Enhanced Selective Electrosorption of Nitrate from Wastewater by Controllably Doping Nitrogen into Porous Carbon with Micropores.

The biological NO3- removal process might be accompanied by high CO2 emissions and operation costs. Capacitive deionization (CDI) has been widely studied as a very efficient method to purify water. Here, a porous carbon material with a tunable nitrogen configuration was developed. Characterization and density functional theory calculation show that nitrogenous functional groups have a higher NO3- binding energy than Cl-, SO42-, and H2PO4-. In addition, the selectivity of NO3- is improved after the introduction of micropores by using the pore template. The NO3- ion removal and selectivity of MN-C-12 are 4.57 and 3.46-5.42 times that of activated carbon (AC), respectively. The high NO3- selectivity and electrosorption properties of MN-C-12 (the highest N content and micropore area) are due to the synergistic effect of the affinity of nitrogen functional groups to NO3- and microporous ion screening. A CDI unit for the removal of nitrogen from municipal wastewater was constructed and applied to treat wastewater meeting higher discharge standards of A (N: 15 mg L-1) and B (N: 20 mg L-1) ((GB18918-2002), China). This work provides new insights into enhanced carbon materials for the selective electrosorption of wastewater by CDI technology.

Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally. Here, we evaluated the impact on AMPAR function of one frameshift and 43 rare missense GRIA3 variants identified in patients with NDD by electrophysiological assays. Thirty-one variants alter receptor function and show loss-of-function (LoF) or gain-of-function (GoF) properties, whereas 13 appeared neutral. We collected detailed clinical data from 25 patients (from 23 families) harbouring 17 of these variants. All patients had global developmental impairment, mostly moderate (9/25) or severe (12/25). Twelve patients had seizures, including focal motor (6/12), unknown onset motor (4/12), focal impaired awareness (1/12), (atypical) absence (2/12), myoclonic (5/12), and generalized tonic-clonic (1/12) or atonic (1/12) seizures. The epilepsy syndrome was classified as developmental and epileptic encephalopathy in eight patients, developmental encephalopathy without seizures in 13 patients, and intellectual disability with epilepsy in four patients. Limb muscular hypotonia was reported in 13/25, and hypertonia in 10/25. Movement disorders were reported in 14/25, with hyperekplexia or non-epileptic erratic myoclonus being the most prevalent feature (8/25). Correlating receptor functional phenotype with clinical features revealed clinical features for GRIA3-associated NDDs and distinct NDD phenotypes for LoF and GoF variants. GoF variants were associated with more severe outcomes: patients were younger at the time of seizure onset (median age one month), hypertonic, and more often had movement disorders, including hyperekplexia. Patients with LoF variants were older at the time of seizure onset (median age 16 months), hypotonic, and had sleeping disturbances. LoF and GoF variants were disease-causing in both sexes but affected males often carried de novo or hemizygous LoF variants inherited from healthy mothers, whereas all but one affected females had de novo heterozygous GoF variants.

Synovium microenvironment-responsive injectable hydrogel inducing modulation of macrophages and elimination of synovial fibroblasts for enhanced treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a progressive autoimmune disease accompanied by joint swelling, cartilage erosion and bone damage. Drug therapy for RA has been restricted due to poor therapeutic effect, recurrence and adverse effects. Macrophages and synovial fibroblasts both play important roles in the pathology of RA. Macrophages secrete large amount of pro-inflammatory cytokines, while synovial fibroblasts are tightly correlated with hypoxia synovium microenvironment, cytokine release, recruitment of pro-inflammatory cells, bone and cartilage erosion. Therefore, in this timely research, an injectable and pH-sensitive peptide hydrogel loading methotrexate (MTX) and bismuthene nanosheet/polyethyleneimine (BiNS/PEI) has been developed to reduce the activity of macrophages and eliminate over-proliferated synovial fibroblasts simultaneously. MTX can reduce the cytokine secretion of macrophages/anti-apoptosis property of synovial fibroblasts and BiNS/PEI can eliminate synovial fibroblasts via photodynamic therapy (PDT) and photothermal therapy (PTT) routes. The hydrogel was injected into the acidic inflammatory synovium for precise targeting and served as a drug reservoir for pH responsive and sustained drug release, while improving the bioavailability and reducing the toxicity of MTX. Excellent therapeutic efficacy has been achieved in both in vivo and in vitro studies, and this unique drug delivery system provides a new and robust strategy to eliminate synovial fibroblasts and modulate immune system for RA treatment in clinical.

[Analysis of differential metabolites of spikes of Prunella vulgaris at different stages based on UPLC-MS/MS].

Prunella vulgaris, aptly named for its withering at the summer solstice, displays significant variation in quality arising from differing harvest time. However, research on the chemical composition changes of its spikes at various stages is limited, and the specific metabolites remain unclear. In order to elucidate the metabolites and metabolic pathways of the spikes of P. vulgaris, the current study deployed ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) and targeted metabolomics to characterize the compound variability in the spikes of P. vulgaris across different periods. Multivariate statistical techniques such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to identify the differences in metabolites, and relevant metabolic pathways were analyzed. A total of 602 metabolites were identified by metabolomics, of which organic acids and their derivatives were the most abundant, followed by flavonoids. Multiple differential metabolites, including p-hydroxybenzoic acids and gallic acids were identified based on variable importance in projection(VIP)>1 and P<0.05. The results of enrichment analysis suggested that isoflavonoids biosynthesis, aminobenzoate degradation, benzoate degradation, anthocyanins biosynthesis, metabolic pathways, microbial metabolism in different environments, secondary plant metabolite biosynthesis, tryptophan metabolism, and phenylpropanoid synthesis were the main metabolic pathways. These results intend to elucidate the dynamic changes of differential metabolites of P. vulgaris and provide a theoretical basis for further study of the harvesting mechanism of spikes of P. vulgaris.

MOF-Derived Ni/ZIF-8/ZnO Arrays on Carbon Fiber Cloth for Efficient Adsorption-Catalytic Oxidation.

The catalytic oxidation of toxic organic pollutants in water requires enhanced efficiency for commercial applications. A ZnO nanorod array grown on a carbon fiber cloth (CFC) serves as the zinc source to ensure that the Ni/ZIF-8/ZnO nanoreactor is constructed. The Ni/ZIF-8/ZnO/CFC nanoreactor efficiently activates peroxymonosulfate (PMS) for bisphenol A (BPA) degradation owing to its high density of active sites, high adsorbability, and dispersibility structure, which concentrates catalytic and adsorptive sites within a confined space. Experimental and theoretical calculations clearly show that the introduction of Ni is beneficial for improving the adsorption of BPA and the activation of PMS. The synergistic mechanism of BPA adsorption-PMS activation is also investigated, and the degradation pathway of BPA is examined. Moreover, a filter catalytic unit is constructed using Ni/ZIF-8/ZnO/CFC to achieve a continuous zero discharge of BPA, which is convenient for nanocatalyst recycling. This study aims to develop a new strategy for the removal of emerging organic pollutants from water using a system with strong adsorption and catalytic capabilities.

Whole grain consumption and risk of radiographic knee osteoarthritis: a prospective study from the Osteoarthritis Initiative.

OBJECTIVES: To assess the association of whole grain consumption with the risk of incident knee OA. MATERIAL AND METHODS: We followed 2846 participants in the Osteoarthritis Initiative ages 45-79 years. Participants were free from radiographic knee OA (Kellgren-Lawrence grade <2) in at least one knee at baseline. Dietary data from baseline were obtained using the Block Brief Food Frequency Questionnaire. We defined radiographic knee OA incidence as a Kellgren-Lawrence grade ≥2 during the subsequent 96 months. Cox proportional hazards models were used to assess the association between whole grain food intake and the risk of incident knee OA. RESULTS: During the 96 month follow-up, 518 participants (691 knees) developed incident radiographic knee OA. Higher total whole grain consumption was significantly associated with a lower knee OA risk [hazard ratio (HR)quartile 4vs1 = 0.66 (95% CI 0.52, 0.84), P for trend < 0.01] after adjusting for demographic and socio-economic factors, clinical factors and other dietary factors related to OA. Consistently, a significant inverse association of dark bread consumption with knee OA risk was observed [HRquartile 4vs1 = 0.68 (95% CI 0.53, 0.87), P for trend < 0.01). In addition, we observed a significant inverse association between higher cereal fibre intake and reduced knee OA risk [HRquartile 4vs1 = 0.61 (95% CI 0.46, 0.81), P for trend < 0.01). CONCLUSIONS: Our findings revealed a significant inverse association of whole grain consumption with knee OA risk. These findings provide evidence that eating a diet rich in whole grains may be a potential nutritional strategy to prevent knee OA.

Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human.

Inappropriate aggression in humans hurts the society, families and individuals. The genetic basis for aggressive behavior, however, remains largely elusive. In this study, we identified two rare missense variants in X-linked GRIA3 from male patients who showed syndromes featuring aggressive outbursts. Both G630R and E787G mutations in AMPA receptor GluA3 completely lost their ion channel functions. Furthermore, a guanine-repeat single nucleotide polymorphism (SNP, rs3216834) located in the first intron of human GRIA3 gene was found to regulate GluA3 expression with longer guanine repeats (rs3216834-10G/-11G) suppressing transcription compared to the shorter ones (-7G/-8G/-9G). Importantly, the distribution of rs3216834-10G/-11G was elevated in a male violent criminal sample from Chinese Han population. Using GluA3 knockout mice, we showed that the excitatory neurotransmission and neuronal activity in the medial prefrontal cortex (mPFC) was impaired. Expressing GluA3 back into the mPFC alleviated the aggressive behavior of GluA3 knockout mice, suggesting that the defects in mPFC explained, at least partially, the neural mechanisms underlying the aggressive behavior. Therefore, our study provides compelling evidence that dysfunction of AMPA receptor GluA3 promotes aggressive behavior.

Regulation of Crystal Structures and Solid-State Photoreactivity of Diolefin Coordination Polymers by Carboxylate Ligands.

Olefinic coordination polymers (CPs) have recently drawn more attention, owing to the many possibilities in conformational conversions and photochemical reactivity that olefin molecules offer. In the presence of different carboxylic acids, we utilize one diolefin ligand 4,4'-((1E,1'E)-(2,5-dimethoxyl-1,4-phenylene)bis(ethene-2,1-diyl))dipyridine (OCH3-bpeb) and Cd(II) to assemble six different crystalline CPs (1-6). By fine-tuning the substituent size, carboxyl group number, and geometrical configuration of carboxylate ligands, these diolefin CPs show quite different crystal architecture models, from one-dimensional intersecting stacking to one-dimensional parallel stacking to three-dimensional interpenetrated structure. Of these, four kinds of CPs (1, 2, 5, and 6) are demonstrated to be photoreactive for [2 + 2] cycloaddition reactions, as confirmed by proton nuclear magnetic resonance and single-crystal X-ray diffraction. Both 2 and 5 can be dimerized into different cyclobutane products in a single-crystal-to-single-crystal manner under visible light, and remarkably, the photocycloaddition reaction of 5 involves a rare phase transition with structural symmetry enhancement from P1̅ to P2/n. This work demonstrates the power of carboxylate ligands in tuning single crystal structures and photocycloaddition reactions of CPs, which provides important references for the further exploration of other physicochemical properties of functionalized olefin-containing complexes.

Reversible Single-Crystal-to-Single-Crystal Transformations between Nanoscale 2D Nanosheets and 3D Metal-Organic Frameworks.

Single-crystal-to-single-crystal (SCSC) transformations provide more possibilities for phase transitions, which have attracted great attention in crystal engineering. In this paper, we report a series of reversible SCSC transformations between nanoscale two-dimensional layered double hydroxide (LDH) crystals and three-dimensional metal-organic framework crystals. They can proceed not only in solution systems but also on the surface of solid-state polyacrylonitrile films and fibers. Specifically, reversible SCSC transformations can be carried out between nanoscale ZIF-67 and Co-LDH. The Co-LDH nanomaterials displayed excellent oxygen evolution reaction performance. This work has good universality and scalability, which provides a novel avenue for the synthesis of crystal materials and is of great significance for the recycling of resources.

Nacre-mimetic cerium-doped nano-hydroxyapatite/chitosan layered composite scaffolds regulate bone regeneration via OPG/RANKL signaling pathway.

Autogenous bone grafting has long been considered the gold standard for treating critical bone defects. However, its use is plagued by numerous drawbacks, such as limited supply, donor site morbidity, and restricted use for giant-sized defects. For this reason, there is an increasing need for effective bone substitutes to treat these defects. Mollusk nacre is a natural structure with outstanding mechanical property due to its notable "brick-and-mortar" architecture. Inspired by the nacre architecture, our team designed and fabricated a nacre-mimetic cerium-doped layered nano-hydroxyapatite/chitosan layered composite scaffold (CeHA/CS). Hydroxyapatite can provide a certain strength to the material like a brick. And as a polymer material, chitosan can slow down the force when the material is impacted, like an adhesive. As seen in natural nacre, the combination of these inorganic and organic components results in remarkable tensile strength and fracture toughness. Cerium ions have been demonstrated exceptional anti-osteoclastogenesis capabilities. Our scaffold featured a distinct layered HA/CS composite structure with intervals ranging from 50 to 200 µm, which provided a conducive environment for human bone marrow mesenchymal stem cell (hBMSC) adhesion and proliferation, allowing for in situ growth of newly formed bone tissue. In vitro, Western-blot and qPCR analyses showed that the CeHA/CS layered composite scaffolds significantly promoted the osteogenic process by upregulating the expressions of osteogenic-related genes such as RUNX2, OCN, and COL1, while inhibiting osteoclast differentiation, as indicated by reduced TRAP-positive osteoclasts and decreased bone resorption. In vivo, calvarial defects in rats demonstrated that the layered CeHA/CS scaffolds significantly accelerated bone regeneration at the defect site, and immunofluorescence indicated a lowered RANKL/OPG ratio. Overall, our results demonstrate that CeHA/CS scaffolds offer a promising platform for bone regeneration in critical defect management, as they promote osteogenesis and inhibit osteoclast activation.

Magnetic Fe3O4 nanoparticles decorated phosphorus-doped biochar-attapulgite/bismuth film electrode for smartphone-operated wireless portable sensing of ultra-trace multiple heavy metal ions.

Pollution caused by both forestry wastes and heavy metals has increasingly drawn attention owing to environmental safety concerns. After essential oil is extracted from Cinnamomum camphoras (L.), the branches are used as forestry wastes to prepare a phosphorus-doped biochar-attapulgite/bismuth film electrode decorated with magnetic Fe3O4 nanoparticles (MBA-BiFE). The smartphone-operated wireless portable sensor is employed for the simultaneous ultratrace voltammetric detection of multiple heavy metal ions (Cd2+, Pb2+, and Hg2+). Cd2+, Pb2+, and Hg2+ exhibit excellent electrochemical responses in linear ranges of 0.1 nM-5 µM, 0.01 nM-7 µM, and 0.1 nM-3 µM with limits of detection equal to 0.036, 0.003, and 0.011 nM, respectively. The recoveries of MBA-BiFE for Cd2+, Pb2+, and Hg2+ are 93.6-109.9%, 86.0-107.5%, and 94.8-104.6%, respectively, and the RSD values for repeated measurements of Cd2+, Pb2+, and Hg2+ are 4.2%, 2.8%, and 3.3%, respectively. A machine learning model based on an artificial neural network algorithm is constructed to enable a smart determination of ultratrace hazardous multiple metal ions. The portable sensor based on the screen-printed integrated three-electrode sensor modified using MBA-BiFE demonstrates advantages and practicability in outdoor detection, compared with conventional sensors based on MBA-BiFE. This study provides a smartphone-operated wireless portable sensing technique for high-potential applications in environmetallomics or agrometallomics using forestry waste-derived biochar as substrate for electrode preparation. HIGHLIGHTS: • Fe3O4 decorated phosphorus-doped biochar-attapulgite/bismuth film electrode. • A smartphone-operated sensor for analysis of multiple heavy metal ions. • An Artificial neural network model for smart analysis of Cd2+, Pb2+, and Hg2+.

Visible Light and Microwave-Mediated Rapid Trapping and Release of Singlet Oxygen Using a Coordination Polymer.

Due to its high reactivity and oxidative strength, singlet oxygen (1 O2 ) is used in a variety of fields including organic synthesis, biomedicine, photodynamic therapy and materials science. Despite its importance, the controlled trapping and release of 1 O2 is extremely challenging. Herein, we describe a one-dimensional coordination polymer, CP1, which upon irradiation with visible light, transforms 3 O2 (triplet oxygen) to 1 O2 . CP1 consists of CdII centers bridged by 9,10-bis((E)-2-(pyridin-4-yl)vinyl)anthracene ligands which undergo a [4+2] cycloaddition reaction with 1 O2 , resulting in the generation of CP1-1 O2 . Using microwave irradiation, CP1-1 O2 displays efficient release of 1 O2 , over a period of 30 s. In addition, CP1 exhibits enhanced fluorescence and has an oxygen detection limit of 97.4 ppm. Theoretical calculations reveal that the fluorescence behaviour is dominated by unique through-space conjugation. In addition to describing a highly efficient approach for the trapping and controlled release of 1 O2 , using coordination polymers, this work also provides encouragement for the development of efficient fluorescent oxygen sensors.

Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene.

AMPA-type glutamate receptors (AMPARs) are postsynaptic ionotropic receptors which mediate fast excitatory currents. AMPARs have a heterotetrameric structure, variably composed by the four subunits GluA1-4 which are encoded by genes GRIA1-4. Increasing evidence support the role of pathogenic variants in GRIA1-4 genes as causative for syndromic intellectual disability (ID). We report an Italian pedigree where some male individuals share ID, seizures and facial dysmorphisms. The index subject was referred for severe ID, myoclonic seizures, cerebellar signs and short stature. Whole exome sequencing identified a novel variant in GRIA3, c.2360A > G, p.(Glu787Gly). The GRIA3 gene maps to chromosome Xq25 and the c.2360A > G variant was transmitted by his healthy mother. Subsequent analysis in the family showed a segregation pattern compatible with the causative role of this variant, further supported by preliminary functional insights. We provide a detailed description of the clinical evolution of the index subjects and stress the relevance of myoclonic seizures and cerebellar syndrome as cardinal features of his presentation.

A BTB/POZ domain-containing protein negatively regulates plant immunity in Nicotiana benthamiana.

Plants have evolved immune systems to fight against pathogens. However, it is still largely unknown how the plant immunity is finely regulated. Here we identified a BTB/POZ domain-containing protein, namely NbBTB, which is predicted to be a member of the ubiquitin E3 ligase complex. The NbBTB expression is downregulated upon the oomycete pathogen Phytophthora parasitica infection. Overexpression of NbBTB in Nicotiana benthamiana promoted plant susceptibility to P. parasitica infection, and silencing NbBTB increased plant resistance to P. parasitica, indicating that NbBTB negatively modulates plant basal defense. Interestingly, overexpressing or silencing NbBTB did not affect plant resistance to two bacterial pathogens Ralstonia solanacearum and Pseudomonas syringae, suggesting that NbBTB is specifically involved in basal defense against oomycete pathogen. Expression of NbBTB suppressed hypersensitive response (HR) triggered by avirulence proteins from both R. sonanacearum and P. infestans, and silencing NbBTB showed the opposite effect, indicating that NbBTB negatively regulates effector-triggered immunity (ETI). Protein accumulation of avirulence effectors in NbBTB-silenced plants was significantly enhanced, suggesting that NbBTB is likely to negatively modulate ETI by affecting effector protein accumulation. Together, our results demonstrated that NbBTB is a negative regulator in both plant basal defense and ETI.

Cation/Anion Dual-Vacancy Pair Modulated Atomically-Thin Sex -Co3 S4 Nanosheets with Extremely High Water Oxidation Performance in Ultralow-Concentration Alkaline Solutions.

The density functional theory calculation results reveal that the adjacent defect concentration and electronic spin state can effectively activate the CoIII sites in the atomically thin nanosheets, facilitating the thermodynamic transformation of *O to *OOH, thus offering ultrahigh charge transfer properties and efficiently stabilizing the phase. This undoubtedly evidences that, for metal sulfides, the atom-scale cation/anion vacancy pair and surface electronic spin state can play a great role in enhancing the oxygen evolution reaction. Inspired by the theoretical prediction, interconnected selenium (Se) wired ultrathin Co3 S4 (Sex -Co3 S4 ) nanosheets with Co/S (Se) dual-vacancies (Se1.0 -Co3 S4 -VS/Se -VCo ) pairs are constructed by a simple approach. As an efficient sulfur host material, in an ultralow-concentration KOH solution (0.1 m), Se1.0 -Co3 S4 -VS/Se -VCo presents outstanding durability up to 165 h and a low overpotential of 289.5 mV at 10 mA cm-2 , which outperform the commercial Co3 S4 nanosheets (NSs) and RuO2 . Moreover, the turnover frequency of Se1.0 -Co3 S4 -VS/Se -VCo is 0.00965 s-1 at an overpotential of 0.39 V, which is 5.7 times that of Co3 S4 NSs, and 5.8 times that of commercial RuO2 . The finding offers a rational design strategy to create the multi-defect structure in catalysts toward high-efficiency water electrolysis.

Coordination Polymer-Mediated Molecular Surgery for Precise Interconversion of Dicyclobutane Compounds.

A Cd(II)-based coordination polymer {[Cd2(5-F-1,3-bpeb)2(FBA)4]·H2O}n (CP1) was obtained from Cd(II) salt, 5-fluoro-1,3-bis[2-(4-pyridyl)ethenyl]benzene (5-F-1,3-bpeb), and p-fluorobenzoic acid (HFBA). Within the one-dimensional chain structure of CP1, a pair of 5-F-1,3-bpeb was arranged in a face-to-face style. Upon UV irradiation and heat treatment, multiple cyclobutane isomers, including specific monocyclobutanes (1 with an endo-cyclobutane ring in CP1-1 and 1' with an exo-cyclobutane ring in CP1-1') and dicyclobutanes (endo,endo-dicyclobutane 2α in CP1-2α, exo,endo-dicyclobutane 2ß in CP1-2ß, and exo,exo-dicyclobutane 2γ in CP1-2γ) were stereoselectively produced. These isomers could be interconverted inside the CP via cutting/coupling specific bonds, which may be regarded as a type of molecular surgery. The precision of cutting/coupling relied on the thermal stability of the cyclobutanes and the alignment of the reactive alkene centers. The conversion processes were tracked through nuclear magnetic resonance, in situ powder X-ray diffraction, and IR spectroscopy. This approach can be considered as skeletal editing to construct complex organic compounds directly from one precursor.

The Role of Transvaginal Two-Dimensional Ultrasound Combined With Color Doppler in the Evaluation of Ovarian Function and Fertility After Uterine Artery Embolization.

OBJECTIVE: Our study seeks to assess the value of transvaginal two-dimensional ultrasound combined with color Doppler in evaluating ovarian function and reproductive function after uterine artery embolization (UAE). METHODS: Totally 64 cases with cesarean scar pregnancy (CSP) were collected. Their information was recorded, including baseline information, intraoperative and postoperative information, preoperative and postoperative uterine receptivity, and preoperative and postoperative levels of sex hormones in serum. Finally, the patients were followed up to observe whether they were pregnant after treatment. RESULTS: In comparison with 24 hours after UAE, decreases were found in endometrial blood flow pulsatility index (PI), endometrial thickness, ovarian artery peak end-systolic velocity (Vs), ovarian artery resistance index (RI), and the ratio of Vs to peak end-diastolic velocity (S/D) 1 and 3 months after embolization, while Vd increased markedly 3 months after embolization. In addition, in terms of sex hormones, a significant increase was revealed in the level of follicle-stimulating hormone, while the reduction in the levels of luteinizing hormone (LH), estrogen (E2), prolactin (PRL), and progesterone (P) in the first month and the third month of menstrual resumption compared with those before treatment. From the follow-up data, there were 50 cases of pregnancy, including 45 cases of intrauterine pregnancy, 2 cases of tubal pregnancy, and 3 cases of recurrent CSP. CONCLUSION: UAE is a safe and effective method to prevent massive hemorrhage of CSP. Transvaginal two-dimensional ultrasound combined with color Doppler can more accurately evaluate its therapeutic effect and provide a basis for effective treatment.

[Advances in Treatment of Human Epidermal Growth Factor Receptor 2-Positve Gastric Cancer].

Gastric cancer ranks as the fifth most common malignant tumor worldwide and the fourth leading cause of cancer-related deaths.Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer is a special type of gastric adenocarcinoma,the prognosis of which can be improved by trastuzumab plus cytotoxic chemotherapy such as cisplatin and fluorouracil.Pembrolizumab on the basis of Tmabplus chemotherapy can further improve the overall response rate,which has become the first-line standardized therapy against HER2-positive gastric cancer.However,there are still some obstacles such as the innate resistance to Tmab in specific populations.The research on HER2-targeted therapy provides clues for clinical decision-making.This review documents the current neoadjuvant and adjuvant therapies against late-stage HER2-positive gastric cancer,as well as the progress in novel HER2 pathway-targeted drugs.

circ-ZNF609: A potent circRNA in human cancers.

Circular RNAs (circRNAs) are a novel group of endogenous RNAs with a circular structure. Growing evidence indicates that circRNAs are involved in a variety of human diseases including malignancies. CircRNA ZNF609 (circ-ZNF609), derived from the ZNF609 gene sequence, has been demonstrated to be involved in the development and progression of many diseases. circ-ZNF609 is thought to be a viable diagnostic and prognostic biomarker for several diseases and might be a new therapeutic target, but further research is needed to accelerate clinical application. Here, we review the biogenesis and function of circRNAs and the functional roles and molecular mechanism related to circ-ZNF609 in neoplasms and other diseases.

16α-Bromoepiandrosterone as a new candidate for experimental diabetes-tuberculosis co-morbidity treatment.

Tuberculosis (TB) is the leading cause of death from a single bacterial infectious agent and is one of the most relevant issues of public health. Another pandemic disease is type II diabetes mellitus (T2D) that is estimated to affect half a billion people in the world. T2D is directly associated with obesity and a sedentary lifestyle and is frequently associated with immunosuppression. Immune dysfunction induced by hyperglycemia increases infection frequency and severity. Thus, in developing countries the T2D/TB co-morbidity is frequent and represents one of the most significant challenges for the health-care systems. Several immunoendocrine abnormalities are occurring during the chronic phase of both diseases, such as high extra-adrenal production of active glucocorticoids (GCs) by the activity of 11-ß-hydroxysteroid dehydrogenase type 1 (11-ßHSD1). 11-ßHSD1 catalyzes the conversion of inactive cortisone to active cortisol or corticosterone in lungs and liver, while 11-ß-hydroxysteroid dehydrogenase type 2 (11-ßHSD2) has the opposite effect. Active GCs have been related to insulin resistance and suppression of Th1 responses, which are deleterious factors in both T2D and TB. The anabolic adrenal hormone dehydroepiandrosterone (DHEA) exerts antagonistic effects on GC signaling in immune cells and metabolic tissues; however, its anabolic effects prohibit its use to treat immunoendocrine diseases. 16α-bromoepiandrosterone (BEA) is a water miscible synthetic sterol related to DHEA that lacks an anabolic effect while amplifying the immune and metabolic properties with important potential therapeutic uses. In this work, we compared the expression of 11-ßHSD1 and the therapeutic efficacy of BEA in diabetic mice infected with tuberculosis (TB) (T2D/TB) with respect to non-diabetic TB-infected mice (TB). T2D was induced by feeding mice with a high-fat diet and administering a single low-dose of streptozotocin. After 4 weeks of T2D establishment, mice were infected intratracheally with a high-dose of Mycobacterium tuberculosis strain H37Rv. Then, mice were treated with BEA three times a week by subcutaneous and intratracheal routes. Infection with TB increased the expression of 11-ßHSD1 and corticosterone in the lungs and liver of both T2D/TB and TB mice; however, T2D/TB mice developed a more severe lung disease than TB mice. In comparison with untreated animals, BEA decreased GC and 11-ßHSD1 expression while increasing 11-ßHSD2 expression. These molecular effects of BEA were associated with a reduction in hyperglycemia and liver steatosis, lower lung bacillary loads and pneumonia. These results uphold BEA as a promising effective therapy for the T2D/TB co-morbidity.