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Highlights Ni3Fe oxide, with an average size of 3.5 ± 1.5 nm, was successfully deposited onto polyaniline (PANI) support through a solvothermal strategy followed by calcination. The catalyst–support interaction between Ni3Fe oxide and PANI can enhance the Ni-O covalency via the interfacial Ni-N bond. Ni3Fe oxide/PANI-assembled Zn-air batteries achieve superior cycling life for over 400 h at 10 mA cm−2 and a low charge potential of around 1.95 V.

To study the surface morphology of Si3N4 ceramics using rotary ultrasonic grinding, changes in the surface morphology under different machining parameters were analyzed based on fractal theory. Orthogonal experiments were designed to compare and analyze the effects of various processing parameters on the fractal dimensions and multifractal spectra of the Si3N4 ceramic surface. Additionally, single-factor experiments were conducted to study the roughness, fractal dimensions, and multifractal spectra of the Si3N4 ceramic surface under different processing parameters. The results show that fractal dimensions can effectively characterize the defect state of the processed surface of Si3N4 ceramics during rotary ultrasonic grinding, while multifractal spectra can better represent the degree of fluctuation in surface defects.

Abstract Background Diabetes mellitus (DM) can aggravate lung ischemia-reperfusion (I/R) injury and is a significant risk factor for recipient mortality after lung transplantation. Metformin protects against I/R injury in a variety of organs. However, the effect of metformin on diabetic lung I/R injury remains unclear. Therefore, this study aimed to observe the effect and mechanism of metformin on lung I/R injury following lung transplantation in type 2 diabetic rats. Methods Sprague–Dawley rats were randomly divided into the following six groups: the control + sham group (CS group), the control + I/R group (CIR group), the DM + sham group (DS group), the DM + I/R group (DIR group), the DM + I/R + metformin group (DIRM group) and the DM + I/R + metformin + Compound C group (DIRMC group). Control and diabetic rats underwent the sham operation or left lung transplantation operation. Lung function, alveolar capillary permeability, inflammatory response, oxidative stress, necroptosis and the p-AMPK/AMPK ratio were determined after 24 h of reperfusion. Results Compared with the CIR group, the DIR group exhibited decreased lung function, increased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, but decreased the p-AMPK/AMPK ratio. Metformin improved the function of lung grafts, decreased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, and increased the p-AMPK/AMPK ratio. In contrast, the protective effects of metformin were abrogated by Compound C. Conclusions Metformin attenuates lung I/R injury and necroptosis through AMPK pathway in type 2 diabetic lung transplant recipient rats.

Abstract With the rapid development of the Internet of Things, numerous devices have been deployed in complex environments for environmental monitoring and information transmission, which brings new power supply challenges. Wireless power transfer is a promising solution since it enables power delivery without cables, providing well-behaved flexibility for power supplies. Here we propose a compact wireless power transfer framework. The core components of the proposed framework include a plane-wave feeder and a transmissive 2-bit reconfigurable metasurface-based beam generator, which constitute a reconfigurable power router. The combined profile of the feeder and the beam generator is 0.8 wavelengths. In collaboration with a deep-learning-driven environment sensor, the router enables object detection and localization, and intelligent wireless power transfer to power-consuming targets, especially in dynamic multitarget environments. Experiments also show that the router is capable of simultaneous wireless power and information transfer. Due to the merits of low cost and compact size, the proposed framework may boost the commercialization of metasurface-based wireless power transfer routers.

Our skin serves as the primary barrier against external environmental insults, the latter of which can cause oxidative stress within cells, while various bioactive peptides sourced from natural resources hold promise in protecting cells against such oxidative stress. In this study, we investigate the efficacy of a low molecular weight extract from the sea cucumber Apostichopus japonicus, denoted as Sample-P, in facilitating cell migration and wound healing under oxidative stress conditions in skin cells. The naturally derived compound is a highly complex mix of peptides exhibiting antioxidative properties, as highlighted through liquid chromatography-mass spectrometry peptide screening and an in vitro antioxidant assay. Our results demonstrate that Sample-P is capable of promoting cell migration while preventing severe stress responses such as visible through mTOR expression. To further identify the molecular pathways underpinning the overall protective mechanism of Sample-P, we have utilised a proteomics approach. Our data reveal that Sample-P regulates protein expression associated with ribosomal pathways, glycolysis/gluconeogenesis and protein processing in the endoplasmic reticulum (ER), which help in preserving DNA integrity and safeguarding cellular organelles, such as mitochondria and the ER, under oxidative stress conditions in skin cells. In summary, in the presence of H2O2, Sample-P exhibits antioxidative properties at both molecular and cellular levels, rendering it a promising candidate for topical skin treatment to wound healing and to address age-related skin conditions.

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignancy characterized by a high incidence and recurrence rate. 5-methylcytosine (m5C) RNA modification is a common alteration affecting cancer progression; however, how m5C operates within the tumor microenvironment of HNSCC remains to be elucidated. Methods: We conducted Nanopore sequencing on 3 pairs of cancer and paracancerous tissues from mid- and late-stage HNSCC, obtaining 132 upregulated genes (transcriptomically upregulated, m5C elevated) and 129 downregulated genes (transcriptomically downregulated, m5C reduced). Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed; a differential gene interaction network (PPI) was constructed, revealing the interactions of each gene with others in the network. Co-expression analysis was performed on the genes within the PPI, unveiling their expression and regulatory relationships. Through GSVA analysis, variations in related pathways under different states were identified. Furthermore, results of m5C in lncRNA were screened, followed by target gene prediction. Results: Sequencing results from the 3 pairs of mid- and late-stage HNSCC cancer and paracancerous tissues demonstrated that RPS27A, RPL8, and the lncRNAs including differentiation antagonizing nonprotein coding RNA (DANCR), DCST1 antisense RNA 1 (CCDC144NL-AS1), Growth Arrest-Specific Transcript 5 (GAS5), Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), and Small Nucleolar RNA Host Gene 3 (SNHG3), etc., under m5Cregulation, have close connections with surrounding genes. The differentially m5Cmodified genes are primarily involved in ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, immunity, and other life processes; pathways like mitochondrial protein import and photodynamic therapy induced unfolded protein response are upregulated in the tumor, while pathways, including the classic P53, are suppressed. Analysis on m5C-regulated long non-coding RNAs (lncRNAs) revealed tight associations with RPS27A and RPL8 as well. Conclusion: Our study identifies the key factors and signaling pathways involving m5C in HNSCC. The findings suggest that ribosome-related genes might regulate ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, and immune response through m5C RNA modification by means like hypoxia and ferroptosis, thereby playing a pivotal role in the onset and progression of HNSCC. Hence, attention should be paid to the role of ribosomes in HNSCC. These findings may facilitate the precision and individualized treatment of patients with mid- and late-stage HNSCC in clinical settings.

Intestinal ischemia/reperfusion is a prevalent pathological process that can result in intestinal dysfunction, bacterial translocation, energy metabolism disturbances, and subsequent harm to distal tissues and organs via the circulatory system. Acute lung injury frequently arises as a complication of intestinal ischemia/reperfusion, exhibiting early onset and a grim prognosis. Without appropriate preventative measures and efficacious interventions, this condition may progress to acute respiratory distress syndrome and elevate mortality rates. Nonetheless, the precise mechanisms and efficacious treatments remain elusive. This paper synthesizes recent research models and pertinent injury evaluation criteria within the realm of acute lung injury induced by intestinal ischemia/reperfusion. The objective is to investigate the roles of pathophysiological mechanisms like oxidative stress, inflammatory response, apoptosis, ferroptosis, and pyroptosis; and to assess the strengths and limitations of current therapeutic approaches for acute lung injury stemming from intestinal ischemia/reperfusion. The goal is to elucidate potential targets for enhancing recovery rates, identify suitable treatment modalities, and offer insights for translating fundamental research into clinical applications.

Abstract Background Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (Psa), is a destructive disease worldwide. Resistance genes that respond to Psa infection urgently need to be identified for controlling this disease. Laccase is mainly involved in the synthesis of lignin in the plant cell wall and plays a prominent role in plant growth and resistance to pathogen infection. However, the role of laccase in kiwifruit has not been reported, and whether laccase is pivotal in the response to Psa infection remains unclear. Results We conducted a bioinformatics analysis to identify 55 laccase genes (AcLAC1–AcLAC55) in the kiwifruit genome. These genes were classified into five cluster groups (I–V) based on phylogenetic analysis, with cluster groups I and II having the highest number of members. Analysis of the exon–intron structure revealed that the number of exons varied from 1 to 8, with an average of 5 introns. Our evolutionary analysis indicated that fragment duplication played a key role in the expansion of kiwifruit laccase genes. Furthermore, evolutionary pressure analysis suggested that AcLAC genes were under purifying selection. We also performed a cis-acting element analysis and found that AcLAC genes contained multiple hormone (337) and stress signal (36) elements in their promoter regions. Additionally, we investigated the expression pattern of laccase genes in kiwifruit stems and leaves infected with Psa. Our findings revealed that laccase gene expression levels in the stems were higher than those in the leaves 5 days after inoculation with Psa. Notably, AcLAC2, AcLAC4, AcLAC17, AcLAC18, AcLAC26, and AcLAC42 showed significantly higher expression levels (p

To investigate the ameliorative effect of the D-α-tocopheryl acetate compound on D-galactose-induced aging in mice, the in vitro antioxidant capacity of the compound of natural oils+phytosterols (VEO), the compound of D-α-tocopheryl acetate+phytosterol (VEZ), and the compound of D-α-tocopheryl acetat+phytosterol+astaxanthin (VEX) were measured. The aging model was established using mice injected with D-galactose on the back of the neck, while the intervention was carried out with different compounds. The results showed that all three groups of compounds had strong antioxidant effects, with the VEZ group showing better in vitro antioxidant effects. Compared with the aging model mice, the intervention of the three compounds increased glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC), decreased malondialdehyde (MDA) (P

Focusing on solving the adverse laser-inducing damage problem, high-power laser-resistant strategies have attracted more attention. In order to improve the laser-resistant property, a novel dynamic porous structure generation idea for laser irradiation was presented in this study, both of high-reflection and reaction endothermic effects. A detailed investigation on phase structure change, optical properties variation, micro-structure evolution, and substrate temperature development during laser irradiation was performed. The initial reflectivity of two coatings at 1064 nm was high, around 80–90%. During laser irradiation, the reflectivity grew continuously, reaching a maximum of 93%. During laser irradiation, a skeleton porous structure formed, promoted by the endothermic reaction of aluminum tri-hydroxide, whose structure contributes to the heat insulation from surface to interior. Thus, the prepared coating showed excellent anti-laser ablation performance, being dependent on its thermal insulation by the reaction-generated porous structure; high reflectivity by surface; and heat dissipation by endothermic reaction. Under 2000 W/cm2, 10 s laser irradiation (spot area is 10 mm × 10 mm), the back-surface temperature is just 159 °C, which is far away from the melting point of aluminum substrate. The coatings and strategy mentioned in this study have a great potential to be applied in the anti-laser field.

Copper-filled vertically aligned carbon nanotubes (Cu@VACNTs) were grown directly on Cu foil substrates of 0.1 mm thicknesses at different temperatures via plasma-enhanced chemical vapor deposition (PECVD). By circumventing the need for additional catalyst layers or intensive substrate treatments, our in-situ technique offers a simplified and potentially scalable route for fabricating Cu@VACNTs with enhanced electrical and thermal properties on thin Cu foils. Comprehensive analysis using field emission scanning microscopy (FESEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS) mappings, and X-ray diffraction (XRD) revealed uniform Cu filling within the VACNTs across a range of synthesis temperatures (650 °C, 700 °C, and 760 °C). Field emission (FE) measurements of the sample synthesized at 700 °C (S700) showed low turn-on and threshold fields of 2.33 V/μm and 3.29 V/μm, respectively. The findings demonstrate the viability of thin Cu substrates in creating dense and highly conductive Cu-filled VACNT arrays for advanced electronic and nanoelectronics applications.

Single-walled carbon nanotube (SWCNT) thin films were synthesized by using a floating catalyst chemical vapor deposition (FCCVD) method with a low flow rate (200 sccm) of mixed gases (Ar and H2). SWCNT thin films with different thicknesses can be prepared by controlling the collection time of the SWCNTs on membrane filters. Transmission electron microscopy (TEM) showed that the SWCNTs formed bundles and that they had an average diameter of 1.46 nm. The Raman spectra of the SWCNT films suggested that the synthesized SWCNTs were very well crystallized. Although the electrical properties of SWCNTs have been widely studied so far, the Hall effect of SWCNTs has not been fully studied to explore the electrical characteristics of SWCNT thin films. In this research, Hall effect measurements have been performed to investigate the important electrical characteristics of SWCNTs, such as their carrier mobility, carrier density, Hall coefficient, conductivity, and sheet resistance. The samples with transmittance between 95 and 43% showed a high carrier density of 1021–1023 cm−3. The SWCNTs were also treated using Brønsted acids (HCl, HNO3, H2SO4) to enhance their electrical properties. After the acid treatments, the samples maintained their p-type nature. The carrier mobility and conductivity increased, and the sheet resistance decreased for all treated samples. The highest mobility of 1.5 cm2/Vs was obtained with the sulfuric acid treatment at 80 °C, while the highest conductivity (30,720 S/m) and lowest sheet resistance (43 ohm/square) were achieved with the nitric acid treatment at room temperature. Different functional groups were identified in our synthesized SWCNTs before and after the acid treatments using Fourier-Transform Infrared Spectroscopy (FTIR).

Mutations in mitochondrial DNA (mtDNA) contribute to a variety of serious multi-organ human diseases, which are strictly inherited from the maternal germline. However, there is currently no curative treatment. Attention has been focused on preventing the transmission of mitochondrial diseases through mitochondrial replacement (MR) therapy, but levels of mutant mtDNA can often unexpectedly undergo significant changes known as mitochondrial genetic drift. Here, we proposed a novel strategy to perform spindle-chromosomal complex transfer (SCCT) with maximal residue removal (MRR) in metaphase II (MII) oocytes, thus hopefully eliminated the transmission of mtDNA diseases. With the MRR procedure, we initially investigated the proportions of mtDNA copy numbers in isolated karyoplasts to those of individual oocytes. Spindle-chromosomal morphology and copy number variation (CNV) analysis also confirmed the safety of this method. Then, we reconstructed oocytes by MRR-SCCT, which well developed to blastocysts with minimal mtDNA residue and normal chromosomal copy numbers. Meanwhile, we optimized the manipulation order between intracytoplasmic sperm injection (ICSI) and SCC transfer and concluded that ICSI-then-transfer was conducive to avoid premature activation of reconstructed oocytes in favor of normal fertilization. Offspring of mice generated by embryos transplantation in vivo and embryonic stem cells derivation further presented evidences for competitive development competence and stable mtDNA carryover without genetic drift. Importantly, we also successfully accomplished SCCT in human MII oocytes resulting in tiny mtDNA residue and excellent embryo development through MRR manipulation. Taken together, our preclinical mouse and human models of the MRR-SCCT strategy not only demonstrated efficient residue removal but also high compatibility with normal embryo development, thus could potentially be served as a feasible clinical treatment to prevent the transmission of inherited mtDNA diseases.

As unsafe food production poses global health threats, especially in developing countries, food safety detection always significantly impacts all fields of the food industry, such as production, processing, transportation, storage, and consumption. Many classical food safety detecting methods have been widely used to provide accurate, sensitive, and reliable analytical characteristics, while they rely on clean laboratories, bulky setups, trained personnel, and long-time detection. Because of those conditions, they are not suitable for on-site food safety detecting applications. To solve this problem, various food safety detecting approaches relying on field-portable devices and field-operable techniques have been designed and successfully used, indicating that they are potentially ideal solutions for on-site applications. This review summarizes the progress on on-site food safety detecting approaches and applications for various risk factors, including bacteria, parasites, viruses, toxins, pesticide and veterinary drug residues, illegal food additives, restricted food ingredients, and heavy metals. It outlines recent advances in field-portable devices and field-operable techniques that provide conditions for on-site food safety detection. Recommended on-site food safety detecting approaches for different food safety risk factors are comprehensively suggested considering detecting feasibility, accuracy, and speed. These approaches reveal an attractive and promising route for future practical food safety detecting applications with the merits of portable devices, simple user-friendly operation, and rapid on-site detection. This review further addresses current challenges, and finally discusses future trends and strategies that could be employed in on-site food safety detection.

Abstract Background The overall survival rate of patients with advanced ovarian cancer (OC) has remained static for several decades. Advanced ovarian cancer is known for its poor prognosis due to extensive metastasis. Epigenetic alterations contribute to tumour progression and therefore are of interest for potential therapeutic strategies. Methods Following our previous study, we identified that CHD4, a chromatin remodelling factor, plays a strong role in ovarian cancer cell metastasis. We investigated the clinical significance of CHD4 through TCGA and GEO database analyses and explored the effect of CHD4 expression modulation and romidepsin treatment on the biological behaviour of ovarian cancer through CCK-8 and transwell assays. Bioluminescence imaging of tumours in xenografted mice was applied to determine the therapeutic effect of romidepsin. GSEA and western blotting were used to screen the regulatory mechanism of CHD4. Results In ovarian cancer patient specimens, high CHD4 expression was associated with a poor prognosis. Loss of function of CHD4 in ovarian cancer cells induced suppression of migration and invasion. Mechanistically, CHD4 knockdown suppressed the expression of EZH2 and the nuclear accumulation of β-catenin. CHD4 also suppressed the metastasis of ovarian cancer cells and prevented disease progression in a mouse model. To inhibit the functions of CHD4 that are mediated by histone deacetylase, we evaluated the effect of the HDAC1/2 selective inhibitor romidepsin. Our findings indicated that treatment with romidepsin suppressed the progression of metastases in vitro and in vivo. Conclusions Collectively, our results uncovered an oncogenic function of CHD4 in ovarian cancer and provide a rationale for clinical trials of romidepsin in ovarian cancer patients.

Abstract The second polar body (PB2) transfer in assisted reproductive technology is regarded as the most promising mitochondrial replacement scheme for preventing the mitochondrial disease inheritance owing to its less mitochondrial carryover and stronger operability. However, the mitochondrial carryover was still detectable in the reconstructed oocyte in conventional second polar body transfer scheme. Moreover, the delayed operating time would increase the second polar body DNA damage. In this study, we established a spindle‐protrusion‐retained second polar body separation technique, which allowed us to perform earlier second polar body transfer to avoid DNA damage accumulation. We could also locate the fusion site after the transfer through the spindle protrusion. Then, we further eliminated the mitochondrial carryover in the reconstructed oocytes through a physically based residue removal method. The results showed that our scheme could produce a nearly normal proportion of normal‐karyotype blastocysts with further reduced mitochondrial carryover, both in mice and humans. Additionally, we also obtained mouse embryonic stem cells and healthy live‐born mice with almost undetectable mitochondrial carryover. These findings indicate that our improvement in the second polar body transfer is conducive to the development and further mitochondria carryover elimination of reconstructed embryos, which provides a valuable choice for future clinical applications of mitochondrial replacement.

A novel water-soluble Amygdalus persica L. flowers polysaccharide (APL) was successfully isolated and purified from Amygdalus persica L. flowers by hot water extraction. Its chemical components and structure were analyzed by IR, GC-MS, and HPLC. APL consisted of rhamnose, arabinose, mannose and glucose in a molar ratio of 0.17:0.034:1.0:0.17 with an average molecular weight of approximately 208.53 kDa and 15.19 kDa. The antioxidant activity of APL was evaluated through radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 3-ethylbenzthiazoline-6-sulfonic acid (ABTS), Hydroxyl radical scavenging, Superoxide radical scavenging, and the reducing power activity was also determined in vitro. Besides, in vivo antioxidant experiment, zebrafish (Danio rerio) embryos were treated with different concentrations of APL and then exposed to LPS to induce oxidative stress. Treatment with APL at 50 or 100 µg/mL significantly reduced LPS-induced oxidative stress in the zebrafish, demonstrating the strong antioxidant activity of APL. Moreover, the effect of APL on zebrafish depigmentation was tested by analyzing the tyrosinase activity and melanin content of zebrafish embryos. APL showed a potential reduction in the total melanin content and tyrosinase activity after treatment. This work provided important information for developing a potential natural antioxidant in the field of cosmetics and food.

In the original publication [...]

Abstract Background Blastomere loss is a common phenomenon that occurs following cryopreservation. To date, studies have drawn conflicting conclusions regarding the impact of blastomere loss on pregnancy outcomes. Besides, limited information is available concerning the neonatal safety of embryos with blastomere loss. In the present study, we aimed to investigate the impact of blastomere loss on pregnancy and neonatal outcomes of vitrified/warmed Day3 cleavage-stage embryos in single embryo transfer cycles. Methods This retrospective cohort study included all vitrified/warmed D3 cleavage-stage single frozen-thawed embryo transfer (FET) cycles between April 2015 and February 2021. We compared pregnancy and subsequent neonatal outcomes between the intact embryos group and the blastomere loss group in single FET cycles. Results A total of 6287 single FET cycles were included in the study, in which 5873 cycles were classified into the intact embryo group and 414 cycles were classified into the blastomere loss group. The outcomes of the blastomere loss group were significantly inferior to those of the intact embryo group, in terms of implantation/biochemical pregnancy/clinical pregnancy/ongoing pregnancy rate and live birth rate per embryo transfer cycle/per clinical pregnancy. Further binary logistic regression confirmed that blastomere loss was negatively associated with live birth. Moreover, the blastomere loss group presented with an elevated early miscarriage rate. The neonatal conditions were broadly similar between the two groups. Additionally, multiple binary logistic regression analysis demonstrated that primary infertility and intracytoplasmic sperm injection (ICSI) were common influencing factors of blastomere loss (aOR 1.447, 95% CI 1.038–2.019, P = 0.029; aOR: 1.388, 95% CI: 1.044–51.846, P = 0.024). Conclusions The transfer of vitrified/warmed D3 embryos with blastomere loss is related to impaired embryo developmental potentials and reduced probabilities of conception. Moreover, even if the embryos with blastomere loss have implanted and reached clinical pregnancies, they present with a lower possibility of developing to live birth owing to a higher early miscarriage rate. However, once the embryos with blastomere loss result in a live birth, no adverse neonatal outcomes are observed. Primary infertility and ICSI were found to be risk factors for blastomere loss.

Background: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. The strong stress response causing by surgical trauma can induce POCD. We hypothesized that stellate ganglion block (SGB) can provide the neuroprotection to POCD by regulating the neuroendocrine response. Methods: Sprague-Dawley male rats, 18–20 months old and weighing 550–650 g were assigned into four groups: sham surgery group (Sham), sham surgery + saline group (Sham + NS), surgery group (Surgery), and surgery + SGB group (Surgery + SGB). The change of body weight, heart rate variability analysis, behavior testing, neuronal damage, inflammatory response, neuroendocrine hormone level were evaluated by their corresponding methods. Results: The results showed that SGB can reduce the number of both types of errors in the postoperative eight-arm maze assay, attenuate neural structural damage, inhibit neuroapoptosis, suppress inflammatory responses, increase the release of neurotrophic factors, accelerate postoperative weight recovery, and promote postoperative recovery in rats. Most importantly, SGB reduced the level of neuroendocrine hormone of TH, Cyp11b1, CRH, and SGB also activated dorsal motor nucleus of vagus (detected by c-fos immunohistochemistry). Conclusions: Our findings indicated that SGB could be a neuroprotective therapy for the cognitive dysfunction induced by exploratory laparotomy model of POCD, which might be attributable for balancing the autonomic nervous system, regulating hypothalamic-pituitary-adrenal (HPA) axis system.

Background:. Hyaluronic acid fillers are the preferred choice for minimally invasive facial volume restoration. In this study, a split-face design was used to compare the effectiveness and safety results of Belotero Balance Lidocaine (BEL) and Restylane (RES, control) to investigate whether BEL is noninferior compared with RES in nasolabial fold (NLF) correction. Methods:. This was a prospective, controlled clinical study in Chinese subjects. Subjects with symmetrical moderate NLFs according to the Wrinkle Severity Rating Scale were randomized to receive BEL in one NLF and RES in the other. The primary objective was to investigate whether BEL is noninferior compared with RES after being injected mid-dermally in moderate NLFs after 6 months. Secondary objectives included responses at other visits and pain sensation. Treatment-emergent adverse events (TEAEs) were assessed. Results:. A total of 220 subjects were enrolled. The Wrinkle Severity Rating Scale response rates at month 6 were 62.9% for BEL versus 64.9% for RES, demonstrating noninferiority. The secondary endpoints supported this. Significantly reduced pain scores were observed for BEL versus RES. For both products, injection site nodule and bruising were the most frequent treatment-emergent adverse events at the injection site. All treatment-related treatment-emergent adverse events were mild. Conclusions:. The study showed that BEL is effective and well tolerated for correction of moderate NLFs in Chinese subjects. Noninferiority of BEL was demonstrated compared with RES, and regardless of applied pain treatment, a further reduction in injection pain was observed in BEL.

To investigate the anti-obesity effect of a noni (Morinda citrifolia L.) fruit polysaccharide (NFP) and its potential mechanisms, 24 male C57BL/6J mice were randomly divided into three groups—normal control group, high-fat diet (HFD) group, and NFP-administration group and were gavaged once a day for 12 weeks. The body weights, serum lipid parameters, bile acid (BA)-related proteins, fecal BA, and cecal bacteria of the mice were obtained and analyzed. Results indicate that NFP supplementation (200 mg/kg·bw) reduced the body weight, energy intake, and serum and liver lipids of the HFD mice. Further studies found that NFP activated the hepatic and colonic farnesoid X receptor and increased the excretion of fecal-conjugated BAs, particularly tauro-alpha-muricholic acid and tauro-beta-muricholic acid. In addition, NFP modulated the intestinal microbiota and increased the relative abundance of Lactobacillus in the HFD mice. In conclusion, NFP modulated gut microbiota and improved BA metabolism, which may be the main mechanism behind NFP alleviation of fat accumulation and dyslipidemia in mice under HFD.

Abstract Background 0PN zygotes have a low cleavage rate, and the clinical outcomes of cleavage-stage embryo transfers are unsatisfactory. Blastocyst culturing is used to screen 0PN embryos, but whether the cell number of 0PN embryos on day 3 affects the clinical outcomes following single blastocyst transfer is unknown and would be helpful in evaluating the clinical value of these embryos. Methods This retrospective study compared 46,804 0PN zygotes, 242 0PN frozen-thawed single blastocyst transfers, and 92 corresponding 0PN singletons with 232,441 2PN zygotes, 3563 2PN frozen-thawed single blastocyst transfers, and 1250 2PN singletons from January 2015 to October 2019 at a tertiary-care academic medical centre. The 0PN and 2PN embryos were divided into two groups: the group with

Long noncoding RNAs (lncRNAs) have a profound effect on biological processes in various malignancies. However, few studies have investigated their functions and specific mechanisms in endometrial cancer. In this study, we focused on the role and mechanism of lncRNA‐ZXF1 in endometrial cancer. Bioinformatics and in vitro and in vivo experiments were used to explore the expression and function of lncRNA‐ZXF1. We found that lncRNA‐ZXF1 altered the migration and invasion of endometrioid endometrial cancer (EEC) cells. Furthermore, our results suggest that lncRNA‐ZXF1 regulates EEC cell proliferation. This regulation may be achieved by the lncRNA‐ZXF1‐mediated alteration in the expression of P21 through two mechanisms. One is that lncRNA‐ZXF1 functions as a molecular sponge of miR‐378a‐3p to regulate PCDHA3 expression and then modulate the expression of P21. The other is that lncRNA‐ZXF1 inhibits CDC20‐mediated degradation of ubiquitination by directly binding to P21. To the best of our knowledge, this study is the first to explore lncRNA‐ZXF1 functioning as a tumor‐suppressing lncRNA in EEC. LncRNA‐ZXF1 may become therapeutic, diagnostic, and prognostic indicator in the future.

In this study, the sensing mechanism of (2E,4E)-5-(4-(dimethylamino)phenyl)-1-(2-(2,4dinitrophenoxy)phenyl)penta-2,4-dien-1-one (DAPH-DNP) towards thiophenols was investigated by density functional theory (DFT) and time-dependent DFT (TD-DFT). The DNP group plays an important role in charge transfer excitation. Due to the typical donor-excited photo-induced electron transfer (d-PET) process, DAPH-DNP has fluorescence quenching behavior. After the thiolysis reaction between DAPH-DNP and thiophenol, the hydroxyl group is released, and DAPH is generated with the reaction showing strong fluorescence. The fluorescence enhancement of DAPH is not caused by an excited-state intramolecular proton transfer (ESIPT) process. The potential energy curves (PECs) show that DAPH-keto is less stable than DAPH-enol. The frontier molecular orbitals (FMOs) of DAPH show that the excitation process is accompanied by intramolecular charger transfer (ICT), and the corresponding character of DAPH was further confirmed by hole-electron and interfragment charge transfer (IFCT) analysis methods. Above all, the sensing mechanism of the turn-on type probe DAPH-DNP towards thiophenol is based on the PET mechanism.

Previous studies on sugarcane harvester extractors have mainly focused on improving harvest quality and reducing the impurity rate and loss rate, which often ignored the issue of high energy consumption. To reduce the energy consumption of the extractor while maintaining the original impurity rate and loss rate stable, firstly, a blade element analysis method with aerodynamic theory was put forward to analyze the stress of the extractor blade, and the energy consumption equation and influencing factors of extraction were obtained. Subsequently, the computational fluid dynamics model of the exhaust extractor was established. Computational fluid dynamics (CFD) and the SST k-ω model were used to analyze the mechanism of various influencing factors on the energy consumption and internal flow characteristics of the extractor. The changes in various parameters were analyzed and discussed with respect to the resulting variations in internal pressure, velocity, vortex structure, and lift–drag coefficient of the extractor. A test bench of the extractor was built, and orthogonal tests were carried out with energy consumption, impurity rate, and loss rate as test indicators. Considering the results of the simulation and bench test comprehensively, the combination of a rotational speed of 1450 RPM, a blade number of 3, an installation angle of 25°, and a blade chord length of 200 mm was optimal for the extractor. Finally, a comparative test was carried out between the optimized extractor and the original extractor. The results demonstrated that the energy consumption of the optimized extractor was reduced by 15.49%. The impurity rate decreased by 3.51%, and the loss rate decreased by 12.39% compared to the original extractor. The study can provide a theoretical and experimental basis for designing and optimizing extractor performance.

Abstract Background The application of artificial oocyte activation (AOA) after intracytoplasmic sperm injection (ICSI) is successful in mitigating fertilization failure problems in assisted reproductive technology (ART). Nevertheless, there is no relevant study to investigate whether AOA procedures increase developmental risk by disturbing subsequent gene expression at different embryonic development stages. Methods We used a mouse model to explore the influence of AOA treatment on pre- and post-implantation events. Firstly, the developmental potential of embryos with or without AOA treatment were assessed by the rates of fertilization and blastocyst formation. Secondly, transcriptome high-throughput sequencing was performed among the three groups (ICSI, ICSI-AOA and dICSI-AOA groups). The hierarchical clustering and Principal Component Analysis (PCA) analysis were used. Subsequently, Igf2r/Airn methylation analysis were detected using methylation-specific PCR sequencing following bisulfite treatment. Finally, birth rate and birth weight were examined following mouse embryo transfer. Results The rates of fertilization and blastocyst formation were significantly lower in oocyte activation-deficient sperm injection group (dICSI group) when compared with the ICSI group (30.8 % vs. 84.4 %, 10.0 % vs. 41.5 %). There were 133 differentially expressed genes (DEGs) between the ICSI-AOA group and ICSI group, and 266 DEGs between the dICSI-AOA group and ICSI group. In addition, the imprinted gene, Igf2r is up regulated in AOA treatment group compared to control group. The Igf2r/Airn imprinted expression model demonstrates that AOA treatment stimulates maternal allele-specific mehtylation spreads at differentially methylated region 2, followed by the initiation of paternal imprinted Airn long non-coding (lnc) RNA, resulting in the up regulated expression of Igf2r. Furthermore, the birth weight of newborn mice originating from AOA group was significantly lower compared to that of ICSI group. The pups born following AOA treatment did not show any other abnormalities during early development. All offspring mated successfully with fertile controls. Conclusions AOA treatment affects imprinted gene Igf2r expression and mehtylation states in mouse pre- and post-implantation embryo, which is regulated by the imprinted Airn. Nevertheless, no significant differences were found in post-natal growth of the pups in the present study. It is hoped that this study could provide valuable insights of AOA technology in assisted reproduction biology.

Abstract Background Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients. Methods The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset. Results We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status. Conclusion In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.

Soft rot causes significant economic losses in the kiwifruit industry. This study isolated strain CTXW 7-6-2 from healthy kiwifruit tissue; this was a gram-positive bacterium that produced the red pigment pulcherrimin. The phylogenetic tree based on 16S ribosomal RNA, gyrA, rpoB, and purH gene sequences identified CTXW 7-6-2 as a strain of Bacillus subtilis. CTXW 7-6-2 inhibited hyphal growth of pathogenic fungi that cause kiwifruit soft rot, namely, Botryosphaeria dothidea, Phomopsis sp., and Alternaria alternata, by 81.76, 69.80, and 32.03%, respectively. CTXW 7-6-2 caused the hyphal surface to become swollen and deformed. Volatile compounds (VOC) produced by the strain inhibited the growth of A. alternata and Phomopsis sp. by 65.74 and 54.78%, respectively. Whole-genome sequencing revealed that CTXW 7-6-2 possessed a single circular chromosome of 4,221,676 bp that contained 4,428 protein-coding genes, with a guanine and cytosine (GC) content of 43.41%. Gene functions were annotated using the National Center for Biotechnology Information (NCBI) non-redundant protein, Swiss-Prot, Kyoto Encyclopedia of Genes and Genomes, Clusters of Orthologous Groups of proteins, Gene Ontology, Pathogen–Host Interactions, Carbohydrate-Active enZYmes, and Rapid Annotations using Subsystem Technology databases, revealing non-ribosomal pathways associated with antifungal mechanisms, biofilm formation, chemotactic motility, VOC 3-hydroxy-2-butanone, cell wall-associated enzymes, and synthesis of various secondary metabolites. antiSMASH analysis predicted that CTXW 7-6-2 can produce the active substances bacillaene, bacillibactin, subtilosin A, bacilysin, and luminmide and has four gene clusters of unknown function. Quantitative real-time PCR (qRT-PCR) analysis verified that yvmC and cypX, key genes involved in the production of pulcherrimin, were highly expressed in CTXW 7-6-2. This study elucidates the mechanism by which B. subtilis strain CTXW 7-6-2 inhibits pathogenic fungi that cause kiwifruit soft rot, suggesting the benefit of further studying its antifungal active substances.

Abstract Pre‐intercalation of metal ions into vanadium oxide is an effective strategy for optimizing the performance of rechargeable zinc‐ion battery (ZIB) cathodes. However, the battery long‐lifespan achievement and high‐capacity retention remain a challenge. Increasing the electronic conductivity while simultaneously prompting the cathode diffusion kinetics can improve ZIB electrochemical performance. Herein, N‐doped vanadium oxide (N‐(Zn,en)VO) via defect engineering is reported as cathode for aqueous ZIBs. Positron annihilation and electron paramagnetic resonance clearly indicate oxygen vacancies in the material. Density functional theory (DFT) calculations show that N‐doping and oxygen vacancies concurrently increase the electronic conductivity and accelerate the diffusion kinetics of zinc ions. Moreover, the presence of oxygen vacancies substantially increases the storage sites of zinc ions. Therefore, N‐(Zn,en)VO exhibits excellent electrochemical performance, including a peak capacity of 420.5 mA h g−1 at 0.05 A g−1, a high power density of more than 10 000 W kg−1 at 65.3 Wh kg−1, and a long cycle life at 5 A g−1 (4500 cycles without capacity decay). The methodology adopted in our study can be applied to other cathodic materials to improve their performance and extend their practical applications.

Abstract Background Diabetes mellitus (DM) is a key contributing factor to poor survival in lung transplantation recipients. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of diabetic lung ischemia–reperfusion (IR) injury. The protective effects of adiponectin have been demonstrated in our previous study, but the underlying mechanism remains unclear. Here we demonstrated an important role of mitophagy in the protective effect of adiponectin during diabetic lung IR injury. Methods High-fat diet-fed streptozotocin-induced type 2 diabetic rats were exposed to adiponectin with or without administration of the SIRT1 inhibitor EX527 following lung transplantation. To determine the mechanisms underlying the action of adiponectin, rat pulmonary microvascular endothelial cells were transfected with SIRT1 small-interfering RNA or PINK1 small-interfering RNA and then subjected to in vitro diabetic lung IR injury. Results Mitophagy was impaired in diabetic lungs subjected to IR injury, which was accompanied by increased oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Adiponectin induced mitophagy and attenuated subsequent diabetic lung IR injury by improving lung functional recovery, suppressing oxidative damage, diminishing inflammation, decreasing cell apoptosis, and preserving mitochondrial function. However, either administration of 3-methyladenine (3-MA), an autophagy antagonist or knockdown of PINK1 reduced the protective action of adiponectin. Furthermore, we demonstrated that APN affected PINK1 stabilization via the SIRT1 signaling pathway, and knockdown of SIRT1 suppressed PINK1 expression and compromised the protective effect of adiponectin. Conclusion These data demonstrated that adiponectin attenuated reperfusion-induced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction via activation of SIRT1- PINK1 signaling-mediated mitophagy in diabetic lung IR injury.

In view of a series of adverse side effects of drugs for anxiety/depression on the market at present, it is imminent to extract and develop novel anti-anxiety and depression drugs from plants and proteins (like casein hydrolysate) as adjuncts or substitutes for existing anti-anxiety and depression drugs. Consequently, this study investigated the improvement of the anxiety/depression function by the compound of casein hydrolysate and γ-aminobutyric acid (GABA) (casein hydrolysate: GABA = 4:1; CCHAA) on mice induced by chronic restraint stress-corticosterone injection. Animal experiments revealed that oral gavage administration of CCHAA significantly reversed the anxiety/depression-like behaviors. Compared to the model control group, body weights were increased after treatment with CCHAA groups [1.5, 0.75 mg/(g⋅d)]. As a diagnostic index of anxiety and depression, we assessed GABA and 5-HT levels in response to CCHAA ingestion. The GABA and 5-HT levels were increasingly enhanced by the CCHAA diet. In addition, histopathological changes in the hippocampus CA3 region of the anxious/depressed mice were also alleviated after the treatment with the CCHAA. Thus, the casein hydrolysate and GABA formula diets may induce beneficial effects on the mice with anxiety/depression.

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common reasons for infertility. The consensus of the treatment of infertile women with PCOS is ovulation induction (OI) for six to nine attempts before in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Nowadays, more attention was paid to a rising, noninvasive treatment, intrauterine insemination (IUI), as some experts claimed IUI could benefit PCOS patients with infertility. Our study means to investigate the outcomes of IUI for PCOS patients and if patients’ previous OI cycles can be a predictive factor for IUI outcomes.MethodsA total of 1,086 PCOS patients was included and 1,868 IUI cycles were performed between January 2007 and July 2021 in the department of assisted reproduction in Shanghai Ninth People’s Hospital. All included patients underwent IUI treatments with letrozole+human menopausal gonadotropin (LE+hMG) for ovarian stimulation.ResultsThe pregnancy outcomes were not associated with the attempts of failed OI cycles previously. Specifically, the clinical pregnancy rate was 21.14% for PCOS patients without previous OI cycles, 21.95% for PCOS patients with 1-2 previous OI cycles and 23.64% for PCOS patients with 3 or more previous OI cycles (p=0.507). The corresponding live birth rate was 16.64%, 18.06%, and 18.68%, respectively, of which the difference was not statistically significant (p=0.627). The cumulative rate per patient was 38.59% for clinical pregnancy and 31.03% for live birth, and approximately 98% of the pregnancies occurred in the first 3 cycles of IUI.ConclusionPCOS women with different attempts of OI cycles had similar pregnancy outcomes after IUI, thus a history of repeated failures of OI treatments was not a predictive factor for the pregnancy outcomes in IUI cycles. Most pregnancies occurred in the first three cycles of IUI, so we strongly recommended three attempts of IUI for PCOS women before they switched to IVF/ICSI. Generally, IUI might be an assist for infertile women with PCOS before IVF/ICSI and might accelerate pregnancy for target women without invasive manipulations.

Hydrogels have been widely applied to the fabrication of tissue engineering scaffolds via three-dimensional (3D) bioprinting because of their extracellular matrix-like properties, capacity for living cell encapsulation, and shapeable customization depending on the defect shape. However, the current hydrogel scaffolds show limited regeneration activity, especially in the application of periodontal tissue regeneration. In this study, we attempted to develop a novel multi-component hydrogel that possesses good biological activity, can wrap living cells for 3D bioprinting and can regenerate periodontal soft and hard tissue. The multi-component hydrogel consisted of gelatin methacryloyl (GelMA), sodium alginate (SA) and bioactive glass microsphere (BGM), which was first processed into hydrogel scaffolds by cell-free 3D printing to evaluate its printability and in vitro biological performances. The cell-free 3D-printed scaffolds showed uniform porous structures and good swelling capability. The BGM-loaded scaffold exhibited good biocompatibility, enhanced osteogenic differentiation, apatite formation abilities and desired mechanical strength. The composite hydrogel was further applied as a bio-ink to load with mouse bone marrow mesenchymal stem cells (mBMSCs) and growth factors (BMP2 and PDGF) for the fabrication of a scaffold for periodontal tissue regeneration. The cell wrapped in the hydrogel still maintained good cellular vitality after 3D bioprinting and showed enhanced osteogenic differentiation and soft tissue repair capabilities in BMP2- and PDGF-loaded scaffolds. It was noted that after transplantation of the cell- and growth factor-laden scaffolds in Beagle dog periodontal defects, significant regeneration of gingival tissue, periodontal ligament, and alveolar bone was detected. Importantly, a reconstructed periodontal structure was established in the treatment group eight weeks post-transplantation of the scaffolds containing the cell and growth factors. In conclusion, we developed a bioactive composite bio-ink for the fabrication of scaffolds applicable for the reconstruction and regeneration of periodontal tissue defects.

Background: Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. Method: To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. Results: Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. Conclusion: The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.

As a group of naturally occurring peptides in various foods, γ-glutamyl peptides possess a unique Kokumi taste and health benefits. However, few studies have focused on the functionality of γ-glutamyl peptides. In this study, the γ-[glutamyl] (n=1, 2, 3)-tryptophan peptides were synthesized from a solution of glutamine (Gln) and tryptophan (Trp) employing L-glutaminase from Bacillus amyloliquefaciens. Four different γ-glutamyl peptides were identified from the reaction mixture by UPLC-Q-TOF-MS/MS. Under optimal conditions of pH 10, 37 °C, 3 h, 0.1 mol/L Gln: 0.1 mol/L Trp = 1:3, and glutaminase at 0.1% (m/v), the yields of γ-l-glutamyl-l-tryptophan (γ-EW), γ-l-glutamyl-γ-l-glutamyl-l-tryptophan (γ-EEW) and γ-l-glutamyl-γ-l-glutamyl-γ-l-glutamyl-l-tryptophan (γ-EEEW) were 51.02%, 26.12% and 1.91% respectively. The antioxidant properties of the reaction mixture and the two peptides (γ-EW, γ-EEW) identified from the reaction media were further compared. Results showed that γ-EW exhibited the highest DPPH•, ABTS•+ and O2•−-scavenging activity (EC50 = 0.2999 mg/mL, 67.6597 μg/mL and 5.99 mg/mL, respectively) and reducing power (EC50 = 4.61 mg/mL), while γ-EEW demonstrated the highest iron-chelating activity (76.22%). Thus, the synthesized mixture may be used as a potential source of antioxidant peptides for food and nutraceutical applications.

Abstract Over the last decade, more than 10 independent SNPs have been discovered to be associated with the risk of renal cell carcinoma among different populations. However, the biological functions of them remain poorly understood. In this study, we performed eQTL analysis, ChIP-PCR, luciferase reporter assay, and Cox regression analysis to identify the functional role and underlying mechanism of rs67311347 in RCC. The ENCORI database, which contains the lncRNA–miRNA–mRNA interactions, was used to explore the possible target miRNA of ENTPD3-AS1. The results showed that the G > A mutation of rs67311347 created a binding motif of ZNF8 and subsequently upregulated ENTPD3-AS1 expression by acting as an enhancer. The TCGA-KIRC and our cohorts both confirmed the downregulation of ENTPD3-AS1 in RCC tissues and demonstrated that increased ENTPD3-AS1 expression was associated with good OS and PFS. Furthermore, ENTPD3-AS1 interacted with miR-155-5p and activated the expression of HIF-1α, which was an important tumor suppressor gene in the development of RCC. The functional experiments revealed that overexpression of ENTPD3-AS1 inhibited cell proliferation in RCC cell lines and the effect could be rescued by knocking down HIF-1α. Our findings reveal that SNP-mediated lncRNA-ENTPD3-AS1 upregulation suppresses renal cell carcinoma via miR-155/HIF-1α signaling.

BackgroundTo date, no consensus has been reached on whether to wait for spontaneous luteinizing hormone (LH) surge to occur or to trigger ovulation regardless of the presence of an LH surge for achieving higher success rate in intrauterine insemination (IUI) cycles. Therefore, we hope to investigate the effect of the presence of a spontaneous LH surge on pregnancy outcomes in letrozole–human menopausal gonadotropin (LE-HMG) IUI cycles.MethodsIn this retrospective cohort study, a total of 6,285 LE-HMG IUI cycles were included between January 2010 and May 2021. Cycles were categorized into three groups: the trigger + LH surge group, the trigger only group, and the LH surge only group. The primary outcome measure was the clinical pregnancy rate. A logistic regression analysis was performed to explore other risk factors affecting the clinical pregnancy rate.ResultsNo significant differences were observed in biochemical pregnancy rate (P =0.640), clinical pregnancy rate (P =0.702), ongoing pregnancy rate (P =0.842), and live birth rate (P =0.951) among the three groups. The binary logistic regression analysis also confirmed that the existence of an LH surge was not associated with clinical pregnancy. There was a difference in ectopic pregnancy rates (P =0.045), but logistic regression showed that the presence of a spontaneous LH surge has no association with ectopic pregnancy. Nonetheless, patients with lead follicles within 18.1-20.0 mm/20.1-22.0 mm and a long duration of LE treatment were less likely to get ectopic pregnant compared with patients with 14.1-16.0 mm lead follicles and shorter LE treatment (OR: 0.142, 95% CI: 0.023–0.891, P =0.037; OR: 0.142, 95% CI: 0.022–0.903, P =0.039; OR: 0.445, 95% CI: 0.235–0.840, P = 0.013).ConclusionsThe presence of a spontaneous LH surge in triggered LE-HMG IUI cycles does not appear to improve pregnancy rates. Thus, we suggest that waiting for an LH surge to occur is not necessary in triggered LE-HMG IUI cycles.

Magnolol is a natural compound extracted from the traditional Chinese medicine Magnolia officinalis, which exhibits antimicrobial properties. However, magnolol is insoluble in water and consists of a phenolic hydroxyl group, which is volatile; these factors hinder its application. In this study, a safe and environmentally friendly method to improve the microbial resistance and storability of harvested fruits is developed using the water-soluble carrier carboxymethyl chitosan (CMCS) and magnolol. Magnolol was loaded on CMCS particles to form Magnolol@CMCS antimicrobial particles, a preservation coating agent. Magnolol@CMCS particles effectively solved the problems of water insolubility and agglomeration of magnolol and reduced the size distribution D50 value of magnolol from 0.749 to 0.213 μm. Magnolol@CMCS particles showed greater toxicity against Staphylococcus aureus, Escherichia coli, and Botryosphaeria dothidea than that of magnolol alone, with effective medium concentration (EC50) values of 0.9408, 142.4144, and 8.8028 μg/mL, respectively. Kiwifruit treated with the Magnolol@CMCS solution showed delayed changes in fruit hardness and soluble solid and dry matter contents and significantly higher ascorbic acid (vitamin C) and soluble total sugar contents and sugar:acid ratios compared with that of the control fruit. In addition, no disease spots were observed on fruit treated with the Magnolol@CMCS solution within 7 days after inoculation with B. dothidea. In conclusion, Magnolol@CMCS particles showed antimicrobial activity on harvested fruits, effectively delayed the hardness and nutritional changes of fruits during storage, and improved the storability of kiwifruit.

Liquid fuel intermediates could be produced via aldol condensation reaction between furfural or 5-hydroxymethylfurfural (HMF) and acetone. It was found that iron-modified MCM-41 zeolite can be an effective Lewis acid catalyst for C—C bond formation via aldol condensation of furfural or HMF with acetone. The 4-(2-furyl)-3-buten-2-one and 1, 5-di-2-furanyl-1, 4-pentadien-3-one (FAc and F2Ac), or 1, 5-di-2-furanyl-1, 4-pentadien-3-one and 1, 5-bis[(5- hydroxlmethyl)-2-furanyl]-1, 4-pentadien-3-one (HAc and H2Ac), as two main condensation products of furfural with acetone or HMF with acetone, were observed. After 24 h at 160 °C, 86.9% conversion of furfural with 60.0% yield of the FAc as well as 7.5% yield of the F2Ac and 88.9% conversion of the HMF with 41.1% yield of the HAc as well as 3.5% yield of the H2Ac were achieved. Although furfural or HMF conversion was almost same after 24 h at 160 °C, iron-modified MCM-41 zeolite catalyst displayed an enhanced selectivity to condensation products of furfural with acetone. In addition, catalysts showed an improved selectivity to the F2Ac and H2Ac at higher reaction temperature. The reusability and regeneration studies showed that iron-modified MCM-41 zeolite catalyst could not be reused directly, but could be regenerated by calcination in air, and the catalytic performance of regenerated catalyst was acceptable.

‘Hongyang’ kiwifruit (Actinidia chinensis, cultivar ‘Hongyang’) black spot disease is caused by the fungal pathogen Didymella glomerata, and is a serious disease, causing considerable losses to the kiwifruit industry during growth of the fruit. Hence, we aimed to identify a potential biocontrol agent against D. glomerata. In this study, bacterial isolates from the rhizosphere soil of kiwifruit were tested for their potential antifungal activity against selected fungal pathogens. Based on a phylogenetic tree constructed using sequences of 16S rDNA and the gyrA gene, BQ-33 with the best antifungal activity was identified as Bacillus mojavensis. We evaluated the antagonistic activity and inhibitory mechanism of BQ-33 against D. glomerata. Confrontation experiments showed that both BQ-33 suspension and the sterile supernatant (SS) produced by BQ-33 possessed excellent broad-spectrum antifungal activity. Furthermore, the SS damaged the cell membrane and cell wall of the mycelia, resulting in the leakage of a large quantity of small ions (Na+, K+), soluble proteins and nucleic acids. Chitinase and β-1,3-glucanase activities in SS increased in correlation with incubation time and remained at a high level for several days. An in vivo control efficacy assay indicated that 400 mL L−1 of SS completely inhibited kiwifruit black spot disease caused by D. glomerata. Therefore, BQ-33 is a potential biocontrol agent against kiwifruit black spot and plant diseases caused by other fungal pathogens. To our knowledge, this is the first report of the use of a rhizosphere microorganism as a biocontrol agent against kiwifruit black spot disease caused by D. glomerata.

Abstract Progestin resistance limits the effectiveness of progestin therapy in endometrial carcinoma for patients who desire to preserve fertility. To investigate the molecular mechanism of progestin resistance in endometrial carcinoma, we performed microarray analysis among Ishikawa and progestin resistant cell IshikawaPR cells. We found that epithelial to mesenchymal transition (EMT) was involved in progestin resistance and dachshund family transcription factor 1 (DACH1) is positively correlated with progesterone receptor (PGR). Knockdown of DACH1 in Ishikawa cell promoted proliferation, metastasis ability, and resistance to progestin. Conversely, overexpression of DACH1 in IshikawaPR cell rendered more sensitive to progestin treatment. Xenograft model assay also had similar results. In addition, our data showed that DACH1 overexpression inhibited EMT and decreased c‐Jun, Notch1 and Hes1expression. Our study demonstrated for the first time that EMT is involved in progestin resistance of EC. The response to progestin could be reserved by DACH1 suppressed EMT through Notch1 pathway via c‐Jun.

The clinical efficiency of everolimus, an mammalian target of rapamycin (mTOR) inhibitor, is palliative as sequential or second-line therapy for renal cell carcinoma (RCC). However, the limited response of everolimus in RCC remains uncertain. In the present study, everolimus-resistant RCC models were established to understand the mechanisms and to seek combination approaches. Consequently, the activation of ERK was found to contribute toward everolimus-acquired resistance and poor prognosis in patients with RCC. In addition, the efficacy and mechanism of combination treatment underlying RCC using everolimus and ERK inhibitors was investigated. The ERK inhibitor in combination with everolimus synergistically inhibited the proliferation of RCC cells by arresting the cell cycle in the G1 phase. The combination treatment markedly attenuated the deoxyribonucleoside triphosphate (dNTP) pools by downregulating the mRNA expression of RRM1 and RRM2 through E2F1. The overexpression of E2F1 or supplementation of dNTP rescued the anti-proliferation activity of the everolimus-SCH772984 combination. The antitumor efficacy of combination therapy was reiterated in RCC xenograft models. Thus, the current findings provided evidence that the everolimus-ERK inhibitor combination is a preclinical therapeutic strategy for RCC. Keywords: renal cell carcinoma, ERK inhibitor, everolimus, dNTP, ribonucleotide reductase

Abstract Background Progesterone resistance is a problem in endometrial carcinoma, and its underlying molecular mechanisms remain poorly understood. The aim of this study was to elucidate the molecular mechanisms of progesterone resistance and to identify the key genes and pathways mediating progesterone resistance in endometrial cancer using bioinformatics analysis. Methods We developed a stable MPA (medroxyprogesterone acetate)-resistant endometrial cancer cell subline named IshikawaPR. Microarray analysis was used to identify differentially expressed genes (DEGs) from triplicate samples of Ishikawa and IshikawaPR cells. PANTHER, DAVID and Metascape were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and cBioPortal for progesterone receptor (PGR) coexpression analysis. GEO microarray (GSE17025) was utilized for validation. The protein–protein interaction network (PPI) and modular analyses were performed using Metascape and Cytoscape. Further validation were performed by real-time polymerase chain reaction (RT-PCR). Results In total, 821 DEGs were found and further analyzed by GO, KEGG pathway enrichment and PPI analyses. We found that lipid metabolism, immune system and inflammation, extracellular environment-related processes and pathways accounted for a significant portion of the enriched terms. PGR coexpression analysis revealed 7 PGR coexpressed genes (ANO1, SOX17, CGNL1, DACH1, RUNDC3B, SH3YL1 and CRISPLD1) that were also dramatically changed in IshikawaPR cells. Kaplan–Meier survival statistics revealed clinical significance for 4 out of 7 target genes. Furthermore, 8 hub genes and 4 molecular complex detections (MCODEs) were identified. Conclusions Using microarray and bioinformatics analyses, we identified DEGs and determined a comprehensive gene network of progesterone resistance. We offered several possible mechanisms of progesterone resistance and identified therapeutic and prognostic targets of progesterone resistance in endometrial cancer.