Microenvironment-responsive electrocution of tumor and bacteria by implants modified with degenerate semiconductor film.

Implantable biomaterials are widely used in the curative resection and palliative treatment of various types of cancers. However, cancer residue around the implants usually leads to treatment failure with cancer reoccurrence. Postoperation chemotherapy and radiation therapy are widely applied to clear the residual cancer cells but induce serious side effects. It is urgent to develop advanced therapy to minimize systemic toxicity while maintaining efficient cancer-killing ability. Herein, we report a degenerate layered double hydroxide (LDH) film modified implant, which realizes microenvironment-responsive electrotherapy. The film can gradually transform into a nondegenerate state and release holes. When in contact with tumor cells or bacteria, the film quickly transforms into a nondegenerate state and releases holes at a high rate, rendering the "electrocution" of tumor cells and bacteria. However, when placed in normal tissue, the hole release rate of the film is much slower, thus, causing little harm to normal cells. Therefore, the constructed film can intelligently identify and meet the physiological requirements promptly. In addition, the transformation between degenerate and nondegenerate states of LDH films can be cycled by electrical charging, so their selective and dynamic physiological functions can be artificially adjusted according to demand.

Effects of Laparoscopic Hyperthermic Perfusion Therapy Combined with Adjuvant Treatment of Compound Yew Capsule on Ovarian Blood Flow Parameters and Immune Function in Patients with Ovarian Cancer.

Objective: To determine the effects of laparoscopic hyperthermic perfusion therapy combined with adjuvant compound yew capsules on ovarian blood flow parameters and immune function in patients with ovarian cancer (OC). Methods: A total of 90 OC patients enrolled in our hospital between January 2019 and January 2020 were randomly distributed into the control (Con group) and experimental group (Exp group) based on the sealed envelope method. The Con group was administered laparoscopic hyperthermic perfusion therapy. On this basis, the Exp group was subjected to compound yew capsules; the ovarian blood flow parameters and immune function indexes were compared between the two groups. Results: The Exp group was reported to perform better than the Con group regarding ovarian blood flow parameters and immune indexes after treatment (p < 0.001). Conclusion: Laparoscopic hyperthermic perfusion therapy combined with adjuvant compound yew capsules for patients with OC can substantially improve the clinical indexes and immune function. Furthermore, research and adequate promotion are needed to elicit the evidence beyond preclinical studies to understand the intricacies of its implementation.

MXene Quantum Dot/Zeolitic Imidazolate Framework Nanocarriers for Dual Stimulus Triggered Tumor Chemo-Phototherapy.

It is critical to construct stimuli-responsive multifunctional nanoparticles for the drug delivery system for cancer treatment. Zeolitic imidazolate framework-8 (ZIF-8) has a large specific surface area and decomposes quickly under acidic conditions, which presents an excellent potential in pH-sensitive drug carriers. However, the mere chemotherapeutic drug loaded into ZIF-8 is a monotherapy and may restrict the therapeutic efficacy of malignancies. In this work, an effective nanoparticle-based delivery platform is established to simultaneously encapsulate doxorubicin (DOX) and MXene quantum dot (MQD) in ZIF-8 nanoparticles (MQD@ZIF-8/DOX). Under near-infrared (NIR) laser (808 nm) and UV light (365 nm) irradiation, MQD@ZIF-8 demonstrates a high photothermal conversion efficiency and reactive oxygen species (ROS) production, which shows excellent photothermal therapy and photodynamic therapy effects. Furthermore, the release of DOX-loaded into MQD@ZIF-8 nanoparticles is significantly increased under NIR laser irradiation and at pH 5.6, indicating that acidic conditions and NIR laser irradiation can be effectively combined to stimulate the drug release. The cellular experiments show that MQD@ZIF-8/DOX has an obvious killing effect on HeLa cells and achieves the combined anti-tumor effect of chemotherapy and phototherapy.

Serum Levels of PDGF, EGF, and sFlt-1 in Patients with Polycystic Ovary Syndrome and Their Predictive Effects on Pregnancy Outcomes.

Polycystic ovary syndrome (PCOS) is a neuroendocrine disease with complex etiology characterized by infrequent menstruation, follicular developmental disorders, insulin resistance, and hyperandrogenism. PCOS patients often suffer from anovulatory infertility, and even after successful pregnancy promotion, spontaneous abortion is easy to occur. At present, PCOS is mainly diagnosed by auxiliary examinations such as sex hormones and B ultrasonography, and there is a lack of specific serological markers for the diagnosis of diseases. Similarly, there is a lack of effective evaluation methods for the risk of abortion in PCOS patients. Therefore, it is extremely important to explore the factors that affect the occurrence of abortion in PCOS patients and to find specific indicators that can guide the pregnancy outcome of PCOS patients. The purpose of this study was to investigate the serum levels of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) in PCOS patients and analyze their predictive effects on the pregnancy outcomes of PCOS patients. The results showed that serum PDGF, EGF, and sFlt-1 levels were secreted abnormally in PCOS patients with abortion and were closely related to the pregnancy outcome of PCOS patients. The combination of the three levels has the highest value in predicting the pregnancy outcome of PCOS patients, which is worth promoting.

A Novel Stimuli-Responsive Injectable Antibacterial Hydrogel to Achieve Synergetic Photothermal/Gene-Targeted Therapy towards Uveal Melanoma.

Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor with a high lethal rate. Patients who undergo conventional enucleation treatments consistently suffer permanent blindness, facial defects, and mental disorders, therefore, novel therapeutic modalities are urgently required. Herein, an injectable and stimuli-responsive drug delivery antibacterial hydrogel (CP@Au@DC_AC50) is constructed via a facile grinding method that is inspired by the preparation process of traditional Chinese medicine. The incorporation of gold nanorods can enhance the mechanical strength of the hydrogel and realize photothermal therapy (PTT) and thermosensitive gel-sol transformation to release the gene-targeted drug DC_AC50 on demand in response to low-density near-infrared (NIR) light. The orthotopic model of UM is built successfully and indicates the excellent efficiency of CP@Au@DC_AC50 in killing tumors without damage to normal tissue because of its synergistic mild temperature PTT and gene-targeted therapy. Moreover, the eyeball infection model reveals the remarkable antibacterial properties of the hydrogel which can prevent endophthalmitis in the eyeball. There is negligible difference between the CP@Au@DC_AC50+NIR group and normal group. This NIR light-triggered gene-targeted therapy/PTT/antibacterial treatment pattern provides a promising strategy for building multifunctional therapeutic platform against intraocular tumors and exhibits great potential for the clinical treatment of UM.

Biological and antibacterial properties of TiO2 coatings containing Ca/P/Ag by one-step and two-step methods.

The porous TiO2 coatings containing Ca/P/Ag were separately prepared on titanium (Ti) surface by one-step (micro-arc oxidation) and two-step methods (micro-arc oxidation and cathodic deposition), and then their surface morphology, composition, biological and antibacterial properties were compared. The results showed that the porous coatings containing Ca/P/Ag achieved by different methods showed similar surface morphology and elemental composition, however, by one-step method, silver existed in the coating as silver phosphate, while in the coatings prepared by two-step method, silver existed as metallic silver. Although both coatings showed excellent antibacterial property (the antimicrobial rate is over 99.9%), the surface coating prepared by one-step method had a more suitable release curve of Ag. In addition, the surface coating prepared by one-step method also presented better biological property, which was due to its enhanced surface roughness and hydrophilicity. Combining with its easy operation and long-term antibacterial property, its prospect for clinical application is more promising.

[Effect of different courses of electroacupuncture intervention on recognition memory and proliferation and differentiation of hippocampal neural stem cells in mice with radiation-induced brain injury].

OBJECTIVE: To observe the influence of different courses of electroacupuncture (EA) intervention on recognition memory and the proliferation and differentiation of hippocampal neural stem cells in mice with radiation-induced brain injury, so as to explore its mechanisms underlying improving radiation-induced brain injury. METHODS: Se-venty 30-day old C57BL/6J mice were randomly divided into control, model and EA groups, and the latter two groups were further divided into 1 week (W), 2 W and 3 W subgroups (n=10 in the control group and each subgroup). The ra-diation-induced brain injury model was established by radiating the mouse' left head at a dose of 8 Gy for 10 min by using a radiation linear accelerator. EA (1.5 V, 2 Hz/10 Hz) was applied to "Baihui" (GV20), "Fengfu" (GV14) and bilateral "Shenshu" (BL23) for 30 min, once daily for 1, 2 and 3 weeks, respectively. The learning-cognition memory ability was detected by using novel object recognition test in an open test box to record the time for exploring a novel object (TN) and a familiar object and to calculate the recognition index (RI). The neural stem cells' proliferation and differentiation in the hippocampus tissues were evaluated by counting the number of bromodeoxyuridine (BrdU)-labeled cells, neuronal nuclei (NeuN)/BrdU-positive cells and BrdU/glia fibrillary acidic protein (GFAP)-positive cells under microscope after immunofluorescence stain. RESULTS: After modeling, the TN at 90 min and 24 h and RI of the model subgroup 3 W at 90 min and RI of the model subgroup 1, 2 and 3 W at 24 h were significantly decreased in comparison with those of the control group (P<0.01, P<0.05). Moreover, the number of BrdU-positive cells in the model subgroup 1 W and 2 W, the BrdU/NeuN double-labeled cells in the 3 model subgroups and BrdU/GFAP double-labeled cells in the model subgroup 1 W and 3 W were significantly decreased (P<0.01, P<0.05). Following EA interventions, the TN in the 3 EA subgroups at both 90 min and 24 h, and RI of EA subgroup 3 W at 90 min and EA subgroup 2 W and 3 W at 24 h were considerably increased compared with those of the corresponding 3 model subgroups (P<0.05, P<0.01). The numbers of BrdU-positive cells as well as BrdU/NeuN and BrdU/GFAP double-labeled cells were significantly increased in the 3 EA subgroups (P<0.05, P<0.01, P<0.001). CONCLUSION: EA of GV20, GV14 and BL23 can improve the recognition memory ability of mice with radiation-induced brain injury, which may be related to its effect in promoting the proliferation and differentiation of stem cells in the hippocampus.

Sodium nitrite negatively affects reproductive ability and offspring survival in female mice.

Sodium nitrite (NaNO2) is an industrial chemical that is frequently used as a food additive to prevent botulism and enhance glossiness, such as curing meat. In addition, in some regions, water source NaNO2 concentrations exceed standard regulatory levels. Whether the excessive intake of NaNO2 has toxic effects on female fertility and fetal development remain unknown. In this study, we administered ICR mice control saline, low-dose NaNO2 (60 mg/kg/day), or high-dose NaNO2 (120 mg/kg/day) by intragastric gavage for 21 days. We then assessed oocyte morphology, spindle-chromosome dynamics, mitochondrial distribution, ATP content, apoptotic cell numbers, DNA damage levels, histone modifications, reactive oxygen species (ROS) levels, and offspring survival. Results showed that NaNO2 treatment decreased oocyte number, impaired polar body extrusion, and increased zona pellucida thickness in oocytes. Furthermore, NaNO2 disrupted MII spindle integrity, caused abnormal mitochondrial distribution, decreased ATP content, and increased levels of ROS and H3K4me2. Moreover, the number of oocytes in early stages of apoptosis and with levels of DNA damage increased in NaNO2-treated mice along with decreased offspring numbers and survival rates. We demonstrated the negative effects of NaNO2 on female reproductive abilities in mice.

Assembled gold nanorods for the photothermal killing of bacteria.

Titanium and its alloys are widely used in many clinical applications, but implant-associated infection may lead to implant failure. Because of the increasing concern about antibiotic resistant pathogen, photothermal therapy (PTT) as a new treatment strategy has received considerable attention. In this work, gold nanorods (GNRs) photoexcited by the near-infrared (NIR) light were immobilized on Ti surface by electrostatic surface self-assembly technique. Field emission scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were used to explore the morphology and composition of the GNRs-modified surface. The photothermal temperature of the immobilized GNRs was measured by an infrared thermal imaging system in real time. In vitro study reveal that the prepared GNRs-modified surface exhibits antibacterial activity against four kinds of bacterial strains including both Gram-negative bacilli (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive cocci (Staphylococcus aureus and Staphylococcus epidermidis) under the irradiation of 808 nm laser. Besides, the antibacterial efficiency of the GNRs-modified surface could keep stable after multiple laser exposure. It should be noted that the GNRs-modified surface shows better antibacterial effect against Gram-negative bacilli compared to Gram-positive cocci. Moreover, the GNRs-modified surface has no obvious adverse effect to the osteoblast precursor cells under NIR irradiation. These data demonstrate that the GNRs-modified surface with negligible cytotoxicity and recyclable antibacterial effect provides a favorable model for the translation of photothermal therapy to the clinical application.

[Changes of transport sugar content in different organs of Rehmannia glutinosa].

Raffinose series oligosaccharides are the transport and storage sugars of many plants, Rehmannia glutinosa is one of the commonly used Chinese herbal medicines, medicinal parts ist he roots. Root and tuber of R. glutinosa contains stachyose, raffinose and other oligosaccharides, but the study about the process of growth and development of other organs in the non-structural changes in sugar content is rare.In this study, leaves, stems and roots of R. glutinosa were used as materials to analyze the diurnal variation and the changes of sugar content of sucrose, raffinose and stachyose in different organs of R. glutinosa. The results showed that the content of sucrose in R. glutinosa leaves gradually increased from seedling stage.However, the content of stachyose did not change much at the early stage of growth, and the stachyose rapidly increased at the later stage of growth. The raffinose content gradually decreased throughout the growing season, young leaves of R. glutinosa have higher ability to sucrose synthesis than mature leaves, while mature leaf has higher raffinose and stachyose synthesis ability than young leaves. Sucrose and stachyose content in stem gradually increased, while there was little change in raffinose content. The content of raffinose and stachyose in root increased rapidly from the beginning of fast growing period, while the content of sucrose did not change much. The content of sucrose in leaves of R. glutinosa did not change much at day and night, while the daily changes of raffinose and stachyose contents were very obvious. The contents of raffinose and stachyose in daytime were higher than those at night. The content of raffinose in root and stem was not changed much, but the change of stachyose in root, stem and leaf was very obvious, especially in stem and leaf. In summary, the leaf is the main synthetic organ of raffinose, leaves, stems and roots are stachyose synthesis organ. Sucrose, raffinose and stachyose are the major transport forms of carbohydrates in R. glutinosa.

Phytosterol Profiles of Common Foods and Estimated Natural Intake of Different Structures and Forms in China.

Phytosterols are well-known for their cholesterol-lowering effects, and the structures and forms of phytosterols affect their bioactivity. We aimed to illustrate the phytosterol profiles in common foods and estimate their natural intake in five geographical regions and among different age groups in China. In total, 12 phytosterols in free and esterified forms of 119 foods from five regions across China were examined using gas chromatography-mass spectrometry. Then, the dietary intake of phytosterols was calculated combined with the dietary foods intake data of Chinese people. The total phytosterol content was highest in vegetable oils (150.4-1230.9 mg/100 g), followed by legumes (129.6-275.6 mg/100 g), nuts (18.9-255.2 mg/100 g), and cereals (11.9-93.8 mg/100 g). Vegetables and fruits contained lower contents of total phytosterols. Phytosterols were mainly esterified in most common foods except in nuts. The predominant phytosterols were ß-sitosterol, campesterol, and stigmasterol, all of which belonged to plant sterols and 4-desmethylsterols. Total phytosterol intake varied across different regions, ranging between 257.7 and 473.7 mg/standard-person (sp)/day, with the highest intake in Beijing, followed by Hangzhou, Wuhan, Chongqing, and Guangzhou. However, phytosterol proportion was similar across regions, with ß-sitosterol accounting for 46.5-50.3% of the natural intake. Phytosterol intake was mainly constituted by plant sterols and 4-desmethylsterols in esterified form (61.9-74.6%). At the age of 2-70 years, phytosterol intake ranged from 154.3 mg/day to 348.0 mg/day in the national scale.

Molecular markers to assess short-term disease local recurrence in nasopharyngeal carcinoma.

An important challenge in nasopharyngeal carcinoma (NPC) research is to develop effective predictors of tumor recurrence following treatment to determine whether immediate adjuvant therapy is necessary. We retrospectively analyzed archived specimens collected from 45 patients with paired samples of primary NPC (pNPC) and recurrent NPC (rNPC). Clinical samples were collected from the Cancer Center Databases of the First People's Hospital of Foshan and Shantou Central Hospital (affiliates of Sun Yat-Sen University) between 2001 and 2012. Expression levels of phosphor-Stat3 (p-Stat3), signalosome complex subunit 5 (Jab1/Csn5), Akt1, C/EBP homologous protein (CHOP), Ki-67, and apoptosis were determined by immunohistochemistry in pNPC and rNPC samples from the same patients. Differences in these markers between the short-term interval to recurrence (ITR) group (ITR <18 months) and long-term ITR group (ITR ≥18 months) were further analyzed. In Cox's regression analysis, the ITR was significantly associated as an independent­negative prognostic factor for overall survival (hazard ratio, 0.211; 95% confidence interval, 0.053-0.841; P=0.027). p-Stat3 was increased in the short-term ITR group (ITR <18 months) and tended to be lower in the long-term ITR group (ITR ≥18 months). In the short-term ITR group, nuclear Akt expression was significantly increased in paired rNPC (P=0.028). In the long-term ITR group, the expression of nuclear Jab1/Csn5 (P=0.047) and assessment of apoptosis measured with TdT-mediated dUTP nick end­labeling (TUNEL) (P=0.003) was significantly increased in paired rNPC. The results suggest that differences between short- and long-term ITR may predict outcome in rNPC. Furthermore, the overexpression of Jab1/Csn5 and Akt may contribute to the carcinogenesis of rNPC, and Akt seems to promote the progression of short-term ITR. Intra-individual changes of Jab1/Csn5, Akt, and TUNEL may help to identify short-term ITR.

Ultrasonic extraction of antioxidants from Chinese sumac (Rhus typhina L.) fruit using response surface methodology and their characterization.

For the first time, response surface methodology (RSM) using a Box-Behnken Design (BBD) was employed to optimize the conditions for ultrasonic assisted extraction (UAE) of antioxidants from Chinese sumac (Rhus typhina L.) fruits. Initially, influencing factors such as liquid-solid ratio, duration of ultrasonic assisted extraction, pH range, extraction temperature and ethanol concentration were identified using single-factor experiments. Then, with respect to the three most significant influencing factors, the extraction process focusing on the DPPH· scavenging capacity of antioxidants was optimized using RSM. Results showed that the optimal conditions for antioxidant extraction were 13.03:1 (mL/g) liquid-solid ratio, 16.86 min extraction time and 40.51% (v/v) ethanol, and the desirability was 0.681. The UPLC-ESI-MS analysis results revealed eleven kinds of phenolic compounds, including four major rare anthocyanins, among the antioxidants. All these results suggest that UAE is efficient at extracting antioxidants and has the potential to be used in industry for this purpose.

Analysis of supercooling activity of tannin-related polyphenols.

Based on the discovery of novel supercooling-promoting hydrolyzable gallotannins from deep supercooling xylem parenchyma cells (XPCs) in Katsura tree (see Wang et al. (2012) [38]), supercooling capability of a wide variety of tannin-related polyphenols (TRPs) was examined in order to find more effective supercooling-promoting substances for their applications. The TRPs examined were single compounds including six kinds of hydrolyzable tannins, 11 kinds of catechin derivatives, two kinds of structural analogs of catechin and six kinds of phenolcarboxylic acid derivatives, 11 kinds of polyphenol mixtures and five kinds of crude plant tannin extracts. The effects of these TRPs on freezing were examined by droplet freezing assays using various solutions containing different kinds of identified ice nucleators such as the ice nucleation bacterium (INB) Erwinia ananas, the INB Xanthomonas campestris, silver iodide and phloroglucinol as well as a solution containing only unintentionally included unidentified airborne ice nucleators. Among the 41 kinds of TRPs examined, all of the hydrolyzable tannins, catechin derivatives, polyphenol mixtures and crude plant tannin extracts as well as a few structural analogs of catechin and phenolcarboxylic acid derivatives exhibited supercooling-promoting activity (SCA) with significant differences (p>0.05) from at least one of the solutions containing different kinds of ice nucleators. It should be noted that there were no TRPs exhibiting ice nucleation-enhancing activity (INA) in all solutions containing identified ice nucleators, whereas there were many TRPs exhibiting INA with significant differences in solutions containing unidentified ice nucleators alone. An emulsion freezing assay confirmed that these TRPs did not essentially affect homogeneous ice nucleation temperatures. It is thought that not only SCA but also INA in the TRPs are produced by interactions with heterogeneous ice nucleators, not by direct interaction with water molecules. In the present study, several TRPs that might be useful for applications due to their high SCA in many solutions were identified.

Characterization of an ethylene-inducible, calcium-dependent nuclease that is differentially expressed in cucumber flower development.

• Production of unisexual flowers is an important mechanism that promotes cross-pollination in angiosperms. We previously identified primordial anther-specific DNA damage and organ-specific ethylene perception responsible for the arrest of stamen development in female flowers, but little is known about how the two processes are linked. • To identify potential links between the two processes, we performed suppression subtractive hybridization (SSH) on cucumber (Cucumis sativus L.) stamens of male and female flowers at stage 6, with stamens at stage 5 of bisexual flowers as a control. • Among the differentially expressed genes, we identified an expressed sequence tag (EST) encoding a cucumber homolog to an Arabidopsis calcium-dependent nuclease (CAN), designated CsCaN. Full-length CsCaN cDNA and the respective genomic DNA sequence were cloned and characterized. The CsCaN protein exhibited calcium-dependent nuclease activity. CsCaN showed ubiquitous expression; however, increased gene expression was detected in the stamens of stage 6 female flowers compared with male flowers. As expected, CsCaN expression was ethylene inducible. It was of great interest that CsCaN was post-translationally modified. • This study demonstrated that CsCaN is a novel cucumber nuclease gene, whose DNase activity is regulated at multiple levels, and which could be involved in the primordial anther-specific DNA damage of developing female cucumber flowers.

Improved tumor vascular function following high-dose epidermal growth factor receptor tyrosine kinase inhibitor therapy.

PURPOSE: To determine if inhibitors of the human growth factor receptor (HER) family can be used to enhance tumor vascular permeability and perfusion and optimize the efficacy of cytotoxic chemotherapeutics. Poor tumor vascular function limits the delivery and efficacy of cancer chemotherapeutics and HER family tyrosine kinases mediate tumor-endothelial signaling in both of these compartments. MATERIALS AND METHODS: BT474 human breast cancer tumors were established in mice and the biologic effects of the HER tyrosine kinase inhibitor (TKI) gefitinib on tumor vascular function was determined by dynamic contrast-enhanced MRI (DCE-MRI), and on tumor vascular architecture and perfusion by immunofluorescence microscopy. RESULTS: A brief dose of gefitinib enhances the antitumor activity of paclitaxel in vivo but not in cell culture, suggesting that its chemoenhancing activity involves the in vivo microenvironment. A brief high dose of gefitinib induces a decrease in endothelial transfer constant (Kps) and a concomitant increase in tumor fractional plasma volume (fPV). These changes are accompanied by a rapid reduction in tumor volume, likely due to decreased tumor edema, and modestly improved tumor vascular architecture and perfusion on microscopy. CONCLUSION: These data suggest that HER family TKIs have the potential to optimize the tumor microenvironment for delivery of cytotoxic chemotherapeutics.

[Xinxibao for the treatment of chronic bacterial prostatitis].

OBJECTIVE: To study the effect of Xinxibao as a supplementary drug in the treatment of chronic bacterial prostatitis (CBP). METHODS: Eighty-one cases of CBP were divided into two groups: Group A (n = 38), treated with Xinxibao combined with sensitive antibiotic, and Group B (n = 43), treated with sensitive antibiotic only. Contrast studies were made on the therapeutic effects in the two groups, and the results were analyzed. RESULTS: The effectivity rate was significantly higher in Group A than in Group B. CONCLUSION: Xinxibao can effectively relieve the symptoms of CBP.