R-induced brain-cell death and neurobehavioral deficits in vivo. Furthermore, these results were recapitulated in cultured neurons. Acridine orange (AO) staining, as well as LysoSensor Green DND-189, cathepsin-B (CTSB), and cathepsin-D (CTSD) activities, showed that TMEM175 deficiency inhibited the hydrolytic function of lysosomes by affecting lysosomal pH. In contrast, TMEM175 upregulation reversed OGD/R-induced lysosomal dysfunction and impaired mitochondrial accumulation in cultured neurons. TMEM175 deficiency induced by cerebral I/R injury leads to compromised lysosomal pH stability, thus inhibiting the hydrolytic function of lysosomes. Consequently, lysosomal-dependent degradation of damaged mitochondria is suppressed and thereby exacerbates brain damage. Exogenous up-regulation of TMEM175 protein level could reverse the neuronal lysosomal dysfunction after ischemia-reperfusion.

Abstract Backgrounds Cyclic nucleotide gated channels (CNGCs) play multifaceted roles in plant physiological processes, especially with respect to signalling processes, plant development, and responses to environmental stresses. However, little information is known about the CNGC family in the large cosmopolitan family Rhamnaceae, which has strong tolerance to biotic and abiotic stresses. Results In the current study, a total of 15 ZjCNGCs which located on 7 chromosomes were firstly identified in Chinese jujube (Ziziphus jujuba Mill.), the most important species of Rhamnaceae in terms of economic and ecological values. Phylogenetic analysis showed that these ZjCNGCs could be classified into four groups, ZjCNGC12 belonged to group IVA, and ZjCNGC13, 14, 15 belonged to group IVB. In addition, the paralogous and orthologous homology duplication of ZjCNGC15 occurred during the evolutionary process. The characteristics of ZjCNGCs regarding to exon-intron numbers and post-translational modifications showed diversified structures and functions. Motif composition and protein sequence analysis revealed that the phosphate-binding cassette and hinge regions were conserved among ZjCNGCs. Prediction of the cis-acting regulatory elements and expression profiles by real-time quantitative PCR analysis showed that some of the ZjCNGCs responded to environmental changes, especially ZjCNGC2, which was significantly downregulated in response to cold stress, and ZjCNGC4 was highly induced in response to cold, salt and alkaline stresses. ZjCNGC13 and 14 were highly induced in the phytoplasma-resistant cultivar and downregulated in the susceptible cultivar. Furthermore, ZjCNGC2 could be regulated by cAMP treatment, microtubule changes and interact with ZjMAPKK4, which suggested that cAMP and microtubule might play important roles in ZjCNGC2 mediated ZjMAPKK4 signalling transduction involved in cold stress. Conclusions The identification and classification analysis of ZjCNGCs were firstly reported, and some key individual ZjCNGCs might play essential roles in the response to biotic and abiotic stresses, especially ZjCNGC2 mediated ZjMAPKK4 signalling transduction involved in cold stress. This systematic analysis could provide important information for further functional characterization of ZjCNGCs with the aim of breeding stress-resistant cultivars.

Objective. This study aimed to analyze changes in occupational stress in new nurses during the first year of employment. Methods. A prospective longitudinal study was conducted from 2020 to 2021 using one questionnaire four times on 127 newly employed nurses in a tertiary general teaching hospital in the province of Fujian. Results. The results showed that new nurses had moderate to high levels of stress in all four stages, with the highest stress level at 4 and 8 months of employment and the lowest stress level at 12 months; the differences in stress scores at different time points were statistically significant (p

The realistic resistance zone of water and salt molecules to transport across a TFC-RO membrane is the topmost polyamide nanofilm. The existence of hollow voids in the fully aromatic polyamide (PA) film gives its surface ridge-and-valley morphologies, which confuses the comprehensions of the definition of the PA thickness. The hollow voids, however, neither participate in salt–water separation nor hinder water penetrating. In this paper, the influence of intrinsic thickness (single wall thickness) of the PA layer on water permeability was studied by adjusting the concentration of reacting monomers. It confirms that the true permeation resistance of water molecules originates from the intrinsic thickness portion of the membrane. The experimental results show that the water permeability constant decreases from 3.15 ± 0.02 to 2.74 ± 0.10 L·m−2·h−1·bar−1 when the intrinsic thickness of the membrane increases by 9 nm. The defects on the film surface generate when the higher concentration of MPD is matched with the relatively low concentration of TMC. In addition, the role of MPD and TMC in the micro-structure of the PA membrane was discussed, which may provide a new way for the preparation of high permeability and high selectivity composite reverse osmosis membranes.

In this paper, we used an octadecylamine functionalized graphene oxide (ODA@GO) to induce the confined growth of a polyamide nanofilm in the organic and aqueous phase during interfacial polymerization (IP). The ODA@GO, fully dispersed in the organic phase, was applied as a physical barrier to confine the amine diffusion and therefore limiting the IP reaction close to the interface. The morphology and crosslinking degree of the PA nanofilm could be controlled by doping different amounts of ODA@GO (therefore adjusting the diffusion resistance). At standard seawater desalination conditions (32,000 ppm NaCl, ~55 bar), the flux of the resultant thin film nanocomposite (TFN) membrane reached 59.6 L m−2 h−1, which was approximately 17% more than the virgin TFC membrane. Meanwhile, the optimal salt rejection at seawater conditions (i.e., 32,000 ppm NaCl) achieved 99.6%. Concurrently, the boron rejection rate was also elevated by 13.3% compared with the TFC membrane without confined growth.

5,6,7,8,3,4′-Hexamethoxyflavone, also called nobiletin (NOB), widely found in the citrus peel, is one of the main byproducts in citrus processing. NOB is considered safe, but its safety for women during pregnancy is unknown. Therefore, the effect of NOB on apoptosis in human choriocarcinoma trophoblast cells (BeWo cells) was evaluated. Cells were divided into four groups and cultured with different concentrations of NOB (0, 10, 33, and 100 μM) for 12, 24, 36, and 48 h respectively. Cell viability was detected by CCK-8 assay, cell morphology was detected by a Cell Imaging Multi-Mode Reader, and cell cycle and apoptosis were detected by flow cytometry. Cleaved PARP level, the expressions of B cell lymphoma 2 (BCL2) family proteins, and p53 pathway proteins were detected by Western blot. The results showed that after 48 h of cell culture, the cell viability was decreased significantly, but apoptosis was significantly increased. Compared to the cells without NOB treatment, the cells treated with NOB at 10 or 33 μΜ showed no significant differences in the number of suspended cells or late apoptosis rate, except the increase of cell viability. Treatment of NOB at the concentration of 100 μM improved cell viability, attenuated apoptosis, decreased suspended cells, and did not alter the G1 phase arrest, compared with the non-NOB-treated group after 48 h of culturing. The 100 μΜ NOB treatment increased the levels of BCL2 and BCLXL, and decreased p53 accumulation in BeWo cells at 48 h, but had no effect on the expression of BAX, BAK, BAD, p21, and G1 phase arrest. These findings provide evidence that NOB (10, 33, and 100 μΜ) was safe for BeWo cells. NOB at the concentration of 100 μΜ could attenuate apoptosis in BeWo cells, which might be helpful to prevent pregnancy-related diseases caused by apoptosis.

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Pieris Japonica, belonging to the Rhododendron family, is known for its anti-insect and analgesic properties. Despite previous research, the components and antioxidant activity of Pieris Japonica extract remain unclear. This study aims to identify the optimal extraction process for Pieris Japonica, determine its components, and evaluate its antioxidant capacity. An L9 (34) orthogonal method was employed to optimize the Pieris Japonica extraction process, with the polyphenol content serving as the extraction efficiency index. The extracted components were identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS-MS). Antioxidant activity was assessed via the DPPH test, ABTS radical scavenging test, and FRAP reduction ability test. The optimal extraction process involved soaking Pieris Japonica powder in 60% ethanol with a weight-to-volume ratio of 1:20 (g/mL), followed by eight hours of reflux at 50°C. Under these conditions, the total polyphenol content was 11.2 ± 0.6 mg/g. HPLC/MS-MS revealed that flavonoids were the primary components in the Pieris Japonica extract. The FRAP method determined the total antioxidant capacity to be 1.00 ± 0.05 µmol/mL, while the DPPH method showed a radical scavenging rate of 42.21±4.02%, and the ABTS method yielded a 85.74% scavenging rate, indicating a strong antioxidant activity. The primary components of Pieris Japonica extract were flavonoids, and the extracted plant material exhibited potent antioxidant activity. [ABSTRACT FROM AUTHOR]