Aldolase A promotes cervical cancer cell radioresistance by regulating the glycolysis and DNA damage after irradiation.

Radioresistance is the major obstacle that affects the efficacy of radiotherapy which is an important treatment for cervical cancer. By analyzing the databases, we found that aldolase A (ALDOA), which is a key enzyme in metabolic reprogramming, has a higher expression in cervical cancer patients and is associated with poor prognosis. We detected the expression of ALDOA in the constructed cervical cancer radioresistance (RR) cells by repetitive irradiation and found that it was upregulated compared to the control cells. Functional assays were conducted and the results showed that the knockdown of ALDOA in cervical cancer RR cells inhibited the proliferation, migration, and clonogenic abilities by regulating the cell glycolysis. In addition, downregulation of ALDOA enhanced radiation-induced apoptosis and DNA damage by causing G2/M phase arrest and further promoted radiosensitivity of cervical cancer cells. The functions of ALDOA in regulating tumor radiosensitivity were also verified by the mouse tumor transplantation model in vivo. Therefore, our study provides new insights into the functions of ALDOA in regulating the efficacy of radiotherapy and indicates that ALDOA might be a promising target for enhancing radiosensitivity in treating cervical cancer patients.

Projections from anteromedial thalamus nucleus to the midcingulate cortex mediate pain and anxiety-like behaviors in mice.

Prior research has demonstrated the involvement of the midcingulate cortex (MCC) and its downstream pathway in pain regulation. However, the mechanism via which pain information is conveyed to the MCC remains unclear. The present study utilized immunohistochemistry, chemogenetics, optogenetics, and behavior detection methods to explore the involvement of MCC, anteromedial thalamus nucleus (AM), and AM-MCC pathway in pain and emotional regulation. Chemogenetics or optogenetics methods were employed to activate/inhibit MCCCaMKIIα, AMCaMKIIα, AMCaMKIIα-MCC pathway. This manipulation evokes/relieves mechanical and partial heat hyperalgesia, as well as anxiety-like behaviors. In the complete Freund,s adjuvant (CFA) inflammatory pain model, chemogenetic inhibition of the AMCaMKIIα-MCCCaMKIIα pathway contributed to pain relief. Notably, this study presented the first evidence implicating the AM in the regulation of nociception and negative emotions. Additionally, it was observed that the MCC primarily receives projections from the AM, highlighting the crucial role of this pathway in the transmission of pain and emotional information.

Treatment strategies for intrauterine adhesion: focus on the exosomes and hydrogels.

Intrauterine adhesion (IUA), also referred to as Asherman Syndrome (AS), results from uterine trauma in both pregnant and nonpregnant women. The IUA damages the endometrial bottom layer, causing partial or complete occlusion of the uterine cavity. This leads to irregular menstruation, infertility, or repeated abortions. Transcervical adhesion electroreception (TCRA) is frequently used to treat IUA, which greatly lowers the prevalence of adhesions and increases pregnancy rates. Although surgery aims to disentangle the adhesive tissue, it can exacerbate the development of IUA when the degree of adhesion is severer. Therefore, it is critical to develop innovative therapeutic approaches for the prevention of IUA. Endometrial fibrosis is the essence of IUA, and studies have found that the use of different types of mesenchymal stem cells (MSCs) can reduce the risk of endometrial fibrosis and increase the possibility of pregnancy. Recent research has suggested that exosomes derived from MSCs can overcome the limitations of MSCs, such as immunogenicity and tumorigenicity risks, thereby providing new directions for IUA treatment. Moreover, the hydrogel drug delivery system can significantly ameliorate the recurrence rate of adhesions and the intrauterine pregnancy rate of patients, and its potential mechanism in the treatment of IUA has also been studied. It has been shown that the combination of two or more therapeutic schemes has broader application prospects; therefore, this article reviews the pathophysiology of IUA and current treatment strategies, focusing on exosomes combined with hydrogels in the treatment of IUA. Although the use of exosomes and hydrogels has certain challenges in treating IUA, they still provide new promising directions in this field.

Electron coupling effect-triggered monatomic copper laccase-mimicking nanozyme for the degradation and detection of guaiacol produced by Alicyclobacillus acidoterrestris.

The generation of guaiacol by Alicyclobacillus acidoterrestris (A. acidoterrestris) in fruit juices negatively affects public health and causes severe environmental pollution. Therefore, the sensitive detection and efficient degradation of guaiacol in real samples are crucial. Here, we develop an electrochemical sensor utilizing a copper single-atom nanozyme (CuN4-G) to detect and degrade guaiacol at the picomolar level. Density functional theory (DFT) calculations verify that the bonding electron coupling effect in the CuN4-G facilitates rapid electron transfer, enhances electrical conductivity, and provides abundant active sites, thereby leading to exceptional catalytic performance. Moreover, CuN4-G demonstrates a Km value similar to that of natural laccase but a higher Vmax, highlighting its potential as a highly efficient biocatalyst. The CuN4-G-based electrochemical sensor achieves a detection from 5 to 50,000 pM for guaiacol, with a 1.2 pM (S/N = 3) detection limit. Additionally, CuN4-G-modified electrodes display high selectivity and excellent stability. CuN4-G nanozyme can keep its activity in conditions of pH (3-9), temperature (30-90 °C), ionic strength (0-400 mM), and organic solvent (0-50% (v/v)), overcoming the deficiencies of natural enzymes. Furthermore, our electrochemical sensor can not only accurately detect guaiacol, but also degrade it in actual fruit juice samples infected by A. acidoterrestris, demonstrating its potential applications in food and environmental monitoring.

Colorimetric sensor array based on Au2Pt nanozymes for antioxidant nutrition quality evaluation in food.

Total antioxidant capacity (TAC) has become an important index to evaluate the food quality. Effective antioxidant detection has been the research hotspot of scientists. In this work, a novel three-channel colorimetric sensor array founded on Au2Pt bimetallic nanozymes for the discrimination of antioxidants in food was constructed. Benefiting from the unique bimetallic doping structure, Au2Pt nanospheres exhibited the excellent peroxidase-like activity with Km of 0.044 mM and Vmax of 19.37 × 10-8 M s-1 toward TMB. The density functional theory (DFT) calculation revealed that Pt atom in the doping system was active sites and there was no energy barrier in catalytic reaction which made Au2Pt nanospheres had excellent catalytic activity. Accordingly, a multifunctional colorimetric sensor array was constructed based on Au2Pt bimetallic nanozymes for rapid and sensitive detection of five antioxidants. Based on the different reduction ability of antioxidants, oxidized TMB could be reduced in different degrees. In the presence of H2O2, the colorimetric sensor array could generate differential colorimetric signals (fingerprints) by using TMB as the chromogenic substrate, which could be accurately discriminated through linear discriminant analysis (LDA) with a detection limit of <0.2 µM. The sensor array was able to the evaluate TAC in three actual samples (milk, green tea and orange juice). Furthermore, we prepared a rapid detection strip to meet the needs of practical application, making a positive contribution to food quality evaluation.

Nanozyme colorimetric sensor array based on monatomic cobalt for the discrimination of sulfur-containing metal salts.

The identification of sulfur-containing metal salts (SCMs) is of great interest because they play an important role in many biological processes and diseases. Here, we constructed a ternary channel colorimetric sensor array to detect multiple SCMs simultaneously, relying on monatomic Co embedded in nitrogen-doped graphene nanozyme (CoN4-G). Due to the unique structure, CoN4-G exhibits activity similar to native oxidases, capable of catalysing directly the oxidization of 3,3',5,5'-tetramethylbenzidine (TMB) by O2 molecules independent of H2O2. Density functional theory (DFT) calculations suggest that CoN4-G has no potential barrier in the whole reaction route, thus presenting higher oxidase-like catalytic activity. Based on different degrees of TMB oxidation, different colorimetric response changes are obtained as "fingerprints" on the sensor array. The sensor array can discriminate different concentrations of unitary, binary, ternary, and quaternary SCMs and has been successfully applied to detect six real samples (soil, milk, red wine and egg white). To advance the field detection of the above four types of SCMs, we creatively propose a smartphone-based autonomous detection platform with a linear range of 1.6-320 µM and a limit of detection of 0.0778-0.218 µM, which demonstrates the potential use of sensor arrays in the application of disease diagnosis and food and environment monitoring.

Effects of drip irrigation frequency on the yield and nutrient utilization efficiency of tomato under long-season cultivation in solar greenhouse.

To improve the utilization efficiency of nutrients and water and determine the best drip irrigation frequency for long-season tomato cultivation in solar greenhouses, we cultivated tomato grafted seedlings in soil using an integrated water and fertilizer technology: drip irrigation under mulch. Seedlings drip-irrigated with balanced fertilizer (containing 20% N, 20% P2O5, and 20% K2O) and high-K fertilizer (containing 17% N, 8% P2O5, and 30% K2O) once every 12 days were set as control (CK) and that with water once every 12 days as CK1, while other seedling groups, drip-irrigated with a nutrient solution of Yamazaki (1978) formula for tomato, were set as treatments (T1-T4). There were four drip-irrigation frequencies, i.e., once every 2 days (T1), 4 days (T2), 6 days (T3), or 12 days (T4), who received the same total amounts of fertilizer and water over the 12 experimental days. The results showed that, with the decreases of drip irrigation frequency, tomato yield, the accumulation of N, P and K in plant dry matter, the fertilizer partial productivity, and the nutrient utilization rate first increased and then decreased, peaking at the T2 treatment. Compared with CK, under the T2 treatment, plant dry matter accumulation and the accumulation of N, P and K increased by 4.9%, 8.0%, 8.0%, 16.8%, the partial productivity of fertilizer and the utilization efficiency of water increased by 142.8% and 12.2%, the use efficiency of N, P and K was better than CK by 241.4%, 466.6% and 235.9%, respectively, and the tomato yield increased by 12.2%. Under the experimental conditions, drip irrigation with the Yamazaki nutrient solution at a frequency of 4 days could increase the tomato yield, as well as the use efficiency of nutrients and water. Under long-season cultivation, these trends would result in considerable saving of water and fertilizer. Overall, our findings provided a basis for improving the scientific management of water and fertilizers under long-season tomato cultivation in protected facilities.

Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice.

Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience.

Characterization of fecal microbiota in cervical cancer patients associated with tumor stage and prognosis.

Cervical cancer (CC) is the fourth most frequent malignancy among women worldwide, and its prevention and treatment are evolving rapidly. The gut microbiota has been reported to play a crucial role both in the preservation of homeostasis and the development of cervical cancer. In this study, we collected fecal samples to investigate the microbial signatures in cervical cancer patients compared with healthy controls using 16S rRNA sequencing analysis and metagenomic next-generation sequencing (mNGS) testing. Our findings demonstrated a substantial difference in the gut microbiota composition of cervical cancer patients and healthy controls. The disease and stage were most significantly negatively correlated with Ruminococcus 2, which might be considered a potential clinically relevant biomarker. Functions of differential microbiomes were also analyzed, indicating significant differences in metabolisms and biosynthesis between the two groups. These findings demonstrate that patients with cervical cancer have certain species of gut microbiota that are exclusive to them and particular species have the potential to be used in the prognosis of cervical cancer.

Projections from the Rostral Zona Incerta to the Thalamic Paraventricular Nucleus Mediate Nociceptive Neurotransmission in Mice.

Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma-aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR-PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIRGABA+-PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIRGABA+-PVT pathway alleviates pain, whereas inhibiting the activities of the ZIRGABA+-PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABAAR) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIRGABA+-PVT pathway acts through GABAAR-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission.

Electrochemical sensor for detecting streptomycin in milk based on label-free aptamer chain and magnetic adsorption.

Exploiting a simple and sensitive sensor to efficiently detect streptomycin (STR) in milk is critical for resolving the harm caused to humans by STR residues. This study reports an electrochemical sensor using magnetic mesoporous carbon materials (MMCM) as a loaded material through magnetic adsorption immobilized on magnetic glassy carbon electrode (MGCE) and adsorbing unlabeled streptomycin aptamer (STP) as the identification element. The sensor can detect STR sensitively with a wide detection range (0.172-17.2 × 103 and 17.2 × 103 -17.2 × 105 nM) and a low detection limit of 0.015 nM. Experimental results revealed that the specific binding of STP with STR on the electrode changed the configuration of STP, thereby causing current change of differential pulse voltammetry curve. Compared with HPLC, this study provides a new method for rapid and sensitive detection of STR in milk (n = 5, 95 % confidence level, RSD＜5%).

Proper irrigation amount for eggplant cultivation in a solar greenhouse improved plant growth, fruit quality and yield by influencing the soil microbial community and rhizosphere environment.

Water scarcity is a worldwide problem, and in order to obtain plenty of production, agricultural irrigation water accounts for a large portion. Many studies have shown that the interaction of root microorganisms and soil can promote crop growth. Developing ways to reduce irrigation to maintain soil fertility and ensure crop yield by regulating the root microenvironment is an important research goal. Here, we developed a reasonable irrigation plan for eggplant cultivation in a solar greenhouse. The maximum theoretical amount of water demand during eggplant planting obtained from a previous study was used as the control (CK), and the irrigation in the treatments was reduced by 10, 20 and 30% relative to this amount. The 10% irrigation reduction treatment (T1) significantly improved soil nutrients and increased soil catalase, urease and alkaline phosphatase activities (p < 0.05). Further analysis of rhizosphere microorganisms revealed the highest richness and diversity of the microbial community under the T1 treatment, with Bacilli as the most abundant bacteria and Aspergillaceae as the most abundant fungi and lower relative abundances of Chloroflexi and Acidobacteria (p < 0.05). Changes in microbial community structure under the influence of different irrigation treatments resulted in improvements in rhizosphere N cycling and nutrient catabolism. The plant-microbe interactions led to significant increases in eggplant plant height, root vigour, root surface area, leaf chlorophyll a, leaf net photosynthetic rate, water use efficiency, transpiration rate, and stomatal conductance under the T1 treatment compared to the CK treatment; soluble sugar, soluble protein and free amino acid contents in eggplant fruit increased by 10.8, 12.3 and 6.7%, respectively; and yield increased by 3.9%. Our research proved that the 10% irrigation reduction treatment (T1) could improve microbial community richness and fruit yield, which would improve irrigation efficiency and cost reduction in agriculture.

Recent progress of the tumor microenvironmental metabolism in cervical cancer radioresistance.

Radiotherapy is widely used as an indispensable treatment option for cervical cancer patients. However, radioresistance always occurs and has become a big obstacle to treatment efficacy. The reason for radioresistance is mainly attributed to the high repair ability of tumor cells that overcome the DNA damage caused by radiotherapy, and the increased self-healing ability of cancer stem cells (CSCs). Accumulating findings have demonstrated that the tumor microenvironment (TME) is closely related to cervical cancer radioresistance in many aspects, especially in the metabolic processes. In this review, we discuss radiotherapy in cervical cancer radioresistance, and focus on recent research progress of the TME metabolism that affects radioresistance in cervical cancer. Understanding the mechanism of metabolism in cervical cancer radioresistance may help identify useful therapeutic targets for developing novel therapy, overcome radioresistance and improve the efficacy of radiotherapy in clinics and quality of life of patients.

Genome-Wide Identification and Functional Characterization of Auxin Response Factor (ARF) Genes in Eggplant.

Auxin response factors (ARFs) are important plant transcription factors that are differentially expressed in response to auxin and various abiotic stresses. ARFs play important roles in mediating plant growth and stress responses; however, these factors have not been studied in eggplants. In this study, genome-wide identification and the functional analysis of the ARF gene family in eggplants (Solanum melongena L.) were performed. A total of 20 ARF (SmARF) genes were identified and phylogenetically classified into three groups. Our analysis revealed four functional domains and 10 motifs in these proteins. Subcellular localization showed that the SmARFs localized in the nucleus. To investigate the biological functions of the SmARFs under 2,4-D and salt stress treatments, quantitative real-time RT-PCR (qRT-PCR) was conducted. Most SmARF genes exhibited changes in expression in response to 2,4-D treatments in the flowers, especially SmARF4 and 7B. All SmARF genes quickly responded to salt stress, except SmARF17 and 19 in leaves, SmARF1A and 7B in roots, and SmARF2A, SmARF7B, and SmARF16B in stems. These results helped to elucidate the role of ARFs in auxin signaling under 2,4-D and salt stress in eggplants.

Organic Photosensitizers Incorporating Rigid Benzo[1,2-b:6,5-b']dithiophene Segment for High-Performance Dye-Sensitized Solar Cells.

Benzo[1,2-b:6,5-b']dithiophene (BDT) entity with rigid skeleton is introduced into the conjugated spacer of organic dyes, with triphenylamine as the electron donor and 2-cyanoacrylic acid as the acceptor, have been prepared for dye-sensitized solar cells. Inserting an aromatic entity between BDT and the anchor extends the absorption wavelength of the dyes and improves the dark current suppression efficiency, and consequently leads to better cell performance. Addition of chenodeoxycholic acid coadsorbent alleviates dye aggregation and results in better cell efficiency. The dye inserted with 4H-cyclopenta[2,1-b:3,4-b']dithiophene entity achieves the best efficiency (9.11%) when I-/I3- was used as the electrolyte. When Co(phen)32+/3+ was used as the electrolyte, the efficiency further boosts to 9.88%.

High-performance aqueous/organic dye-sensitized solar cells based on sensitizers containing triethylene oxide methyl ether.

Metal-free dyes (EO1 to EO4) containing the hydrophilic triethylene oxide methyl ether (TEOME) unit in the spacer have been synthesized and used in dye-sensitized solar cells (DSSCs). Efficient lithium-ion trapping by TEOME results in improved open-circuit voltage (VOC ), leading to excellent conversion efficiency of the cells, ranging from 9.02 to 9.98 % with I(-) /I3 (-) electrolyte in acetonitrile under AM 1.5 illumination. The TEOME unit also enhances the wettability of the dye molecules for application in aqueous-based DSSCs. Aqueous-based DSSCs with a dual TEMPO/iodide electrolyte exhibit high VOC values (0.80-0.88 V) and very promising cell performances of up to 5.97 %.

Anthracene/phenothiazine π-conjugated sensitizers for dye-sensitized solar cells using redox mediator in organic and water-based solvents.

Metal-free dyes (MD1 to MD5) containing an anthracene/phenothiazine unit in the spacer have been synthesized. The conversion efficiency (7.13 %) of the dye-sensitized solar cell using MD3 as the sensitizer reached approximately 85 % of the N719-based standard cell (8.47 %). The cell efficiency (8.42 %) of MD3-based dye-sensitized solar cells (DSSCs) with addition of chenodeoxycholic acid is comparable with that of N719-based standard cell. The MD3 water-based DSSCs using a dual-TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl)/iodide electrolyte exhibited very promising cell performance of 4.96 % with an excellent Voc of 0.77 V.

Reversine induces cell cycle arrest, polyploidy, and apoptosis in human breast cancer cells.

BACKGROUND: Reversine, a small synthetic purine analogue, has been reported to be effective in tumor suppression. In the present study, we demonstrated an antitumor activity of reversine that could suppress cellular proliferation and induce cell cycle arrest and apoptosis in human breast cancer cell lines. METHODS: To evaluate whether reversine could suppress cell growth of MCF-7 and MDA-MB-231 cells and induce cell death, the cell viability, cell cycle, and apoptosis were determined in this study. RESULTS: Reversine treatment in human breast cancer cells reduced cell viability in a dose-dependent manner. Cell cycle accumulation at the G2/M phase in reversine-treated cells was also determined. Moreover, polyploidy was also found in reversine-treated cells. Apoptosis in reversine-treated cells was exhibited with PARP cleavage and caspase-3 and caspase-8 activation, but not caspase-9 activation, indicating that caspase-dependent apoptosis mediated by an extrinsic pathway took place in reversine-treated cells. Furthermore, reversine attenuated cell death in cells pretreated with a pan-caspase inhibitor before reversine treatment. CONCLUSIONS: In the present study, we demonstrated that reversine contributes to growth inhibition in human breast cancer cells through cell cycle arrest, polyploidy, and/or apoptosis induction. The apoptosis mediated by reversine was induced by the mitochondria-independent pathway. Therefore, the potential role of reversine as a novel therapeutic agent for the treatment of breast cancer is worthy of further investigation.

An echovirus 18-associated outbreak of aseptic meningitis in Taiwan: epidemiology and diagnostic and genetic aspects.

In 2006, an outbreak of aseptic meningitis was noted in Taiwan. From January to October 2006, a total of 3283 specimens collected from patients with viral infection, including 173 cerebrospinal fluid (CSF) samples, were examined for virus isolation and identification. Overall, 339 enterovirus (EV)-positive cases were identified by virus culture: echovirus 18 (E18) formed the majority (27.4 %, 93 cases), followed by coxsackievirus B2 (13.8 %, 47 cases) and coxsackievirus A2 (10.8 %, 37 cases). The manifestations of the 93 E18 cases were aseptic meningitis (44.1 %), viral exanthema (23.6 %), acute tonsillitis (15.1 %), acute pharyngitis (14.0 %), acute gastritis (11.8 %), herpangina (7.5 %) and bronchopneumonia (5.3 %). Of 107 E18 isolates identified, 100, 62.5 and 19 % were obtained following culture in RD, MRC-5 and A549 cells, respectively. E18 was identified most frequently from throat swabs (67.2 %) and less frequently from stool samples (15.9 %) and CSF (16.8 %). The detection rate of E18 was 78.2 % from CSF, 50 % from stool samples and 22.9 % from throat swabs. Phylogenetic relationships among the E18 strains were examined. Analysis of the partial VP1 gene showed 3.7-23.8 % variation in sequence compared with sequences from GenBank and, notably, the amino acid change V152S was detected in a protruding loop within the VP1 protein. These results indicate that a genetic variant of E18 was circulating and caused an outbreak of aseptic meningitis in Taiwan in 2006.

Methyl 1-benzyl-1H-1,2,3-triazole-4-carboxyl-ate.

In the title compound, C(11)H(11)N(3)O(2), prepared by the [3+2] cycloaddition reaction of benzyl azide with methyl propiolate, the dihedral angle between the ring planes is 67.87 (11)°.