Quality of life and survival analyses of breast cancer cases treated with integrated traditional Chinese and Western medicine.

BACKGROUND: Breast cancer (BC) is the second leading cause of tumor-related mortality after lung cancer. Chemotherapy resistance remains a major challenge to progress in BC treatment, warranting further exploration of feasible and effective alternative therapies. AIM: To analyzed the quality of life (QoL) and survival of patients with BC treated with integrated traditional Chinese and Western medicine (TCM-WM). METHODS: This study included 226 patients with BC admitted to the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine between February 2018 and February 2023, including 100 who received conventional Western medicine treatment (control group) and 126 who received TCM-WM treatment (research group). The total effective rate, side effects (alopecia, nausea and vomiting, hepatorenal toxicity, and myelosuppression), QoL assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), 1-year overall survival (OS), recurrence and metastasis rates, and serum inflammatory factors [interleukin (IL)-6, IL-10, and tumor necrosis factor alpha] were comparatively analyzed. RESULTS: The research group showed statistically better overall efficacy, EORTC QoL-C30 scores, and 1-year OS than the control group, with markedly lower side effects and 1-year recurrence and metastasis rates. Moreover, the posttreatment levels of serum inflammatory in the research group were significantly lower than the baseline and those in the control group. CONCLUSION: Overall, TCM-WM demonstrated significantly improved therapeutic efficacy while ensuring drug safety in BC, which not only improved patients' QoL and prolonged survival, but also significantly inhibited the inflammatory response.

The role of circular RNA during the urological cancer metastasis: exploring regulatory mechanisms and potential therapeutic targets.

Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated. With the deepening of research, circular RNAs (circRNAs) have been found to not only play a significant role in tumor progression and prognosis but also show aberrant expression in various tumor metastases, consequently impacting tumor metastasis through multiple pathways. Therefore, circRNAs are emerging as potential tumor markers and treatment targets. This review summarizes the research progress on elucidating how circRNAs regulate the urological cancer invasion-metastasis cascade response and related processes, as well as their role in immune microenvironment remodeling and circRNA vaccines. This body of work highlights circRNA regulation as an emerging therapeutic target for urological cancers, which should motivate further specific research in this regard.

Assessing the effect of scanning parameter on the size and density of pulmonary nodules: a phantom study.

BACKGROUND: Lung cancer remains a leading cause of death among cancer patients. Computed tomography (CT) plays a key role in lung cancer screening. Previous studies have not adequately quantified the effect of scanning protocols on the detected tumor size. The aim of this study was to assess the effect of various CT scanning parameters on tumor size and densitometry based on a phantom study and to investigate the optimal energy and mA image quality for screening assessment. METHODS: We proposed a new model using the LUNGMAN N1 phantom multipurpose anthropomorphic chest phantom (diameters: 8, 10, and 12 mm; CT values: - 100, - 630, and - 800 HU) to evaluate the influence of changes in tube voltage and tube current on the size and density of pulmonary nodules. In the LUNGMAN N1 model, three types of simulated lung nodules representing solid tumors of different sizes were used. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were used to evaluate the image quality of each scanning combination. The consistency between the calculated results based on segmentation from two physicists was evaluated using the interclass correlation coefficient (ICC). RESULTS: In terms of nodule size, the longest diameters of ground-glass nodules (GGNs) were closest to the ground truth on the images measured at 100 kVp tube voltage, and the longest diameters of solid nodules were closest to the ground truth on the images measured at 80 kVp tube voltage. In respect to density, the CT values of GGNs and solid nodules were closest to the ground truth when measured at 80 kVp and 100 kVp tube voltage, respectively. The overall agreement demonstrates that the measurements were consistent between the two physicists. CONCLUSIONS: Our proposed model demonstrated that a combination of 80 kVp and 140 mA scans was preferred for measuring the size of the solid nodules, and a combination of 100 kVp and 100 mA scans was preferred for measuring the size of the GGNs when performing lung cancer screening. The CT values at 80 kVp and 100 kVp were preferred for the measurement of GGNs and solid nodules, respectively, which were closest to the true CT values of the nodules. Therefore, the combination of scanning parameters should be selected for different types of nodules to obtain more accurate nodal data.

Lemon essential oil nanoemulsions: Potential natural inhibitors against Escherichia coli.

Lemon essential oil (LEO) is a common natural antibacterial substance, and encapsulating LEO into nanoemulsions (NEs) can improve their stability and broaden its application. Our study aimed to investigate the bacterial inhibitory effect of LEO-NEs against Escherichia coli (E. coli). Results showed that the minimum inhibitory concentration (MIC) of LEO-NEs was 6.25 mg/mL, and the time-kill curve showed that E. coli were significantly killed by LEO-NEs after 5 h of treatment at 1MIC. Flow-cytometry analysis showed that LEO-NEs adversely affected the cell-membrane depolarisation, cell-membrane integrity, and efflux pump function of E. coli. Confocal laser scanning microscopy demonstrated that 8MIC of LEO-NEs induced changes in the cell-membrane permeability and cell-wall integrity of E. coli. Proteomic results suggested that the mode of action LEO-NEs against E. coli was to enhance bacterial chemotaxis and significantly inhibit ribosomal assembly. They may also affect butyric acid, ascorbic acid and aldehyde metabolism, and sulphur-relay system pathways. In conclusion, LEO-NEs had potential application as a natural antibacterial agent for the control of E. coli in the food industry.

Nanocomposites based on nanoceria regulate the immune microenvironment for the treatment of polycystic ovary syndrome.

The immune system is closely associated with the pathogenesis of polycystic ovary syndrome (PCOS). Macrophages are one of the important immune cell types in the ovarian proinflammatory microenvironment, and ameliorate the inflammatory status mainly through M2 phenotype polarization during PCOS. Current therapeutic approaches lack efficacy and immunomodulatory capacity, and a new therapeutic method is needed to prevent inflammation and alleviate PCOS. Here, octahedral nanoceria nanoparticles with powerful antioxidative ability were bonded to the anti-inflammatory drug resveratrol (CeO2@RSV), which demonstrates a crucial strategy that involves anti-inflammatory and antioxidative efficacy, thereby facilitating the proliferation of granulosa cells during PCOS. Notably, our nanoparticles were demonstrated to possess potent therapeutic efficacy via anti-inflammatory activities and effectively alleviated endocrine dysfunction, inflammation and ovarian injury in a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Collectively, this study revealed the tremendous potential of the newly developed nanoparticles in ameliorating the proinflammatory microenvironment and promoting the function of granulosa cells, representing the first attempt to treat PCOS by using CeO2@RSV nanoparticles and providing new insights in combating clinical PCOS.

Prognostic signature analysis and survival prediction of esophageal cancer based on N6-methyladenosine associated lncRNAs.

Esophageal cancer (ESCA) has a bad prognosis. Long non-coding RNA (lncRNA) impacts on cell proliferation. However, the prognosis function of N6-methyladenosine (m6A)-associated lncRNAs (m6A-lncRNAs) in ESCA remains unknown. Univariate Cox analysis was applied to investigate prognosis related m6A-lncRNAs, based on which the samples were clustered. Wilcoxon rank and Chi-square tests were adopted to compare the clinical traits, survival, pathway activity and immune infiltration in different clusters where overall survival, clinical traits (N stage), tumor-invasive immune cells and pathway activity were found significantly different. Through least absolute shrinkage and selection operator and proportional hazard (Lasso-Cox) model, five m6A-lncRNAs were selected to construct the prognostic signature (m6A-lncSig) and risk score. To investigate the link between risk score and clinical traits or immunological microenvironments, Chi-square test and Spearman correlation analysis were utilized. Risk score was found connected with N stage, tumor stage, different clusters, macrophages M2, B cells naive and T cells CD4 memory resting. Risk score and tumor stage were found as independent prognostic variables. And the constructed nomogram model had high accuracy in predicting prognosis. The obtained m6A-lncSig could be taken as potential prognostic biomarker for ESCA patients. This study offers a theoretical foundation for clinical diagnosis and prognosis of ESCA.

The adhesion behavior of the retina.

Ocular diseases and treatment related to rhegmatogenous retinal detachment (RRD) are highly correlated with retinal adhesion behavior. Therefore, this paper proposes to study the adhesion behavior of the intact retina. This can provide theoretical guidance for the treatment and research of retinal detachment (RD) related diseases. To systematically analyze this aspect, two experiments were performed on the porcine retina. The pull-off test combined with the modified JKR theory was used to study the adhesion behavior of the vitreoretinal interface, while the peeling test was used to study the adhesion behavior of the chorioretinal interface. In addition, the adhesion phase involved in the pull-off test was simulated and analyzed by building the corresponding finite element method (FEM). The experimental results of adhesion force on the vitreoretinal interface were obtained by pull-off test with five sizes of rigid punch. The experimental value of the pull-off force FPO tends to increase gradually with increasing punch radius in the range of 0.5-4 mm. A comparison of the experimental results with the simulation results shows that they are in a well agreement. And there is no statistical difference between the experimental and theoretical values of the pull-off force FPO. In addition, the values of retinal adhesion work were also obtained by pull-off test. Interestingly, there is a significant scale effect of the retinal work of adhesion. Finally, the peeling test gave a maximum peeling strength TMax of about 13 mN/mm and a stable peeling strength TD of about 11 mN/mm between the retina and the choroid. The pull-off test well shows the process of retinal traction by the diseased vitreous at the beginning of RRD. A comparison of the experimental results with the finite element results verifies the accuracy of the simulation. The peeling test well investigated the adhesion behavior between the retina and the choroid and obtained key biomechanical data (peeling strength, etc.). The combination of the two experiments allows a more systematic study of the whole retina. This research can provide more complete material parameters for finite element modeling of retina-related diseases, and it also can provide the theoretical guidance for individualized design of retinal repair surgery.

Development of Citrus-Based Functional Jelly and an Investigation of Its Anti-Obesity and Antioxidant Properties.

Intervention with natural products is becoming a promising obesity control strategy as healthy eating becomes increasingly popular. The present study aimed to prepare a citrus-based functional jelly (CFJ) from citrus by-products and investigate its bioactive effects in mice. The results of the CFJ preparation showed that the optimal formula of CFJ was 29.12%, 20%, and 3.61% for chenpi, orange juice, and pectin, respectively. The optimized CFJ can be personalized and designed with jelly shapes using 3D food printing technology. The evaluation of the biological activity of the CFJ showed that it was low in calories, with a total phenolic content of 12.44 ± 0.26 mg GAE/g. Moreover, the CFJ has a good free radical scavenging ability for ABTS. The results of the mouse experiments showed that the CFJ significantly suppressed the body weight gain and fat deposits with a dose-dependent effect, compared with the control group (p < 0.05). In addition, the activities of the antioxidant-related enzymes (CAT and SOD) of the mice were also enhanced after a supplementation with the CFJ. In short, the CFJ is a functional snack enriched in phenolic substances with low-calorie, antioxidant and anti-obesity properties. This work promotes the utilization of citrus by-products and the healthy development of its processing industry.

Development of Functional Kiwifruit Jelly with chenpi (FKJ) by 3D Food Printing Technology and Its Anti-Obesity and Antioxidant Potentials.

With the growing popularity of the concept of healthy diet, modern obesity treatment is gradually shifting from surgical or pharmacological treatment to nutritional intervention. As a safe and effective measure, natural product interventions are a potential strategy of obesity management. The present study aimed to develop a kind of functional food rich in bioactive compounds (chenpi, kiwifruit, and pectin as raw materials) and investigate their bioactive effects on a mouse model. For development of functional kiwifruit jelly with chenpi (FKJ), the results of single-factor and response surface experiments showed that the optimized formulation was composed of a 30.26% addition of chenpi, 35% addition of kiwifruit juice, and 2.88% addition of pectin. The FKJ obtained with the optimal formulation could be used as a 3D printing raw material to print the desired food shapes successfully. For bioactivity evaluation of FKJ, the results with a mouse model showed that the food intake, liver weight, and adipose tissue weight were significantly decreased after administration of FKJ with dose-dependent effect compared to the CON group (p < 0.05). Meanwhile, the serum levels of several inflammatory factors (TG, IL-6, and TNF-α) were decreased and the activities of several antioxidant-related enzymes (SOD, GSH-PX, and CAT) were increased. In short, a functional kiwifruit jelly with chenpi was developed in this study. It is a functional snack food rich in active phenolic compounds, low in calories, with antioxidant and anti-inflammatory activity, and prevents fat accumulation. FKJ could well meet the needs of modern people for nutrition and health and also promote the processing and utilization of natural products, and has good development prospects in the functional food industry.

Histological, metabolomic and transcriptomic analyses reveal mechanisms of cold acclimation of the Moso bamboo (Phyllostachys edulis) leaf.

The Moso bamboo (Phyllostachys edulis) leaf copes well with cold winters in southeastern China. However, until now, there has been almost no research on its adaptation mechanisms to cold weather. Herein, we found that the Moso bamboo leaf has evolved several anatomical structures that may play a role in enhancing its cold tolerance. These structures include fewer fusiform cells, smaller bulliform cells, lower stomata density and many more trichomes, as well as lower relative water content than in the leaf of a cold-sensitive bamboo species, Bambusa ventricosa. Untargeted metabolomic analysis revealed that the winter leaf of Moso bamboo had 10- to 1000-fold higher stress-resistant metabolites such as glutathione, trehalose and ascorbic acid than the leaf of B. ventricosa on both warm and cold days. In contrast to the leaves that grew on a warm day, some metabolites such as glutathione and trehalose increased dramatically in the leaves of Moso bamboo that grew on a cold day. However, they unexpectedly decreased in the leaf of B. ventricosa growing at cold temperatures. Transcriptome analysis revealed a cold stress response network that includes trehalose, glutathione, flavonoid metabolism, DNA repair, reactive oxygen species degradation, stress-associated genes and abiotic stress-related plant hormones such as jasmonic acid, abscisic acid and ethylene. The potential mediator transcription factors, such as EREBP, HSF, MYB, NAC and WRYK, were also significantly upregulated in Moso bamboo leaves growing at cold temperatures. Interestingly, many newly identified genes were involved in the transcriptome of the winter leaf of the Moso bamboo. Most of these new genes have not even been annotated yet. The above results indicate that the Moso bamboo leaf has evolved special histological structures, metabolic pathways and a cold stress-tolerant transcriptome to adapt to the cold weather in its distribution areas.

Preparation, Characterization, and Antioxidant Activity of Nanoemulsions Incorporating Lemon Essential Oil.

Lemon essential oil (LEO) is a kind of citrus essential oil with antioxidant, anti-inflammatory, and antimicrobial activities, but low water solubility and biological instability hinder its industrial application. In this study, LEO was nanoemulsified to solve these problems. The preparation procedure of lemon essential oil nanoemulsions (LEO-NEs) was optimized, and the physicochemical characterization and antioxidant activities were explored. Single-factor experiments (SFEs) and response surface methodology (RSM) were conducted for the effects on the mean droplet size of LEO-NEs. Five factors of SFE which may influence the droplet size were identified: HLB value, concentration of essential oil, concentration of surfactant, ultrasonic power, and ultrasonic time. On the basis of the SFE, the RSM approach was used to optimize the preparation procedure to obtain LEO-NEs with the smallest droplet size. LEO-NEs exhibited good antioxidant activity when the HLB value was 13, content of surfactant was 0.157 g/mL, ultrasonic time was 23.50 min, and ultrasonic power was 761.65 W. In conclusion, these results can provide a good theoretical basis for the industrial application of lemon essential oil.

Closed Reduction Percutaneous Intramedullary Fixation with Kirschner Wires in 4 Children with Displaced Fractures of the Distal Humerus.

BACKGROUND This study describes the use of closed reduction percutaneous intramedullary fixation with Kirschner wires in 4 children with displaced metaphyseal-diaphyseal junction (MDJ) fractures of the distal humerus. MATERIAL AND METHODS Between August 2016 and August 2019, 4 patients (3 boys and 1 girl), whose mean age was 4 years 5 months (range: 3 years 6 months to 5 years 4 months), with displaced MDJ fractures of the distal humerus were treated using closed reduction percutaneous intramedullary fixation with Kirschner wires. Three of the fractures were oblique and 1 was transverse. The operation time and the frequency of intraoperative fluoroscopy were recorded. All children were followed up for greater than 18 months, taking anteroposterior and lateral radiographs of the elbow joint to evaluate the outcomes. At the last follow-up, the Flynn elbow joint function score was used to evaluate clinical outcomes, and complications were recorded. RESULTS The mean operation time was 37.5 min (range: 35-40 min) and the frequency of intraoperative fluoroscopy was 11.7 times (range: 8-15 times). All of the fractures were confirmed to be healed based on radiographic results at 4 weeks after surgery. At the last follow-up, 4 children had normal elbow joint motion without elbow deformity. The Flynn score showed their outcomes were excellent. CONCLUSIONS Closed reduction percutaneous intramedullary fixation using Kirschner wires was an effective treatment for displaced MDJ fractures of the distal humerus in the 4 children described and was shown to be easy to perform with a short operation time.

Effects of melatonin on intestinal function and bacterial compositions in sucking piglets.

Melatonin has been reported to affect intestinal function by targeting microbiome, morphological structure, barrier integrity and nutrient absorptive system. While the effect of melatonin on intestinal development in newborn infants is obscure, thus, this study firstly attempted to investigate the hypothesis that melatonin treatment improves intestinal development in sucking piglets. 14 healthy newborn piglets received 10 ml melatonin solution (1 mg/ml) or drinking water (n = 7) for 21 days. The results showed that oral administration of melatonin increased liver relative weight (p < 0.05) but failed to affect growth performance in sucking piglets (p > 0.05). Immunostaining jejunal samples from melatonin group showed high expressions of nnos and claudin1, indicating that melatonin improved intestinal neural development and barrier integrity. Also, melatonin promoted intestinal absorptive function evidenced by the increased serum proline concentration in melatonin-treated piglets compared with the control (p < 0.05). Gut microbiota compositions were tested by 16S rDNA sequencing and the results showed that melatonin increased the relative abundance of Actinobacteria compared with the control (p < 0.05) at the phylum level. However, Selenomonadales was markedly reduced compared with the control at the order level (p < 0.05). Gut and faecal volatile fatty acids were tested to evaluate the microbiota metabolism, but no difference was noticed in volatile fatty acid concentrations (p > 0.05). Melatonin improved intestinal development by affecting neural development, barrier integrity, nutrient absorption and microbiota in sucking piglets.

[Finite element analysis of the effect of local posterior sclera collagen cross-linking on eyeball shape].

China is the country with high incidence of high myopia in the world. High myopia can cause severe vision impairment. So far, there is no effective treatment for high myopia in clinic. Scleral collagen cross-linking surgery has been proven to be effective in preventing animal eye axial elongation in vitro and in vivo. However, the influence of posterior scleral collagen cross-linking on the deformation of the whole eyeball is still unclear. In this study, finite element simulation were used to analyze the changes of eyeball shape and the position of light casting on the retina after posterior sclera cross-linking, and the mathematical algorithm was written to verify their similarity. The results showed that the shape of the whole eyeball was still very similar before and after cross-linking, and the diopter of the eyeball after cross-linking had little change, which had almost no effect on the position of light projection on the retina. Our results indicate that posterior sclera cross-linking wouldn't lead to distortion to the optometry, that is, the increase of elastic modulus in local scleral tissue after cross-linking wouldn't cause new problem of optometry and vision.

Insights into Temperature and Hypoxia Tolerance in Cowpea Weevil via HIF-1.

Cowpea weevil (Callosobruchus maculatus) is a major pest that leads to severe damage of the stored leguminous grains. Several management approaches, including physical barriers, biological or chemical methods, are used for controlling bruchid in cowpea. These methods usually target the metabolically active state of weevil. However, it becomes less effective at early stages as egg, larva, or pupa under low temperature and oxygen conditions. Since hypoxia-inducible factor-1 (HIF-1) is known to coordinate multiple gene responses to low oxygen or low temperature signals, we examined the HIF-1α gene expression under low temperature and hypoxic treatments. At -20 °C, it took 4 h to reduce the survival rate for eggs, larvae, and pupae down to 10%, while at 4 °C and 15 °C, the survival rate remained higher than 50% even after 128 h as HIF-1α gene expression peaked at 15 °C. Moreover, HIF-1 protein offers a valuable target for early stage pest control complementary to traditional methods. In particular, HIF-1 inhibitor camptothecin (CPT), one of the five HIF-1 inhibitors examined, achieved a very significant reduction of 96.2% and 95.5% relative to the control in weevil survival rate into adult at 4 °C and 30 °C, respectively. Our study can be used as one model system for drug development in virus infections and human cancer.

MicroRNA­16­5p/BIMP1/NF­κB axis regulates autophagy to exert a tumor­suppressive effect on bladder cancer.

Bladder cancer (BC) is the second most common urological disease worldwide. Previous studies have reported that microRNA (miR)­16­5p is associated with the development of BC, but whether miR­16­5p regulates BC cell autophagy remains unknown. Thus, the aim of the present study was to investigate this issue. miR­16­5p expression in BC cells was assessed by reverse transcription­quantitative PCR. Cell viability and apoptosis were detected via Cell Counting Kit­8 and flow cytometry assays, respectively. For cell autophagy detection, autophagic flux was detected using a mCherry­green fluorescent protein­microtubule­associated proteins 1A/1B light chain 3B (LC3) puncta formation assay, followed by determination of autophagy­related protein markers. The targeting relationship between miR­16­5p and caspase recruitment domain family member 10 (BIMP1) was confirmed using a dual­luciferase reporter assay, followed by detection of the BIMP1/NF­κB signaling pathway. The results showed that miR­16­5p overexpression inhibited cell viability, whereas miR­16­5p knockdown promoted cell viability in BC. Furthermore, miR­16­5p overexpression induced autophagy, which was accompanied by increased autophagic flux and expression of the autophagy­related proteins LC3­II and beclin 1, as well as decreased p62 expression, whereas miR­16­5p silencing led to an inhibition of autophagy in BC cells. Moreover, autophagy inhibitor 3­methyladenine treatment inhibited cell autophagy and apoptosis in miR­16­5p­overexpressing cells. Mechanistic studies demonstrated that miR­16­5p could inhibit the BIMP1/NF­κB signaling pathway and this inhibition was achieved by directly targeting BIMP1. Furthermore, it was found that blockade of the BIMP1/NF­κB signaling pathway inversed the inhibitory effects of miR­16­5p knockdown on autophagy in BC cells. In vivo experiments further verified the tumor­suppressive effect on BC of the miR­16­5p/BIMP1/NF­κB axis. Therefore, the results of the present study indicated that miR­16­5p promotes autophagy of BC cells via the BIMP1/NF­κB signaling pathway, and an improved understanding of miR­16­5p function may provide therapeutic targets for clinical intervention in this disease.

Global transcriptomic response of Listeria monocytogenes exposed to Fingered Citron (Citrus medica L. var. sarcodactylis Swingle) essential oil.

Listeria monocytogenes, which could cause severe disease of listeriosis, is one of the most concerned foodborne pathogens worldwide. Citrus medica L. var. sarcodactylis Swingle (Fingered Citron) is one of the citrus species cultivated in south China. Here, we investigated the efficacy of Fingered Citron essential oil (FCEO) against L. monocytogenes and explored the response of L. monocytogenes in the presence of FCEO using genome-wide transcriptome analysis. FCEO exhibited strong anti-listeria activity and obvious alterations of cell morphology were observed by scanning electron microscopy and transmission electron microscopy. Moreover, GO analysis demonstrated many potential cell responses, including metabolic process, cellular process, single-organism process, cell part, membrane, catalytic activity, binding, and transporter activity. KEGG analysis suggests that L. monocytogenes respond and adapt by (1) increasing motility through the enhancement of flagella rotation; (2) promoting cell tumbles and re-orientating to escape from FCEO; (3) enhancing the uptake of carbohydrates from environment to gain more energy; (4) changing the uptake of several metallic cations, including iron, zinc, cobalt, and nickel. Our research contributes to the understanding of the adaptive responses of L. monocytogenes exposed to FCEO and provides novel insights for finding new targets of anti-listeria therapy.

Identification of processes mobilizing organic molecules and arsenic in geothermal confined groundwater from Pliocene aquifers.

Organic matter (OM) has been accepted as an important trigger fueling Fe(III) oxide reduction and arsenic release in the late Pleistocene-Holocene anoxic aquifers, whereas its fates and roles on arsenic mobility in the Pliocene aquifer are unclear. To fill this gap, groundwaters from a confined Pliocene aquifer (CG) and an unconfined Holocene aquifer (UG) were sampled in the Guide Basin, China, to monitor evolutions of groundwater geochemistry and OM molecular signatures along the groundwater flow path. The outcomes showed that groundwater pH, temperature, and arsenic concentrations in the CG samples generally increased along the groundwater flow path, which were much higher than those in the UG samples. The numbers and intensities of recalcitrant molecules (polycyclic aromatics and polyphenols) in the CG samples remarkably increased along the path, but relatively labile molecules (highly unsaturated and phenolic compounds and aliphatic compounds) showed the opposite trends. The arsenic-poor (<10 µg/L) UG samples contained more labile molecules than the arsenic-rich CG samples. High groundwater pH, temperature, and sediment age in the confined aquifers may be responsible for the selective mobilization of the unique polycyclic aromatics and polyphenols. The mobilized recalcitrant organic molecules may enhance arsenic release via electron shuttling, complexation, and competition. Furthermore, high temperature and pH may also facilitate arsenic desorption. The study provides molecular-scale evidences that the mobilization of recalcitrant organic molecules and arsenic were concurrent in the geothermal confined groundwater.

PLK1 promotes proliferation and suppresses apoptosis of renal cell carcinoma cells by phosphorylating MCM3.

Minichromosome maintenance 3 (MCM3) protein has been widely studied due to its essential role in DNA replication. In addition, it is overexpressed in several human tumor types. However, the role of this protein in renal cell carcinoma (RCC) is not widely known. In this study, we demonstrated that polo-like kinase 1 (PLK1)-mediated MCM3 phosphorylation regulates proliferation and apoptosis in RCC. Our results confirm that PLK1 and phospho-MCM3 (p-MCM3) are highly expressed in renal cell carcinoma. The expression of PLK1 is closely related to the clinical characteristics of renal cell carcinoma. They play important roles in the proliferation and apoptosis of RCC. In vitro, after overexpression of PLK1 or MCM3, the proliferation of RCC cells was significantly enhanced and cell apoptosis was inhibited, while after knockout, the proliferation of RCC cells was weakened and cell apoptosis was promoted. In addition, Mn2+-Phos-tag SDS-PAGE, western blotting, and immunofluorescence were utilized to determine that MCM3 is a physiological substrate of PLK1, which is phosphorylated on serine 112 (Ser112) in a PLK1-dependent manner. PLK1-mediated MCM3 phosphorylation promotes RCC cell cycle proliferation and suppresses apoptosis in vitro. Moreover, we found that PLK1-mediated MCM3 phosphorylation induced cellular proliferation and decreased apoptosis, as well as tumor growth in mice. Overall, we conclude that PLK1-mediated MCM3 phosphorylation is a novel mechanism to regulate RCC proliferation and apoptosis.